REFERENCE RANGES Most hematologic and biochemical reference ranges were established in-housc at the University o f Penn...
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REFERENCE RANGES Most hematologic and biochemical reference ranges were established in-housc at the University o f Pennsylvania using at least 65 dogs and cats that appeared healthy upon physical examination and had normal laboratory values. The Cell D y n 3500 was used for hematology, the O r t h o 350 for che mistries, and the Stago Compact for Coagulation Profiles. All readers are urged to use reference values specific for the laboratory or instrumentation device used when interpreting values for individual patients. Reference intervals depend on the region of the world/country, the type of sample (whole blood vs. plasma or serum), and the type of instrument that is being used.
Hematology Reference Ranges Value RBC
x 10
6
/nL
Canine
Feline
5.83-8.87
6.56-11.20
HGB (g/dl)
13.3-20.5
10.6-15.6
HCT (%)
40.3-60.3
31.7-48.0
PCV (%)
37-55
25-45
MCV (fl)
62.7-75.5
36.7-53.7
MCH (pg)
22.5-26.9
12.3-17.3
MCHC (g/dl)
32.3-36.3
30.1-35.6
RDW (g/dl)
13.2-17.4
16.7-22.9
PLTS (x10 /ml)
177-398
175-500
MPV (fl)
7.37-14.2
3
3
WBC ( x 1 0 /ml) 3
SEG/NEUT (x10 /ml) 3
BAND/NEUT (x10 /ml) 3
LYMPHS (x10' /ml) 3
MONOS (x10" /ml) EOS
(x 10
3
/ml) 3
BASO (x10 /ml)
5.3-19.8
4.04-18.70
3.1-14.4
2.3-14.0
0.0-0.2
0.0
0.9-5.5
0.8-6.1
0.1-1.4
0.0-0.7
0.0-1.6
0.0-1.5
0.0-0.1
0.0-0.1
Reference Ranges for Biochemical Parameters Value
Canine
Feline
Value
Canine
Feline
A/G ratio
0.7-1.5
Albumin (g/dl)
2.5-3.7
0.6-1.1
Folate (ug/dl)
7.5-17.5
7.5-17.5
2.4-3.8
GGT (U/L)
7-24
5-19
ALKP (U/L) ALT(U/L)
20-155
22-87
Globulin (g/dl)
2.4-4.0
3.1-5.0
16-91
33-152
Glucose (mg/dl)
65-112
67-168
Amylase (U/L)
339-1536
433-1248
Ionized calcium (mmol/L)
1.25-1.5
1.1-1.4
Anion Gap (mmol/L)
8-21
12-16
Ionized magnesium (mmol/L)
0.43-0.6
0.43-0.7
AST (U/L)
23-65
1-37
Iron (ug/dl)
94-122
68-215
0.3-0.9
0.1-0.8
Lactate (mmol/L)
0.5-2.0
0.5-2.0
Bili-T (mg/dl) BUN/creat ratio
9.0-33
10-24.6
Lipase (U/L)
72-1310
157-1715
Calcium (mg/dl)
9.8-11.7
9.1-11.2
Magnesium (mg/dl)
1.6-2.5
1.9-2.6
Calc osmol
264-292
287-307
Phosphorous (mg/dl)
2.8-6.1
3.0-6.6
Chloride (mEq/L)
109-120
116-126
PLI (ng/L)
4.4-276.1
1.2-3.8
Cholesterol (mg/dl)
128-317
96-248
Potassium (mEq/L)
3.9-4.9
3.5-4.8
CK (U/L)
46-467
49-688
Protein (g/dl)
5.4-7.1
6.0-8.6
C0 (mmol/L)
17-28
16-25
Sodium (mEq/L)
140-150
146-157
Cobalamin (ng/L)
284-836
276-1425
TIBC (ug/dl)
280-340
170-400
Colloid osmotic pressure (mm Hg)
17.94-21.96 (whole blood) 14.3-20.3 (plasma)
21-28.4 (whole blood) 17.4-22.2 (plasma)
TLI (ng/L)
5-35
28-115
Creatinine (mg/dl)
0.7-1.8
1.0-2.0
Triglyceride (mg/dl)
29-166
21-155
Fibrinogen (mg/dl)
200-400
200-400
Urea nitrogen (mg/dl)
5-30
15-32
2
Thyroid Function Test Reference Values
Liver Function Tests Reference Values
Canine
Feline
T (jig/dl)
1.52-3.60
1.2-3.8
T post-SH (ng/dl)
>3-4 fold
>3-4 fold
T (ng/dl)
48-154
T post-TSH (ng/dl)
>10 ng increase
4
4
3
3
TSH (mlU/L)
0.14
0.37
Canine
Feline
Ammonia (ng/dl)
45-120
30-100
NH3 post ATT (ng/dl)
Minimal change from normal
No change from normal
Bile acids—fasting (nM)
15 to 20 m m Hg) w i l l promote the for mation of pulmonary edema, further impairing oxygenation and overall oxygen transport. Despite potential benefits, the use of a P A C does not necessarily translate into reduced mortality in the critically i l l shock patient; it is an invasive monitoring technique that is not without r i s k . In addition, the accuracy o f measurements provided by the P A C relies o n catheter placement, calibration o f transducers, coexisting cardiac or pericardial disease, and correct interpretation o f waveforms and values. 2
10
Mixed Venous Oxygen Saturation (SvO ) and Central Venous Oxygen Saturation (ScvO ) 2
2
Changes i n the global tissue oxygenation (oxygen supply-todemand) can be assessed using S v O measurements. A s s u m ing V O is constant, S v O is determined by cardiac output, hemoglobin concentration, and S a O . S v O is decreased i f D O decreases (low C O , hypoxia, severe anemia) or i f V O increases (fever). W i t h conditions such as the hyperdynamic stages o f sepsis and cytotoxic tissue hypoxia (e.g., cyanide poisoning), S v O is increased. A reduction i n S v O may be an early indicator that the patient's clinical condition is dete riorating. In addition, S v O may be an alternative to measur ing cardiac index during resuscitative efforts. 2
2
2
2
2
2
2
2
2
2
Ideally, S v O is measured i n a b l o o d sample from the p u l monary artery. However, i n animals that do not have a P A C , venous oxygen saturation can be measured from the central circulation, using a central venous catheter i n the cranial vena cava. S v O is then termed S c v O (central venous oxy gen saturation). Although the S c v O values are generally higher than S v O i n critically i l l patients with circulatory failure, the two measurements closely parallel one another. Therefore a pathologically low S c v O likely indicates an even lower S v O . A recent prospective, randomized study c o m paring two algorithms for early goal-directed therapy in patients with severe sepsis and septic shock showed that maintenance of a continuously measured S c v O above 70% (in addition to maintaining central venous pressure above 8 to 12 m m H g , [ M A P ] pressure above 65 m m H g , and urine output above 0.5 ml/kg/hr) resulted i n a 15% absolute reduction in mortality compared to the same treatment without S c v O m o n i t o r i n g . T h o u g h it is not clear i f these exact parameters can be readily applied to veterinary patients, early recognition o f shock followed by aggressive 2
2
2
2
2
2
2
2
11
2
TREATMENT Treatment o f shock is based on early recognition o f the con d i t i o n and rapid restoration o f the cardiovascular system so that D O to the tissues is normalized as soon as possible. The mainstay o f therapy for all forms o f shock except that of shock o f cardiogenic origin is based o n rapid administra tion o f large volumes o f intravenous fluids to restore an effective circulating volume and tissue perfusion. Vascular access is essential for successful treatment o f shock, but can be difficult due to poor vascular filling and a collapsed car diovascular state. Since speed o f fluid administration is pro portional to the diameter o f the catheter lumen and inversely proportional to its length, short, large-bore catheters should be placed i n a central or peripheral vein. In cases i n which intravenous access is difficult or delayed due to cardiovascu lar collapse, a cut-down approach or intraosseous catheteri zation may be necessary (see Chapters 61 to 63, Peripheral Venous Catheterization, Intraosseous Catheterization, and Central Venous Catheterization, respectively). 2
The type o f fluid selected for the treatment o f shock may vary (see Chapter 65, Shock Fluids and Fluid Challenge). Replacement isotonic crystalloids such as lactated Ringer's solu tion, 0.9% sodium chloride (NaCl), or N o r m o s o l R form the mainstay of therapy for shock, administered rapidly at doses equivalent to 1 blood volume (90 ml/kg for the dog, 40 to 60 ml/kg for the cat). The administered fluid rapidly distributes into the extracellular fluid compartment so that only approxi mately 25% o f the delivered volume remains i n the intravascu lar space by 30 minutes after infusion, and some animals will therefore require additional resuscitation at this time point. In patients that are bleeding, it may even be advantageous to per form hypotensive resuscitation (to an M A P o f ~ 6 0 m m Hg) until the hemorrhage is controlled, because aggressive fluid therapy in this setting can worsen bleeding and outcome. For animals with coexisting head trauma, the isotonic crystal loid of choice is 0.9% N a C l because it contains the highest con centration of sodium and is least likely to contribute to cerebral edema. The "shock doses'' o f crystalloids serve as useful guide lines for fluid resuscitation o f the shock patient; however, the actual volume administered should be titrated according to the patient's clinical response in order to prevent volume over load. Excessive fluid administration is often evidenced by pulmonary or peripheral edema due to any combination of increased hydrostatic pressure, hypoalbuminemia, and increases i n vascular endothelial permeability. Animals with uncontrolled hemorrhage or deranged compensatory mechan isms may not respond adequately to crystalloid resuscitation and will require additional therapeutic, diagnostic, and m o n i toring strategies. Additional fluid therapy options i n these patients include synthetic colloid solutions, hypertonic saline, blood products, and hemoglobin-based oxygen carrying ( H B O C ) solutions. 12
13
Synthetic colloids such as hetastarch or dextran 70 are hyperoncotic to the n o r m a l animal and therefore p u l l fluid into the vascular space following intravenous administra tion. They therefore cause an increase i n b l o o d volume that is greater than that o f the infused volume and help to retain this fluid i n the intravascular space i n animals w i t h normal
capillary permeability. They are appropriately used for shock therapy i n acutely hypoproteinemic animals (total protein 40
3
16;
WBC (x10 ); % bands
>3%
>19 or 3.5g/dl) with a relatively low nucleated cell count (50% of the RR interval) SVT. Important identifying char acteristics and mechanisms of the more common SVTs are reviewed in Table 46-1 and Figure 46-1. The most commonly occurring SVTs in small animals appear to be atrial fibrilla tion, intraatrial reentrant tachycardia, orthodromic AV recip rocating tachycardia (a macroreentrant circuit in which an impulse is carried from the atria to the AV node-His¬ Purkinje system to the ventricles to a retrograde-conducting accessory pathway to the atria), and automatic atrial tachy cardia. Because the retrograde conduction properties of the canine AV node are poor, AV nodal reentrant tachycardia has not been identified in dogs undergoing electrophysio logic study for clinical tachyarrhythmias. 1
E X A M I N I N G THE E L E C T R O C A R D I O G R A M Distinguishing Supraventricular from Ventricular Tachyarrhythmias It is most important to distinguish ventricular tachyarrhythmias from SVTs because the treatment and differential diagnoses for each will differ. A narrow QRS complex tachyarrhythmia will almost always be an SVT. The vast majority of wide complex tachyarrhythmias are ventricular tachyarrhythmias. Up to 80% of wide complex tachyarrhythmias in human case series are ventricular in origin. If the patient has prior ECGs when in sinus rhythm or exhibits conversion, even briefly, to sinus rhythm during the tachyarrhythmia, the QRS complexes can be compared with those during tachyarrhythmia. Preexisting bundle branch block can thus be identified. Distinguishing ven tricular arrhythmias from SVTs with bundle branch aberration that develops during SVT or antegrade conduction of a tachy cardia over an accessory pathway (very rare in companion animals) is the most difficult task for the clinician. No criteria are absolute; however, the following rules are helpful : 1. Identification of P' waves (representing atrial depolari zation that originates outside the sinoatrial node) with a consistent relationship to the QRS is indicative of an SVT with aberration. In dogs undergoing electrophysio logic studies, retrograde AV nodal conduction is rare and has a long effective refractory period when it does occur. As many leads as possible should be run to iden tify P' waves. Lewis leads, using the right and left arm electrodes of the standard E C G placed on various 7
7,8
TREATMENT OF SUPRAVENTRICULAR TACHYARRHYTHMIAS It is essential to identify predisposing factors that are contrib uting to the initiation or perpetuation of SVT in a given patient. Acid-base abnormalities, electrolyte disturbances, significant anemia, and hypoxemia should be corrected. AV node-dependent tachyarrhythmias are treatment in some cases by single-agent therapy aimed at interrup ting conduction through the AV node. Other AV nodedependent SVTs require that an additional drug be added to suppress another site in the circuit. Atrial tachyarrhyth mias are best addressed by dual therapy: one drug to slow AV nodal conduction and a second drug to inhibit the atrial automatic focus or interrupt conduction in an atrial
Table 46-1 SVT Mechanism
Characteristics of Common Supraventricular Tachyarrhythmias Response to AV Block
P' Waves Visible?
P Wave Morphology
RP' vs. RR Interval Initiation and Termination
Automatic atrial
Yes
Variable, differs from sinus P
Varies with SVT Gradual rate acceleration rate, often long and deceleration
SVT continues
Intraatrial reentry
Yes
Variable, differs from sinus P
Varies with SVT Abrupt onset and offset at rate, often long SVT rate
SVT continues
Atrial flutter f Waves
Identical saw-toothed F waves
Not applicable
Abrupt onset and offset at SVT rate
SVT continues
Atrial fibrillation
No visible P waves; Not applicable f waves may be seen
Abrupt onset and offset at SVT rate, often incessant
SVT continues
Atrial
No, f waves may be seen
AV Node-dependent OAVRT
Often visible within ST-T segment
Retrograde: (-) in II, III, avF
Typically short
Abrupt onset and offset
SVT terminates
Automatic junctional
Generally yes; AV dissociation common
Variable
Variable
Gradual rate acceleration and deceleration
SVT continues with AV dissociation
AV nodal reentry
Generally no
Retrograde: (-) in II, III, avF
Short
Abrupt onset and offset
SVT terminates
AV, A t r i o v e n t r i c u l a r ; OAVRT, o r t h o d r o m i c a t r i o v e n t r i c u l a r r e c i p r o c a t e d t a c h y c a r d i a ; S V T , s u p r a v e n t r i c u l a r t a c h y c a r d i a .
F i g u r e 46-1 R e p r e s e n t a t i o n o f t h e m e c h a n i s m s a n d e l e c t r o c a r d i o g r a p h i c c h a r a c t e r i s t i c s of t h e m o r e c o m m o n s u p r a v e n t r i c u l a r t a c h y a r r h y t h m i a s . AP, A c c e s s o r y p a t h w a y ; AV, a t r i o v e n t r i c u l a r ; ECG, e l e c t r o c a r d i o g r a m ; LAF, left a n t e r i o r fascicle; LBB, left b u n d l e b r a n c h ; LPF, left p o s t e r i o r fascicle; RBB, right b u n d l e b r a n c h ; SA, sinoatrial. (From B o n a g u r a J D : Kirk's current veterinary therapy XIII, e d 13, P h i l a d e l p h i a , 2 0 0 0 , S a u n d e r s . )
reentrant circuit. Sites of antiarrhythmic drug action in SVT are shown in Figure 46-2. Emergent Therapy Animals in incessant, rapid SVT require interruption of the tachyarrhythmia. Vagal maneuvers may be tried first and may terminate the SVT if it is AV node dependent. Subjectively, the most effective vagal maneuver in small animals is carotid sinus massage. Sustained, gentle compression is applied for 5 to 10 seconds over the carotid sinus, which is located immediately caudal to the dorsal aspect of the larynx. The ECG needs to be monitored continuously throughout the procedure. More often, however, the SVT does not terminate with such maneu vers and drug therapy must be initiated. Parenteral negative dromotropic agents can be used to interrupt a tachyarrhythmic circuit that uses the AV node and is causing hemodynamic compromise. In atrial tachyar rhythmias, such agents will not terminate the arrhythmia but will slow conduction to the ventricles. Intravenous calcium channel blockers, β-blockers, or adenosine have been used for this purpose. Blood pressure and ECG should be moni tored before and throughout the procedure. A comparison of the electrophysiologic and hemody namic responses of intravenous diltiazem, esmolol, and adenosine in normal dogs demonstrated the superior efficacy of intravenous diltiazem in slowing AV nodal conduction while maintaining a favorable hemodynamic profile. Esmo lol was a significantly less effective negative dromotrope than diltiazem and caused a severe drop in left ventricular con tractility measurements at dosages which did prolong AV nodal conduction. Adenosine, even at dosages of 2 mg/kg, was ineffective in slowing canine AV nodal conduction. A similar study has not been performed in cats. Diltiazem is administered at dosages of 0.125 to 0.35 mg/kg slow IV over 2 to 3 minutes. A constant rate infusion (CRI) (0.125 to 0.35 mg/kg/hr) can be used if frequent recurrence of the arrhythmia occurs before the onset of efficacious oral antiarrhythmic therapy. Esmolol is an ultrashort-acting β -selective blocker that typically is administered at 0.5 mg/kg IV over 1 minute. Its brief half-life compared with that of propranolol makes esmolol the preferred parenteral (βblocker. It should nonetheless be used very cautiously in ani mals with impaired ventricular systolic function, because it will markedly depress ventricular contractility. 9
1,9
1
1
Other agents can prolong the effective refractory period or slow conduction within the myocardium, including an accessory pathway or atrial myocardium. These agents can terminate both atrial and AV node-dependent tachyar rhythmias. Of these, procainamide is the agent most com monly used in veterinary medicine. A sodium and potassium channel blocker, procainamide decreases abnor mal automaticity, slows conduction, and prolongs the effective refractory period in atrial (and ventricular), acces sory pathway, and retrograde fast AV nodal tissue. In atrial tachyarrhythmias, other agents are used first to slow AV nodal conduction before administration of procainamide. Parenteral procainamide is administered in dosages of 6 to 8 mg/kg IV over 5 to 10 minutes or 6 to 20 mg/kg IM in dogs. A CRI of 20 to 40 μg/kg/min can be used once a therapeutic response is obtained with bolus administration. Parenteral procainamide in cats is used cautiously at dosages of 1 to 2 mg/kg IV or 3 to 8 mg/kg IM and a CRI of 10 to 20 μg/kg/min. Direct current (DC) cardioversion or overdrive pacing can be used to terminate certain hemodynamically unstable, sustained SVTs. DC cardioversion in a proper critical care environment with appropriate hemodynamic and electro cardiographic monitoring offers certain distinct advantages over emergency drug therapy. The need to distinguish between supraventricular and ventricular tachyarrhythmias to design appropriate drug therapy is less important when DC cardio version is employed. Sinus rhythm may be restored immedi ately with successful D C cardioversion, avoiding the slower titration and potential side effects seen with parenteral drug administration. The need for general anesthesia (albeit brief) is a risk factor for DC cardioversion but should not preclude its use in patients who would benefit from it. DC cardioversion and overdrive pacing are effective in ter minating SVTs caused by reentry rather than abnormal auto maticity. Overdrive pacing can be performed without general anesthesia if the patient is depressed or moribund. The jugular furrow can be locally anesthetized with lidocaine, a catheter introducer placed in the external jugular vein, and a multipo lar catheter guided fluoroscopically into the right atrium (for intraatrial reentry) or ventricle (more effective for terminating orthodromic AV reciprocating tachycardia). The distal and second poles of this catheter are then attached to a program mable pacemaker. An electrophysiologic recorder (ideal but not necessary) or multilead surface ECG is used to continu ously record cardiac electrical activity. Once the myocardium is captured, the pacing rate is increased to 10 to 20 beats/min faster than the tachyarrhythmia rate. One-to-one capture is ensured for a brief period, and then pacing is stopped once intracardiac electrograms confirm termination of the SVT. If only the surface ECG is recorded, pacing is stopped after a brief period to determine if the tachyarrhythmia terminated. If not, a longer period or slightly faster pacing rate is used. Failure to terminate or rapid resumption of the tachyarrhyth mia can indicate either an SVT caused by an automatic mech anism or successful termination but then rapid reinitiation of a reentrant SVT. 10
Long-Term Therapy Medical Treatment F i g u r e 46-2 Sites of a c t i o n f o r v a r i o u s a n t i a r r h y t h m i c d r u g s , h i g h l i g h t i n g t h e i r utility f o r specific s u p r a v e n t r i c u l a r t a c h y a r r h y t h m i a s . AV, A t r i o v e n t r i c u l a r ; S A s i n o a t r i a l . ( F r o m B o n a g u r a J D : Kirk's current veteri nary therapy XIII, e d 1 3 , P h i l a d e l p h i a , 2 0 0 0 , S a u n d e r s . )
Long-term antiarrhythmic drug therapy must be tailored to each patient based on the type of SVT, the presence or absence of congestive heart failure or structural heart disease,
comorbid conditions (particularly hepatic or renal dysfunc tion, acid-base disturbances, or endocrine diseases that alter the metabolism of specific antiarrhythmic drugs), and con current drug administration. Atrial tachyarrhythmias typi cally are managed by dual antiarrhythmic therapy, one drug to slow AV nodal conduction and a second to terminate the atrial tachyarrhythmia itself. This general rule is violated when persistent atrial fibrillation is present, when rate con trol becomes the goal. AV node-dependent tachyarrhythmias sometimes will respond to single agent therapy aimed at slowing AV nodal conduction. In reality, however, these tachyarrhythmias often are managed by combination ther apy as well. For instance, with orthodromic AV reciprocating tachycardia, one agent is used to slow AV nodal conduction and a second agent is used to block conduction or prolong the effective refractory period within an accessory pathway. Drugs that slow AV nodal conduction include the classes that were discussed under emergency therapy. The three major classes include: digitalis glycosides, calcium channel blockers, and β-blockers. Animals with systolic dysfunction classically are placed on digoxin as a first-line negative dromo¬ trope (0.005 to 0.01 mg/kg PO ql2h in a normokalemic dog with normal renal function; 0.0312 mg PO q24-48h in a nor mokalemic cat with normal renal function). The ventricular rate is almost never slowed adequately with digoxin as a single agent, however, and other drugs must be added. The calcium channel blocker diltiazem is effective in prolonging the effective and functional refractory periods of the AV node. This effect is most notable at faster stimulation rates (use dependence) and in depolarized fibers (voltage dependence). Diltiazem has gained preference over verapamil because of its more favorable hemodynamic profile (i.e., minimal negative inotropic effect) at effective antiarrhythmic dosages. Diltiazem is administered 3 times a day, which can be difficult particularly for cat owners. Sus tained release preparations, however, appear to have more variable absorption in companion animals, with resultant poorer arrhythmia control. Such preparations also have had a high incidence of side effects in cats, including vomiting, inappetence, and hepatopathies. 10
9
Atenolol is a relatively β1-selective blocker that competi tively inhibits the effects of catecholamines on cardiac βreceptors. Thus, underlying sympathetic tone plays an important role in determining the effectiveness of atenolol in prolonging AV nodal conduction and refractoriness or suppressing abnormal atrial foci. Because of its negative inotropic effects, the dosages required to affect AV nodal conduction significantly are often not well tolerated by ani mals with left ventricular (LV) systolic dysfunction. The ben eficial effects of β-adrenergic blockade in the face of impaired LV systolic function have been well demonstrated in human patients; therapy must begin at very low dosages and up-titration performed very slowly. Patients with rapid SVTs do not have the luxury of this prolonged time for con trol of their ventricular rate. Remember that the rapid ven tricular rate is worsening or may be the sole cause for their myocardial dysfunction. Atenolol is particularly useful in cats with hypertrophic cardiomyopathy and SVTs. Because of its renal clearance, the dosage of atenolol must be decreased in the face of concurrent renal disease. 9,10
11
Class I antiarrhythmic drugs block fast sodium channels and thus suppress abnormal automaticity and slow myocar dial conduction velocity. The most commonly used class I drug in small animals with SVT is procainamide, a class la drug that also prolongs repolarization through its potassium channel blocking capabilities. Oral procainamide typically is used as an extended release preparation, administered 10 to 30 mg/kg PO q8h in dogs and 3 to 8 mg/kg PO q8h in cats. Poor absorption of sustained release procainamide prepara tions can limit their effectiveness in certain animals. The need for 2-hour to 6-hour dosing of formulations that are not extended release makes compliance nearly impossible. GI side effects can be prominent, and proarrhythmia is a definite concern with long-term procainamide therapy. Class III antiarrhythmic agents are used to prolong the effective refractory period of atrial myocardium and acces sory pathways. Sotalol and amiodarone, the two agents used in small animals, have additional antiarrhythmic actions, including slowing of AV nodal conduction. Sotalol typically is administered at 1 to 2 mg/kg PO q8h for SVTs, but amio darone dosing varies and typically includes a loading period. The author uses 15 mg/kg q24h for 7 days, then 10 mg/kg q24h for 7 days, then 5 mg/kg q24h for mainte nance. Serum amiodarone levels can be measured but may not correlate with tissue concentrations. The high incidence of reported side effects in dogs receiving long-term amiodar one therapy has limited its widespread use. Amiodarone has not been used in cats. 9
9,12
Catheter Ablation Certain SVTs can be cured, rather than simply controlled, with transvenous radiofrequency catheter ablation. The tachyarrhythmia circuit is first mapped with numerous multielectrode catheters. Once, for example, an accessory pathway is identified, detailed mapping is used to locate pre cisely the pathway along the AV groove. A specialized cathe ter with a 4-mm to 5-mm distal electrode is positioned at this critical site, and radiofrequency energy is delivered to the tip electrode causing thermal dessication of a small vol ume of tissue, to permanently interrupt the tachycardia cir cuit. This technique has been used by this author and others in a number of canine cases. 6,13
SUGGESTED FURTHER READING* Moise NS: Electrocardiography and cardiac arrhythmias. In Ettinger S, Feldman B, editors: Textbook of veterinary medicine, ed 6, St Louis, 2005, Saunders. An excellent review chapter of the basic ECG, arrhythmias, and antiarrhythmic drugs for the small animal clinician. Wright K N : Assessment and treatment of supraventricular tachyarrhyth mias. In Bonagura ID, editor: Kirk's current veterinary therapy XIII, ed 13, St Louis, 2000, Saunders. A good, brief overview of supraventricular tachyarrhythmias in companion animals. Wright K N : Interventional catheterization for tachyarrhythmias. In Abbott JA, editor: Veterinary clinics of North America: small animal practice, Philadelphia, 2004, Saunders. An excellent review of the progress made in the field of catheter ablation ther apy to cure certain tachyarrhythmias in dogs. *See the C D - R O M for a complete list of references.
Chapter 47 VENTRICULAR TACHYARRHYTHMIAS Romain Pariaut,
DVM, DACVIM (Cardiology), DECVIM-CA (Cardiology)
K E Y POINTS • W i d e Q R S c o m p l e x tachycardia w i t h atrioventricular dissociation, fusion beats, a n d c a p t u r e beats are electrocardiographic features d i a g n o s t i c o f v e n t r i c u l a r t a c h y c a r d i a (VT). • C l i n i c a l signs s e c o n d a r y t o V T a r e d e t e r m i n e d by its rate a n d duration. • T h e m o s t c o m m o n n o n c a r d i a c causes o f V T are h y p o x e m i a , electrolyte i m b a l a n c e s ( h y p o k a l e m i a ) , a c i d - b a s e disorders, a n d d r u g s . • T h e m o s t c o m m o n c a r d i a c diseases a s s o c i a t e d w i t h clinical V T a r e B o x e r c a r d i o m y o p a t h y a n d d i l a t e d c a r d i o m y o p a t h y in D o b e r m a n Pinschers. • Antiarrhythmic medications d o not prevent sudden death. • A n t i a r r h y t h m i c t h e r a p y is i n i t i a t e d if clinical signs a s s o c i a t e d w i t h V T are present. • W h e n the origin (supraventricular or ventricular) of a w i d e Q R S t a c h y c a r d i a c a n n o t b e d e t e r m i n e d , it m u s t b e m a n a g e d as if it were VT. • L i d o c a i n e is t h e f i r s t - c h o i c e p a r e n t e r a l a n t i a r r h y t h m i c d r u g f o r t r e a t m e n t o f V T in d o g s .
INTRODUCTION Physiologically, specialized ventricular cells, known as Purkinje fibers, may work as a pacemaker when the sinus and atrioventricular nodes fail to function appropriately, resulting in a ventricular escape rhythm or idioventricular rhythm at a rate of about 30 to 40 beats/min in dogs and 60 to 130 beats/min in cats. Three arrhythmogenic mechan isms known as enhanced automaticity, triggered activity, and reentry (Box 47-1) may affect Purkinje cells or any excitable ventricular myocyte and result in ventricular tachycardia (VT). They result in a ventricular rhythm faster than the physiologic idioventricular rhythm. Most human cardiolo gists define VT as three or more consecutive ventricular beats occurring at a rate faster than 100 beats/min, the conventional upper limit for normal sinus rhythm. In our patients, normal sinus rhythm can probably reach 150 to 180 beats/min in dogs and 220 beats/min in cats. These rates define the lower limit for VT. If a ventricular rhythm is faster than the physiologic idioventricular rhythm and slower than VT, it is called acceler ated idioventricular rhythm (AIVR). The rate of an AIVR is within the range of the underlying sinus rhythm. Therefore both rhythms are seen competing on a surface electrocardio gram (ECG) because the faster pacemaker inhibits the slower one, a property known as overdrive suppression. Besides rate, an important feature of VT is duration, because both deter mine the clinical consequences of the arrhythmia. V T is described as nonsustained if it lasts less than 30 seconds and sustained if it lasts longer. 1,2
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Box 47-1 Electrophysiologic Mechanisms of Ventricular Tachycardia Reentry: Requires an impulse to leave a point of departure and return to its starting point with a sufficient delay that the cardiac tissue has recovered its excitability. It usually circles around an area of nonconductive tissue (fibrosis, vessel). Shortening of the refrac tory period and slow conduction favor this self-perpetuating mechanism. Enhanced automaticity: A myocardial cell that never possessed the property of automaticity while healthy gets the ability to depo larize spontaneously when depressed. Its membrane potential is less negative, and the action potential becomes similar to that of the sinus node. Triggered activity: Results from small membrane depolarizations that appear after and are dependent on the upstroke of the action potential. They trigger an action potential when they reach the threshold potential. When they occur during the process of repolar ization they are called early afterdepolarizations (EADs), and when they occur after full repolarization they are called delayed afterdepo larizations (DADs). Hypokalemia and drug-induced prolongation of the Q T segment increase the risk of EADs. D A D s occur second ary to intracellular calcium overload associated with sustained tachycardia and digoxin toxicity.
E L E C T R O C A R D I O G R A P H I C DIAGNOSIS In the intensive care unit, V T is first suspected on physical examination or detected on a continuous ECG monitor. Confirmation of V T relies on a good-quality 6-lead to 12-lead surface E C G recording with the patient placed in right lateral recumbency. Ventricular tachycardia is identified as a broad QRS tachycardia with complexes wider than 0.06 second in dogs and 0.04 second in cats. Each QRS complex is followed by a large T wave, directed opposite to the QRS deflection. The challenge of ECG interpretation is to differentiate VT from supraventricular tachycardias (SVTs) with broad QRS complexes because of aberrant conduction of the electrical impulse within the ventricles. Aberrant ventricular conduc tion results from a structural bundle branch block, a func tional or rate-related bundle branch block, or finally an accessory atrioventricular pathway causing preexcitation. The three most reliable diagnostic criteria of V T are atrioventricular dissociation, fusion beats, and capture beats (Figure 47-1). Atrioventricular dissociation is demonstrated when P waves are occasionally seen on the ECG tracing but are not related to ventricular complexes. These P waves reflect atrial activity independently from the ventricle. 4
F i g u r e 47-1 E l e c t r o c a r d i o g r a p h i c r e c o r d i n g f r o m a d o g ; p a p e r s p e e d is 2 5 m m / s e c . T h e r e is v e n t r i c u l a r t a c h y c a r d i a (V) at a rate of 1 5 0 b e a t s / m i n . P w a v e s (p) n o t related t o t h e w i d e Q R S c o m p l e x e s (V) i n d i c a t e a t r i o v e n t r i c u l a r ( A V ) d i s s o c i a t i o n . T h e r e a r e f u s i o n b e a t s (F) w i t h a n i n t e r m e d i a t e m o r phology a n d c a p t u r e b e a t s (C). N o t e t h a t t h e PR interval o f t h e c a p t u r e b e a t is p r o l o n g e d c o m p a r e d w i t h a n o r m a l sinus b e a t (S). It results f r o m r e t r o grade d e p o l a r i z a t i o n of t h e A V n o d e by t h e p r e c e d i n g v e n t r i c u l a r i m p u l s e a n d s e c o n d a r y s l o w i n g o f t h e p r o p a g a t i o n of t h e sinus i m p u l s e in a partially refractory n o d e , a p h e n o m e n o n k n o w n as concealed AV conduction.
On occasion apparent atrioventricular association may be seen, or ventricular beats can conduct in a retrograde fashion to the atrium in a 1:1 ratio. Therefore signs of atrioventricu lar association do not rule out VT. Fusion beats and capture beats are seen with paroxysmal V T and AIVR. Fusion beats result from the summation of a ventricular impulse and a simultaneous supraventricular impulse resulting in a QRS complex of intermediate morphology and preceded by a P wave (unless there is concurrent atrial fibrillation). A cap ture beat is a supraventricular impulse conducting through the normal conduction pathways to the ventricle during an episode of VT or AIVR. This complex occurs earlier than expected and is narrow if the conduction system is intact. Regularity of the rhythm is a less accurate criterion because VT can be slightly irregular. When the RR interval varies by 100 msec or more, it is suggestive of atrial fibrillation with aberrant ventricular conduction. Other criteria have been sug gested by human cardiologists to make the correct diagnosis; for example, QRS complexes are usually wider with V T than with SVT. Although rarely effective, vagal maneuvers can be done to slow the atrioventricular conduction, revealing P waves associated to the QRS complexes in case of SVT. It is also important to consider the overall clinical picture. For exam ple, Boxers and Doberman Pinschers usually have VT. Finally, it is accepted that managing SVT as VT is usually less danger ous than the opposite, because drugs used to stop SVT or to slow the ventricular response rate to rapid atrial impulses (i.e., calcium channel blockers and β-blockers) do not inter rupt VT and worsen hypotension with their vasodilatory or negative inotropic effects. 4
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If doubt persists, treat as if it were VT. A P P R O A C H TO THE PATIENT WITH VENTRICULAR T A C H Y C A R D I A Once VT is confirmed on a surface ECG, the possible causes for the initiation and maintenance of the arrhythmia must be identified. The knowledge will help planning an effective treat ment protocol and predicting the short-term and long-term
prognoses. It is useful to differentiate cardiac from noncardiac causes of VT. Noncardiac Causes of Ventricular Tachycardia Ventricular cells are sensitive to hypoxemia, electrolyte and acid-base imbalances, sympathetic stimulation, and various drugs. These changes typically affect the passive and energydependent ion exchanges across the cellular membrane of the myocyte during the initiation and propagation of the action potential. Hypokalemia is the most commonly reported electrolyte disturbance responsible for or contributing to VT. It increases phase 4 depolarization, increasing spontaneous automaticity, and prolongs the action potential duration, which promotes arrhythmias from triggered activity/ Because digoxin com petes with potassium on its receptors, hypokalemia increases the risk of digoxin toxicity. Similar arrhythmias result from hypomagnesemia, because magnesium is necessary for proper functioning of the sodium-potassium ATP pump, which maintains normal intracellular potassium concentration. Hypocalcemia and hypercalcemia are also responsible for ventricular arrhythmias. Increased adrenergic tone potentiates arrhythmias through various mechanisms. In the intensive care unit, drugs with sympathetic or sympatholytic activity are used commonly and should be stopped when possible to assess their role in the perpetuation of VT. It is also important to evaluate the potential proarrhyth¬ mic effects of all the medications given to a patient with VT. There are many publications on drug-induced prolonga tion of the QT segment. Prolongation of the QT segment reflects prolongation of the cardiac cell membrane repolari zation and indicates a risk of ventricular arrhythmia from triggered activity. Antiarrhythmic drugs, such as procaina mide and sotalol, but also domperidone, cisapride, chlor¬ promazine, and erythromycin, are known to prolong the QT segment. Bradycardia and hypokalemia contribute to this effect on repolarization and increase the risk of VT. 6
Oxygen therapy, identification and correction of all elec trolyte disturbances, and discontinuation of proarrhythmic medications are the initial and necessary first steps in the treatment of all patients with VT. Cardiac Causes of Ventricular Tachycardia In most patients with VT an echocardiogram is indicated as soon as possible to identify an underlying cardiac disease as the cause for the arrhythmia. In humans the association of sustained V T and heart failure is a marker of increased risk of sudden death from arrhythmia, and this is probably true in our patients as well. Identification of cardiac disease may help to elaborate an effective treatment strategy, to know what to expect from the intervention, and to give the most accurate prognosis to the owner. Today there is valuable information on some breed-specific VTs. VT is on occasion observed in patients with cardiac tumors (with or without associated tamponade), myocardi tis, endocarditis, and acute coronary events associated with hypothyroidism. VT is an important part of the clinical picture of dilated cardiomyopathy in some breeds. The prevalence of ventricu lar arrhythmias was 21% in a pool of breeds with dilated cardiomyopathy, 16% in Newfoundlands and 92% in Dober¬ man Pinschers. The natural history of the disease has been studied extensively in Doberman Pinschers. There is an occult stage of the disease with no clinical signs but with echocardiographic indicators of left ventricular dysfunction and a risk of sudden death of approximately 30%. It can last 2 to 4 years. In the overt stage of the disease, congestive heart failure is present and the risk of sudden death is about 30% to 50%. In Doberman Pinschers, most ventricular ectopies have a right bundle branch block morphology in lead II of the surface ECG, indicating their origin in the left ventricle. Cardiomyopathy of Boxers is known as arrhythmogenic right ventricular cardiomyopathy (ARVC). It is an adult-onset disease with a concealed form characterized by occasional ventricular ectopies only, followed by an overt form with VT associated with exercise intolerance and collapse. On occasion myocardial failure is observed. In ARVC, ventricu lar ectopies typically have a left bundle branch block mor phology, indicating their right-sided origin. An inherited ventricular arrhythmia has been identified in some German Shepherds. In the most severe form of the dis ease these dogs have a propensity for sudden death until 18 months of age. The form of V T responsible for sudden death is polymorphic, rapid (more than 300 beats/min), nonsustained, and usually preceded by a pause. Dogs with severe subaortic stenosis and pulmonic stenosis are prone to syncope and sudden death. VT progressing to ven tricular fibrillation may contribute to some of these episodes. In cats, V T may be seen in association with idiopathic hypertrophic cardiomyopathy and with concentric hypertro phy secondary to hypertension and hyperthyroidism. 7
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ANTIARRHYTHMIC TREATMENT
medicine, there is no indication that antiarrhythmic agents can prevent sudden death, and on some occasions they may precipitate it. Hemodynamic compromise usually is associated with rapid (more than 200 beats/min) and sustained V T in a patient with concurrent cardiac disease. Slower nonsustained VT and AIVR are usually auscultatory or ECG findings in patients with motor vehicle-related trauma, gastric dilatationvolvulus, or metabolic imbalances and resolve spontaneously, with no antiarrhythmic medications within 4 days. Some ECG characteristics of VT are viewed as indicators of an increased risk for sudden death and may influence the decision of the clinician toward treatment. Hemodynamic col lapse is more likely to result from polymorphic VT, which is characterized by a continuously changing QRS complex pat tern, than monomorphic VT. Antiarrhythmic agents are generally considered for sustained VT with rates greater than 180 to 200 beats/min. The presence of polymorphic VT may encourage treatment at the lower rate range. "R-on-T phenom enon" describes the superimposition of an ectopic beat on the T wave of the preceding beat. Some observations suggest that it may represent an increased risk for VT and sudden death from ventricular fibrillation. Nevertheless strong evidence is lacking and this finding by itself cannot justify treatment. Regardless of its cause, rate, duration, or morphology, the decision to treat V T with antiarrhythmic medications must be dictated primarily by the clinical signs related to it. 7
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Antiarrhythmic Drugs A few antiarrhythmic agents will manage most VTs. Because studies in veterinary medicine are lacking and antiarrhyth mic medications are complex drugs with many side effects including proarrhythmic effects, it is important to gain expe rience with only a few commonly used drugs. Lidocaine Lidocaine is the first-choice intravenous agent to control VT. It works better on rapid VTs and in normokalemic animals. In dogs boluses of 1 to 2 mg/kg can be repeated every 10 to 15 minutes. A maximum dose of 8 mg/kg/hr is recom mended to avoid neurotoxic effects. The arrhythmia can be controlled over time with a continuous infusion of lidocaine at a rate between 25 and 80 μg/kg/min. In cats, the safety margin is smaller and lower dosages of lidocaine can be used, but β-blockers usually are preferred. Mexiletine has properties similar to those of lidocaine and is available as an oral medication. Mexiletine, 4 to 8 mg/kg q8h, combined with atenolol, 0.5 mg/kg ql2-24h, has been shown to control VT in Boxers with A R V C . 9,12
Procainamide Procainamide is used intravenously for VTs that do not respond to lidocaine. A bolus of 10 to 15 mg/kg over 1 to 2 minutes can be followed by a constant rate infusion at 25 to 50 μg/kg/min. Rapid intravenous injection can cause hypo tension. Long-term management of VT can be attempted with oral procainamide at 10 to 20 mg/kg q6h, or q8h if the sustained-release form is used. 12
Decision to Treat
β-Blockers
Antiarrhythmic agents are indicated to treat symptomatic VT and prevent its recurrence. Despite many large-scale rando mized studies in humans and a few publications in veterinary
Sympathetic activation has been implicated in the patho genesis of ventricular arrhythmia. β-Blockers provide adren ergic system blockade and may help control arrhythmias.
Esmolol is a short-acting β-blocker that can help control sympathetically driven VTs such as those associated with pheochromocytoma or thyrotoxic disease in cats, but its negative inotropic effects may be too pronounced in some patients and cause cardiovascular collapse. Sotalol Sotalol is an oral medication usually effective in controlling VT. It was the second most effective treatment protocol after a combination of mexiletine and atenolol in Boxers with ARVC. In Boxers, sotalol usually is given at 2 mg/kg q l 2 h . 9,12
POSTINTERVENTION M O N I T O R I N G Because the response to antiarrhythmic agents cannot be predicted, continuous E C G monitoring is essential after the medication is started and for a minimum of 24 hours. It will give valuable information on the control of the arrhythmia and the possible proarrhythmic effects of the drugs. Twentyfour hour Holter recording is more adapted to long-term management of the arrhythmia.
SUGGESTED FURTHER
READING*
Kittleson M D : Diagnosis and treatment of arrhythmias (dysrhythmias). In Kittleson M D , Kienle RD, editor: Small animal cardiovascular medicine, St Louis, 1999, Mosby. Complete review of supraventricular and ventricular arrhythmias featuring many ECG tracings. Meurs K M : Boxer cardiomyopathy: an update. In Abbott IA, editor: Veteri nary Clinics of North America current issues in cardiology, Philadelphia, 2004, Saunders. Excellent review on Boxer cardiomyopathy. Presents the studies that led to the reclassification of the disease as arrhythmogenic right ventricular dysplasia. Moise NS: Diagnosis and management of canine arrhythmias. In Fox RP, Sisson D, Moise NS, editors: Textbook of canine and feline cardiology. Prin ciples and clinical practice, Philadelphia, 1988, Saunders. Describes the mechanisms of action and use of antiarrhythmic drugs. Details their effects at the cellular level. O'Grady MR, O'Sullivan M L : Dilated cardiomyopathy: an update. In Abbott JA, editor: Veterinary Clinics of North America current issues in cardiology, Philadelphia, 2004, Saunders. Review of dilated cardiomyopathy in dogs with emphasis on Doberman cardiomyopathy. Marriott H(L, Boudreau Conover M : Arrhythmogenic mechanisms and their Modulation. In Marriott H | L , Boudreau Conover M , editors: Review of the electrophysiologic mechanisms of arrhythmia: advanced concepts in arrhythmias, ed 3, St Louis, 1998, Mosby. *See the C D - R O M for a complete list of references.
Chapter 48 MYOCARDITIS Meg Sleeper,
VIVID, DACVIM (Cardiology)
KEY POINTS
canine myocarditis are most common in immunocompro mised or immunonaive patients.
• Myocarditis is a n i n f l a m m a t o r y process involving t h e heart. Inflammation m a y involve t h e m y o c y t e s , interstitium, o r vascular tree. • Myocarditis h a s b e e n a s s o c i a t e d w i t h a w i d e variety o f diseases. Infectious a g e n t s (viral, b a c t e r i a l , p r o t o z o a l ) m a y c a u s e m y o c a r d i a l damage by myocardial invasion, p r o d u c t i o n of myocardial toxins, or activation of i m m u n e - m e d i a t e d d i s e a s e . • Myocarditis c a n also be a s s o c i a t e d w i t h physical a g e n t s (doxorubicin), u n d e r l y i n g m e t a b o l i c d i s o r d e r s (uremia), t o x i n s (heavy metals), or physical a g e n t s (heat stroke).
INTRODUCTION Myocarditis is a rare cause of heart failure in dogs and extremely rare in cats. Clinical features vary, including those of asymptomatic patients who may have electrocardiographic abnormalities and patients with or without heart enlarge ment, systolic dysfunction, or even full-blown congestive heart failure (CHF). The patient's history (i.e., environment and exposure) is often critical in determining likely risk and suggesting appropriate diagnostic tests. Clinical reports of
INFECTIOUS M Y O C A R D I T I S Viral Myocarditis Numerous viruses have been associated with myocarditis in humans. In dogs, viral myocarditis appears most com monly in immunonaive patients, and the virus most commonly associated with the disease is parvovirus. However, at this time the entity appears to be very rare. In the late 1970s and early 1980s, when the parvovirus pandemic first was recognized, puppies did not receive maternal antibo dies and very young puppies developed a fulminant infection with acute death due to pulmonary edema when exposed to the virus. Older puppies (2 to 4 months) often died subacutely from CHF, but others developed a milder myocar ditis and later developed dilated cardiomyopathy ( D C M ) usually as young adults. Basophilic intranuclear inclusion bodies are found in the myocardium of acutely affected younger puppies, but may be absent in older puppies.'
Older dogs typically have gross myocardial scarring. Rare cases of parvovirus-induced myocarditis have been reported since the early to mid-1980s. Rarely, other viruses have been associated with myocardi tis in dogs. In 2001, Maxson and others evaluated myocar dial tissue from 18 dogs with an antemortem diagnosis of D C M and 9 dogs with a histopathologic diagnosis of myocarditis based on a polymerase chain reaction analysis to screen for canine parvovirus, adenovirus types 1 and 2, and herpesvirus. Canine adenovirus type 1 was amplified from myocardium of only one dog with D C M and none of the dogs with myocarditis, suggesting these pathogens are not commonly associated with D C M or active myocarditis in the dog. Distemper virus-associated cardiomyopathy with a mild inflammatory infiltrate has been produced by experimental infection of immunonaive puppies. Natural infection with West Nile virus was associated with myocardi tis in a wolf and a dog in 2002, the third season of the West Nile virus epidemic in the United States. Viral genomic deoxyribonucleic acid has also been identified in feline myo cardial tissue from patients with hypertrophic cardiomyo pathy, D C M , and restrictive cardiomyopathy, suggesting that viral myocarditis may be a factor in these feline-acquired diseases. 2
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were seroreactive to Bartonella vinsonii subspecies. Lyme dis ease (secondary to infection by the spirochete Borrelia burg dorferi) has been implicated as a cause of myocarditis in dogs, but documented cases are rare. Clinical signs are often vague and nonspecific, and serologic testing is not a reliable method to determine active infection. In humans, Lyme myocarditis may be due to direct toxic effects or immunemediated mechanisms, and the disease is usually selflimiting. Fungal infections of the myocardium are extremely rare but have occurred in immunocompromised patients. A group of cats was described with transient fever and depression that appeared to be infectious in nature. Postmor tem examination revealed microscopic lesions consistent with myonecrosis and an inflammatory cell infiltrate. A viral etiol ogy was suspected, but no organism was identified. In a retrospective study reviewing 1472 feline necropsies over a 7-year period, 37 cases were diagnosed with endomyocardi¬ tis. The cats with endomyocarditis had a mean age at death of 3.4 years, and 62% of them had a history of a stressful event 5 to 10 days before being brought for treatment. Interstitial pneu monia was present in 77% of the cats at postmortem examina tion. Special stains for bacteria and fungi were negative. Parasitic agents can also lead to myocarditis. Toxoplasma gondii bradyzoites can encyst in the myocardium, resulting in chronic infection. Eventually the cysts rupture, leading to myocardial necrosis and hypersensitivity reactions. Neos¬ pora caninum can infect multiple tissues, including the heart, peripheral muscles, and central nervous system. Clinical signs associated with noncardiac tissues typically predomi nate; however, collapse and sudden death has been reported in affected dogs. Infestation with Trichinella spiralis is a common cause of mild myocarditis in humans. The par asite has been associated with at least one case of canine myocarditis complicated by arrhythmias (Figure 48-1). 1
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Protozoal Myocarditis Chagas Disease Chagas disease is caused by Trypanosoma cruzi, a protozoal parasite. Chagas disease is the leading cause of D C M in humans of Latin America, but it is rare in North America. In North American dogs, Chagas disease occurs most com monly in Texas and Louisiana. There have been no reported feline cases in North America. The organism is transmitted by an insect vector (Reduviidae), and reservoir hosts include rodents, raccoons, opossums, dogs, cats, and humans. The trypomastigote is the infective stage, but on entering host cells the organism enters the reproductive stage and becomes an amastigote. Amastigotes multiply until the host cell ruptures. Dogs with clinical Chagas disease have an acute or a chronic syndrome. In the acute stage, circulating trypomas¬ tigotes may be seen in a thick blood smear, and most dogs are brought for treatment because of sudden development of signs of right-sided heart failure (ascites, tachycardia, leth argy). Dogs with chronic Chagas disease may enter a quies cent stage free of clinical signs for months or even years. Nervous system damage often causes ataxia and weakness in these patients.
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NONINFECTIOUS M Y O C A R D I T I S
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Bacterial and Other Causes of Myocarditis Bacterial myocarditis is possible whenever bacteremia or sepsis is present, with the most common agents being staph ylococcal and streptococcal species. Myocarditis associated with Citrobacter koseri, an opportunistic pathogen of immu¬ nosuppressed human patients, has been described in two 12-week-old sibling Boxer puppies. Tyzzer disease (infection with Bacillus piriformis) was associated with severe necrotizing myocarditis in a wolf-dog hybrid puppy. Myocarditis has also been recognized secondary to rick ettsial organisms such as Rickettsia rickettsii, Ehrlichia canis, and various Bartonella species. Myocarditis has been noted in 2 of 12 dogs diagnosed with endocarditis, 11 of which 1
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Doxorubicin Toxicity Doxorubicin cardiotoxicity may be manifested as arrhyth mias, myocardial failure, or both. Cardiotoxicity is dosagedependent and irreversible and is more common at cumula tive doses exceeding 250 mg/m ; however, in one study in which only two doses of 30 mg/m were administered, 3% of dogs developed cardiomyopathy. The time to onset of CHF in affected dogs is highly variable. Although pathologic changes have been seen in the feline myocardium following administration, no antemortem echocardiographic or elec trocardiographic changes associated with doxorubicin toxic ity have been reported. Other causes of noninfectious myocarditis, although rarely recognized in veterinary medicine, include allergic reactions, systemic diseases such as vasculitis, or physical agents such as radiation or heat stroke. Numerous chemicals and drugs may lead to cardiac damage and dysfunction. A severe revers ible D C M has been observed in humans with pheochromocy¬ toma, and similar findings have been observed in experimental animals receiving prolonged infusions of nor epinephrine. Myocardial coagulative necrosis was found in a dog that died suddenly after an episode of severe aggression, restraint, and sedation for grooming. Myocardial lesions were presumed to be caused by catecholamine toxicity. 2
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Figure 48-1 E l e c t r o c a r d i o g r a m f r o m a m i x e d - b r e e d d o g w i t h t r i c h i n o s i s i n v o l v i n g t h e heart. T h e d o g w a s b r o u g h t in f o r c o l l a p s e d u e t o c o m p l e x arrhythmias. N o t e t h e v e n t r i c u l a r e s c a p e b e a t s . A n u n d e r l y i n g s u p r a v e n t r i c u l a r t a c h y c a r d i a is likely as w e l l .
DIAGNOSIS Definitive diagnosis, unless the history clearly suggests myo carditis (e.g., doxorubicin toxicity) is elusive (Box 48-1). Supportive clinical laboratory tests include leukocytosis or eosinophilia, particularly in parasitic or allergic myocarditis. Elevated cardiac troponin I levels provide evidence of myocardial cell damage in patients suspected of having myocarditis. If a high suspicion for Chagas disease is present, serologic examination for T. cruzi is diagnostic. Demonstra tion of a rising titer is also helpful to establish the diagnosis of myocarditis associated with T. gondii or N. caninum. Viral and rickettsial testing should be performed if indicated. Blood cultures should be performed if a bacterial cause is suspected. Thoracic radiographs may show normal heart size or heart enlargement with or without evidence of CHF. The electrocardiographic findings may also be varied, and ven tricular arrhythmias or conduction disturbances are com mon. Echocardiography most often demonstrates systolic dysfunction, either global or regional, and cardiac chambers may be normal or increased in size. Endomyocardial biopsy (the gold standard for diagnosis of myocarditis in humans ) may allow definitive antemor tem diagnosis (Color Plate 48-1). However, a focal myocar ditis can still be missed because the sample size is small. At postmortem examination, immunohistochemistry or elec tron microscopy can confirm the diagnosis of N. caninum infection. Gross pathology findings may be insignificant, or they may reveal cardiac dilation or ventricular hypertrophy, focal petechiae, and myocardial abscesses. Specific findings depend on the underlying etiology. Focal or diffuse myocar ditis is definitively diagnosed by histopathology when myo cyte necrosis, degeneration, or both are associated with an inflammatory infiltrate. 10
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Box 48-1 Characteristics Suggestive of Myocarditis • History suggests it is possible (e.g., oncology patient receiving doxorubicin, dog lives i n Texas) • Unusual signalment for heart disease (e.g., Irish Setter, German Shepherd) • Supportive electrocardiographic findings that include conduction abnormalities or arrhythmias • Supportive echocardiographic findings that include myocardial dysfunction (which may be regional) with or without heart enlargement • Supportive clinical laboratory findings that include leukocytosis, eosinophilia, elevated cardiac troponin I levels
with myocardial dysfunction caused by systemic autoimmune disease. Nonsteroidal antiinflammatory agents are contrain¬ dicated during the acute phase of myocarditis in humans (dur ing the first 2 weeks), because they increase myocardial damage. However, they appear to be safe later in the course of disease. In a murine model of viral myocarditis, angiotensin-converting enzyme inhibition (with captopril) was beneficial. Similarly, interferon therapy is beneficial in the experimental model of myocarditis and may be useful clinically. When diagnosis of acute Chagas disease is possible, sev eral agents appear to inhibit T. cruzi; however, by the time a diagnosis is made it is often too late for this approach. Patients with chronic Chagas disease are treated symptomat¬ ically for CHF. Similarly, successful treatment has been reported using several agents in dogs affected with N. cani num myocarditis, but severely ill dogs often die. Clindamy cin is the drug of choice for treating clinical toxoplasmosis in dogs and cats; however, significant damage to the heart is irreversible. Dogs with evidence of bacteremia should be treated with antibiotics pending culture and sensitivity results. Empiric treatment should be effective against staphylococcal and streptococcal species (see Chapter 108, Gram-Positive Infec tions). Animals with suspected rickettsial disease should be treated with doxycycline (5 mg/kg PO or IV ql2h) pending titer results. 10
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TREATMENT Most recommendations for managing myocarditis in dogs and cats are extrapolated from human medicine or research with models of viral myocarditis. Supportive care is the first line of therapy for patients with myocarditis. In those patients with signs of CHF, typical therapy should include preload reduction with diuretics and afterload reduction with angiotensin-converting enzyme inhibitors (see Chapter 21, Pulmonary Edema). Digoxin increased expression of proin flammatory cytokines and increased mortality in experimen tal myocarditis, so it is recommended to be used with caution and at low dosages. Intravenous inotropic therapy in the form of dobutamine can be useful if significant systolic dys function is present. Eliminating unnecessary medications may help reduce the possibility of allergic myocarditis. Results of recent studies sug gest that immunosuppression is not routinely helpful in myo carditis patients, but it may have an important role in patients 10
SUGGESTED FURTHER
READING*
Dubey IP, Lappin MR: Toxoplasmosis and neosporosis. In Green CE, editor: Infectious diseases of the dog and cat, ed 3, St Louis, 2006, Saunders. Excellent and detailed chapter on these parasitic diseases. Fox PR, Sisson D, Moise NS: Textbook of canine and feline cardiology, ed 2, Philadelphia, 1999, Saunders. Excellent and detailed general small animal cardiology text with several sec tions of relevance to this topic. Kittleson M D : Primary myocardial disease leading to chronic myocardial failure (dilated cardiomyopathy and related diseases). In Kittleson M D , Kienle RD, editors: Small animal cardiovascular medicine, Philadelphia, 1999, Mosby.
Excellent general and detailed text on small animal cardiology, one chapter in particular focusing on this topic. Maxson TR, Meurs K M , Lchmkuhl LB, et al: Polymerase chain reaction analysis for viruses in paraffin-embedded myocardium from dogs with dilated cardiomyopathy or myocarditis, Am J Vet Res 62:130, 2001.
Study using polymerase chain reaction technology to screen myocardial speci mens from IS dogs (with an antemortem diagnosis of DCM) and 9 dogs (with a histopathologic diagnosis of myocarditis) for various viral genomes. "See the C D - R O M for a complete list of references.
Chapter 49 ARTERIAL CATHETERIZATION Elisa M. Mazzaferro,
M S , D V M , PhD, D A C V E C C
information that helps guide lifesaving therapeutic interven tions in the most critically ill veterinary patients.
K E Y POINTS
3
• A r t e r i a l c a t h e t e r s c a n b e p l a c e d in t h e d o r s o p e d a l , radial, f e m o r a l , c o c c y g e a l , a n d a u r i c u l a r arteries. • A r t e r i a l c a t h e t e r s c a n b e u s e d f o r d i r e c t b l o o d pressure m o n i t o r i n g a n d p r o c u r e m e n t o f arterial b l o o d s a m p l e s f o r b l o o d g a s a n d o t h e r analyses.
PATIENT P R E P A R A T I O N
• Arterial catheters are generally well tolerated, but they c a n b e c o m e d i s l o d g e d easily w i t h excessive p a t i e n t m o v e m e n t .
A patient's coagulation status should be considered carefully before arterial catheter placement. If a coagulopathy is not found or suspected, the site should be chosen based on the patient's anatomy and consideration of underlying diseases, such as vomiting, diarrhea, pyoderma, or aural hematomas. For example, use of a radial arterial catheter may be inappro priate in a vomiting patient because of the risk of contamina tion. Similarly, femoral, coccygeal, or dorsopedal placement may be inappropriate in a patient with severe diarrhea. Patients with aural hematomas frequently shake their heads, and thus can easily dislodge an auricular arterial catheter, even when placed in a healthy ear. Because of the increased risks of auricular, coccygeal, and radial catheter dislodgement in ambulatory patients, dorsopedal catheters are preferred when ever possible.
• A r t e r i a l c a t h e t e r s s h o u l d b e a v o i d e d i n p a t i e n t s w i t h severe c o a g u l a t i o n a b n o r m a l i t i e s w h e n e v e r p o s s i b l e b e c a u s e o f t h e risk o f arterial h e m o r r h a g e . • A r t e r i a l c a t h e t e r s a r e n o t w e l l t o l e r a t e d in c a t s a n d s h o u l d b e k e p t in p l a c e n o l o n g e r t h a n 6 t o 8 h o u r s . • A l l arterial c a t h e t e r s s h o u l d b e l a b e l e d " A r t e r i a l C a t h e t e r — N o t f o r IV I n f u s i o n " t o p r e v e n t i n a d v e r t e n t i n j e c t i o n o f fluids o r d r u g s i n t o t h e arterial line.
INTRODUCTION A N D INDICATIONS FOR A R T E R I A L C A T H E T E R I Z A T I O N
1
An indwelling arterial catheter is a necessary and useful proce dure for many critically ill veterinary patients. Arterial cathe ters can be used to collect arterial blood samples when measuring an animal's arterial oxygenation and ventilation and for invasive direct arterial blood pressure monitoring. To avoid complications associated with hemorrhage or arterial thrombosis, the animal's coagulation status should be checked before considering placement of a catheter in any artery. Ideally, a platelet count or estimate, activated partial thrombo plastin time (APTT), and prothrombin time (PT) should be evaluated before catheter placement. If severe thrombocy topenia (180 mEq/L) or occurs rapidly, it may be associated with CNS signs such as obtundation, head pressing, seizures, coma, and death. All cells that have Na /K -ATPase pumps shrink as a result of hypernatremia as water moves out of the cell down its osmotic gradient to the relatively hyperosmolar extracellular compartment, but those of the CNS are clinically the least tolerant of this change in cell volume. An experimental study found decreased myocardial con tractility during injection of hypernatremic or hyperosmolar solutions in dogs. Hypernatremia has also been associated with hyperlipidemia, possibly a result of the inhibition of lipoprotein lipase. Artifactual hemogram changes in the blood of two hypernatremic cats have been reported with a specific hematology analyzer. +
+
18
10
19
Physiologic Adaptation to Hypernatremia
This formula gives the total volume of free water that needs to be replaced. This volume of free water, usually 5% dextrose in water, is infused over the number of hours calcu lated for safe reestablishment of normal plasma sodium con centration. This rate of free water replacement may be inadequate in cases of ongoing free water loss, as seen with diuresis of electrolyte-free water in patients with DI or unregulated diabetes mellitus, but it is a safe starting point in most cases. Plasma sodium concentration should be monitored no less frequently than every 4 hours to assess the adequacy of treatment, and CNS status should be monitored continu ously for signs of obtundation, seizures, or other abnormal ities. The rate of free water supplementation should be adjusted as needed to ensure an appropriate drop in plasma sodium concentration, the goal being a drop of no more than 1 mEq/hr and no signs of cerebral edema. Water may be supplemented intravenously (as 5% dextrose in water) or orally on an hourly schedule in animals that are alert, willing to drink, and not vomiting. It is important to note that free water replacement alone will not correct clinical dehydration or hypovolemia, because free water replacement does not provide the sodium required to correct these problems (see Total Body Sodium Content Versus Plasma Sodium Concentration). Free water replacement in the hypernatremic patient is relatively safe, even in animals with cardiac or renal disease, because two thirds of the volume administered will enter the cells.
Hypernatremia causes free water to move out of the rela tively hypoosmolar intracellular space into the hyperosmolar extracellular space, leading to decreased cell volume. When the cell shrinks, intracellular mechanisms sense the decreased cell volume and build idiogenic osmoles, or osmolytes, such as inositol to increase intracellular osmolality, which causes Complications of Therapy water to move back into the cell and restores cell volume for Hypernatremia to normal. Generation of these idiogenic osmoles begins within a few hours of cell shrinkage, but full compensation Cerebral edema is the primary complication of therapy for takes approximately 24 hours. This restoration of intracellu hypernatremia. Clinical signs of cerebral edema include obtun lar volume is important for cellular function and is an dation, head pressing, coma, seizures, and other disorders of important consideration during treatment of hypernatremia, behavior or movement. If these signs develop during the treat as discussed later. ment of hypernatremia, immediately stop the administration of any fluid that has a lower sodium concentration than the patient and disallow drinking. The patient's plasma sodium Treatment of the Normovolemic, concentration should be measured to confirm that it is lower Hypernatremic Patient than it was when treatment was instituted. This is an important step, because signs of worsening hypernatremia may be similar Hypernatremia should be treated, even if no clinical signs are to those seen with cerebral edema. If the plasma sodium con apparent. Patients with hypernatremia have a free water def centration has decreased, even if it has dropped at less than icit, so free water is replaced in the form of fluid with a lower 1 mEq/L/hr, cerebral edema should be considered. effective osmolality than that of the patient. Treatment must be cautious, and close monitoring of plasma or serum Cerebral edema is treated with a slow, single bolus dose of sodium concentration and CNS signs is imperative. mannitol at 0.5 to 1 g/kg IV over 20 to 30 minutes. Mannitol should be administered via a central vein if possible, but it In patients with mild to moderate hypernatremia ( [ N a ] may be diluted 1:1 in sterile water and given through a 180 mEq/L), it should be decreased at a maximum sider a dose of 7.2% N a sodium chloride at 3 to 5 ml/kg rate of 0.5 to 1 mEq/L/hr. This slow decrease in plasma over 20 minutes. The administration method is similar to sodium concentration ([Na ] ) is important to prevent cel that used for mannitol. Do not administer hypertonic saline lular swelling. Idiogenic osmoles are broken down slowly, so as a rapid bolus, because it can cause vasodilation. rapid drops in plasma sodium concentration (and thus plasma osmolality) cause free water to move back into the relatively hyperosmolar intracellular space and can lead to HYPONATREMIA neuronal edema. Free water deficit can be calculated by the formula: Hyponatremia is defined as plasma or serum sodium con Free water deficit = ([current[Na ] / normal[Na ] ] — 1) centration below the reference interval. Clinically relevant x (0.6 x body weight in kg) hyponatremia is uncommon in critically ill dogs and cats. +
p
+
p
+
+
p
+
+
p
p
2
Etiology
content, and those with SIADH are usually adequately hydrated with excessive free water retention. 30
Dogs and cats with hyponatremia almost always have free water retention in excess of total body sodium. Generation of hyponatremia usually requires water intake in addition to impaired water excretion.
Decreased Effective Circulating Volume A common cause of hyponatremia in dogs and cats is decreased effective circulating volume, which causes A D H release and water intake in defense of intravascular volume, and thus decreases plasma sodium concentration. Possible causes include congestive heart failure, excessive gastro intestinal losses, excessive urinary losses, body cavity effusions, and edematous states. Note that in the case of congestive heart failure, the patient has increased total body sodium (is "overhydrated") because of activation of the renin-angiotensin-aldosterone system, yet is hyponatre¬ mic due to increased water retention in excess of sodium retention. In the case of excessive salt and water losses from the GI or urinary tract, the patient is total body sodium depleted (is "dehydrated") and is hyponatremic due to com pensatory water drinking and retention to maintain effective circulating volume. 3
20,21
22,23
Hypoadrenocorticism Hypoadrenocorticism leads to hyponatremia through decreased sodium retention (due to hypoaldosteronism) combined with increased water drinking and retention in defense of inade quate circulating volume. Animals with atypical hypoadre nocorticism, whose aldosterone production and release are normal, may also develop hyponatremia, because low circulat ing Cortisol concentration leads to increased A D H release and resultant water retention regardless of intravascular volume status. 24
Diuretics Thiazide or loop diuretic administration can lead to hypo natremia by induction of hypovolemia, hypokalemia that causes an intracellular shift of sodium in exchange for potas sium, and the inability to dilute urine. Renal failure can cause hyponatremia by similar mechanisms. 24
Syndrome of Inappropriate Antidiuretic Hormone Secretion Syndrome of inappropriate A D H secretion (SIADH) causes hyponatremia through water retention in response to impro perly high circulating concentrations of A D H . The syndrome has been reported in dogs and has many known causes in humans (see Chapter 71, Syndrome of Inappropriate Antidiuretic Hormone). 25,26
24
Other Causes of Hyponatremia Hyponatremia has been reported in animals with GI parasitism, other infectious diseases, psychogenic poly dipsia, and pregnant dogs. A syndrome of cerebral salt wasting has been described in humans with CNS disease but has not been reported clinically in dogs or cats. Cerebral salt wasting is differentiated from SIADH by evaluation of hydration status: patients with cerebral salt wasting are clini cally dehydrated because of a decrease in total body sodium 21
27,28
29
Clinical Signs Mild to moderate hyponatremia usually causes no specific clinical signs. If hyponatremia is severe (usually 20 mmol/L), normal metabolic recovery when perfusion or oxygenation is restored can return the lactate to normal levels within 3 hours. The real problem occurs when increased lactate levels are sustained. The most common forms of type A lactic acidosis are managed by adjusting the parameters of oxygen delivery: 1
Oxygen delivery = Arterial oxygen content x Cardiac output
Arterial oxygen content = 1.34 x Hemoglobin (Hb) concentration x % Hb saturation+ 0.003 x Partial pressure of arterial oxygen Cardiac output = Stroke volume x Heart rate Management is therefore aimed at restoring an effective cir culating volume and arterial oxygen content. With most acuteonset lactic acidosis, a rapid response to treatment is expected and lactate levels should decline with no long-term residual effects. Sustained type A lactic acidosis is a consequence of either inadequate management or ongoing pathology such as aber rations of microcirculation or ischemic tissue. It is a very serious clinical finding that warrants immediate interven tion. If cellular injury is extensive as a result of tissue hy poxia, type A lactic acidosis can convert to type B. In this instance oxygenation and circulation may be restored, but cellular injury is too extensive to reestablish normal metabo lism and correct the lactic acidosis. Sustained lactic acidosis can occur with type B, and improve ment of perfusion and oxygenation will not resolve the problem. The clinician must identify the underlying cause of the disruption of cellular function and take steps to correct it. Toxins must be bound, metabolized, excreted, or dialyzed. Glucose metabolism must be normalized with adequate glucose supplementation, insulin therapy, or both. Septic patients probably have a combi nation of type A and type B lactic acidosis because, although oxy gen levels may be adequate and perfusion is normal at the organ level, at the tissue level there is often enough disruption of micro vascular perfusion such that many tissue beds are operating anaerobically. There may also be a hypermetabolic component that creates pyruvate faster than it can be metabolized in the Krebs cycle. In addition, sepsis can lead to acquired mitochon drial function defects and reduced lactate clearance. ' ' ' 1 2 4 7
LACTIC ACIDOSIS WITH CARDIOPULMONARY ARREST Cardiopulmonary arrest and cardiopulmonary resuscitation (CPR) create a special case of lactic acidosis. During the arrest state, perfusion and oxygen delivery fall to zero and tissue metabolism becomes anaerobic on a global scale. Plasma lactate levels measured in venous blood rise steadily. As CPR is initiated, lactate levels will continue to rise until effective tissue perfusion is achieved. The key to correcting the lactic acidosis of cardiac arrest is the return of spontane ous circulation. 1
TREATMENT OF LACTIC ACIDOSIS Treatment of type A (hypoxic) lactic acidosis is best accom plished by rapidly correcting the underlying cause. The use of sodium bicarbonate or other alkalinizing agents such as Carbicarb (an equimolar mixture of sodium bicarbonate and sodium carbonate), dichloroacetate, or T H A M (tris-buffer) should be reserved for type B lactic acidosis that involves fail ure of cellular function that cannot be reversed, so primary treatment of the acidemia is the only therapeutic option.
Figure 60-1 Schematic of lactate metabolism in the cell. Underaerobic conditions with normal mitochon drial function, pyruvate enters the mitochondria and fuels the Krebs cycle. When pyruvate cannot enter the mitochondrion it will be metabo lized to lactate instead.
Box 60-1 Causes of Type B Lactic Acidosis • • • • • • • • •
Systemic inflammatory response syndrome Diabetes mellitus Malignancy—hematologic malignancies in particular Thiamine deficiency Liver failure Hypoglycemia Inborn errors of metabolism Mitochondrial myopathies Toxins • Cyanide • Ethanol • Ethylene glycol • Drugs • Salicylate • Lactulose • β -Agonists • Nitroprusside • Acetaminophen • Propylene glycol • Phenformin
When treating type A lactic acidosis, while working to correct the underlying problem, the clinician may feel that the patient's p H is so low that the elevated hydrogen ion concentration has become the patient's most immediate problem. Severe acidosis does impair cardiovascular func tion and can be a serious barrier to resuscitating a patient in cardiopulmonary arrest. Alkalinizing agents such as sodium bicarbonate and Carbicarb may be used, but it is important to recognize that the lactic acidosis is not cor rected with these agents. The acidemia improves, which may be helpful, but if spontaneous circulation is restored and the lactate is cleared quickly, the patient may be left with a hyperosmolar problem and an iatrogenic metabolic alkalosis. For this reason, sodium bicarbonate is rarely indicated for the treating of type A lactic acidosis. 2 , 4
2
SUGGESTED FURTHER READING*
DiBartola SP, editor: Fluid, electrolyte and acid-base disorders in small anim practice, ed 3, Philadelphia, 2006, Saunders. The quintessential collection on veterinaryfluid,electrolyte, and acid-
disorders. A good balance between basic information and supporting Packer details RA, Cohn LA, Wohlstadler G, et al: d-Lactic acidosis secondary to that link the underlying research. exocrine pancreatic insufficiency in a cat, / Vet Intern Med 19:106, 2005. Fall PJ, Szerlip HM: Lactic acidosis: from sour milk to septic shock, / Inten A very interesting case report of a cat with encephalopathy and gastrointestinal sive Care Med 20:255, 2005. disease. Also provides a nice review of d-lactic acidosis. An excellent review of lactate metabolism, types A and B lactic acidosis, Salway and JG: Metabolism at a glance, ed 3, Oxford, 2004, Blackwell. treatment of hyperlactatemia. A wonderful book with large graphics that includes normal and abnormal Hughes D: Clinical use of lactate, Proceedings of the 11th International Emerpathways and a discussion of the pathophysiology behind the biochemistry. gency and Critical Care Symposium, Veterinary Emergency and Critical A great reference to have on hand when you need a reminder of what is hap pening at the biochemical level. Care Society, Atlanta, September 7-11, 2005. A fun and eclectic discussion of lactic acidosis with great clinical application. Stockham SL, Scott MA: Fundamentals of veterinary clinical pathology, Ames, Includes many good references to human and veterinary studies that describe IA, 2002, University of Iowa Press. the clinical relevance of sustained elevations in plasma lactate. A good veterinary clinical pathology reference. Includes an excellent basic review of both traditional Henderson-Hasselbalch acid-base physiology and Luft FC: Lactic acidosis update for critical care clinicians, / Am Soc Nephrol also a discussion of strong ions. 12:S15-S19, 2001. A good review of lactic acid pathophysiology from the physician's perspective, with a discussion of therapies that directly address lowering the hydrogen *See the CD-ROM for a complete list of references. ion concentration.
Part VI FLUID THERAPY Chapter
61
PERIPHERAL VENOUS CATHETERIZATION
Chapter
62
INTRAOSSEOUS CATHETERIZATION
Chapter 63
CENTRAL VENOUS CATHETERIZATION
Chapter 64
DAILY INTRAVENOUS FLUID THERAPY
Chapter 65
SHOCK FLUIDS AND FLUID CHALLENGE
Chapter
TRANSFUSION MEDICINE
66
Chapter 61 PERIPHERAL VENOUS CATHETERIZATION Harold Davis,
BA, RVT, VTS (Emergency/Critical Care and Anesthesia)
KEY POINTS • There are four primary catheter types: winged, over-the-needle, through-the-needle, and multilumen. • Catheter insertion site selection depends on several factors, including vessel availability and the intended purpose of catheterization. • Proper vessel immobilization facilitates catheter placement. • There are several catheter-related complications, phlebitis, thrombosis, catheter embolus, subcutaneous fluid infiltration, and infection, that can be minimized by appropriate attention to detail.
INTRODUCTION Peripheral venous access is a cornerstone of the treatment of the emergency or critically ill patient. Patients often require tempo rary venous access for medications, fluid and electrolyte replacement, or transfusion of blood products. Medications and fluids with osmolalities 600 mOsm or less may be administered safely via a peripheral vein. Site selec tion depends on the available vessels, condition of the ves sels and patient, expense, and the urgency of the situation. Vascular access traditionally involves the insertion of a catheter into the cephalic, saphenous, or auricular vein; how ever, any visible vessel is a potential candidate for catheteriza tion. Various techniques are used to insert catheters, including percutaneous, facilitative relief holes, and venous cutdowns. 1
CATHETER TYPES A variety of catheters are commercially available (Figure 61-1). The length and gauge (diameter) of the catheter to be used are dependent on the species and size of the patient, the veins available and their condition, and the needs of the patient. Both the radius and the length of the catheter determine the maximum flow rate. A large-gauge, short catheter is needed if fluids are to be administered rapidly, such as in a severely hypovolemic patient. If a slow infusion is acceptable, then a small-gauge catheter might be appropriate. A smaller catheter-to-vein ratio is considered more "vein friendly." There are four general categories of intravenous access devices. They include the winged needle, over-the-needle, through-the-needle, and multilumen catheters.
Winged or Butterfly Needle The winged needle (butterfly) is for short-term use when the animal is not moving around very much. Applications might include blood collection or administration of nonirritating
Figure 61-1 Example of various types of catheters: A, Winged needle or butterfly, B, over-the-needle catheter, C, TwinCath double-lumen catheter, and D, through-the-needle catheter with needle guard.
medications. Common needle size ranges from 25 to 19 gauge. The needles have plastic wings on the shaft to facili tate placement or taping in place. Plastic tubing of various lengths extends from the needle to the syringe connector port. These catheters are easy to place but difficult to main tain because of the ease with which the indwelling sharp nee dle punctures the vessel wall, allowing for subcutaneous infiltration of fluids or medications.
Over-the-Needle The over-the-needle catheter is the most commonly used type. It is inexpensive and easy to place. The needle point extends a millimeter or so beyond the catheter tip. Overthe-needle catheters are available in a variety of lengths and gauges and are made of various materials (Teflon, polypro pylene, polyvinyl chloride, and polyurethane).
Through-the-Needle Catheters passed through the needle are called through-theneedle or inside-the-needle catheters. Through-the-needle catheters are usually longer (8 to 12 inches) than over-theneedle catheters and come in a variety of diameters. These catheters are used primarily in the jugular vein but can be used peripherally in the medial or lateral saphenous veins. These catheters can be inserted to the level of the posterior vena
cava, allowing for administration of hyperosmotic solutions. They can also be inserted into the cephalic vein but are often dif ficult to pass beyond the axilla into the larger anterior vena cava. A plastic sleeve prevents catheter contamination during inser tion. Once the catheter is placed, the needle is withdrawn from the skin puncture site and covered with a needle guard to prevent the needle from shearing the catheter.
INSERTION TECHNIQUE Percutaneous The area of the insertion site is generously shaved. Surgical preparation is performed with antiseptic scrub and solu tion. Aseptic technique is important to prevent indwelling catheter-related infection. Proper aseptic technique may be bypassed in emergency situations, but these catheters should be removed once the crisis has passed. Following skin preparation, the vein is occluded upstream of the insertion site by a tourniquet or an assistant. The dis tal portion of the leg is grasped in the palm of the hand of the operator and the leg is extended to tense and immobilize the vein. The thumb should not be used to stabilize the vein, because this compresses and collapses the vein. Flexion of the carpus will increase the stretch on the vessel and improve vessel immobilization in achondroplastic breeds. With the bevel up, the catheter is inserted through the skin at approx imately a 15-degree angle. The catheter is advanced into the vessel; when blood appears in the flash chamber (hub), the needle and catheter are advanced as a unit for an additional 1 to 4 mm. This will ensure that the end of the catheter is entirely inside the lumen of the vessel. While holding the needle steady and maintaining the longitudinal tension on the leg, the catheter is then advanced off of the needle and into the vessel lumen. The catheter is capped with an injec tion cap or T-set and flushed with heparinized saline. 3
Multilumen Arrow International (Reading, PA) produces a double-lumen over-the-needle catheter called a TwinCath. The TwinCath is more expensive than regular single-lumen catheters, but it allows simultaneous infusions of otherwise incompatible fluids via one catheter. Catheter placement is identical to that of any single-lumen over-the-needle catheter.
CATHETER INSERTION SITE Peripheral insertion sites include the cephalic, lateral and medial saphenous, and the auricular vein.
Cephalic Vein The cephalic vein is located on the anterior antebrachium. It crosses from the medial aspect of the leg an inch or so prox imal to the carpus to join the brachial vein proximal to the elbow, which ultimately joins the external jugular vein. A n accessory cephalic vein on the anterior aspect of the metacar pus passes over the carpus and joins the cephalic vein. If possible, it is best to avoid the insertion of the catheter over the carpus, because it will be difficult to secure. 2
Saphenous Vein The cranial branch of the lateral saphenous obliquely crosses the lateral aspect of the distal tibia. The lateral saphenous vein is larger than the medial saphenous in the dog, and the medial saphenous is larger than the lateral and is more commonly catheterized in the cat. 2
Auricular Vein The auricular veins are prominent in some breeds of dogs (Basset, Dachshund, and Bloodhound) and are fairly easy to catheterize.
Advantages of Peripheral Vein Catheterization • Peripheral catheters tend to be relatively inexpensive, tech nically simple to place and well tolerated by most patients. • Peripheral veins are easily accessible for quick catheterization such as in cardiac arrest or seizures. Two peripheral catheters may be indicated if rapid fluid resuscitation is required. • Peripheral catheter placement generally requires minimal restraint. Patients suffering respiratory distress do not tol erate the stress of restraint (e.g., as would be required for central vein catheterization). • Peripheral vein catheterization is generally associated with fewer significant complications such as hemorrhage, infec tion or thrombosis in comparison with central venous access.
The technique for percutaneous catheterization of the auricular vein is similar to that for any peripheral vein. It may be useful to place roll gauze on the underside of the pinna to stabilize the ear. Not all procedures are associated with spontaneous bleed back into the hub. If the operator thinks that the needle is in the vessel but does not see a flashback, the next step is to attach a syringe filled with heparinized saline and aspirate. Some times the flashback occurs, but following catheter insertion blood cannot be aspirated. There are two possibilities: (1) the catheter is in the vein but the vein collapsed around the end of the catheter, or (2) the catheter is not in the vein. 1. Excessive pressure to aspirate may collapse the vein; very gentle aspiration should be attempted. • The appearance of any amount of blood in the hub suggests proper placement; the operator should not expect free-flowing blood samples, because it is difficult to aspirate from many peripheral catheters. • The catheter tip may be occluded by a kink in the vein such as at the flexed elbow for a cephalic catheter; the leg should be extended. • The catheter may be large for the vein, obstructing blood flow past it; the vein should be occluded proximally and the foot squeezed to milk more blood into the vein. • If the catheter position still cannot be confirmed, inject a volume of saline into the catheter while watching for a subcutaneous bleb. If a large volume of saline can be injected without forming a subcutaneous bleb, the catheter must be in the vein. 2. The catheter may not be in the vein even though a flash back of blood was observed initially, and this can be attributed to several common technical misssteps. • After the flashback, the tension on the leg and skin was relaxed, allowing the vein to retract off the end of the needle; the tension must be maintained until after the catheter is inserted.
• The flashback was associated with the needle tip being in the vein, but the catheter tip was not wholly within the lumen of the vein; when the catheter was intro duced it pushed the vein off the needle. • The needle-and-catheter unit must be inserted a short distance beyond initial vein entry. Sometimes when the needle-and-catheter unit is advanced, it passes through the deep wall of the vein; the catheter will be pushed through the vein. If this is suspected, the needle-and-catheter unit is carefully withdrawn until backflow is evident ("catch the lumen on the way out"). Then readvancing the catheter into the vessel in the routine manner can be tried.
swelling, tenderness on palpation, and erythema of the skin over the vessel. Phlebitis may be caused by the following: 1. Mechanical damage to the vessel by movement of the catheter, so it should be well stabilized. 2. Administration of hyperosmotic fluids; the osmolality of peripherally administered fluids should not exceed 600 mOsm. 3. Infection; aseptic technique should be maintained at all times if possible. Some patients seem prone to catheter phlebitis for no apparent reason despite good technique.
Thrombosis Facilitative Incision or Relief Hole Failed catheterization attempts may also be caused by cathe ter flaring. Flaring of the tip of the catheter may occur when the tip is torn or peeled back during its insertion through the skin. After a failed attempt, inspect the catheter tip for such flaring before reuse. A facilitative incision or relief hole reduces the skin tension and friction against the catheter, minimizing catheter flaring, and is an especially important procedure in severely dehydrated patients or those with tough skin. A facilitative incision may be made with a No. 11 scalpel blade or a 20-gauge needle. A 0.5-mm incision is made directly over the vessel, extending through the der mis and taking care to avoid lacerating the underlying vessel. Local anesthetic blocks are rarely needed; intradermal or subcutaneous lidocaine stings. Following the facilitative pro cedure, the catheter is inserted as previously discussed.
Venous Cutdown A venous cutdown is indicated when the veins are small (small patients, or patient that is severely hypovolemic) or when the veins are obscured (obesity, subcutaneous edema, or hema toma). Following aseptic skin preparation awake animals will require local anesthesia of the region, taking care not to inject any agent intravenously. A 1- to 2-cm incision is then made through the skin parallel to the vessel, being careful not to lacer ate the vein. The vessel is dissected free of the surrounding tis sue. An encircling suture is placed around the vein proximal and distal to the intended venotomy site. The catheter can be inserted directly through the superficial vessel wall or, if a cath eter is to be used without a needle, an incision can be made into the vein while applying traction on the preplaced sutures. If an incision is made, once the catheter is inserted, both sutures are tied proximally to prevent bleeding (Color Plate 61-1). The skin is closed and the catheter site is bandaged.
Peripherally Inserted Central Venous Catheters Central venous catheterization can be achieved by passing a long catheter from a peripheral insertion site to a central vessel. This can allow easy sample aspiration, administration of hypertonic fluids, and long-term catheter maintenance (see Chapter 63, Central Venous Catheterization).
COMPLICATIONS ASSOCIATED WITH CATHETERIZATION Phlebitis Phlebitis is inflammation of the vessel wall occurring as a result of damage to the endothelial lining. Phlebitis is characterized by
Thrombosis is the formation of a thrombus on the catheter or vessel wall (as a consequence of phlebitis). Thrombosis can result from endothelial trauma or an inflammatory reaction to the catheter material. A vein that "stands up" without being held off and feels thick and cordlike characterizes thrombosis.
Catheter Embolism Catheter embolism occurs when a fragment of the catheter breaks off and enters the circulation. The fragment may be severed when withdrawing an inside-the-needle catheter. It can also occur if the catheter is cut during bandage change or the patient molests its bandage.
Subcutaneous Fluid Infiltration Infiltration of fluids into the tissues surrounding the vein may occur if: 1. The catheter was never in the vein in the first place. 2. The catheter is displaced out of the vein by excessive skin movement. 3. Upstream vein occlusion by thrombosis has occurred. Signs of infiltration are swelling and tenderness around the insertion site.
Infection An indwelling catheter is an excellent pathway for microorgan isms to enter the tissues and the venous system. Infection may be heralded by phlebitis and cellulitis (a purulent discharge from the insertion site). Aseptic technique in catheter placement and maintenance will help to decrease the risk of infection. Fever of unknown origin in a critically ill patient should prompt consid eration of replacement of all indwelling catheters.
CATHETER MAINTENANCE Intravenous catheter care should be performed every 48 hours or on an as-needed basis if the site gets soiled. The catheter dressing should be removed and the site inspected. Look for clinical signs of phlebitis, infection, and thrombosis and, if present, the catheter should be removed. While flush ing the catheter with heparinized saline, the insertion site should be observed for fluid leakage or pain during injec tion. If either is observed, the catheter should be removed. If any portion of the catheter is exposed, this should be recorded in the medical record and the catheter should not be reinserted. If the catheter site looks good, the site should be cleaned with an iodophor or chlorhexidine solution. When the catheter site is dry, a sterile 2 x 2 gauze pad is placed over it and the bandage reapplied.
Traditionally it has been recommended not to leave a catheter in place any longer than 72 hours. These recom mendations come from human medicine. The likelihood of complications increases the longer a catheter is left in place. It has been our experience that as long as routine catheter care is performed, and the catheter removed when problems are first noticed, one can often exceed the 72-hour rule. A study looking at peripheral and jugular venous catheter contamination in dogs and cats supports our experience. Intravenous catheters should be observed several times a day. If the catheter bandage is wet, the reason should be identified and the bandage should be changed. Swelling distal to the cath eter may be indicative of an excessively tight bandage or tape. Swelling proximal to the catheter may be due to infiltration. 3
4
A very interesting prospective study in which significantly more venous cathe ters placed without aseptic skin preparation (48%) had a positive bacterial culture at the time of removal compared with those placed using aseptic tech nique (15%) in a total of 88 dogs. Evans HE: Miller's anatomy of the dog, Philadelphia, 1993, Saunders. The bible of veterinary anatomy. Hansen B: Technical aspects of fluid therapy. In DiBartola SP, editor: Fluid, electrolyte and acid-base disorders in small animal practice, St Louis, 2006, Saunders. Fluid therapy chapter that includes a discussion of catheter selection and place ment techniques; includes an excellent discussion of skin preparation for venous catheterization. Mathews KA, Brooks MJ, Valliant AE: A prospective study of intravenous catheter contamination, / Vet Emerg Crit Care 6:33, 1996. A prospective study that found no association between dwell time and incidence of intravenous catheter contamination in a veterinary intensive care unit. *See the CD-ROM for a complete list of references.
SUGGESTED FURTHER READING* Burrows C: Inadequate skin preparation as a cause of intravenous catheterrelated infection in the dog, J Am Vet Med Assoc 180:747, 1982.
Chapter 62 INTRAOSSEOUS CATHETERIZATION Massimo Giunti,
DVM, PhD •
Cynthia M. Otto,
KEY POINTS • Intraosseous catheterization is an emergency procedure that allows access to the central circulation comparable to that achieved with a central venous line. • Intraosseous catheterization is indicated when emergency vascular access is required and intravenous access cannot be performed in a timely manner. • Intraosseous catheterization is an easy, fast, and inexpensive technique that can be performed effectively in various species. • Intraosseous infusion is contraindicated in recently fractured bones, those in which catheterization has been already attempted, and pneumatic bones of birds. • The rate of complications for intraosseous infusion is extremely low, and osteomyelitis is the major risk. • Blood samples obtained from intraosseous catheters can be analyzed for some hematologic, biochemical, and blood gas parameters in steady-state, low-flow conditions, and during the early phase of cardiopulmonary resuscitation.
INTRODUCTION Rapid establishment of vascular access is crucial in criti cally i l l patients, particularly those with life-threaten ing conditions. In animals with hemodynamic failure,
DVM, PhD, DACVECC
peripheral vessels may constrict or collapse and grossly dis appear. Finding and cannulating vessels is particularly challenging in small and neonatal patients. Attempts to catheterize a peripheral vein can be frustrating, time con suming, and unsuccessful even for the most skilled person nel. In pediatric prehospital and emergency department settings, peripheral intravenous access could not be obtained in 6% of patients and required over 10 minutes in 24%, with significantly prolonged times in children under 2 years of age. Compared with percutaneous peripheral vein catheteriza tion, both surgical cutdown and central venous line placement increase the likelihood of successful circulatory access, but they require greater expertise and more time. Peripheral venous catheterization within 90 seconds is successful in only 18% of cases. The success rate increases to 37% with subsequent percutaneous femoral vein catheterization. There are limited alternative routes for drug delivery in cases that require cardiovascular support but lack venous access. The endotracheal route is a last-resort option recom mended by the American Heart Association for some resusci tation drugs during cardiac arrest in both adult and pediatric patients. This route obviously cannot provide for fluid resuscitation, and even for commonly recommended drugs 1
1,2
2
3,4
such as epinephrine the clinical effect is less predictable than when intravenous administration is used. Additionally, the dosage of intratracheal epinephrine has to be increased up to 10-fold. Furthermore, lower circulating epinephrine con centration, from endotracheal administration, could result in counterproductive β -adrenergic stimulation, which leads to peripheral vasodilation, low diastolic aortic pressure, and decreased myocardial perfusion pressure. Two proposed but inadvisable routes of drug administra tion are the sublingual and intracardiac routes. Intracardiac injections are associated with risks (e.g., hemopericardium, coronary artery perforation, myocardial ischemia, arrhyth mias) that exceed the benefits. Alternatives to intravenous access are reported, but they are indicated mainly for volume replacement in states of dehydration (subcutaneous or intra peritoneal infusion) and are not effective for hypovolemia. Curiously, an unusual emergency vascular access, such as corpus cavernosum, was demonstrated to be fast and feasible for fluid resuscitation in dogs with severe hypovolemia, offering new therapeutic perspectives, even if limited to male dogs. In pediatric and adult patients, intraosseous access is now recom mended as the first choice if intravenous access is unavailable. The intraosseous route is safe, practical, and reliable for fluid resuscitation, drug administration, and even blood sampling for analysis. This chapter focuses on what makes the intraoss eous route suitable for fluid infusion and drug administration. The main indications, contraindications, complications, proce dures, and future perspectives for intraosseous access in veteri nary patients will be presented based on veterinary reports, human studies, and experimental animal models.
PHYSIOLOGY
5
6
2
6
7
7
8
3,4
HISTORICAL PERSPECTIVES The possibility of perfusing the tibia of the dog was demon strated in 1922 by Drinker and colleagues, who were study ing vascular physiology of the bone marrow. Starting from this scientific observation, the potential use of the intraoss eous route for parenteral infusion of drugs and fluids was addressed by several studies in Europe and North America during the 1930s and 1940s. In rabbits, intraosseous infusions of whole blood and hypertonic glucose solutions rapidly corrected anemia and hypoglycemia, respectively. In dogs, intramedullary injection of citrated blood into the sternum effectively restored blood volume. Moreover, an injection of epinephrine into the marrow of the tibia resulted in a clinical response similar to that achieved by injection into the femoral vein. Intraosseous infusion was established as a reliable and safe technique for rapid, short-term access into the central circulation in adults and children when veins were inaccessi ble (e.g., peripheral circulatory failure, burns, and very young patients). However, with the introduction of plas tic catheters for peripheral venous access during the late 1950s, intraosseous infusions fell into disuse. A renewed interest in the intraosseous procedure appeared during the 1980s because of its utility in hypotensive patients and effi cacy for the administration of lifesaving drugs. The intraosseous route was recommended as an alternative emer gency access in pediatric advanced life support for children under 6 years of age and, more recently, resuscitation guide lines extended its use to children of any age and even to adults.
The bone marrow is a semifluid blood-forming tissue enclosed in a nonexpandable bony case. This protective osse ous coating prevents bone marrow vessels from collapsing during peripheral circulatory failure. A rich capillary net work drives substances injected into the marrow to the large medullary venous channels and quickly through the nutrient and emissary veins to the central circulation. Several types of fluids (blood and blood components, colloids, crystalloids) and several drugs, administered through an intraosseous, a central, or a peripheral intravenous line, are equally effective in reaching the central circulation despite normotensive, hypotensive, or arrest conditions. Particularly during hemodynamic failure, intraosseous infu sion of resuscitative fluids (e.g., hydroxyethyl starch) and drugs (e.g., sodium bicarbonate) seems to guarantee a higher magnitude of the peak effect and even a prolonged duration of action compared with peripheral venous administration. Although intraosseously administered drugs reach peak effect more slowly because of a reduction in blood flow and an increase in vascular resistance in the bone marrow during systemic hypotension, this effect can be overcome partially by pressurized infusion, especially when using vis cous fluids likes colloids, or by a fluid bolus following the injection of a drug into the intraosseous space. Mean intraosseous infusion flow rates of crystalloid solutions delivered under pressure (300 mm Hg) are limited to approximately 29 ml/min in puppies and 47 ml/min in foals. Thus rapid delivery (90 ml/kg within 30 minutes) of fluids during severe hypovolemia may not be possible in dogs that weigh more than 10 kg. However, intraosseous infusion of hyperoncotic, hypertonic, and even crystalloid solutions effectively reversed hypotension in several animal models of hemorrhagic shock (see Chapter 65, Shock Fluids and Fluid Challenge). 9-11
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INDICATIONS There are no studies documenting the incidence or impact of intraosseous catheterization in veterinary medicine. Most of the indications have been extrapolated from human expe rience and experimental animal models. The informa tion obtained from pediatric patients, in whom the time required to complete an intraosseous catheterization can be less than 1 minute with over 70% to 80% success, may be particularly relevant to small and neonatal animals. Early implementation of the intraosseous route as an alter native to failed intravenous access is now widely accepted and is included in the guidelines for management of cardiac arrest in pediatric and adult human patients. These recommenda tions are applicable to veterinary patients as well, particularly for small and neonatal animals whose veins can be difficult to visualize normally and tend to grossly disappear completely during shock. Fluid resuscitation through an intraosseous catheter can restore a vascular volume sufficiently to allow subsequent catheterization of a peripheral vein. Conditions such as peripheral vascular thrombosis, peripheral edema, status epilepticus, obesity, and burns may be indications for obtaining intraosseous access. An additional advantage of intraosseous catheterization during emergency situations is the potential for blood sampling. 7,12,17
18,19
13,18,19
Initial assessment of hematologic, biochemical, and acid-base status and subsequent monitoring of the therapeutic response are essential in critically ill patients. Blood sampling, however, can be challenging during cardiovascular collapse. The reliability of results obtained from blood collected from intraosseous lines has been investigated in both steady-state and circulatory failure conditions. In normal animals, hemoglobin, hematocrit, some biochemical param eters (blood urea nitrogen, creatinine, total solids, albumin, bilirubin, sodium, chloride, calcium, phosphorus) and blood gases are sufficiently comparable to those of peripheral or central venous blood to be of clinical value. Values obtained for potassium and glucose, however, need to be interpreted with caution. Acid-base values from intraosseous sam ples in cardiopulmonary resuscitation (CPR) models reflect the mixed venous blood acid-base balance during the first 15 minutes of CPR, and beyond that time values can be influenced by local acidosis. In one CPR study, intraosse ous and central venous blood biochemical and hemoglobin values remained similar for the first 30 minutes if the intraoss eous site was not used for drug infusions.
Box 62-1 Supplies Necessary for an Intraosseous Catheter Kit • • • • •
•
20,21
22,23
•
• • •
24
•
CONTRAINDICATIONS
Topical antiseptic Sterile gloves Local anesthetic for the skin and periosteum A scalpel blade for making a stab incision through the skin Needles • Hypodermic (18- to 30-gauge) • Spinal (18- to 22-gauge) • Bone marrow or intraosseous infusion needles (Figure 62-1, Jamshidi/Illinois, Cardinal Health, or Cook Critical Care) Bone injection gun: Optional device for more rapid access to the intraosseous space (Figure 62-2, WaisMed Ltd Houston, TX) Syringe for aspiration of bone marrow to confirm correct placement and potentially collect samples for hematologic or biochemical analysis Heparinized saline solution Fluid with administration set or catheter cap and a pressure bag Mechanism to secure the catheter: • Tape butterfly and suture material • Cyanoacrylates to secure suture directly to hub of needle • Commercial intraosseous catheter with flange • Bandaging material Triple antibiotic ointment or appropriate antiseptic ointment or cream
The only absolute contraindication to intraosseous catheteriza tion is a fracture in the bone to be used. In cases of failed intraosseous catheter placement where the cortex has been penetrated, the risk of fluid or drug extravasation increased. To minimize risk, a second cannula of larger diameter should be placed through the same entry site or preferably a separate bone should be used. Intraosseous infusions in pneumatic bones of birds are contraindicated. Clearly, intraosseous catheters should not be placed through infected tissues. Sepsis and septic shock have been suggested as contraindications for intraoss eous lines; however, reported complication rates in septic children were low.1
METHODS The increased use of intraosseous catheterization during the last 15 to 20 years has been accompanied by the develop ment of new medical equipment. Intraosseous catheters range from traditional manually placed hypodermic needles to the newly dedicated catheters with automated delivery systems. The main requirements of any intraosseous delivery system are ease of handling, ability to reload, small expense, and adaptability to most conditions. The supplies necessary for an intraosseous catheterization kit are described in Box 62-1. Commercial disposable intraosseous infusion needles with a central stylet (Cook Critical Care; Bloomington, IN; Cardinal Health, McGaw Park, IL.) are designed to penetrate the bony cortex, prevent occlusion of the cannula lumen, and establish rapid access to the marrow sinusoids and vas cular system. However, an 18- to 30-gauge hypodermic needle is useful in neonates with soft cortical bone, an 18- to 22-gauge spinal needle is excellent in cats, small dogs, and birds, and a bone marrow or intraosseous infusion needle is essential in mature dogs. A bone injection gun is a spring-loaded, impact-driven intraosseous device developed for use in pediatric and adult 1,19
19,24
19
18
Figure 62-1
Intraosseous infusion needle. (Courtesy Cardinal Health.)
humans. It propels the intraosseous cannula at high speed through skin, subcutaneous tissues, and bone cortex to a fixed depth. This automatic device was significantly faster than a standard Jamshidi bone marrow needle in obtaining intraosseous access in the proximal tibia of dogs. The high speed of insertion helps to minimize pain; however, local anesthesia is recommended in conscious patients. 24
24
Figure 62-2 TX.)
Bone injection gun. (Courtesy WaisMed Ltd, Houston,
Other devices such as a drill for intraosseous access ( E Z IO, Vida Care, San Antonio, T X ) and a sternal intraosseous device ( F A S T I , Pyng Medical, R i c h m o n d , B C , Canada) are now available. Applications in veterinary medicine still need to be verified. The access site should be easily accessible and should not interfere with ongoing procedures such as C P R . The most c o m m o n l y used sites include the flat medial surface o f the proximal tibia (1 to 2 c m distal to the tibial tuberosity), the tibial tuberosity itself, or the trochanteric fossa o f the femur (Color Plate 62-1). Alternative approachable points can be considered such as the wing o f the ilium, the ischium, and the greater tubercle o f the h u m e r u s . However, no studies in animal patients suggest any one site to be superior. Finally, the choice o f a particular site will depend on the experience and preference o f the clinician, the anticipated duration, and the mobility o f the patient. The trochanteric fossa o f the femur seems to be well tolerated, allows m o b i l ity, and is generally easy to place. In obese or very edema tous animals or those i n status epilepticus, the tibia is probably more accessible. 19
18,25
18
18
In humans, alternative sites include sternum, radius, ulna, and calcaneus. Aseptic preparation o f the site is required. The periosteum is highly innervated; therefore in stable patients, local infiltration with local anesthetic (e.g., 1% lidocaine) is recommended. A preemptive skin stab incision over the site o f penetration o f the catheter may prolong the life o f the needle. For placement in the medial tibia, the needle must be directed into the bone slightly distally and away from the proximal growth plate. To prevent sciatic nerve involvement during placement in the femur, the needle should be walked off the medial aspect o f the greater trochanter into trochan teric fossa, with the hip joint i n a neutral and internally rotated position. Once the desired orientation o f the needle is reached, firm pressure should be applied in clockwise, then counterclockwise rotation. This procedure normally generates a small depression that seats the needle in the bone; by increasing the pressure maintaining the same rota tion pattern, the needle should proceed through the near cortex. A sudden loss o f resistance indicates that the needle has crossed the cortex. 19
Before administration o f fluids or drugs through an intraosseous catheter, verification o f correct placement is required. O n e o f the most frequently reported causes o f fail ure of intraosseous catheterization is an error in identifying landmarks. A well-positioned catheter should be firmly seated in the bone and move with the limb without being
dislodged. Gentle aspiration should bring bone marrow into the syringe, although in older animals this may not always be possible. A bolus o f heparinized saline solution should flow easily, and there should be no accumulation of fluid in the subcutaneous tissue. If resistance is encountered, the needle can be rotated 90 to 180 degrees to move the beveled edge away from the inner cortex. The subcutaneous tissue must be observed for fluid extravasation. If extravasation is detected, the needle should be removed to prevent further complications and an alterna tive bone should be chosen for catheter placement. Once correct placement of the needle is verified, administration of fluids or drugs can be started by syringe or by using a standard intravenous administration set. To maintain patency during intermittent usage, a catheter plug can be applied and the catheter flushed with heparinized saline solution. Initial infusion o f fluids under pressure causes pain, last ing approximately 1 to 2 minutes, i n conscious human patients. In humans, recommendations to minimize pain include withdrawal o f a small volume o f bone marrow, and slow injection o f 1% lidocaine over 60 seconds before initiating the infusion. To properly secure the needle, a tape butterfly can be wrapped around the hub and sutured to the skin or the periosteum. The suture may also be fixed to the hub o f the needle with a cyanoacrylate glue. Some intraosseous needles come with permanent butterflies for suturing. Coverage o f the area with antiseptic or antibiotic cream is suggested and, when possible, a protective bandage can prevent damage to the needle. Intraosseous catheters require the same nursing care as intravenous catheters. In most cases, the intraosseous catheter is considered a tem porary access that should be replaced by an intravenous catheter as soon as possible. W h e n prolonged intraosseous infusion is required, guidelines for intravenous catheter care should be followed. Although there are limited data, the risk o f complications is thought to be m i n i m a l for catheters remaining for up to 72 hours with proper maintenance. 18,25
COMPLICATIONS The documented complication rate associated with intraos seous infusions in humans and animals is low. The types of complications include infection, fat embolism, extravasation of fluids, compartment syndrome, and bone f r a c t u r e s . One o f the most c o m m o n concerns when performing intraosseous infusion is osteomyelitis. Proper sterile technique during placement reduces the risk o f infection to 0.6% of cases, with potentially lower risk if the catheter is removed as soon as intravenous access is established or within 72 hours. Several studies have demonstrated that administration of fluids and drugs through an intraosseous route does not impair bone g r o w t h . Fat embolism can occur during intraosseous infusion; however, evidence for clinical significance is lacking. Although unlikely with proper technique, extravasation of fluids and compartment syndrome can be associated with major morbidity in humans. Improper catheter placement combined with irritating or hypertonic fluids, high fluid rates, pressure infusion, and large infusion volumes can all predispose to extravasation o f fluids and compartment syndrome. The latter does not appear to be a major issue in animals; however, if any infiltration is detected the intraosseous infusion should be 13,19
1
26
13,19
discontinued immediately. In addition, it is imperative that no additional catheter be placed in the same bone. Intraosseous infusion of hypertonic solutions is effective and apparently safe from major and long-term complica tions. Soft tissue and bone marrow necrosis secondary to intraosseous infusion of hypertonic saline has been reported in piglets, in which major clinical signs developed 48 hours postoperatively; therefore caution should be exer cised when using hypertonic solutions. Finally, appropri ate insertion technique, asepsis, frequent monitoring of the intraosseous access site, and prompt removal of the needle once an intravenous line has been established help to reduce risk factors and complication rates. 27
SUGGESTED FURTHER
READING*
DeBoer S, Seaver M , Morissette C: Intraosseous infusion: not just for kids anymore, Emerg Med Serv 34:54, 2005. A practical and updated nursing review describing the main indications for intraosseous infusion in humans and looking at the available devices. Otto C M , Kaufman MG, Crowe DT: Intraosseous infusion of fluids and therapeutics, Comp Cont Educ Pract Vet 11:42, 1989. One of the early review articles that resurrected the use of intraosseous infu sions in veterinary practice, including a series of cases and technique. Tocantins LM: Rapid absorption of substances injected into the bone mar row, Proc Soc Exp Biol Med 45:292, 1940. One of the first and most cited studies of intraosseous infusion in animals. *See the CD-ROM for a complete list of references.
Chapter 63 CENTRAL VENOUS CATHETERIZATION Harold Davis,
BA, RVT, VTS (Emergency/Critical Care and Anesthesia)
KEY POINTS • Indications for central venous catheter placement include hemodynamic monitoring, drug administration, and serial blood sampling. • Saphenous veins can be used as access points to the central venous circulation. • Medications with osmolalities of greater than 600 mOsm/L should be administered via a central vein. • Multilumen catheters minimize the number of veins that need to be catheterized. • Patient positioning and immobilization of the vein are key to successful catheterization.
• • • • •
•
known to cause phlebitis, such as diazepam, pentobar bital, and mannitol Measurement of central venous pressure Frequent aspiration of blood samples Total parenteral nutrition Maintenance of venous access for long periods When peripheral catheters are at risk of contamination from vomiting, polyuria, diarrhea, or vaginal discharge, because it may be easier to keep a jugular catheter site clean To facilitate transvenous pacing
GENERAL CONCEPTS INTRODUCTION Central venous catheters terminate in the cranial or caudal vena cava. These catheters may be inserted directly into a large central vein such as the jugular vein or inserted via a peripheral vein: a peripherally inserted central catheter (PICC). Indications for central venous catheter placement include hemodynamic monitoring, drug administration, and serial blood sampling. Central venous catheters often can be left in place for longer periods than peripheral cathe ters, making them very useful in critically ill patients. The following are situations in which a central catheter may be preferable to a peripheral venous catheter: • Administration of multiple fluid and drug types that are not compatible with each other, necessitating mul tiple catheter lumens • Administration of fluids that have an osmolality greater than 600 mOsm/L and constant rate infusions of drugs 1
Because introduction of foreign material or infectious agents into the central circulation can have far more serious conse quences than peripheral vessel contamination, maintenance of aseptic technique when placing and using central venous catheters is of utmost importance (see Chapter 116, CatheterRelated Bloodstream Infection). General recommendations for central venous catheter maintenance are to wipe all injec tion ports with alcohol before needle puncture, keep inser tion sites bandaged, prevent catheter hubs dragging on the ground, and immediately respond to witnessed catheter contamination. This may require cleaning and changing injection ports and fluid lines, or it may necessitate catheter removal. Inadvertent disconnection of fluid lines from a cen tral venous catheter or animal-induced trauma to the catheter can lead to significant hemorrhage. Leaving ports of a central venous catheter open to the atmosphere places the patient at risk of air embolism. For this reason the catheter should be occluded by a catheter lock or manual kinking whenever the
catheter hub is open to the atmosphere (e.g., when connect ing and disconnecting syringes for blood aspiration).
Multilumen Catheters
Through-the-needle catheters were discussed in Chapter 61, Peripheral Venous Catheterization. They c o m m o n l y are used to catheterize jugular veins. The Drum-Cartridge is a very long through-the-needle catheter that is an effective P1CC for large patients (see Figure 63-1).
M u l t i l u m e n catheters are placed using the Seldinger guidewire technique or a peel-off sheathed needle technique. M i l a and A r r o w make multilumen catheters. The catheters may be double, triple, or quadruple lumen. They are available in sizes ranging from 4 to 8.5 Fr and 2 to 24 inches (5 to 60 cm) in length. M u l t i l u m e n catheters are extremely useful in the critical care setting; they reduce the number o f catheters that need to be placed in the critically ill patient. Fluids and drugs that are incompatible can be administered simultaneously. The catheters can be purchased individually or as a kit that con tains all the components necessary for insertion. In addition to the catheter and dilators, the kits include local anesthetic, scalpel, syringe, and so on. M u l t i l u m e n catheters are more expensive than the commonly used single-lumen catheters.
Over-the-Needle
Percutaneous Sheath Catheter Introducer
Over-the-needle catheters were discussed in Chapter 61, Peripheral Venous Catheterization. W h e n used for jugular catheterization, they must be o f a length appropriate for the patient's size. The subcutaneous tissues in the region o f the jugular vein are very loose, resulting in a lot o f skin movement. Even though the catheter is well secured to the skin, short catheters can be pulled out o f the vein easily.
Percutaneous sheath introducer systems are large-bore (typi cally 6 to 8 Fr), relatively short (4 inches) catheters that have a hemostasis valve located in the hub. They also have a short T-extension port for the fluid administration. A central venous catheter, pulmonary artery catheter, or transvenous pacing lead can be passed through the hemostasis valve into the jugular vein. The hemostasis valve acts as a seal to prevent entry o f air into the circulation as well as to prevent blood or fluid loss around the catheter. The introducer must be placed with the Seldinger guidewire technique.
CATHETER TYPES Through-the-needle, long over-the-needle, long singlelumen, multilumen catheters, and catheter introducers can all be used to access central veins (Figure 6 3 - 1 ) . 1-3
Through-the-Needle
Long Single-Lumen Catheter This type o f catheter is inserted using the Seldinger guidewire technique or a peel-off sheathed needle technique. These catheters come in a variety o f sizes and lengths. M i l a Interna tional (Florence, K Y ) and A r r o w International (Reading, PA) make central venous catheters that are 14 or 16 gauge by 6 or 8 inches (15 or 20 c m , respectively). A r r o w also makes a 20gauge by 5-inch (12 cm) and a 22-gauge by 4-inch (10 cm) single-lumen catheter. SurgiVet (Waukesha, WI) makes 5, 6, 7, and 8 Fr central venous catheters; the 5 Fr is 6 inches (15 cm) in length and all others are 10 inches (25 cm). 2
CATHETER INSERTION SITE Central vein insertion sites include the jugular vein and the lat eral and medial saphenous veins (see Chapter 61, Peripheral Venous Catheterization). Long catheters theoretically can be inserted in the cephalic vein and passed up to the level of the cranial vena cava, but they frequently will not pass beyond the elbow. For this reason the cephalic vein rarely is used for P I C C lines.
Saphenous Vein To achieve central vein catheterization via the saphenous vein, long catheters must be used; they are threaded so that they lie in the caudal vena cava. In dogs the lateral saphenous vein is used most commonly, but the medial saphenous vein can also be catheterized. In cats the medial saphenous vein tends to be larger and more easily stabilized for catheterization.
Jugular Vein
Figure 63-1 Examples of catheters used for central venous catheteri zation. A, Examples of two through-the-needle catheters; the top catheter is a Drum-Cartridge and the other is an Intracath. B, A long over-the-needle-catheter. C, Central venous catheter. D, Triple-lumen catheter. E, Catheter sheath introducer.
The jugular vein is catheterized directly in the cervical region. It lies along a line drawn between the angle o f the mandible and the thoracic inlet. Jugular vein catheterization is feasible in both dogs and cats, and the vein may be visible in hemodynamically unstable patients when peripheral venous access is challenging. The key to jugular catheter insertion is patient position ing and vessel i m m o b i l i z a t i o n . If the patient is not positioned properly it can be difficult to visualize and i m m o b i l i z e the vein. Jugular catheters are placed antegrade, with the tip o f the catheter always directed toward the
heart. Placement of the jugular catheter is best done with the patient in lateral recumbency. The patient's head is extended and its forelimbs positioned caudally by an assis tant. Sedation of uncooperative patients is recommended. A bag of fluid, a sandbag, or rolled towels placed under the neck may be helpful (Color Plate 63-1). This flexes the neck and helps to make the vessel more accessible. The assistant should hold off the vein by pressing into the thoracic inlet; this should cause the vein to engorge and "stand up." The other end of the vein is immobilized by extending the head. In some cases venous cutdown may be needed to facilitate placement of a central catheter (see Chapter 61, Peripheral Venous Catheterization).
CATHETER INSERTION Strict aseptic technique is followed for all central venous catheterization. Sterile gloves should be worn and the inser tion site draped if the Seldinger technique is used or if the catheter will be used for total parenteral nutrition.
Seldinger Technique The Seldinger technique uses a smaller introducing catheter or trochar and a guidewire to gain access to vessels or hollow organs. It avoids the requirement of initially puncturing the ves sel with a large-bore catheter or trochar. It maybe used to place single-lumen catheters, multilumen catheters, or percutaneous catheter introducer systems. It can also be used to replace an existing catheter in the same location. The Seldinger technique for introduction of a multilumen catheter is described here. The basic concept of this technique will be the same for any type of catheter placement in any vessel. Before beginning the procedure, the required distance for catheter insertion is premeasured. The aim for a jugular catheter is to have the tip lying within the thoracic cavity, just cranial to the right atrium. This distance commonly is estimated by measuring the distance from the intended insertion site to the caudal edge of the triceps muscle or first rib. For PICC lines the distance from the insertion site to the vena cava is measured. These measurements will then aid in choosing the most appropriate catheter for that patient. The insertion site is clipped widely and surgically prepared in a routine manner. Infiltration of the intended insertion site with local anesthetic is recommended in con scious animals. The catheter kit, sterile gauze, scalpel blade, suture material, and instruments are opened on a sterile field. The operator wears sterile gloves; in some circum stances a hat, mask, and sterile gown may also be appropri ate, and an assistant can be helpful in challenging cases. The distal port of the multilumen catheter is identified. This is the port that terminates at the very tip of the catheter and will be the one through which the guidewire is passed. A l l ports of the multilumen catheter are flushed with heparin ized saline and all ports, with the exception of the distal port, are capped. The insertion site is draped; this is impor tant because the guidewire is long and flimsy, and the risk for contamination is high if draping is not sufficient. A small relief incision is made through the dermis with a scal pel blade at the site of intended insertion. The introducing nee dle or short over-the-needle catheter (Color Plate 63-3, A) enters the skin through the relief incision and is inserted into the underlying vessel. The guidewire is threaded through the insert ing needle or catheter into the vein (Color Plate 64-3, B). The distal end of the wire has a flexible J-tip to prevent puncturing the vessel wall. In some instances when it is difficult to pass the J-tip along the vessel, it maybe advantageous to use the straight end of the guidewire instead. It is important to recognize that this will be more traumatic to the vessel and that gentle tech nique should be maintained at all times. To prevent embolism of the guidewire, the operator should keep hold of it at all times. Once the guidewire is inserted, approximately two thirds to three fourths of its length is fed into the vessel. It is held in place while the introducing needle or catheter is removed and a vessel dilator is threaded over the wire. The skin entry site may need to be enlarged with a No. 11 scalpel blade to accommodate the dilator. The dilator is grasped near the distal tip and, using a forward twisting motion, is advanced into the vessel (Color Plate 63-3, C). To minimize blood loss, pressure is applied over the insertion site with sterile gauze pads as the dilator is removed, leaving the guidewire in place. In the case of a sheath introducer, the dilator is incorporated in the sheath and is removed once the sheath is in place. The multi lumen catheter is threaded over the guidewire until the proximal end of the guidewire protrudes from the hub of the catheter. 3
3
1
Through-the-Needle Catheter The catheter needle should be introduced subcutaneously. The needle tip is positioned over the vein and aligned as close as pos sible to the longitudinal axis of the vein. The needle tip is inserted into the vein; it maybe necessary to angle the needle somewhat in order to pick up the superficial vein wall. Once it is estimated that the entire needle tip is within the lumen of the vein, the needle is stabilized and the catheter is threaded into the vein. Once the catheter is fully advanced into the vein, apply pressure over the venous puncture site and back the needle out. Once the bleeding has stopped, secure the needle guard around the needle. The catheter is aspirated to confirm proper place ment and to clear it of air. It is then flushed with heparinized saline. The catheter should be capped with an injection cap or T-port and flushed again with heparinized saline. The catheter is sutured or stapled close to the insertion site. The insertion site is then covered with a sterile 2 x 2 gauze pad and the catheter site is bandaged. An alternative insertion of the through-the-needle cathe ter is to remove the long single-lumen catheter from the insertion needle provided and thread it through a short over-the-needle catheter instead. Appropriate aseptic tech nique is maintained. This is particularly useful for placing PICC lines in saphenous vessels of small patients. The large needle provided with these catheters is commonly too large for effective venipuncture of a peripheral vessel. Using an over-the-needle catheter as an introducer makes initial veni puncture relatively simple, and the through-the-needle cath eter is generally more affordable than a multilumen catheter. In this situation, a common approach is to first insert a short over-the-needle catheter into the medial or lateral saphenous vein (Color Plate 63-2, A). A through-the-needle catheter (with the needle removed) is advanced into the pre¬ placed catheter (Color Plate 63-2, B). The two catheter hubs are joined tightly together (Color Plate 63-2, C). Butterfly wing tape is used at the catheter hub juncture to prevent accidental dislodgement. The tape is sutured to the catheter (to prevent the tape from slipping) and the tape wings are sutured to the skin proximally to pull the catheter back toward the insertion site (Color Plate 63-2, D).
If the guidewire was advanced too far into the vessel, it will be necessary to back it out of the vessel to achieve this. Finally, while the proximal end of the guidewire is held, the catheter is advanced into the vessel the desired distance as determined by previous measurement (Color Plate 63-3, D). The wire is removed. All ports are then aspirated to remove any air and to ensure that blood is easily drawn through the catheter. If necessary the catheter may be repositioned to allow aspira tion of blood. Aseptic technique must be maintained throughout. A l l ports are flushed with heparinized saline. The catheter is then sutured in place; the insertion site is covered with sterile gauze and bandaged appropriately.
Peel-Off Sheathed Needle Technique The peel-off sheathed needle (Mila International and SurgiVet) is similar to an over-the-needle catheter. The sheath has two tabs on the proximal end near the hub of the needle; when the tabs are pulled the sheath will split or peel away. The peel-off sheath technique can be used to place long single-lumen and multilumen catheters. Peel-off sheath placement is similar to over-the-needle catheter technique. Once the needle and sheath placement is confirmed by bleeding, the needle is removed leaving the sheath in the vessel. The catheter is threaded down the sheath. The sheath is then peeled apart by grasping the tabs and pulling outward and upward. Once the sheath is completely separated, the catheter is positioned and secured.
COMPLICATIONS AND CATHETER MAINTENANCE The same complications and catheter maintenance as dis cussed in Chapter 61, Peripheral Venous Catheterization,
apply to central venous catheters (see Chapter 116, CatheterRelated Bloodstream Infection).
Heparinized Saline All unused ports on central venous catheters should be flushed with heparinized saline. The author uses 4 U/ml of heparinized saline (1000 U/250 ml normal saline) q4h. Bags of heparinized saline should be discarded every 12 to 24 hours to minimize the risk of contamination. If a catheter port is not going to be used for a prolonged period, an alter native is to use a heparin lock. The dead space of the catheter is filled with 100 U/ml heparin ql2h. The concentrated hep arin solution is never flushed into the patient; instead, it is aspirated before administering medications or before repla cing the heparin lock. Clear labeling of such ports to avoid inadvertent flushing of the concentrated heparin into the patient is important.
SUGGESTED FURTHER READING* Beal MW Placement of central venous catheters: Seldinger technique, NAVC Clinician's Brief, Oct 7-10, 2005. An excellent review of the Seldinger technique with step-by-step photographs. Hansen B: Technical aspects of fluid therapy. In DiBartola SP, editor: Fluid, electrolyte and acid-base disorders in small animal practice, St Louis, 2006, Saunders. Fluid therapy chapter that includes a discussion of catheter selection and place ment techniques with an excellent discussion of skin preparation for venous catheterization. White RN: Emergency techniques. In King L, Hammond R, editors: Manual of canine and feline emergency and critical care, Cheltenham, 1999, Brit ish Small Animal Veterinary Association. Review of most catheterization techniques, including peripheral and central venous catheters. *See the CD-ROM for a complete list of references.
Chapter 64 DAILY INTRAVENOUS FLUID THERAPY Deborah C. Silverstein,
D V M , DACVECC
KEY POINTS • Daily intravenous fluid therapy is used to correct dehydration, provide maintenance fluid and electrolyte needs, and replace ongoing losses. • The movement of fluid within the body is determined by hydrostatic pressure, colloid osmotic pressure, vascular endothelial permeability, and osmolality. • Total body water is distributed in the intracellular and extracellular (plasma and interstitium) fluid compartments. The intracellular space is much larger than the extracellular space. • The most common types of daily intravenous fluids include isotonic crystalloids, hypotonic crystalloids, free water solutions, and synthetic colloids. • The fluid type and rate should be tailored to the individual patient's needs. • Potential complications of fluid therapy include pulmonary edema, subcutaneous edema, organ edema, and electrolyte imbalances.
INTRODUCTION Intravenous fluid therapy is vital for the management of shock, dehydration, and maintenance in animals that require parenteral fluid therapy (see Chapters 61,62, and 63, Peripheral Venous Catheterization, Intraosseous Catheterization, and Central Venous Catheterization, respectively, and Chapters 65 and 66, Shock Fluids and Fluid Challenge and Transfusion Medicine, respectively). This chapter focuses primarily on the distribution of total body water, patient assessment, and the delivery of synthetic intravenous fluids to maintain normal water, electrolyte, and acid-base status in critically ill dogs and cats that are hemodynamically stable. Because critically ill ani mals often have fluid and electrolyte balance derangements, overall recovery often depends on recognition and appropriate treatment of these disorders, in addition to diagnosing and treating the primary disease process.
Figure 64-1 The distribution of total body water (TBW). ECF, Extracel lular fluid; ICF, intracellular fluid.
membrane, which is very permeable to water but imperme able to most solutes. Cell membranes contain numerous pro teins, including ion channels and active solute pumps. The most important active pump is the sodium-potassium ATPase pump, which extrudes three sodium ions out of the cell in exchange for bringing two potassium ions into the cell. This pump is responsible for generation of the electrochemi cal gradient across cell membranes, typified by a high intra cellular potassium concentration, high extracellular sodium concentration, and a negative resting membrane potential. Therefore the most prevalent cation in the ICF is potassium, with much smaller contributions made by magnesium and sodium. The most prevalent anions in the ICF are phosphate and the polyanionic charges of the intracellular proteins. The ECF comprises the remaining 33% of the total body water and 20% of body weight. The ECF is subdivided into the plasma (25% of ECF) and interstitial (75% of ECF) fluid compartments. The interstitial fluid bathes all cells and includes lymph. The primary cation in the ECF is sodium and the most prevalent anions are C I and H C O 3 . The pro teins in plasma and the interstitial space also contribute to the negative charges. The oncotic pressure gradient between the intravascular and interstitial spaces is determined by the ratio of proteins in these two compartments. 1,2
-
-
1,2
MOVEMENT OF FLUIDS WITHIN THE BODY TOTAL BODY WATER Living organisms are predominantly composed of water. Total body water content is approximately 60% of body weight in a nonobese adult dog or cat. Total body water is distributed between two main compartments: intracellular fluid (ICF) and extracellular fluid (ECF) (Figure 64-1). Each compartment consists of solutes, primarily electrolytes, dis solved in water. The most important determinant of the size of each body fluid compartment is the quantity of solutes contained in that compartment. The ICF compartment is the larger of the two and com prises 66% of the total body water and 40% of body weight. It is separated from the ECF compartment by the cell 1,2
Water moves freely within most compartments in the body. Small particles such as electrolytes move freely between the intra vascular and interstitial compartment, but cannot enter or leave the cellular compartment without a transport system. Larger molecules (>20,000 daltons) do not easily cross the vascular endothelial membrane and may attract small, charged particles, thus creating the colloid osmotic pressure (COP). There are three main natural colloid particles: albumin, globulins, and fibrino gen. An increase in the pressure of fluid within a compartment that pushes against a membrane is known as hydrostatic pressure. In health, fluid balance is determined by the balance between forces that favor reabsorption of fluid into the vas cular compartment (increased COP or decreased hydrostatic
pressure) and those that favor filtration out of the vascular space (decreased COP or increased hydrostatic pressure). Changes in the osmolality between any of the fluid compart ments within the body will cause free water movement across the respective membrane. In disease states, both increased fluid losses and decreased intake may lead to dehydration. The nature of the fluid loss (hypotonic, isotonic, or hypertonic) will determine the subsequent changes in osmolality. This will in turn dictate the relative impact on the ICF and ECF compartments.
FLUID THERAPY PLAN
1
Isotonic Fluid Loss Isotonic fluid losses, as seen in animals with polyuric renal failure or bleeding, will lead to depletion of the ECF com partment and dehydration. If severe ECF losses are not replaced, hypovolemia may become clinically apparent. Because isotonic losses will not alter ECF osmolality, there will be no movement of water across the cell membrane and ICF volume will remain unchanged. In order to replace the ECF deficit, isotonic crystalloids should be administered (see Fluid Deficit).
Hypotonic Fluid Loss Hypotonic fluid losses, as seen with diabetes insipidus or excessive panting, will cause hypernatremia and an increase in ECF osmolality. This will lead to movement of water out of the ICF space. Consequently, there is a depletion of both the ICF and ECF compartments. Isotonic fluid therapy may be sufficient if the hypernatremia is not severe, but in animals with significant hypotonic fluid losses, free water administration is indicated. Care must be taken to lower serum sodium slowly to avoid causing potentially life-threat ening cerebral edema (see Chapter 54, Sodium Disorders).
Hypertonic Fluid Loss Loss of hypertonic fluid, such as with heat exhaustion or highly concentrated urine, may cause hyponatremia and hypoosmol¬ ality. This maybe a direct result of the loss of high solutecontaining fluid or may be exacerbated by a combination of isotonic or hypertonic fluid loss with hypotonic fluid replace ment (i.e., oral water intake). Hypoosmolality will lead to water movement into the ICF compartment, resulting in dehydration and intracellular edema. Significant hyponatremia or hypoos molality will require careful fluid therapy to avoid rapid (>0.5 mEq/L increase per hour) changes in sodium concentra tion and subsequent central pontine myelinolysis.
Increased Vascular Permeability Disease processes that cause an increase in vascular perme ability may lead to high-protein fluid extravasation from the intravascular space. This can lead to a decrease in intra vascular volume, possibly associated with interstitial edema. Because this will not alter the osmolality of the ECF com partment, increased vascular permeability alone is not expected to alter the ICF volume. Patient history, physical examination, and laboratory data can provide useful information concerning the route of fluid losses, timeline of these losses, food and water consumption, and current clinical status. This will guide formulation of an appropriate fluid therapy plan.
The fluid type and rate of administration chosen depend pri marily on the clinical status of the animal based on the physical examination and laboratory parameters. For animals with evi dence of chronic dehydration on physical examination, but sta ble cardiovascular parameters, fluid deficits should be replaced over 4 to 24 hours. Isotonic replacement fluids are administered according to the patient's estimated dehydration, maintenance needs, and anticipated ongoing losses. To determine the quantity of fluid necessary for the stable patient with evidence of dehydration, the following formula is used: Body weight(g) x percentage dehydration (= deficit) + estimated ongoing losses (ml) + maintenance (ml) = amount to be given (ml) over next 4 to 24 hours
Fluid Deficit Volume deficiencies in each of the body fluid compartments exhibit different clinical signs or laboratory abnormalities. ICF deficits lead to cerebral obtundation, hypernatremia, and hyperosmolality. ICF deficits alone will not cause clinical evidence of dehydration. In contrast, interstitial volume def icits typically are associated with a decrease in skin turgor (increased skin tenting) and dry mucous membranes. Skin turgor provides only a rough estimate of dehydration, and severe emaciation or obesity can make this assessment diffi cult. Intravascular volume deficits commonly are associated with compensatory vasoconstriction, pale mucous mem branes, poor pulse quality, tachycardia, prolonged capillary refill time, and cold extremities. These symptoms are sugges tive of poor tissue perfusion and require rapid intervention. Physical examination findings in animals with evidence of dehydration are listed in Table 64-1.
Maintenance Daily maintenance fluid needs have not been well studied in the dog and cat, so it is especially important that animals
Table 64-1 Physical Examination Findings in Dehydrated Patients Percentage of Dehydration
Clinical Signs
12
All of the above plus signs of shock, often life threatening
CRT, Capillary refill time.
receiving intravenous fluids be assessed several times per day. The formula most commonly used is (BW x 30) + 70 (ml per day). For animals that weigh less than 2 or more than 50 kg, an alternative formula should be used: ( B W )70. These calculations take into account the sensible and insen sible ongoing fluid losses (feces, urine, panting, sweating). Because there is less water in fat than in muscle, these calcula tions will overestimate the maintenance needs of overweight patients. kg
0.75
kg
3,4
Ongoing Losses Ongoing fluid losses are estimated from an understanding of the underlying disease process and historical data. For exam ple, when treating animals with gastrointestinal losses the approximate volume and frequency of vomiting and diar rhea is estimated. Obviously this predicted volume may be inaccurate; it allows calculation of an initial fluid therapy plan, but close patient monitoring and reevaluation are imperative. If the estimate of ongoing fluid losses is signifi cantly inaccurate, the fluid plan should be altered accordingly.
Route of Administration Although subcutaneous fluid administration can be effective in the management of fluid deficits, it is not adequate for the critically ill patient. Fluid therapy should be administered via an intravenous catheter that is checked regularly for evidence of phlebitis or inadvertent subcutaneous fluid administration.
FLUID TYPE The type of fluid that should be administered depends on the individual patient. Options for the critically ill patient include replacement fluids, maintenance fluids, free water solutions, and synthetic colloids.
Replacement Fluids Replacement fluids, also known as isotonic crystalloids, are electrolyte-containing fluids with a composition similar to that of the ECF. They have the same osmolality as plasma (290 to 310mOsm/L); the electrolytes are small in size, and they do not significantly change the osmolality of the vascular or extravascular space in animals with a normal osmolality. ' They may also contain acid-base components and dextrose. Isotonic crystalloids are commonly used to expand the intravascular and interstitial spaces and maintain hydration. The constituents of commonly used isotonic fluids can be found in Table 64-2. Additional electrolytes, such as potassium, may be added to maintenance or replace ment fluids as needed for an individual patient (see Part V, Electrolyte and Acid-Base Disturbances). Following infusion of isotonic crystalloids into the vascu lar space, the small electrolytes and water pass freely across the vascular endothelium. These fluids are extracellularexpanding fluids; 75% redistributes to the interstitial space, and only 25% remains in the vascular space after 30 min utes. Although so-called replacement fluids are used com monly for maintenance of hydration, most animals are able to easily excrete the electrolyte constituents that are in excess of the body's needs. This practice is common, 4 5
6
because most hospitalized animals have ongoing electrolyte losses and poor enteral intake, and it is much easier to hang one bag of isotonic crystalloids than two separate bags (one for replacement and one for maintenance). The rate of fluid replacement is determined as outlined earlier in this chapter. Not all isotonic fluids are created equal, as seen in Table 64-2. Isotonic saline solution (0.9% NaCl) contains a higher concentration of sodium and chloride (154mEq/L of each) than does normal blood, and will cause propor tional changes (increases) in the recipient electrolytes. Therefore large amounts of 0.9% NaCl will cause a mild increase in serum sodium, a marked increase in chloride, and a moderate decrease in bicarbonate and potassium. The kidneys typically will compensate, if possible, by excreting the excess electrolytes and conserving potassium. Isotonic crystalloids can cause harm, especially in critically ill animals. The interstitial fluid gain can lead to interstitial edema, pulmonary edema, and cerebral edema. Patients with a low COP, pulmonary contusions, cerebral trauma, fluidunresponsive renal disease, or cardiac failure are at highest risk for complications. In addition, substantial hemodilution of blood constituents that are not found in the crystalloids can occur. Anemia, hypoproteinemia, and hypocoagulability can occur following large-volume crystalloid administration. Although all isotonic crystalloids have a similar composi tion, there are situations in which a specific fluid type may be preferable over another. Specifically, animals with diabetic ketoacidosis or liver disease should not receive lactate¬ containing fluids because of their decreased ability to convert the lactate to bicarbonate in the liver. However, lactated Ring er's solution may be preferred in very young animals because lactate is the preferred metabolic fuel in neonates with hypo glycemia. Patients with a hypochloremic metabolic alkalosis will benefit from 0.9% sodium chloride, because this is the highest chloride-containing fluid, but animals with a severe acidosis may benefit from an alkalinizing fluid containing lac tate, acetate, or gluconate (see Table 64-2). Animals with head trauma or increased intracranial pressure may benefit from 0.9% sodium chloride, because this isotonic crystalloid is least likely to cause a decrease in osmolality that might promote water movement into the brain interstitium.
Maintenance Fluids Maintenance fluids refer to the volume of fluid and amount of electrolytes that must be consumed on a daily basis to keep the volume of total body water and electrolyte con tent within the normal range. Obligate fluid losses are hypotonic and hyponatremic, but contain relatively more potassium than does the ECF. Maintenance fluids are therefore hypotonic crystalloids that are low in sodium, chloride, and osmolality, but high in potassium compared with normal plasma concentrations (Table 64-3). The inclusion of dextrose may make the fluid isoosmotic to plasma, but the dextrose is metabolized rapidly to carbon dioxide and water, so these fluids are still hypotonic in nature. As mentioned earlier, daily maintenance needs are calculated as ( B W x 30) + 70 (mL per day). For animals that weigh less than 2 or more than 50 kg, an alternative formula should be used: ( B W ) 7 0 . Maintenance-type fluids are distributed into all body fluid compartments and should never be administered as a bolus or cerebral edema may result. 7
kg
0.75
kg
Table 64-2
Isotonic Crystalloid Compositions [Mg ++] (mEq/L)
[Ca ++] (mEq/L)
Lactate (mEq/L)
Acetate (mEq/L)
Gluconate (mEq/L)
154
—
—
—
—
4
109
—
3
28
— —
140
5
98
3
—
27
23
140
5
98
3
—
27
23
Fluid Type
Osmolality
[Na+ ] (mEq/L)
[K+] (mEq/L)
0.9% NaCI
308
154
—
Lactated Ringer's solution
273
130
Plasmalyte 148
295
Normosol-R
295
Table 64-3
[CI-] (mEq/L)
—
Maintenance and Free Water Solution Compositions [Ca++]
Fluid Type
Osmolality
[Na+ ] (mEq/L)
[K+ ] (mEq/L)
[CI- ] (mEq/L)
[Mg++ ] (mEq/L)
Lactate (mEq/L)
Acetate (mEq/L)
0.45% NaCI
150
77
0
77
—
0.45% NaCI with 2.5% dextrose
203
77
—
77
— —
—
—
—
— —
—
2.5%
Plasmalyte 56
110
40
13
40
3
Normosol-M
110
40
13
40
— —
— —
16
3
16
— —
1/2 LRS with 2.5% dextrose
265
130
4
109
—
3
28
—
2.5%
D5W
252
—
—
—
—
5%
(mEq/L)
Dextrose
D5W, 5% dextrose in water; LRS, lactated Ringer's solution.
Free Water Administration In order to give free water (fluids with no electrolytes or buff ers) intravenously without using a dangerously hypotonic fluid, the water is combined with 5% dextrose to yield an osmolality of 252 mOsm/kg (safe for intravenous adminis tration). This fluid is indicated in animals with a free water deficit (i.e., hypernatremia) or severe ongoing free water losses (i.e., diabetes insipidus). In order to safely lower the sodium concentration by 1 mEq/hr, a rate of 3.7 ml/kg/hr is a good starting point and can be adjusted based on the patient's response. Close monitoring of electrolyte status is advised. Dextrose 5% in water should never be administered as a bolus because acute decreases in osmolality will cause potentially fatal cerebral edema.
Synthetic Colloids The most commonly used synthetic colloid solutions include dextran-70 and hydroxyethyl starch (hetastarch). Colloids are large molecules (molecular weight >20,000 daltons) that do not readily sieve across the vascular membrane. The base solution of most products is 0.9% sodium chloride, and the colloidal particles are suspended within the crystalloid. These fluids are polydisperse (they contain molecules with a variety of molecular weights) and hyperoncotic to the nor mal animal, and therefore cause the movement of fluid from the extravascular to the intravascular space. Synthetic col loids lead to an increase in blood volume that is greater than that of the infused volume and also aid in the retention of this fluid in the vascular space (in animals with normal cap illary permeability). Dextran-70 is a 6% colloidal solution with particles that range from 15,000 to 3,400,000 daltons, a number average molecular weight of 41,000, and a COP of 60 mm Hg in vitro. Hetastarch is also a 6% solution, with particles ranging from 10,000 to 1,000,000 daltons in
molecular weight, a number average molecular weight of 69,000 daltons, and a COP of 34 mm Hg in vitro. Excessive volumes may lead to volume overload, coagulopathies, and hemodilution. Synthetic colloids typically are used in combi nation with isotonic crystalloids to maintain adequate plasma volume expansion with lower interstitial fluid vol ume expansion. Continuous rate infusions are commonly used at a rate of 0.5 to 2 ml/kg/hr in animals with acute decreases in COP or total protein levels. The use of fresh or stored whole blood, packed red blood cells, or plasma products is often necessary in critically ill animals. A thorough discussion of transfusion medicine can be found in Chapter 66. 7,8
MONITORING Animals receiving intravenous fluids should be monitored closely. Body weight should be monitored daily (or more often if indicated) and a physical examination should be performed at least twice daily to assess the animal's mental status, skin turgor, heart rate and pulse quality, mucous membrane color, capillary refill time, extremity temperature, and respiratory rate and effort. Serial lung auscultation should be performed to monitor for increased breath sounds, crackles, or wheezes. Clinical signs in animals receiving too much fluid include serous nasal discharge, chemosis, jugular venous distention, and interstitial pitting edema. In the early stages of pulmonary edema, an increase in the respiratory rate will occur, followed by inspiratory crackles, wheezes, and dyspnea. It is therefore of utmost importance to monitor the respiratory rate and effort of all patients receiving fluid therapy. If an indwelling urinary catheter is present, urine output can be compared with fluid input to help guide fluid ther apy and prevent the administration of too much or too little
fluid. Serum blood urea nitrogen and creatinine levels can be evaluated in conjunction with the urine specific gravity to determine whether there is prerenal or renal azotemia (or a Combination of both). A n increase in blood urea nitrogen and creatinine with an increase in urine specific gravity would suggest that the animal is receiving insufficient fluid volume. Inadequate tissue perfusion may result in an increase in blood lactate levels secondary to anaerobic metabolism. Serial lactate measurements may help guide fluid therapy as an indicator of tissue perfusion. Moderate to severely elevated lactate levels should alert the clinician that more aggressive treatment may be required. If a central venous catheter is in place, central venous pressure monitoring may be used to help guide fluid ther apy. Although this is a measurement of the pressure in the vena cava, it is used commonly to evaluate volume, because there is normally a direct relationship between the two para meters (see Chapter 203, Hemodynamic Monitoring). Addi tional monitoring techniques that might be helpful include arterial blood pressure, electrocardiogram, and repeated measurements of packed cell volume, total solids, blood glu cose, electrolytes, and acid-base status. A n increase in the activated partial thromboplastin time (APTT) may develop in animals that receive large amounts of synthetic colloid therapy, although the quantitative APTT change is not pre dictive of clinical bleeding. Coagulation times should be monitored and transfusion therapy initiated as needed. Pul monary capillary wedge pressure monitoring, cardiac output monitoring, and mixed venous oxygen saturation measure ments may be helpful in select patients.
DISCONTINUATION OF FLUID THERAPY In most animals, fluid therapy should not be discontinued abruptly, especially if high flow rates are being administered.
These animals may have renal medullary washout and there fore the urine concentrating ability will be impaired for several days. This can lead to severe dehydration and hypovolemia in animals that are not drinking large amounts of water. Ideally, intravenous fluid therapy should be decreased gradually over a 24-hour period. Some animals may require slower weaning protocols, especially those receiving high flow rates. Owners should be informed that the animal may have increased water requirements for a few days after the discontinuation of intra venous fluid therapy. In conclusion, intravenous fluid therapy should be used to maintain normal water, electrolyte, and acid-base status in dogs and cats that are hemodynamically stable. The fluid plan should be tailored to the animal's state of hydration, continued maintenance needs, coexisting diseases, labora tory abnormalities, and anticipated ongoing losses. Critically ill animals commonly require intravenous fluid therapy, and an understanding of body fluid compartments and the dis tribution of various fluid types is essential when formulating a treatment strategy. Judicious monitoring is vital, and a gradual weaning from fluid therapy is recommended.
SUGGESTED FURTHER
READING*
DiBartola SP: Fluid, electrolyte and acid-base disorders in small animal prac tice, ed 3, Philadelphia, 2006, Saunders. A thorough and detailed fluid therapy and electrolyte/acid-base textbook for small animal veterinarians. Greco DS: The distribution of body water and general approach to the patient, Vet Clin North Am Small Anim Pract 28:473, 1998. A nice review of water composition in the small animal patient and practical guide for fluid therapy based on these concepts. Kirby R, Rudloff E: The critical need for colloids: maintaining fluid balance, Comp ContEd Pract Vet 19:705, 1997. This review paper provides a clear overview of use of colloid therapy in animals and the various products available. *See the CD-ROM for a complete list of references.
Chapter 65 SHOCK FLUIDS AND FLUID CHALLENGE Janet Aldrich,
DVM, DACVECC
KEY POINTS • The primary goal of shock therapy is to improve delivery of oxygen and other nutrients to metabolically active cells. • Isotonic crystalloids and colloids, each at their appropriate dosages, are equally effective for managing shock. Hypertonic saline is usually combined with a colloid. • Fluids should be chosen with consideration of concurrent conditions, such as dehydration, active bleeding, or brain injury. • The fluid challenge technique is useful for hemodynamically unstable patients to determine if inadequate resuscitation is the cause of instability.
Table 65-1
Shock Fluid Dosage Ranges
SHOCK Circulatory shock refers to states of inadequate tissue perfu sion causing the partial pressure of oxygen at the tissues to fall below a critical level required to maintain adequate energy production. Circulatory shock can be further cate gorized as hypovolemic, cardiogenic, obstructive, or distrib utive in nature. Hypovolemic shock is due to an absolute or relative reduction in blood volume. Cardiogenic shock describes inadequate tissue perfusion as a consequence of cardiac disease. Obstructive shock occurs when there is an obstruction such as an embolus or pericardial effusion impeding blood flow out of the heart or venous return to the heart. Distributive shock is due to inappropriate gene ralized vasodilation leading to inadequate perfusion. This is generally a consequence of systemic circulation of inflam matory mediators as can occur with the systemic inflamma tory response syndrome or anaphylaxis. The primary goal of shock therapy is to improve delivery of oxygen and other nutrients to metabolically active cells. Intravenous fluid therapy is essential in the resuscitation of patients with hypovolemic, distributive, and obstructive shock. ' There may be a role for fluid therapy in some specific instances of cardiogenic shock, but it must be admi nistered with caution and requires intensive monitoring (see Chapter 35, Cardiogenic Shock). Fluids that are effective volume expanders in shock are isotonic crystalloids, hypertonic crystalloids, and synthetic colloids suspended in isotonic crystalloid solutions.
*Shock fluid therapy should be given in increments and the total dosage determined by the individual response.
1
2
3 4
ISOTONIC CRYSTALLOIDS The composition of isotonic (or nearly isotonic) crystalloid fluids is similar to that of extracellular fluid. They have sodium concentrations in the 130 to 154 mEq/L range and concentrations of other ions (potassium, magnesium,
calcium) similar to those in extracellular fluids, and may contain bicarbonate-like anions (Table 65-1).
Physiology Rapid intravenous infusion of isotonic crystalloids causes continuous vascular volume expansion until the infusion stops, at which time most of the administered volume is in the vascular compartment. When 80 ml/kg was administered in 12 minutes to experimental, healthy dogs, blood volume was increased by 76% at the end of the infusion, 35% after 30 minutes, and 18% after 4 hours. Because of the fairly rapid distribution out of the vascular space, isotonic crystalloids must be administered at rapid rates to get the desired vascular volume expansion. Isotonic crystalloids have little effect on intracellular volume (see Chapter 64, Daily Intravenous Fluid Therapy). 5
Benefits Isotonic crystalloids are inexpensive, readily available, and have a long track record of success as resuscitation fluids. The redistribution to the interstitium is beneficial for many dogs and cats in shock, because their underlying problem often involves preexisting severe salt and water losses that have depleted the extracellular volume (dehydration).
Adverse Effects If isotonic crystalloids are delivered too slowly, the desired vascular volume expansion is not achieved but 75% of the
administered volume is still distributed to the interstitium, predisposing the patient to interstitial fluid overload, possi bly to pulmonary edema. However, the lung is richly sup plied with lymphatic vessels, which, among other factors, can protect it from interstitial fluid overload. Large-volume isotonic crystalloid resuscitation did not cause increases in lung water or hypoxemia in a canine hemorrhagic shock model. Inappropriate and overzealous administration of isotonic crystalloids risks adverse effects of worsened pulmo nary edema, increased intracranial pressure, and abdominal compartment syndrome. Isotonic crystalloids dilute all plasma elements except those ions present in the administered fluid at plasma con centrations. Of major concern is dilution of albumin and therefore decrease in colloid osmotic pressure, and dilution of the red blood cell mass. With redistribution of crystalloid fluids this effect will be reduced. Alterations in immunologic and proinflammatory states, such as neutrophil activation or increase in apoptosis, have occurred in experimental animals treated for shock with lactated Ringer's solution. Pulmonary apoptosis was increased when the D isomer of lactate was substituted for L isomer in lactated Ringer's solution. Intestinal hyperperme¬ ability was decreased in an experimental hemorrhagic shock model when Ringer's ethyl pyruvate solution was used. 6
7-9
10
11
Fluid Prescription The estimated dosage of isotonic crystalloids for treating shock is equal to the patient's healthy blood volume (approxi mately 80 ml/kg for dogs, 50 ml/kg for cats). The actual fluid requirements of each patient will vary and must be pre scribed individually. The total amount administered depends on the response to treatment and is usually one half to one blood volume (see Table 65-1). One strategy is to set up the fluid delivery system to deliver the prescribed amount in 20 minutes, and to slow or discontinue the infusion if the tissue perfusion parameters improve before the end of the infusion. Pressure bags are helpful for rapid administration of large volumes of isotonic crystalloids. For cats, rapid infusion of fluids can be performed easily with a 60-ml syringe. This allows accurate measurement of the volume given and avoids the risk of inadvertent fluid overload. Patients are monitored continually throughout the resuscitation period, and rapid administration is stopped when the goals of resuscitation are accomplished.
COLLOIDS Synthetic colloids (hydroxyethyl starch, dextran, gelatins) are isotonic crystalloid solutions to which large molecules have been added to achieve colloid concentrations of about 6%. Hydroxyethyl starch is available suspended in either isotonic saline (Hespan) or a solution similar to lactated Ringer's (Hextend). Dextran-70 is suspended in isotonic saline.
Physiology Synthetic colloids redistribute into the interstitial space at a much lower ratio than the isotonic crystalloid fluids. They
are expected to increase serum colloid osmotic pressure, which will lead to movement of fluid from the interstitial space into the vascular space. Consequently, colloid adminis tration will increase blood volume by an amount greater than the infused volume. This means that effective resuscita tion may be possible by administering smaller volumes. When the full dose of 20 ml/kg was administered in 5 minutes to experimental healthy dogs, blood volume was increased by 25% at the end of the infusion, 36% after 30 minutes, and 26% after 4 hours. These fluids are isoosmotic, so there is little effect on intracellular volume (see Chapter 64, Daily Intravenous Fluid Therapy). 5
Benefits Colloid solutions produce vascular volume expansion with less interstitial expansion than do crystalloid solutions. They support colloid osmotic pressure and are useful in patients who are symptomatic from their hypoalbuminemia. In the ory, the larger molecular weight colloids, because of their molecular size and configuration, might seal capillary leaks in patients with capillary leak syndrome. Some have postu lated that capillaries have both small pores, which reflect col loids, and large pores, which do not. The capillary leak syndrome that occurs in critical illness causes a change in the number of these pores but not in their size. For this rea son, the molecular weight distribution of hydroxyethyl starch would not be a determining factor. Some studies have supported the benefits of colloids in capillary leak, others have n o t . 12
13
14,15
13,16
Adverse Effects The most important adverse effect of synthetic colloids is on coagulation. High molecular weight hydroxyethyl starch (the only available formulation in the United States) and dextran at dosages greater than 20 ml/kg q24h are likely to prolong clotting times. The causes of these changes in coagulation are many, includ ing decreases in factor VIII and von Willebrand factor. Clini cally significant bleeding associated with these products is unpredictable, probably because concurrent disease affects coagulation in many critically ill patients. They should be used in caution with patients already showing blood clotting abnormalities or in those in which blood clotting ability is a major concern, such as in those undergoing emergency surgery. Colloids dilute red blood cell mass and albumin, as do crystalloids, and this effect is long lasting in proportion to the persistence of colloids in the vascular space. Allergic reactions to hydroxyethyl starch, dextran, and gelatin are reported but are extremely rare. 17-19
Fluid Prescription In anticipation that most of the administered volume will remain in the vascular space, and because of potential toxicity, the dosage of colloids is smaller than that of crystalloids. The usual volume for management of shock is 10 to 20 ml/kg for dogs and 5 to 10 ml/kg for cats (see Table 65-1). As described for isotonic crystalloid resuscitation, colloid administration should be titrated according to the individual patient's response. The total volume usually is administered over 5 to 10 minutes.
HYPERTONIC SALINE The usual concentration of hypertonic saline used to treat shock is 7.2% to 7.5%. The approximate osmolality is 2400 mOsm/L.
patient's effective osmolality is already high, the hypernatre¬ mia could be severe enough to cause neurologic signs of tremors, altered mentation, and seizures. At recommended dosages, the hypernatremia is not associated with clinical complications. Overly fast administration (>1 ml/kg/min) of hypertonic saline can cause bradycardia, hypotension, and bronchoconstriction. In patients with decreased reservoirs of intracellular vol ume, the efficacy of hypertonic saline may be diminished. But, in a hemorrhagic shock model of pigs previously dehy drated by 8% of their body weight, the hemodynamic response to resuscitation was maintained. Hypertonic saline may dilate precapillary sphincters and alter distribution of blood flow. 23,24
Physiology Hypertonic saline creates an osmotic gradient from the intracellular to extracellular fluid space, leading to a reduc tion in intracellular volume and an increase in extracellular volume. The recruited fluid distributes in the extracellular space according to the 1:3 vascular-to-interstitial ratio. Con sequently the increase in intravascular volume is greater than the infused volume. When 4 ml/kg was administered over 5 minutes to experimental healthy dogs, the increase in blood volume was 17% at the end of the infusion, 12% after 30 minutes, and 3% after 4 hours. These fluids are highly effi cient, because they expand blood volume about 3.5 times the amount administered. However, because the volume infused is small the absolute increase in vascular volume is small. 5
Benefits
25
Fluid Prescription Hypertonic saline (7.5%) can be administered at a dosage of 4 to 6 ml/kg in dogs and 3 to 4 ml/kg in cats over approxi mately 5 minutes (see Table 65-1). Hypertonic saline often is combined with a colloid fluid, to prolong the volumeexpanding effect.
FLUID COMBINATIONS
The small volume of hypertonic saline to be administered in shock makes it attractive for situations in which limited sup port is available, such as in prehospital resuscitation in humans. Hypertonic saline is an effective resuscitation fluid despite its relatively small impact on vascular volume in com parison with other fluids. Its effectiveness has been attributed to other physiologic benefits such as vasodilation, increased cardiac contractility, and immunomodulatory effects. Hyper tonic saline causes arteriolar vasodilation and improved microcirculatory perfusion. This leads to improved regional blood flow of coronary, renal, and intestinal circulations. There is contradictory evidence in the literature regarding the effect of hypertonic saline on cardiac contractility. Some reports describe a direct positive inotropic effect, and others attribute all hemodynamic benefits of hypertonic saline to a combination of volume expansion and decreased afterload. In one study, hypertonic saline was found to be a negative inotrope in normovolemic dogs. The effect of hypertonic saline on cardiac contractility in clinical veterinary patients remains unclear. Experimental studies have found numerous immuno modulatory effects of hypertonic saline, including increases in cell-mediated immune function, reduced antiinflamma tory cytokine production, inhibition of neutrophil activa tion, and altered pulmonary macrophage activity. These findings have led to the suggestion that hypertonic saline may be beneficial in the resuscitation of victims of trauma and patients in septic shock, but randomized clinical trials evaluating this therapy are lacking. Hypertonic saline can be beneficial for intracranial hyper tension by virtue of its hypertonicity, and has been sug gested to be the resuscitation fluid of choice for patients with traumatic brain injury. '
More than one fluid type may be used for shock fluid administration. Two common combinations are crystalloids with colloids and hypertonic saline with colloids. The rationale of these combinations is to provide the immediate volume-expanding effects of crystalloids or hypertonic saline with the advantage of longer lasting vascular volume expan sion of colloids. Crystalloid-colloid combinations have also been used in patients with hypovolemic shock and concur rent hypoproteinemia, as seen in diseases such as hemor rhagic gastroenteritis. The fluid dosage of a crystalloidcolloid combination is determined by response to therapy. Each fluid is given in increments as previously described and the patient's clinical response evaluated before further administration. When hypertonic saline-colloid combina tions are given, they generally are used together and admi nistered rapidly. Dextran-70 is used most commonly in this protocol, but it could be replaced by hydroxyethyl starch. Proposed dosages for a solution of 7.5% saline in a col loid (dextran-70 or hydroxyethyl starch) are 4 to 6 ml/kg in dogs, and 3 to 4 ml/kg in cats. Again, response to therapy should be monitored and the low end of the dosage range used for cats (see Table 65-1). 26-28
29
20
CHOOSING A FLUID FOR TREATMENT OF SHOCK The fluids described have distinctly different characteristics. Although most patients in shock can be resuscitated satisfac torily with any of them, certain patients are likely to benefit more from one fluid than another.
21 22
Preexisting Losses Adverse Effects Hypernatremia always follows administration of hyper tonic saline. If excessive volumes are administered or if the
Most preexisting volume losses in dogs and cats are a combina tion of salt and water in nearly isotonic proportions (urinary or gastrointestinal losses) such that the patient has extracellular
volume depletion with normal or nearly normal effective osmo lality. Thus intracellular volume is normal. These patients are usually described as dehydrated (de = loss, hydra = water), but the term is taken to mean loss of both salt and water. Iso tonic crystalloids are the resuscitation fluid of choice because they replace vascular and interstitial volume deficits. Failure to repair the interstitial deficit puts the patient at risk of inade quate resuscitation and recurrent episodes of hypovolemia, especially when colloid fluids are used. Preexisting losses that are entirely water come from all body compartments, with two thirds of the lost volume being taken from the intracellular space and one third from the extracellular compartment. The patient is hypernatremic. These patients are dehydrated in the strict sense of the word; they have suffered a water loss. Shock fluids should have a sodium concentration equal to the patient's current sodium concentration until signs of shock are resolved, in order to avoid sudden changes in serum sodium concentration that can have life-threatening consequences. To create a shock resuscitation fluid for a hypernatremic patient, an appropriate amount of hypertonic saline is added to a bag of 0.9% saline. Hypertonic saline at a con centration of 23.4% (Na = 4 mEq/ml) is useful for this purpose. The aim is to make a fluid with a sodium concen tration close (within 5 mEq/L) to the patient's serum sodium concentration. There is some variation in sodium concentration and in the actual volume (slightly overfilled) in bags of fluid. One can analyze the baseline sodium concentration of the fluid and weigh the bag before calcu lating the volume of hypertonic saline to add. The resultant fluid can be given safely as a bolus in large amounts, if needed, to the hypernatremic patient. Once the patient has been resuscitated, a fluid therapy plan to resolve the hypernatremia is indicated (see Chapter 54, Sodium Disorders). 30
Brain Injury Brain-injured patients suffering from shock must be resus citated adequately. Outcomes have been shown to be poorer for human patients with brain injury when they are not fully resuscitated to end points such as restoration of adequ ate blood pressure. If otherwise indicated, hypertonic saline combined with a colloid is a good choice (see Chapters 100 and 152, Intracranial Hypertension and Traumatic Brain Injury, respectively). 35
CRYSTALLOIDS OR COLLOIDS The increase in blood volume expected at the end of rapid infusion is different among isotonic or hypertonic crystal loids or colloids. In experimental healthy dogs given the usual doses at rapid rates, the end-infusion blood volume was about 76% for isotonic saline (80 ml/kg in 12 min utes), 25% for colloids (20 ml/kg in 5 minutes), and 17% for hypertonic saline (4 ml/kg in 5 minutes). At 30 minutes post infusion the blood volume for isotonic crys talloids or colloids was approximately equal at 35%, and was 12% for hypertonic saline. What is not estab lished is whether the initial, larger increase in blood vol ume obtained with isotonic crystalloids is better than the more modest increase gained with colloids. Hyper tonic saline should usually be combined with another fluid to ensure more vascular volume expansion. The vol ume expansion achieved at the end of rapid infusion is dependent on the volume administered, and that obtained after 30 minutes is dependent on the characteristics of the fluid. Many randomized, controlled clinical trials of crystalloids compared with colloids for treatment of shock in human patients have been performed and several metaanalyses of these trials published. Overall, there were no consistent differences in outcome. However, subgroup analysis showed that the use of isotonic crystalloids in trauma patients was associated with improved survival. A recent review con cluded that there was no evidence that resuscitation with colloids reduced the risk of death. A clinical trial in dogs suffering from trauma compared a hypertonic saline and dextran combination with isotonic crystalloids for resuscitation and found no significant differ ences in the responses measured. Considering these and other clinical trials, and especially considering the differences among patients, it is likely that equivalent effects can be expected when any of these fluids is used appropriately and titrated to the same end points. 36-38
Preexisting Volume Excess Extracellular volume excess (edema) may occur from admin istration of isotonic crystalloid fluids in amounts that exceed the patient's output capacity. These patients have peripheral edema and are at risk for pulmonary edema. The vascularto-interstitial volume ratio in these patients may be as high as 1:6 rather than the normal 1:3. If isotonic crystalloids are administered, they will redistribute out of the vascular space in accordance with the new vascular-to-interstitial volume ratio. Hence shock resuscitation of these patients with isotonic crystalloids is unlikely to provide the desired vascular volume expansion. Hypertonic saline and colloid solutions can be considered, with the caveat that colloid solutions contain isotonic saline.
39
40
Venous Access and Fluid Delivery Systems Active Hemorrhage In patients with hemorrhage, administration of large volumes of crystalloid or colloid fluids is likely to promote more bleed ing. Restraint in the volume prescribed is suggested, but inad equate resuscitation puts the patient at risk for global impairment of tissue perfusion. Control of bleeding before administration of resuscitation (delayed resuscitation) may be feasible if the appropriate facilities and staff are available, but limited early resuscitation to at least minimal end points is likely to be a better option.
31
32-34
Fluids for shock are delivered intravenously or by the intraosseous route. Other routes, such as subcutaneous and intraperitoneal, are not desirable, because shockinduced vasoconstriction impairs absorption by these routes. The fluid delivery system should be chosen so that a large volume can be delivered at a fast rate. The best choice is usually a large-gauge, short catheter with a short length of tubing between the fluid and the patient. The flow rate can be raised by adding a pressure bag to the delivery system.
End Points of Resuscitation Fluid therapy for shock is continued until end points have been reached. The most common end points are improve ments in mental state, mucous membrane color, capillary refill time, pulse rate, and pulse quality. Improvements in hyperlactatemia or base deficit are expected, if these were abnormal before treatment. Other end points of resuscita tion, such as mixed venous oxygen saturation and oxygen extraction ratio, have also been used. Early goal-directed therapy where end points of resuscitation such as oxygen content and central venous hemoglobin saturation were maximized early was found to be beneficial in human patients in septic shock and is recommended. 41
Fluid Challenge One of the limits of the physical examination is the evaluation of vascular volume status. This is a significant limit, because vascular volume is an important contributor to delivery of oxygen and other nutrients to metabolically active cells, which is the goal of fluid therapy for shock. A practice that is comple mentary to physical evaluation of vascular volume status is to use response to therapy, also called fluid challenge, which has been reviewed. The fluid challenge technique is for hemodynamically unstable patients. The goal is to optimize cardiac filling pressures and forward blood flow. If the parameters of concern (restoration of arterial blood pressure, improvement of physical parameters related to tissue perfusion, and improved diuresis) improve after the fluid challenge, then there was a vascular volume deficit even if the physical exami nation did not clearly identify it. Also, failure to respond to a fluid challenge raises the question of whether the patient has a cause of shock other than vascular volume deficit. In such patients more advanced hemodynamic monitoring may be indicated (see Chapters 203 and 212, Hemodynamic 42
Monitoring and Cardiac Output Monitoring, respectively). The fluid challenge technique is useful in patients whose phys ical examination is equivocal. For a fluid challenge to be effective it must be of sufficient volume and be given rapidly enough that a change in cardio vascular status can be appreciated. Suggested dosages are 10 to 20 ml/kg of an isotonic crystalloid fluid (for cats and dogs, respectively) or 3 to 5 ml/kg of a colloid fluid (for cats and dogs, respectively) infused over 10 minutes (see Table 65-1).
SUGGESTED FURTHER
READING*
Day TK, Bateman S: Shock syndromes. In DiBartola SP, editor: Fluid, elec trolyte, and acid-base disorders, ed 3, St Louis, 2006, Saunders. An excellent reference text for all aspects of fluid therapy. Driessen B, Brainard B: Fluid therapy for the traumatized patient, / Vet Emerg Crit Care 16:276, 2006. A comprehensive veterinary review paper. Schertel ER, Allen DA, Muir WW, et al: Evaluation of a hypertonic salinedextran solution for treatment of dogs with shock induced by gastric dilatation-volvulus, J Am Vet Med Assoc 210:226, 1997. Hypertonic saline and dextrans compared with lactated Ringer's solution, both effective. Silverstein DC, Aldrich J, Haskins SC, et al: Assessment of changes in blood volume in response to resuscitative fluid administration in dogs, / Vet Emerg Crit Care 15:185, 2005. Experimental study of continuous measurement of hematocrit during and after administration of resuscitation fluids demonstrating the minute-to-minute various effects of isotonic crystalloid, colloid, or hypertonic saline on blood volume. Vallet B, Wiel E, Lebuffe G: Resuscitation from circulatory shock. In Fink MP, Abraham E, Vincent JL, Kochanek PM, editors: Textbook of critical care, ed 5, Philadelphia, 2005, Saunders. One of the definitive textbooks in human medicine for the care of critically ill patients. Most sections, especially those on common problems, and basic science applicable to veterinary patients. *See the CD-ROM for a complete list of references.
Chapter 66 TRANSFUSION MEDICINE Urs Giger,
PD, Dr.Med.Vet., MS, FVH, DACVIM, DECVIM, DECVCP
KEY POINTS • Transfusion therapy refers to the safe and effective replacement of blood or one of its components, thereby offering support for many critically ill anemic or bleeding patients. • The indications for transfusions need to be clearly determined, and ideally only the deficient blood component is replaced at the appropriate dosage. • Although red blood cells and plasma clotting factors are crucial, the indications and efficacy of transfusing platelets, leukocytes, and other plasma proteins are limited. • Blood products represent a limited resource; hence they should be given only when indicated, using the minimal dosage required and after carefully considering all alternatives. • All canine and feline donor blood must be typed for the dog erythrocyte antigen (DEA) 1.1 and the feline AB blood groups, respectively, and all donors must have regular health examinations including blood and infectious disease screening. • All canine and feline recipient blood should be typed for DEA 1.1 and feline AB blood groups, respectively. Blood from any previously transfused (more than 4 days prior) animal should also be crossmatched before receiving another red blood cell transfusion. • Although acute hemolytic transfusion reactions are feared most, they can be avoided by prior compatibility testing; other transfusion reactions may not be predictable. • The efficacy and survival of transfused blood cells and plasma proteins should be monitored during and after transfusion using appropriate clinical and laboratory parameters.
INTRODUCTION Since the early 1980s, blood product administration to treat critically ill animals or those undergoing surgical procedures has increased tremendously. However, it is important to note that blood products are obtained from donor animals and rep resent a limited resource that is not available in all situations. Because they are biologic products, they bear the inherent risks of transmitting infectious diseases or causing other adverse reactions. Clinicians in the critical care setting play a key role in providing safe and effective transfusion therapy and therefore should be aware of the principles of transfusion medi cine. The interested reader is referred at the end of the chapter to more comprehensive reviews and books on veterinary trans fusion medicine.
INDICATIONS FOR TRANSFUSION THERAPY Blood transfusions are indicated for management of anemia, coagulopathy, and rarely for other conditions such as thrombo cytopenia, thrombopathia, and hypoproteinemia (Table 66-1).
The disorders that lead to these medical problems and their detailed management are described in separate chapters. Fresh whole blood (FWB) contains all cellular and plasma compo nents of blood, but specific blood component therapy provides the most effective and safest support and allows for optimal use of every donation. The decision to transfuse is based on the overall clinical assessment of a patient's history and clinical signs, routine laboratory test results, underlying cause, and sound clinical judgment. Although the optimal packed cell vol ume (PCV) may be above 30%, oxygen delivery in a normovo lemic resting animal can be maintained down to a Hct of 10% (although this is inadequate under most disease conditions). Thus there is no specific transfusion trigger in all patients (i.e., certain PCV or coagulation times). Because transfusion carries inherent risks, blood should never be given without a clear indi cation or before exhausting alternative therapies. Furthermore, blood components represent a scarce resource and should therefore not be used without a proper indication and assess ment of the prognosis.
Red Blood Cell Transfusions The most common indication for transfusions in dogs and cats is anemia (see Chapter 120, Anemia). Transfusions are generally required after loss of the blood's oxygen-carrying capacity (i.e., loss of hemoglobin) and subsequent tissue/organ ischemia, and not as a simple volume expander. Depending on the type, degree, rapidity, and course of the anemia, a transfusion with blood products, such as stored packed red blood cells (pRBCs), fresh whole blood FWB, or stored whole blood, may be warranted. Animals with rapidly progressive anemia should be transfused when the Hct is approximately 20% to 25%, and a patient with chronic anemia may not require transfusion despite having a much lower Hct. Healthy animals can readily tolerate a loss of up to 20% of blood volume (blood donors regularly give 20 ml/kg body weight q6-12wk) without any ill effects. However, animals with acute hemorrhage exceeding 20% of the blood volume may require a blood transfusion in addition to the initial shock fluid therapy (see Chapter 65, Shock Fluids and Fluid Challenge). It should be noted that animals with peracute blood loss will not show a drop in Hct for hours following hemorrhage, until intercompartmental fluid shifts occur or fluid therapy is instituted. Hence, other parameters are used to decide if transfusion therapy is indicated, such as mucous membrane color, capillary refill time, heart rate, blood pre ssure, and possibly blood lactate levels. A n assessment of an arterial blood gas and respiratory rate and effort are useful to evaluate animals with coexisting respiratory disease (venti¬ lation-perfusion mismatch). In most animals with anemia secondary to acute blood loss, fluid therapy alone will restore
Table 66-1
Blood Products, Storage Guidelines, and indications
Blood Product
Storage
Temperature in Celsius
Fresh whole blood (FWB)
2 month) survival was only 12%. Outcome was not predicted by pres ence of neurologic signs, serum glucose concentration, measured serum sodium concentration, corrected serum sodium concentration, or total and effective serum osmolality. Long-term survivors had curable concurrent diseases. 14,27-29
4
1
2 26
SUGGESTED FURTHER R E A D I N G *
DiBartola SP: Fluid, electrolyte, and acid-base disorders in small animal practice, ed 3, St Louis, 2006, Saunders. Excellent review of electrolytes and acid-base physiology. Feldman EC, Nelson RW: Canine and feline endocrinology and reproduction, ed 3, St Louis, 2004, Saunders. The most comprehensive reference on small animal endocrinology. Excellen review of pathophysiology, clinical characteristics, and management of all forms of diabetes. Koenig A, Drobatz K, Beale AB, King L: Hyperglycemic, hyperosmolar syn drome in feline diabetics 17 cases (1995-2001), JVECC 14:30, 2004. A retrospective study evaluating clinical and laboratory findings and outcome in HHS cats. *See the CD-ROM for a complete list of references.
Chapter 69 HYPOGLYCEMIA Amie Koenig,
D V M , BS, D A C V I M , D A C V E C C
KEY POINTS • Normoglycemia is maintained by a balance between the glucoselowering hormone insulin and glucose-elevating hormones glucagon, Cortisol, epinephrine, and growth hormone. • Hypoglycemia occurs via one of several mechanisms: inadequate dietary intake, excessive glucose utilization, dysfunctional glycogenolytic or gluconeogenic pathways or inadequate precursors for these pathways, or endocrine abnormalities. • The most common causes of hypoglycemia include exogenous insulin overdose, hypoglycemia of puppies and toy breeds, sepsis, insulinoma and other insulin analog-secreting tumors, hypoadrenocorticism, and severe liver disease. • Neuroglycopenia causes alterations in mentation, seizures, blindness or alterations in vision, somnolence, and weakness or ataxia. • Adrenergic stimulation in response to declining blood glucose accounts for other common clinical signs of restlessness, anxiety, tachypnea, vomiting or diarrhea, and trembling. • In hypoglycemic crises, parenteral dextrose administration is the most effective therapy. Food should be offered as soon as possible. Glucagon infusion may be used for cases of intractable hypoglycemia secondary to insulinoma or insulin analog-secreting neoplasms.
utilization by insulin-sensitive cells, and decreases glucagon secretion. Insulin also promotes triglyceride formation in adipose tissue and the synthesis of protein and glycogen in muscle. Decreased levels of insulin stimulate gluconeogenesis and reduce glucose used by peripheral tissues. As blood glucose concentrations fall, the counter regulatory hormones glucagon, epinephrine, Cortisol, and growth hormone are released. Both glucagon and epi nephrine levels rise within minutes of hypoglycemia and have a transient effect on increasing glucose production; they subsequently support basal rates of glucose production. Cortisol and growth hormone are released after a few hours, but their effects are also longer lasting. Glucagon is secreted from pancreatic α-cells. It acts on the liver to stimulate glycogenolysis and, to a lesser extent, gluconeogenesis, thereby increasing hepatic glucose produc tion. This is transient, however, and glucose production quickly declines toward basal rates as increasing levels of insulin counteract the effects of glucagon. Glucagon directly stimulates hepatic glycogenolysis and gluconeogenesis, mobi lizes gluconeogenic precursors, and reduces peripheral glu cose utilization. Epinephrine limits insulin secretion and increases glucagon secretion. Cortisol increases glucosefacilitating lipolysis and release of amino acids from muscle for gluconeogenesis in the liver. Growth hormone antago nizes effects of insulin by decreasing peripheral glucose utili zation and promoting lipolysis. Hypoglycemia results when glucose utilization exceeds glucose entry into circulation. General mechanisms of hypo glycemia include: (1) inadequate dietary intake, (2) excessive glucose utilization, (3) dysfunctional glycogenolytic or gluco neogenic pathways or inadequate precursors for these path ways, and (4) endocrine abnormalities. On its own accord, inadequate dietary intake is unlikely to cause hypoglycemia, because gluconeogenic and glycolytic pathways dominate dur ing periods of fast. In most animals, a concurrent defect in one of the other mechanisms is required. 2
INTRODUCTION Euglycemia is maintained by a balance of glucose produc tion, storage, and release from storage forms. Many dis ease processes can interfere with normal glucose homeostasis and lead to hypoglycemia. This chapter will review normal glucose homeostatic mechanisms, clinical signs and causes of hypoglycemia, and treatment of a hypoglycemic crisis.
NORMAL GLUCOSE HOMEOSTASIS Glucose comes from three sources: (1) intestinal absorption of glucose from digestion of carbohydrates; (2) breakdown of the storage form of glucose (glycogen) via glycogenolysis; and (3) production of glucose from precursors lactate, pyruvate, amino acids, and glycerol via gluconeogenesis. Glucose homeostasis is maintained by a balance between the glucose-lowering hormone insulin and glucose-elevating hormones, primarily glucagon, epinephrine, Cortisol, and growth hormone. Insulin is secreted by β-cells of the pancreas in response to the rising concentrations of glucose, amino acids, and gas trointestinal (GI) hormones (gastrin, secretin, cholecystoki¬ nin, and gastric inhibitory peptide) present after a meal. Insulin inhibits gluconeogenesis and glycogenolysis, pro motes glycogen storage, stimulates glucose uptake and 1
CLINICAL SIGNS AND CONSEQUENCES OF HYPOGLYCEMIA Glucose is an obligate energy source for the brain. The brain has limited ability to use other substrates, can store minimal amounts of glycogen, and cannot manufacture glucose; there fore the brain relies on a constant stream of glucose for its energy needs. Glucose enters the brain by facilitated diffu sion. Adequate arterial glucose concentration is essential to maintaining a diffusion gradient. Because brain cells rely so heavily on glucose for energy, neuroglycopenia, or hypoglyce mia of the central nervous system (CNS), results primarily in 3
neurologic signs. The degree, rate of decline, and duration of hypoglycemia all contribute to type and severity of symptoms. Neuroglycopenic signs occur as a direct result of CNS hypoglycemia. These include altered mentation or dullness, sleepiness, weakness or recumbency, ataxia, blindness or altered vision, and seizures. ' Prolonged neuroglycopenia can lead to permanent brain injury and neurologic signs, especially blindness, that persist beyond resolution of the hypoglycemia. Neurogenic signs result from activation of the adrenergic system in response to the hypoglycemia. Humans describe being hungry, a tingling sensation, tremors or shaki¬ ness, a pounding heart, and anxiety or nervousness. Similar signs noted in hypoglycemic dogs and cats include anxiety manifest as pacing, vocalizing or restlessness, and shaking or trembling. Vomiting, anorexia, panting or tachypnea, diar rhea, and urination have been noted in hypoglycemic dogs and cats. Bradycardia and circulatory collapse have also been documented. Signs may be episodic. Some animals, especially those with prolonged hypoglycemia, demonstrate no asso ciated signs. This hypoglycemia unawareness may occur in patients whose brains are induced by chronic or recurrent hypoglycemia to upregulate cerebral glucose uptake, thereby decreasing the perception of peripheral hypoglycemia by the brain. 2 4
2
4
treatment of other disorders such as hyperkalemia or cal cium channel blocker overdose. Insulin overdoses in diabetic animals occur more commonly in cats than dogs, in obese animals, and in cats receiving more than 6 units of insulin per injection. Anorexic or hyporexic diabetics receiving insulin are also at risk. Clinical signs are consistent with hypoglycemia. Treatment includes discontinuation of insulin therapy, feed ing the animal as soon as possible, and administration of intravenous dextrose if the animal is too severely affected to eat. Duration of the hypoglycemia varies and is not neces sarily dependent on the amount and type of insulin that caused the overdose. Once the animal is stabilized and eating, the dextrose infusion can be tapered off while blood glucose levels continue to be monitored. Some diabetic animals may not need insulin for several days, and others will become hyperglycemic more quickly. The animal should be monitored for onset of polyuria and polydipsia 4
4
5
4
3
Box 69-1
Causes of Hypoglycemia
Artifact* Pseudohypoglycemia* Hand-held glucometer*
Excess Insulin or Insulin Analogues
DIAGNOSIS OF HYPOGLYCEMIA By definition, hypoglycemia is diagnosed by a blood glucose level of 60 mg/dl or less, although clinical signs often do not develop until the level is less than 50 mg/dl. Whipple's triad provides guidelines for identifying hypoglycemia: clinical signs consistent with hypoglycemia, a low blood glucose level, and abatement of signs with correction of the hypoglycemia. Hand-held glucometers tend to underestimate serum glucose. Low glucose values obtained on a hand-held glu¬ cometer should be confirmed via other methods. Falsely low glucose values, or pseudohypoglycemia, can be obtained if the serum is not separated from the red blood cells within 30 minutes of collection, because the red blood cells continue to consume glucose for glycolysis. If centrifugation and serum separation must be delayed longer than 30 minutes, collection in a sodium fluoride tube will arrest glycolysis. Once hypoglycemia is identified, additional diagnostic modalities may be indicated to identify its etiology. Com plete blood cell count, serum chemistry analysis, urinalysis, chest and abdominal radiographs, abdominal ultrasonogra phy, insulin levels, and other endocrine testing may be indicated. 2
Exogenous insulin overdose Insulinoma Paraneoplastic syndrome • Hepatomas, hepatocellular carcinoma • Leiomyomas, leiomyosarcomas • Pulmonary, mammary, and salivary carcinoma • Lymphoma, plasmacytoid tumors • Oral melanoma, hemangiosarcoma Toxins and medications • Sulfonylureas • Xylitol
6
7
CAUSES OF HYPOGLYCEMIA Many causes of hypoglycemia (Box 69-1) fall into the cate gories of excess insulin or insulin analog, inadequate glucose production, and excess cellular glucose consumption.
Excess Insulin or Insulin Analogs Exogenous Insulin Overdose Exogenous insulin overdose is possible in any animal receiv ing insulin therapy, whether for diabetes mellitus or for
Excess Glucose Utilization Infection • Sepsis • Babesiosis Exercise-induced (hunting dog) hypoglycemia Paraneoplastic Polycythemia Leukocytosis Pregnancy
Decreased Glucose Production Neonatal hypoglycemia Hepatic dysfunction • Portosystemic shunt • Inflammatory or infectious hepatitis • Hepatic lipidosis • Cirrhosis • Neoplasia • Glycogen storage disease Hypocortisolism Counterregulatory hormone deficiencies • Glucagon, growth hormone • Thyroid hormone, catecholamines • Hypopituitarism Glycogenic or gluconeogenic enzyme deficiencies β-Blockers *Cause of apparent, not true, hypoglycemia.
and hyperglycemia to verify need for insulin. Remission in transiently diabetic cats may be marked by a hypoglycemic epi sode. Once the need to restart insulin is confirmed, it is pru dent to reduce the dosage by 25% to 50% initially and follow up with normal diabetic monitoring to attempt regulation. ' There may be another underlying problem that predisposed the animal to hypoglycemia, and additional workup is war ranted if hypoglycemia is ongoing or if the animal has addi tional history or signs unrelated to hypoglycemia. 8 9
Insulinoma Insulinomas are insulin-secreting, usually malignant, tumors of the pancreas. They are described more commonly in middle-aged to older dogs than in cats. Patients often exhibit weakness or collapse, and severe hypoglycemia is an unexpected and isolated finding. Other clinical pathology data are generally unremarkable. Diagnosis is made by eval uating blood insulin concentration on a sample taken during an episode of hypoglycemia. High or sometimes normal insulin levels in the face of hypoglycemia is indicative of insulinoma. Some animals will have intermittent episodes of hypoglycemia and hyperinsulinemia that may require a supervised fast or multiple samples to identify. Low fructo¬ samine values may also lend support to a diagnosis. If insulin levels are equivocal, an amended insulin-to-glucose ratio (AIGR) can be calculated. 9-14
15
16
AIGR = (insulin x 100) / (plasma glucose - 30). A denominator of 1 is used if the plasma glucose is less than 30 mg/dl. An AIGR over 30 suggests insulinoma, although is not definitive. Abdominal ultrasonography may or may not reveal a mass or nodule in the pancreas. Computed tomogra phy, scintigraphy, and surgical exploration are other options for attempted localization of insulinoma. Emergency treatment for symptomatic hypoglycemia is outlined below. The treatment of choice for insulinoma is surgical excision. Medical options for animals not under going surgery or for those with metastatic disease and persis tent hypoglycemia include small frequent feedings of a food low in simple sugars and glucocorticoids (prednisone 0.5 to 1 mg/kg in divided doses PO ql2h ). Higher doses of glucocorticoids and diazoxide (10 mg/kg initially up to 60 mg/kg, divided ql2h ), which directly inhibits pancreatic insulin secretion, can be used in patients with refractory disease. Other adjunctive therapies include streptozocin (which selectively destroys pancreatic β-cells), somatostatin analogs such as octreotide ' (which suppress synthesis and secretion of insulin), or alloxan (a β-cell cytotoxin). Prognosis is guarded and depends on the extent of both dis ease and treatment. In one study, median survival time was 74 days for dogs with medical treatment only, and 381 days for dogs undergoing surgery. In another study, median survival time was 18 months for dogs with disease confined to the pan creas and local lymph nodes, and less than 6 months for dogs with distant metastases. Nelson and Feldman reported that 10% to 15% of dogs undergoing surgery died or were eutha nized within 1 month of surgery, 25% died within 6 months, and 60% to 70% lived more than 6 months, with many living longer than 1 year and some even longer than 2 years. 17
associated with hypoglycemia include hepatomas and hepa tocellular carcinoma, leiomyomas and leiomyosarcomas, and other carcinomas or adenocarcinomas (especially those of pulmonary, mammary, and salivary origin), lymphoma, plasmacytoid tumors, oral melanoma, and hemangiosarcoma. Neoplasia can cause hypoglycemia via secretion of insulin or insulin-like peptides, accelerated consumption of glucose by the tumor cells, or by failure of glycogenolysis or gluconeogen esis by the liver. Historical and clinical findings and treatment are consistent with the specific tumor. 26
Toxins and Medications Certain toxins have been associated with hypoglycemia in dogs and cats. Excessive dosages of oral glucose-lowering agents such as the sulfonylurea drugs chlorpropamide and glipizide may cause hypoglycemia. These drugs are thought to stimulate insulin secretion from the pancreas, enhance tissue sensitivity to insulin, and decrease basal hepatic glucose production. Xylitol-sweetened products, such as sugar-free gum, can cause hypoglycemia in dogs via its stimulation of insulin release from β-cells. β-Blockers, such as atenolol, are also thought to contribute to hypoglycemia via interfer ence with adrenergic counterregulatory mechanisms. A history of exposure or known ingestion coupled with consistent signs or low blood glucose levels would substanti ate the diagnosis. In addition to treating hypoglycemia, induced emesis and activated charcoal administration may be indicated if the ingestion is identified early and the patient is not clinically impaired by hypoglycemia (see Chapter 77, Approach to Poisoning and Drug Overdose). 21
27
9
9,18-20
21
21
22
23 24
9
25
Inadequate Glucose Production Hypoglycemia of Puppies and Toy Breeds Most commonly, hypoglycemia of neonatal and pediatric animals stems from inadequate substrate for glycolysis or glu coneogenesis. Glycogen stores are small and easily depleted in the face of inadequate food intake. Hepatic enzyme systems may also be immature. Additionally, the brain accounts for most of the basal metabolic rate in the neonate, thus contributing to the frequent development of hypoglycemia in the young. In the nursing puppy, factors predisposing to hypoglycemia include premature birth, debilitation of the bitch at parturition, being the runt of the litter, and diabetes in the bitch. Toy or small breed dogs are also at risk. In the weaned puppy, factors predisposing to hypoglycemia include concurrent infection, vaccinations, vigorous exercise, GI upset, hypothermia, poor nutrition, and extended fast. Most puppies and toy breeds respond readily to supplementa tion and increased feeding frequency. Recurrent or persistent hypoglycemia warrants further investigation. Other differ entials for hypoglycemia that must be considered in a hypoglycemic puppy or kitten include portosystemic shunt or other hepatic disease, sepsis, glycogen storage disease, and counterregulatory hormone deficiency. 28
28
28
10
9
Paraneoplastic Hypoglycemia Although any tumor can be associated with hypoglyce mia, the most commonly described non-β-cell neoplasms
Hepatic Disease Portosystemic shunt, glycogen storage disease, severe inflam matory or infectious hepatitis, hepatic lipidosis, cirrhosis, and hepatic neoplasia are specific etiologies of hepatic failure that can lead to hypoglycemia via dysfunctional glycogen storage, glycogenolytic, and gluconeogenic capabilities. Eugly¬ cemia usually is maintained until late in the course of hepatic disease until approximately 70% of hepatic function
7
is lost. Patients with portosystemic shunt and glycogen stor age disease are usually young and may be small or unthrifty. Evaluation of an animal with severe liver disease may reveal a poor body condition score, microhepatica or enlarged liver, icterus, ascites, melena, vomiting, diarrhea, anorexia, or signs of hepatic encephalopathy such as depression or sei zures. Clinical pathology data may show hypoalbuminemia, low blood urea nitrogen, hypocholesterolemia, hyperbilirubinemia, elevated liver enzyme activities, and low urine specific grav ity (see Chapters 126, 127, and 146, Hepatitis and Cholan¬ giohepatitis, Hepatic Failure, and Portosystemic Shunt Management, respectively).
Exercise-Induced Hypoglycemia Exercise-induced hypoglycemia, also called hunting dog hypoglycemia, is generally seen in lean hunting or working dogs engaging in vigorous exercise. Glucose utilization by muscle markedly increases during exercise and endogenous glucose production, via glycolysis and gluconeogenesis, increases to meet this demand. This form of hypoglycemia is believed to occur secondary to glycogen depletion in the face of increased glucose utilization. Affected ani mals should be fed small amounts frequently during exer cise or should discontinue working if hypoglycemia continues. 2
Hypocortisolism and Other Counterregulatory Polycythemia and Leukocytosis Hormone Deficiencies Hypoadrenocorticism, specifically hypocortisolism, may lead to hypoglycemia via loss of cortisol-induced counter regulatory mechanisms. History may include anorexia, vomiting, diarrhea, melena or hematochezia, weakness, and possibly polyuria and polydipsia. Physical examination may reveal dehydration, bradycardia, muffled heart sounds, poor pulse quality, hypotension, and shock. Clinical pathol ogy evaluation may reveal lack of stress leukogram, azote mia, hypercalcemia, hyponatremia, hypochloremia, and hyperkalemia. Confirmation of hypocortisolism is via the adrenocorticotropic hormone stimulation test. Treatment includes physiologic doses of glucocorticoids, and either fludrocortisone acetate (Florinef) or desoxycorticosterone pivalate if mineralocorticoids are also deficient. Fluid therapy is required in Addisonian crisis (see Chapter 76, Hypoadrenocorticism). Deficiencies in other hormones such as glucagon, growth hormone, thyroid hormone, and catecholamines can all lead to hypoglycemia due to interference with counterregulatory mechanisms designed to prevent hypoglycemia. These occur uncommonly.
Excess Glucose Utilization Infection, extreme exercise, polycythemia or leukocytosis, and pregnancy can all lead to excessive cellular glucose consumption.
Infection Sepsis is a common cause of hypoglycemia. Decreased intake, decreased hepatic function and, most significantly, non-insulin-mediated increased consumption play a role in sepsis-induced hypoglycemia. Increased glucose consump tion is believed to be induced by inflammatory mediators, such as tumor necrosis factor, especially in macrophage-rich tissues such as the spleen, liver, and lungs. Hypotension or hypoxemia may also induce excess glucose consumption via increases in anaerobic glycolysis. Patients with sepsis will be extremely ill. Vasodilatory shock may be evident by injected mucous membranes and hypoten sion. Other clinical signs will depend on the type and location of infection. A complete workup and blood cultures are indi cated (see Chapters 106 and 107, Sepsis and Septic Shock, respectively). Canine babesiosis is an infection specifically associated with hypoglycemia. ' Hypoglycemia at admis sion is a poor prognostic indicator in canine babesiosis and may occur secondary to the same mechanisms as bacterial sep sis or by consumption of glucose by the parasites. 29
30 31
Hypoglycemia in polycythemia occurs secondary to increased metabolism of glucose by the large red blood cell mass. Massive leukocytosis can have the same effect.
7
TREATMENT OF HYPOGLYCEMIC CRISIS Initial treatment for a symptomatic hypoglycemic patient, regardless of etiology, is usually intravenous dextrose. A bolus of 1 ml/kg of 50% dextrose (0.5 g/kg) can be diluted 1:2 to 1:4 and is then given intravenously over 5 minutes. This solution is hypertonic and can cause phlebitis. In the absence of intravenous access, such as in the home setting, Karo syrup, pancake syrup, or honey can be applied to the oral mucous membranes. Marked improvements in neuroglycopenic signs usually are seen within 1 to 2 minutes of supplementation. If the patient is alert and it is not contraindicated, the animal should be offered small frequent meals that are low in simple sugars. Otherwise, a constant rate infusion (CRI) of 2.5% to 5% dextrose should be administered until the cause of the hypoglycemia is identified and resolved. Dextrose infusions should be formulated by adding the appropriate amount of 50% dextrose to an isotonic fluid such as lactated Ringer's solution or 0.9% saline. Dextrose 5% in water should not be used as the sole fluid for hypoglycemia treatment, because it can result in severe, possibly life-threatening electrolyte abnormalities. Blood glucose should be monitored fre quently to assess response to therapy. If a solution contain ing greater than 5% dextrose is needed to maintain blood glucose concentrations, it should be administered via a cen tral line. Care should be taken using intravenous dextrose in ani mals with suspected insulinoma or other tumors secreting insulin-like analogs. In these patients, a bolus of intravenous dextrose can stimulate release of even more insulin from the tumor, leading to a vicious cycle of dextrose infusion fol lowed by rebound hypoglycemia. Additionally, hyperinsuline¬ mia has been shown to depress glucagon secretion in humans, thus removing one of the counterregulatory mechanisms vital to maintaining euglycemia. Glucagon CRI is another option for treating animals with insulin or insulin-like peptide¬ secreting tumors that are in a hypoglycemic crisis. Glucagon is reconstituted according the manufacturer's instructions and diluted in 0.9% saline. This resulting 1000 ng/ml solution is first administered as a bolus of 50 ng/kg followed by a CRI of 5 to 40 ng/kg/min, the lowest rate necessary to maintain low normal euglycemia. 32
33
21
Moore AS, Nelson RW, Henry C), et al: Streptozocin for treatment of pan creatic islet cell tumors in dogs: 17 cases (1989-1999), I Am Vet Med Assoc Feldman EC, Nelson RW: Online and feline endocrinology and reproduction, 221:811, 2002. Prospective study evaluating safety and efficacy of streptozocin. ed 3, St Louis, 2004, Saunders. The most comprehensive reference on small animal endocrinology. Excellent Wess G, Reusch C: Evaluation of five portable blood glucose meters for use review of pathophysiology, clinical characteristics, and treatment of all forms in dogs, / Am Vet Med Assoc 216:203, 2000. Systematic evaluation of glucometer reliability. of diabetes. Mclntire DK: Diabetic crises: insulin overdose, diabetic ketoacidosis, and hyperosmolar coma, Vet Clin North Am Small Anim Pract 25:639, 1995. *See the CD-ROM for a complete list of references. Good review of clinical characteristics and treatment of diabetic crises.
SUGGESTED FURTHER R E A D I N G *
Chapter 70 DIABETES INSIPIDUS Richard E. Goldstein, D V M , D A C V I M ,
DECVIM-CA
KEY POINTS • Diabetes insipidus results from a lack of secretion of or a lack of an appropriate renal response to a hormone known as vasopressin or antidiuretic hormone. • Primary diabetes insipidus is most commonly acquired and central in origin. Common causes include trauma and intracranial masses. • Secondary diabetes insipidus is usually renal in origin. Common causes include hypercalcemia, gram-negative sepsis, and severe hypokalemia. • The manifestation of diabetes insipidus that requires emergency intervention is severe hypernatremia and dehydration caused by urinary free water losses without appropriate intake. • The water deprivation test does provide valuable diagnostic information and can be dangerous, resulting in severe dehydration and hypernatremia.
INTRODUCTION By definition diabetes insipidus is the tasteless or nonsweet diabetes. This differentiates it, of course, from the sweet dia betes, the better known diabetes mellitus. Diabetes insipidus is caused by a lack of the hormone vasopressin (otherwise known as antidiuretic hormone or ADH), a lack of renal receptors to vasopressin, or an inability of those receptors to respond to vasopressin. The presence of vasopressin and its ability to activate renal receptors are crucial to the kidneys' urine concentration capabilities. Vasopressin is a nonapeptide (nine amino acids) composed of six amino acids in a disulfide ring and three amino acids in a tail. In small animals the eighth amino acid in vasopressin is argi¬ nine, sometimes also called AVP or arginine vasopressin. 1
Urine Concentration Mechanism In a normally functioning kidney, as the solute within the tubule travels through the thick ascending loop of Henle, sodium (and subsequently chloride) is extracted by an energy-requiring
ion pump from the solute in an area that is impermeable to water. This unusual feat renders the remaining solute hyposthe nuria or of lower osmolality than serum. The final urine con centration then depends on the presence and function of vasopressin. When the presence and/or function of vasopressin is lacking (diabetes insipidus), the final urine concentration will remain hyposthenuric, or perhaps isosthenuric or mildly hypersthenuric with partial disease.
Vasopressin Secretion and Sodium Homeostasis Whole body water and sodium concentrations are kept con stant despite a huge variability in dietary sodium intake and hydration status. Much of this control is due to vasopressin release from the neurohypothesis. The neurohypothesis con sists of hypothalamic nuclei that secrete oxytocin and vaso pressin. Following the nuclear synthesis of these hormones they are transported in their axons and finally secreted from the termini in the posterior lobe of the pituitary gland. Important stimuli for vasopressin release include low arterial blood pressure sensed by low-pressure receptors located in the heart and arterial vasculature, increased osmolality as sensed by central nervous system osmoreceptors, and increased angiotensin II levels. 2
Antidiuretic Effects of Vasopressin The antidiuretic effects of vasopressin occur in response to the binding of vasopressin to its receptor on the cells of the distal tubule and collecting duct. These are V cyclic adenosine monophosphate-dependent receptors, which when activated cause an increase in water permeability of the luminal mem brane by the insertion of aquaporin-2 water channels in the apical membrane of the renal epithelial cells. This allows a more rapid passive flow of water from the lumen through the epithelial cells and into the solute rich, concentrated 2
interstitium, causing a rapid and marked increase in osmolal ity within the tubular lumen. Theoretically the maximum urine concentration of a given animal would be equal to the maximum solute concentration of the medullary interstitium. Thus in times of hypernatremia due to excess salt intake or, more commonly, free water loss, resulting in a free water defi cit or a hyperosmolar contraction of the extracellular space, the secretion of vasopressin causes an increase of water reab¬ sorption from the kidney, a decrease in water excretion, and the normalization of sodium concentration. 3
CENTRAL DIABETES INSIPIDUS Central diabetes insipidus (CDI) is the most common pri mary cause of diabetes insipidus. It is caused by a complete or partial lack of secretion of vasopressin from the axon termini in the anterior lobe of the pituitary gland. Docu mented causes of CDI in small animals include neoplastic, traumatic, inflammatory, congenital, and idiopathic condi tions. ' Glucocorticoid administration is thought to decrease vasopressin release in dogs, and therefore can be included in the causes of canine acquired CDI. In humans CDI is associated most commonly with brain surgery, trauma, and immune-mediated disease. Neoplasia, infectious disease, and hereditary disorders are also relatively common in this population. Following brain trauma, at least 25% of long-term survivors suffer from what is defined in humans as posttraumatic hypopituitarism. This syndrome most often includes suppression of hormone release from the anterior pituitary gland, but can also include decreased vasopressin secretion from the posterior pituitary gland. Posttraumatic CDI is thought to resolve within a few days in most human cases but may also be a sign of permanent or late brain damage. Postsurgical CDI may be the most common cause in humans. As intracranial surgery, including hypophysectomies, and better care of head trauma become more and more common in small animal practice, veterinary intensive care units will likely experience more of these cases, as well. In humans pituitary gland radiation therapy can cause long-lasting pituitary gland damage with hormonal deficiencies. Interestingly, these rarely, if ever, include CDI. In dogs, there are no large case series reporting the most common causes of CDI. Documented causes have included traumatic, neoplastic, and idiopathic conditions and have occurred secondary to iatrogenic steroid administration or hyperadrenocorticism. 4 5
1
6
7
8
9
NDI has been documented in a few rare reports in young dogs, never in cats. The canine reports included a Miniature Poodle, a German Shepherd, and a family of Huskies. By far the more common form of NDI in human and veterinary patients is the acquired form. A partial list of causes of acquired NDI is included in Box 70-1. This syn drome is commonly seen in the emergency or critical care setting, caused by conditions such as pyometra or other causes of gram-negative sepsis, hypercalcemia, hypokalemia, liver failure, and hypoadrenocorticism. Each of these condi tions causes an inability of the vasopressin to effectively bind and activate its receptor. In gram-negative sepsis bacterial endotoxins, especially from Escherichia coli, are thought to compete with vasopressin for binding sites on the tubular cell membranes, resulting in marked polyuria and polydip sia, and possibly hypernatremia if water intake is insufficient. Similarly, hypercalcemia and severe hypokalemia are thought to interfere with vasopressin binding and subsequent activa tion of the V receptor. 1
11
2
Another common mechanism of secondary NDI is the abolition of the medullary hypertonicity gradient. As men tioned previously the presence and proper function of vaso pressin and its receptors allow water channels to be open in the tubular cells of the collecting duct. The passage of water, then, from the tubular lumen into the interstitium is still passive and based on the hypertonicity of the renal medulla, enabled by the renal counter-current mechanism. If this hypertonicity, a condition referred to as medullary washout, is absent the urine will not become concentrated; it will be isosthenuric or even hyposthenuric. Medullary washout occurs in small animal patients for two common reasons: 1. Washout results from large amounts of urine passing through the tubules. This can occur in severely polyuric and polydipsic animals, such as dogs with hyperadreno corticism or dogs and cats receiving high volumes of intravenous fluids for extended periods. 2. The solutes necessary to produce the medullary hyperto nicity gradient are lacking, such as insufficient urea in dogs and cats with hepatic insufficiency or insufficient sodium in dogs with hypoadrenocorticism. In both instances these animals may be severely polyuric and have a functional secondary NDI, despite absolutely normal renal function and normal vasopressin concentrations.
4
DIAGNOSING DIABETES INSIPIDUS
1
NEPHROGENIC DIABETES INSIPIDUS Nephrogenic diabetes insipidus (NDI) is caused by the fail ure of the kidney to respond to vasopressin. It is commonly divided into primary and secondary causes. Although pri mary NDI is uncommon and often congenital, secondary NDI is extremely common and likely the most common cause of diabetes insipidus seen in veterinary practice and intensive care units. Primary N D I is most often hereditary in humans. Early diagnosis of this condition in humans through genetic screening has allowed for better care and increased survival. Most humans with congenital NDI have the X-linked form, causing the disease to manifest almost exclusively in male children. In small animal patients primary or congenital 10
Diabetes insipidus should be high on the differential diagnosis list for any dog or cat with severe polyuria and polydipsia, especially when the urine is hyposthenuric. The first step in
Box 70-1 Common Causes of Secondary Nephrogenic Diabetes insipidus in Dogs and Cats • • • • • • • •
Hypercalcemia Hypokalemia Pyelonephritis Pyometra and gram-negative sepsis Portal systemic shunts Liver insufficiency Hypoadrenocorticism (more common in dogs) Hyperthyroidism (more common in cats)
the diagnosis of primary diabetes insipidus is to exclude most other common causes of polyuria and polydipsia. This can be accomplished by evaluating the signalment and complaint, a complete history, physical examination, a serum biochemistry profile, and a complete urinalysis and urine culture. Normal serum biochemistry results would rule out many causes of secondary NDI, including hypercalcemia, severe hypokalemia, low serum urea concentrations associated with liver disease, and low sodium concentrations associated with Addison's disease. Normoglycemia would rule out diabetes mellitus and a cause of polyuria and polydipsia. Normal uri nalysis results and negative urine culture findings would exclude diabetes mellitus and primary renal glycosuria, and would make pyelonephritis much less likely (Figure 70-1). Additional testing may also be necessary when appropriate, including preprandial and postprandial serum bile acid con centrations to further exclude liver disease, serum T concen trations to exclude hyperthyroidism, and imaging. Chronic 4
kidney disease as a cause of polyuria and polydipsia is unlikely if the urine is hyposthenuric. If the urine is consistently iso¬ sthenuric, with normal or high-normal serum concentrations of blood urea nitrogen and creatinine, then a glomerular fil tration study may be necessary to definitively rule out chronic kidney disease. A relatively common scenario we are faced with is an older dog with severe polyuria, polydipsia, and hyposthenuric urine, and no abnormal findings on a physical examination, a complete blood count, serum biochemistry profile, urinaly sis (except the hyposthenuria), urine culture, and abdominal radiographs or ultrasonography. At this point in our diagnos tic workup, the most likely remaining causes of the severe polyuria and polydipsia in this dog are hyperadrenocorticism, CDI or NDI, and primary or psychogenic polydipsia. The lat ter is a condition which is sometimes referred to as psycho genic diabetes insipidus, in which a dog drinks excessively for no apparent physiologic reason. Often these dogs are thought
Figure 70-1 The diagnostic plan in a dog or cat with severe polydipsia and polyuria. ACTH, Adrenocorticotropic hormone; CDI, central diabetes insipidus; NDI, nephrogenic diabetes insipidus; PP, primary (psychogenic) polydipsia; RIO, rule out (a diagnosis); SG, specific gravity.
to drink this way because they are bored, stressed, or perhaps just enjoy drinking water. The next step in the diagnosis is to attempt to exclude hyper¬ adrenocorticism and psychogenic polydipsia. The first can be deemed much less likely based on a urine cortisol-to-creatinine ratio within the reference range or a low-dose dexamethasone suppression test with results within the reference range. A n adrenocorticotropic hormone stimulation test is a less advisable option for this purpose, because in many dogs with hyperadre¬ nocorticism the results of an adrenocorticotropic hormone stimulation test lie within the normal reference range. It is abso lutely essential to make every effort to exclude hyperadrenocor¬ ticism in these cases. If this step is missed and a water deprivation test or desmopressin acetate trial is used to confirm CDI, a misdiagnosis may occur. Dogs with hyperadrenocorti¬ cism may appear to have CDI per results of these tests, and therefore will be mistakenly treated with desmopressin acetate instead of the proper diagnosis and treatment of their hyperadrenocorticism. A random serum osmolality test may be used to attempt to diagnose psychogenic polydipsia. In this case dogs drink excessively as their primary disturbance and as a consequence are also polyuric. This is in contrast to diabetes insipidus, hyperadrenocorticism, and other causes or polyuria and poly dipsia in which the primary disturbance is excessive urination. The polydipsia then, in these dogs, is an attempt to remain hydrated or to "catch up" with their urination. Theoretically the dogs with primary or psychogenic polydipsia should always be slightly overhydrated (with a low serum sodium concentration and low serum osmolality), and dogs with other causes of polyuria and polydipsia including diabetes insipidus should be slightly dehydrated (with a relatively high serum sodium concentration and serum osmolality). On a random serum osmolality assay a result of less that 280 mOsm/L would be most consistent with psychogenic polydipsia. A result greater than 280 mOsm/L is hard to interpret, because even if the dog did have psychogenic poly dipsia, if it did not drink excessively that day (possibly due to the visit to the veterinarian), the osmolality could be over 280 mOsm/L. If the random serum osmolality was indeed over 280 mOsm/L, an additional test to confirm the diagno sis of primary diabetes insipidus and to differentiate between the more common CDI and the rare primary N D I is war ranted. Two options are available to achieve these goals, a modified water deprivation test and a desmopressin acetate (synthetic vasopressin) trial.
Modified Water Deprivation Test A modified water deprivation test is based on the premise that a dog that truly suffers from diabetes insipidus will not be able to concentrate its urine even under conditions of moderate dehydration. This is because of either a lack of vasopressin (CDI) or lack of an appropriate renal response to vasopressin (NDI). An appropriate rise in urine specific gravity while dehydrated would be suggestive of psychogenic polydipsia. Once dehydration has been achieved without an appropriate rise in urine concentration, desmopressin is given intramus cularly. A marked increase in urine specific gravity at that time would be diagnostic for CDI, and a complete lack of response to desmopressin would be suggestive of NDI. Although in many cases this test does provide a definitive diagnosis of dia betes insipidus, we do not recommend its routine use. This is because many problems and possible misdiagnoses are
associated with the analysis of the test results and, more importantly, grave risks can be associated with this test includ ing severe dehydration, hypernatremia, and even death. 1
Problems and Risks Causes of Misdiagnoses 1. Medullary washout may occur. If the medullary intersti tium has been "washed out" of solutes because of chronic severe polyuria and polydipsia for any reason, no urine concentration will occur despite the presence of endoge nous vasopressin, desmopressin, and intact renal V receptors. These dogs are then mistakenly diagnosed as suffering from NDI. The modified water deprivation test protocol attempts to eliminate this problem by recom mending mild water restriction for a number of days before the test. Although helpful, this does not always eliminate the problem, is not always possible, and can be dangerous if dehydration is induced at home without proper monitoring. 2. Partial CDI, or a relative lack of vasopressin, can be very hard to diagnose, because a rise in urine specific gravity will be induced by dehydration. This rise, though, will be of inappropriately low magnitude, a very subjective value, and these dogs can be misdiagnosed as having psy chogenic polydipsia. A n additional rise in urine specific gravity should occur after desmopressin is given. Their response should be more dramatic, though, than in dogs with psychogenic polydipsia. This is a subjective value, making a definitive diagnosis of partial CDI very difficult. 3. Dogs with hyperadrenocorticism may appear to have CDI or partial CDI per a water deprivation test, leading to a misdiagnosis. This underlines the importance of estab lishing or excluding a diagnosis of hyperadrenocorticism in dogs before administering this test. 2
Associated Risks The main and most important risk, and the reason why we do not recommend the routine use of this test, is severe dehydra tion than can be associated with acute severe hypernatremia. This occurs in cases of CDI or NDI when dehydration con tinues past 5% of body weight because of a lack of intensive monitoring. In cases of complete diabetes insipidus this could happen in a very short time (a few hours). This may be accompanied with a rapid rise in serum sodium concentra tions resulting in neurologic symptoms. Despite aggressive fluid therapy, normal sodium concentrations may be difficult to restore. Desmopressin therapy is warranted in this case to slow the free water loss associated with the marked polyuria and to allow normalization of serum sodium concentrations. Prevention of this complication includes only mild water deprivation at home during the days before the test, as well as aggressive monitoring of body weight, serum sodium, urea nitrogen, and creatinine frequently (at least hourly) during the test. The test should be stopped at 5% loss of body weight or any marked increase in the above serum values. Water, intravenous fluids (an intravenous catheter should be preplaced), and desmopressin should be available for immediate use.
Desmopressin Acetate Trial The other diagnostic option available for the diagnosis of diabetes insipidus is the desmopressin acetate trial. Although
this test does not yield immediate results, it is a much safer option for most dogs than the modified water deprivation test. This test is performed at home by the owner. The owner is instructed to collect urine, first thing in the morning, for a few days; to slightly limit access to water, if possible, for a few days; and then to begin therapy with desmopressin. On days 5, 6, and 7 of this therapy urine is again collected first thing in the morning. All urine should be refrigerated after collection. At the end of the trial the urine samples are brought to the veterinarian for specific gravity measure ment or, ideally, osmolality assays. The owners are encour aged to measure water intake during the trial, if possible. The theory behind this therapeutic trial is that given mild water deprivation and desmopressin, the dog's urine concen tration will steadily increase over the trial period. Medullary washout will be eliminated slowly if it was present initially, and a dog with CDI should have a marked increase in urine concentration. No increase in urine concentration by the end of the trial would be consistent with NDI or psychogenic polydipsia. Because primary NDI is so uncommon in an adult dog, this is usually not a big problem. A definitive dif ferentiation between those two conditions would require a modified water deprivation test.
Imaging Following a Diagnosis of CDI An extremely high percentage of adult dogs with acquired CDI appear to have intracranial mass lesions identifiable with magnetic resonance or computed topography imaging. Such imaging is therefore recommended following the diag nosis of CDI, and radiation therapy is recommended if a lesion is identified. 4
TREATMENT OF DIABETES INSIPIDUS A list of treatment options for CDI and NDI is included in Box 70-2. Most commonly CDI (partial or complete) is treated with desmopressin (oral or human nasal preparation given as eye drops). This treatment is extremely effective and when given consistently will enable the dog to concentrate urine normally. Other therapies can also be used in those with CDI as well as those with NDI. These include therapies aimed at lowering total body sodium and commonly include thiazide diuretics and salt-restricted diets. These therapies typically have minimal success in those with NDI. Another option for owners of pets suffering from CDI or NDI is not to treat. Theoretically, as long as these animals are allowed free access to water, allowed to urinate outside, and are kept in conditions that help prevent dehydration through additional fluid loss (shade, no strenuous exercise in warm conditions), they will remain hydrated and may exhibit no clinical signs. This is especially important because of the high cost of desmopressin therapy for dogs with CDI and the lack of effective therapy for dogs with NDI.
Emergency Treatment The most challenging aspect of this condition to an emer gency or critical care clinician is the treatment of the severe dehydration, ongoing free water losses, and marked hyperna tremia associated with small animals suffering from diabetes
Box 70-2 Therapies Available for Polydipsic/ Polyuric Dogs With CDI, NDI, or Primary (Psychogenic) Polydipsia A. Central diabetes insipidus (severe) 1. DDAVP (desmopressin acetate) a. Effective b. Expensive c. May require drops in conjunctival sac if oral is ineffective 2. LVP (lypressin [Diapid]) a. Short duration of action; less potent than DDAVP b. Expensive c. Requires drops into nose or conjunctival sac 3. No treatment—provide continuous source of water B. Central diabetes insipidus (partial) 1. DDAVP 2. LVP 3. Chlorpropamide a. 30% to 70% effective b. Inexpensive c. Pill form d. Takes 1 to 2 weeks to obtain effect of drug e. May cause hypoglycemia 4. Clofibrate—untested in veterinary medicine 5. Thiazides a. Mildly effective b. Inexpensive c. Pill form d. Should be used with low-sodium diet 6. Low-sodium diet 7. No treatment—provide continuous source of water C. Nephrogenic diabetes insipidus 1. Thiazides—as above 2. Low sodium diet 3. No treatment—provide continuous source of water D. Primary (psychogenic) polydipsia 1. Water restriction at times 2. Water limitation 3. Behavior modification a. Exercise b. Another pet c. Larger living environment From Feldman EC, Nelson RW: Canine and feline endocrinology and reproduction, ed 3, St. Louis, 2004, Saunders.
insipidus (primary or secondary) that for some reason have not had adequate access to water. This can be a result of vomiting or adipsia from an additional disease process, water deprivation by the owner (because of a belief that this will prevent urination in the house, or accidentally), the pet being lost without water, and animals that have sustained trauma (e.g., dog with diabetes insipidus that has been hit by a car and is presented in for veterinary care hours or days later). In these instances the clinician is presented with a patient with inappropriately high free water losses, dehydration, and high sodium concentrations. The first challenge is recog nition of this state by the clinician, and then aggressive med ical therapy. Aggressive therapy includes fluids, therapy for acute or chronic hypernatremia, and possibly desmopressin. Desmopressin therapy (injectable or eye drops) should be considered when dehydration and hypernatremia persist despite appropriate fluid therapy, urine volumes are high, and urine concentration is inappropriately low for the degree of clinical dehydration (see Chapter 54, Sodium Disorders).
PROGNOSIS The prognosis for dogs with CDI is good if they respond to therapy. Unfortunately, because of an apparently high inci dence of intracranial masses in these dogs, the prognosis must remain guarded until advanced imaging can be pur sued. The prognosis for dogs with primary NDI is guarded because of the lack of therapy for this condition. The prog nosis for dogs with severe dehydration and hypernatremia is guarded, as well, especially if the condition is chronic. Proper medical therapy can often induce complete resolu tion of these complications and allow long-term medical treatment of CDI or the primary cause of secondary NDI.
An excellent comprehensive chapter on diabetes insipidus, including n and pathophysiology, differential diagnosis, clinical signs, a diagn approach, and treatment. Ghirardello S, Malattia C, Scagnelli P, Maghnie M: Current perspective on the pathogenesis of central diabetes insipidus, / Pediatr Endocrinol Metab 18:631, 2005. An interesting review of the causes of CDI in humans, with many aspect vant to the advanced critical care veterinary practice. Harb MF, Nelson RW, Feldman EC, et al: Central diabetes insipidus in dogs: 20 cases (1986-1995), J Am Vet Med Assoc 209:1884, 1996. The largest case series of dogs with CDI published to date. It includes in ingfindingsand the causes and prognosis of this disease in dogs. Robertson GL: Physiology of ADH secretion, Kidney Int 21:S20, 1987. An in-depth review and excellent overview of the physiology of ADH secre beyond what is found in the typical textbook. Sands IM, Bichet DG: Nephrogenic diabetes insipidus, Ann Intern Med 144:186, 2006. An interesting review of NDI in humans, with many aspects that are rel to the advanced critical care veterinary practice.
SUGGESTED FURTHER R E A D I N G * *See the CD-ROM for a complete list of references. Feldman EC, Nelson RW: Water metabolism and diabetes insipidus. In Feldman EC, Nelson RW, editors: Canine and feline endocrine and reproduc tion, St Louis, 2004, Mosby.
Chapter 71 SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE C. B. Chastain,
D V M , MS, D A C V I M
1-6
KEY POINTS • Hyponatremia is the cardinal finding of the symptomatic syndrome of inappropriate antidiuretic hormone (SIADH). • SIADH can be caused by cerebral disorders, pulmonary disease, or adverse effects of medications. Idiopathic causes have been reported in dogs. • Hyponatremia of SIADH is characterized by hypoosmolality and inappropriately concentrated urine and urine sodium excretion. • Renal, adrenal, and thyroid functions are normal, and neither edema, dehydration, nor azotemia is present in animals with SIADH.
INTRODUCTION One of the most frequent electrolyte abnormalities in veteri nary patients is hyponatremia. Most cases are temporary and without clinical signs. One cause of hyponatremia that may be associated with signs and can be fatal is syndrome of inappropriate antidiuretic hormone (SIADH). Antidiuretic hormone (ADH) deficiency is relatively well known and is referred to as central diabetes insipidus. The antithesis of diabetes insipidus, an excess of A D H remains an obscure rarity in animals based on the frequency of case
reports, but its true incidence may be more common than diabetes insipidus. SIADH, also called Schwartz-Bartter syn drome, is characterized clinically in humans by signs of depression and confusion. Affected animals may have central nervous system (CNS) disease, pulmonary disease, or condi tions requiring drugs that can cause SIADH. The failure to recognize the true incidence of SIADH may be caused by lack of clinical suspicion, transient nature of some forms of SIADH, insufficient monitoring, rapid demise of the patient, or clinician distraction from investigating and treating concurrent diseases. Recognition of SIADH is impor tant for many reasons, including causes that can be iatrogenic and remedied by drug withdrawal, or patient death that can be iatrogenic if SIADH is treated too aggressively.
CAUSES A D H , also known as vasopressin, normally is secreted in response to an increase in serum osmolality (serum sodium concentration) or to maintain normal blood pressure and intravascular volume (see Chapter 177, Vasopressin). A D H actions are achieved by the promotion of free water resorp tion by the kidneys. Serum osmolality is monitored by the
anterior portion of the hypothalamus. If blood pressure is normal or elevated, A D H secretion normally is inhibited by pressure receptors in the atria and great veins. A rise in serum osmolality is a more sensitive monitor (1% rise) and typical stimulus for A D H secretion than a decrease in blood pressure (9% decrease). ' SIADH is defined as an excess of A D H without hypovolemia or hyperosmolality. SIADH can be caused by cerebral disorders, pulmonary disease, or adverse effects of medications (Box 71-1). The cause in some cases remains idiopathic. Three cases of idio pathic SIADH have been reported in dogs. ' Cerebral causes of SIADH in humans include hypothalamic tumors, head trauma, meningitis, encephalitis, cerebrovascular accidents, and hydrocephalus. Hypothalamic tumors, granulomatous meningoencephalitis, and probable distemper encephalitis have been reported to cause SIADH in dogs. ' Intracranial disease may directly stimulate the supraoptic or paraventric ular nuclei to secrete A D H or may alter the osmoreceptors to inappropriately stimulate A D H secretion. Other cerebral causes of SIADH are perception of nausea, pain, and psycho logic stress. Pulmonary diseases causing SIADH include tumors that ectopically produce A D H or diseases that interrupt the inhibitory impulses in vagal afferents from stretch receptors in the atria and great veins. Examples in humans have included tuberculosis pneumonia, aspergillosis, and lung abscesses. A dog had SIADH associated putatively with 7 8
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Box 71-1 Some Causes of the Syndrome of Inappropriate Secretion of ADH 7
Central Nervous System Disorders Head trauma Hydrocephalus Cerebrovascular accidents Brain tumor Meningitis Encephalitis
Pulmonary Lesions Bacterial pneumonia Aspergillosis Lung tumors Positive-pressure ventilation Dirofilariasis
Malignancies Pancreatic carcinoma Prostatic carcinoma Thymoma Osteosarcoma
Drugs Antidepressants Neuroleptics Antineoplastics Nonsteroidal antiinflammatory drugs Opioids
Others Pain Nausea Psychological stress ADH, Antidiuretic hormone.
1
dirofilariasis. Rarely, SIADH in humans has been caused by malignant tumors outside the thorax that have ectopically produced A D H . In addition, positive-pressure ventilation may inhibit low-pressure baroreceptors and stimulate the release of A D H . Drugs may either increase A D H secretion or potentiate its action. ' Drugs that are known to increase A D H secretion in humans include antidepressants (especially tricyclic antidepres sants and monoamine oxidase inhibitors), anticancer drugs (intravenous cyclophosphamide and vinca alkaloids), opioids, and neuroleptics. Drugs that potentiate A D H action include cyclophosphamide and nonsteroidal antiinflammatory drugs. The thirst center in the hypothalamus monitors plasma osmolality and extracellular fluid volume. If the patient is con scious, psychologically normal, and has a normal thirst center, water intake will subside to compensate for the reduction in plasma osmolality and expanded extracellular fluid volume of SIADH. Patients receiving fluid therapy, under sedation or anesthesia, that are psychologically deranged, or with CNS disease affecting the thirst center have impaired ability to compensate for SIADH. 7
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CLINICAL SIGNS The clinical signs found in patients with SIADH depend on the cause of the syndrome and on the serum sodium concentration. Signs of a CNS disease, pulmonary disor der, surgical or traumatic stress, or drug intoxication may overshadow signs of SIADH. This may account, i n part, for its rare recognition in companion animals. Regardless of its cause, if the serum sodium is severely decreased (less than 120 mEq/L), signs of hyponatremia may prevail. These include nausea, anorexia, vomiting, irritable behavior, confusion, head pressing, seizures, car diac arrhythmias, and coma. Neither hypertension nor edema will be present.
LABORATORY FINDINGS The outstanding initial abnormal laboratory finding in patients with clinical manifestations of SIADH is hyponatre mia secondary to renal retention of free water and ongoing urinary sodium losses. Sodium is lost in the urine despite hyponatremia, because the secretion of renin and aldoste rone is inhibited by normovolemia with expanding extracel lular fluid caused by water retention. Serum osmolality will be less than 280 mOsm/kg, urine osmolality will be more than 150 mOsm/kg; urine sodium values are usually more than 20 mEq/L. Atrial natriuretic peptide is secreted in response to expanding extracellular fluid volume, which fur ther inhibits renin and aldosterone and promotes natriuresis. Even though water is retained, edema usually does not develop because of continuing natriuresis. The degree of natriuresis is quite variable and is dependent on the quantity of dietary sodium. 7
Other serum constituent concentrations, such as potas sium and chloride, may also be diluted. Hypochloridemia may be severe enough to cause metabolic alkalosis. Blood urea nitrogen and uric acid concentrations are decreased by dilution and increased glomerular clearance. A n increased blood urea nitrogen concentration excludes a diagnosis of SIADH. 7
DIAGNOSTIC IMAGING FINDINGS If non-drug-induced SIADH is suspected, evidence for possible intrathoracic or intracranial lesions should be sought by routine radiographs and, in some cases, computed tomography or magnetic resonance imaging.
DIAGNOSIS A clinical diagnosis can be based on finding the characteris tic clinical features of SIADH and the exclusion of other causes of hyponatremia. Plasma A D H determination is unnecessary for diagnosis. The water loading test can aggra vate water intoxication of SIADH and is unnecessarily hazardous. The clinical features of SIADH are most easily confused with those of primary hypoadrenocorticism. It differs from primary hypoadrenocorticism in having normal to low levels of blood urea nitrogen and serum potassium concentrations. Primary hypoadrenocorticism is associated with azotemia and hyperkalemia. Other differential diagnoses for hypona tremia include congestive heart failure, nephrosis, severe liver disease, hyperglycemia, and hyperlipidemia. In SIADH without unrelated disease, renal, adrenal, cardiac, and liver functions are normal, and blood glucose concentration is normal.
inhibit reabsorption of water in the renal tubules to reduce the risk of volume overload. Sodium and potassium should be supplemented as needed. A tetracycline, demeclocycline, inhibits the action of A D H on the renal tubules. It has been effective in treating humans with SIADH caused by excessive secretion from hypotha lamic nuclei or by the secretion of ectopic A D H . However, it is potentially nephrotoxic and renal function must be monitored closely. Improvement from demeclocycline treat ment may take 1 to 2 weeks. A safe and effective dosage of demeclocycline in dogs has not been established. Lithium will also inhibit the action of A D H on the renal tubules, but its use is precluded by its toxicity, which is greater than that of demeclocycline.
PROGNOSIS The prognosis for patients with SIADH depends on the cause. If caused by infection or drugs, withdrawal of the drug and successful treatment of the infection will lead to a cure. If secondary to a malignant tumor that cannot be excised completely or destroyed by radiation, SIADH usually is incurable but can be controlled with water restriction and sodium supplementation.
SUGGESTED FURTHER R E A D I N G *
TREATMENT Whenever possible, the cause for SIADH should be deter mined and corrected. The treatment of choice is discontin ued fluid administration and restricted access to water. However, this may be insufficient in severe cases. In acute severe cases, emergency treatment may include hypertonic (3%) saline, which should be given slowly in an intravenous dose over 2 to 4 hours if neurologic signs are thought to be secondary to acute hyponatremia and result ing cerebral edema. Isotonic saline infusion is unsuitable because of its low concentration of sodium, which will be excreted in the urine while the water will be retained, wors ening the hyponatremia. When hyponatremia may have been present for more than 48 hours, care must be taken to pre vent central pontine myelinolysis (osmotically induced demyelination). Serum sodium should not increase with treatment by more than 12 mEq/L q24h. The initial goal should be to increase serum sodium concentration to 125 to 130 mEq/L in a carefully controlled manner. When hyper tonic saline is used, furosemide may also be beneficial to 9
Biewenga WI, Rijnberk A, Mol JA: Inappropriate vasopressin secretion in dogs, Tijdschr Diergeneeskd 113:104, 1988. Description of a dog with idiopathic SIADH. Brofman PJ, Knostman KAB, DiBartola SP: Granulomatous amebic menin goencephalitis causing the syndrome of inappropriate secretion of anti diuretic hormone in a dog, ] Vet Intern Med 17:230, 2003. Description of a young dog with amebic meningoencephalitis that deve SIADH. First reported cases of encephalitis or meningitis causing SIA in dogs. Houston DM, Allen DG, Kruth SA, et al: Syndrome of inappropriate anti diuretic hormone secretion in a dog, Can Vet } 30:423, 1989. Description of a 4-year-old dog with a meningeal sarcoma in the region o dorsal hypothalamus and SIADH. O'Brien DP, Kroll RA, fohnson GC, et al: Myelinolysis after correction of hyponatremia in two dogs, / Vet Intern Med 8:40, 1994. Case report of two dogs, the first describing delayed neurologic deterio from central myelinolysis in dogs after rapid correction of severe hyp mia (500 μg/24 hours, which is equivalent to about 7 μg/kg/24 hours). Dogs should be monitored closely for these complications. Administration of IV levothyroxine may have led to the development of pneumonia in two dogs. When the hypothyroid crisis is resolved, the oral route can be used (0.1 mg/5 to 7 kg PO ql2h). 1
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DIFFERENTIAL DIAGNOSIS Many of the clinical and clinicopathologic abnormalities observed in dogs with myxedema coma are nonspecific. Dif ferential diagnosis for obesity, lethargy, mental dullness, weakness, dermatologic abnormalities, and nonregenerative anemia are discussed elsewhere. Some nonspecific differen tials might include chronic inflammatory disease, cardiac disease, metabolic disease (i.e., hypoadrenocorticism), intra cranial disease, hypothermia, and sepsis. Differential diagnoses for edema can be divided into those caused by increased hydrostatic pressure, decreased oncotic pressure, lymphatic obstruction, sodium retention, and vascular endothelial leak syndromes. Such differential diagnoses include heart failure, constrictive pericarditis, asci tes, venous obstruction or compression, heat, hormonal imbalance, protein-losing nephropathy or enteropathy, liver disease, malnutrition, neoplasia, renal hypoperfusion, sepsis, and excess secretion of renin, angiotensin, or aldosterone. Differential diagnoses for hypercholesterolemia includes hypothyroidism, diabetes mellitus, hyperadrenocorticism, pro tein-losing glomerulopathy, cholestatic disease, postprandial hyperlipidemia, primary hyperlipidemia (Miniature Schnau¬ zers, Shetland Sheepdogs), lipoprotein lipase deficiency (cats), idiopathic causes (Doberman Pinschers, Rottweilers), and iatrogenic causes (glucocorticoids).
TREATMENT Treatment is divided into supportive care, thyroid hormone supplementation, and treatment of concurrent conditions. Hypotension can be treated cautiously with fluids and vaso pressors (see Chapter 176, Vasoactive Catecholamines). Dogs must be observed carefully for signs of fluid overload, which may exacerbate underlying cardiac disease or dysfunc tion. Hypothermia is treated by wrapping the dog with blankets and keeping the room warm. Heating pads are avoided because they can lead to vasodilation and worsening hypotension. If respiratory depression is profound, mechan ical ventilatory support is needed. ' Hyponatremia can be corrected slowly (no more than 0.5 mEq/hr) with 0.9% saline solution. 11
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Treatment of concurrent disease such as pneumonia, other infections, cardiac disease, concurrent endocrinopathy, or any other illness will facilitate recovery. Discontinuation of any medication that may have exacerbated the hypothy roid crisis is also recommended.
OUTCOME Most dogs with myxedema coma respond well to therapy when given IV levothyroxine. Seven of eight reported dogs that received IV levothyroxine were discharged from the hos pital (87%). Subjective improvement in mentation or ambulation occurs within 24 to 30 hours of administration of IV levothyroxine in most dogs. Severity of concurrent dis ease, persistent hypothermia, advanced age, and degree of mental alteration (coma) is associated with a poor prognosis in humans. 1,3
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SUGGESTED FURTHER R E A D I N G * Fliers E, Wiersinga WM: Myxedema coma, Rev Endocr Metab Disord 4:137, 2003. A review of myxedema coma in humans that offers some insight on pathophys iology, diagnosis, and treatment. Pullen WH, Hess RS: Hypothyroid dogs treated with intravenous levothyr oxine, / Vet Intern Med 20:32, 2006. A retrospective study which is the largest, most detailed report of canine myx edema reported to date, bringing to light the need to treat dogs in hypothy roid crisis but do not necessarily have myxedema or coma. Rodriguez I, Fluiters E, Perez-Mendez LF, et al: Factors associated with mor tality of patients with myxoedema coma: prospective study in 11 cases treated in a single institution, J Endocrinol 180:347, 2004. A prospective study that found that a coma, the Glasgow score, and the APACHE II score were associated with fatal outcome. Wall CR: Myxedema coma: Diagnosis and treatment, Am Earn Physician 62:2485, 2000. A review of myxedema coma in humans that focuses on diagnosis and treat ment but not on pathophysiology. Yamamoto T, Fukuyama J, Fujiyoshi A: Factors associated with mortality of myxedema coma: report of eight cases and literature survey, Thyroid 9:1167, 1999. A retrospective study of five patients and literature review of 82 additional patients. The authors report that age, high-dosage thyroid hormone supple mentation, and cardiac disease are risk factors for fatal outcome of myx edema coma.
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*See the CD-ROM for a complete list of references.
Chapter 74 PHEOCHROMOCYTOMA Benjamin M. Brainard,
V M D , D A C V A , DACVECC
• Deborah C. Mandell, V M D ,
DACVECC
1,5 8
to be older (10 to 12 years), ' and there is no gender predilection. ' Clinical signs may include hypertension, manifestations of hypertension (e.g., blindness from retinal detachment), weakness, collapse, lethargy, vomiting, diar rhea, tachypnea, abdominal distention, syncope, tachyar rhythmias, and/or abdominal pain. These signs may be sustained or paroxysmal. Because the pheochromocytoma is not innervated like a normal adrenal gland, it is unclear what stimuli cause secretion of catecholamines from the tumor. A Budd-Chiari-like syndrome resulting from tumor invasion and extension up the caudal vena cava has been reported in a dog. Approximately 15% to 38% of dogs with a pheochromocytoma have neoplastic invasion of the caudal vena cava; however, clinical signs are not reliably associated with the extent or presence of vena caval invasion. '
KEY POINTS
7 8
• Pheochromocytoma is a tumor of the chromaffin cells of the adrenal medulla. • Clinical signs may include hypertension and manifestations of hypertension, weakness, syncope, lethargy, vomiting, diarrhea, tachypnea, abdominal distention, tachyarrhythmias, and/or abdominal pain. • Most pheochromocytomas in small animals are diagnosed either by abdominal imaging or during postmortem examination. • Definitive treatment for a pheochromocytoma is surgical excision. • Preoperative, perioperative, and postoperative treatment may be challenging. • With complete surgical resection and an uneventful postoperative course, even dogs with vena caval thrombi may experience a significant survival time, reported from 18 months to 3 years.
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INTRODUCTION
Concurrent pheochromocytoma and hyperadrenocorticism have been reported in six dogs, and some clinical signs (e.g., panting) may overlap. Rupture of pheochromocytomas may result in hemoperitoneum or hemoretroperitoneum. ' Dogs may exhibit neurologic deficits or paraparesis secondary to metastatic tumor in the spinal canal, or secondary to aortic thromboembolic disease. ' ' Cardiac arrhythmias may include third-degree atrioventricular block, supraventricular tachycardia, or ventricular ectopy. Of the few cats in the literature with an antemortem diag noses of a pheochromocytoma, clinical signs consisted of lethargy, vomiting, polyuria, polydipsia, or were associated with systemic hypertension (congestive heart failure and retinal detachment). " 11
12 13
Pheochromocytoma is a tumor of the chromaffin cells of the adrenal medulla. These cells synthesize, store, and secrete catecholamines in response to sympathetic stimulation (Color Plates 74-1 and 74-2). Chromaffin cells are also termed A P U D cells, because they are responsible for amine precursor uptake and decarboxylation. Pheochromocytoma may occur alone, or as part of the multiple endocrine neoplasia syndrome. In humans this is a heritable constellation of two or more endo crine neoplasias (or hyperplasia), usually involving the parathy roid and thyroid glands in addition to the adrenal gland. Extraadrenal pheochromocytomas (paragangliomas) occur rarely. Most (48% to 80%) of pheochromocytomas in small ani mals and 30% to 76% in humans are diagnosed on postmortem examination, or as incidental findings on abdominal ultraso nography, and the patient may be clinically asymptomatic. ' " It is thought that pheochromocytomas represent between 0.01% and 0.13% of all canine tumors; however, this number may be low, because the tumor may be benign or nonfunctional and thus not suspected. These tumors may be both locally inva sive and metastatic. ' Most pheochromocytomas in humans secrete norepinephrine (NE) (versus epinephrine), but this has not been studied in dogs or cats. It is thought that negative feed back of NE on tyrosine hydroxylase (which converts tyrosine to dopa, leading to synthesis of more NE) does not work normally in the tumor cells, or that the tumor metabolizes NE so quickly that the levels required for negative feedback are never reached. 1
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CLINICAL SIGNS In dogs with a pheochromocytoma, approximately 30% to 50% have clinical signs attributable to the tumor. Dogs tend
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DIAGNOSIS As in humans, most pheochromocytomas in small animals are incidental findings, diagnosed by abdominal imaging or postmortem examination. In some dogs, an abdominal mass may be palpated. ' Abdominal radiography may show mineralization in the area of the adrenal glands, or may demonstrate retroperitoneal effusion or an abdominal mass effect associated with the tumor (30% to 50% of cases). ' Chest radiographs may show cardio¬ megaly and pulmonary venous congestion or pulmonary edema secondary to chronic hypertension or tachycardia. ' These findings may be confirmed via echocardiography. Rarely, met astatic disease may be seen on thoracic radiographs. ' Sixty-five to eighty-three percent of pheochromocytomas in dogs are detected via abdominal ultrasonography, making it a useful first-line imaging modality. The origin and archi tecture of the mass, as well as blood flow within the mass and invasion into adjacent structures, may be determined. Pheochromocytomas seem to have a higher likelihood for 5 8
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Figure 74-1 Transverse helical postcontrast computed tomography image at the level of the cranial pole of the right kidney. A right adrenal mass is seen, and a large filling defect is present in the caudal vena cava at that level (arrow). This mass was determined to be a pheochromocy¬ toma by histopathology.
Figure 74-1 Transverse helical postcontrast computed tomography image at the level of the cranial pole of the right kidney. A right adrenal mass is seen, and a large filling defect is present in the caudal vena cava at that level (arrow). This mass was determined to be a pheochromocytoma by histopathology. 16
vena caval invasion than do adrenocortical tumors, but ultrasonographically they appear similar to adenocarcino mas. It is difficult to determine the cellular origin of an adrenal mass based on ultrasonography, and some masses may be too small for detection by this means. Invasive pheochromocytomas have been reported to invade not only the vena cava, but also the aorta, renal veins, and hepatic veins. Ultrasound-guided biopsies may be obtained, if indicated, but caution should be exercised. Advanced imaging techniques such as computed tomog raphy (CT) or magnetic resonance imaging (MRI) are very helpful for determining the size of the tumor and the extent of tumor invasion, although these require general anesthesia in the veterinary patient. Nonionic, low-osmolar contrast media is recommended for CT studies to minimize adverse reactions.'" Gadolinium contrast for MRI studies is not contraindicated in patients with a suspected pheochromocytoma. CTfindingsin dogs with pheochromocytoma show a lobulated, irregularly shaped mass associated with the adrenal gland. Areas of decreased intensity are interspersed with highly vascu lar areas with increased intensity (Figures 74-1 and 74-2). MRI may be used to differentiate between histologic types of adrenal tumors. Scintigraphy using iodinemetaiodoben¬ zylguanidine (an NE analog) or technetium-methylene diphosphonate has been used in the dog to identify a pheochro mocytoma. One group used p-[ F]fluorobenzylguanidine to identify tumors in dogs using positron emission tomography. These techniques are useful for identifying metastatic tumors. Laboratory test results in animals with a pheochromocytoma are generally unremarkable. In dogs, a mild nonregenerative ane mia may be present secondary to chronic disease, or an increased mean cell volume or packed cell volume may be seen secondary to catecholamine or erythropoetin-like stimulation of the bone marrow. A regenerative anemia may reflect hemorrhage from the tumor. Leukocytosis or a stress leukogram may be found secondary to catecholamine release or inflammatory changes associated with the tumor. If there has been hemorrhage or intravascular coagulation from the tumor, a consumptive 17
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Figure 74-2 Sagittal reconstruction of the helical computed tomogra phy scan in Figure 74-1 showing invasion of the caudal vena cava along the length (4 cm) of the mass. Irregular filling of the cava is present cra nial and caudal to the mass, likely representing thrombus formation. The cranial aspect of the caudal vena cava is denoted with an arrow.
thrombocytopenia may occur. Evidence of hypercoagulability may be present, but this has not been investigated in veterinary medicine (see Chapter 117, Hypercoagulable States). Serum chemistry profiles may be normal, or may show elevations in liver enzymes (unrelated to liver metastasis). ' Dogs with multiple endocrine neoplasia syndrome may be hypercalcemic as a result of elevated parathyroid hormone or parathyroid hormone-related peptide (PTH or PTH-rp). Dogs may be hyperglycemic from catecholamine stimulation of hepatic glucose production and decreased insulin release from α-receptor stimulation.' Pheochromocytomas may also secrete hormones such as vasoactive intestinal peptide, which may contribute to clinical signs such as diarrhea. In two retrospective reports of dogs with pheochromocytoma, hypercholesterolemia was present in 25% of dogs, possibly secondary to increased fat mobilization from catecholamine secretion or due to concurrent hyperadrenocorticism. In 20 dogs with a pheochromocytoma, but without concur rent disease, 50% showed proteinuria, likely caused by a hypertensive glomerulopathy. Measurement of urinary cate cholamine concentrations (metanephrine, normetanephrine, vanillylmandelic acid) as a spot check referenced to urine cre atinine, or over a 24-hour period, is performed in humans with suspected pheochromocytomas and has been investi gated in dogs. Secondary factors, such as excitement, exercise, vanilla-containing foods, and radiographic contrast agents may result in false-positive elevations. Because of the similarity in clinical signs and ultrasono graphic appearance of pheochromocytomas and adrenocortical tumors, and reports of the coexistence of hyperadrenocorticism and pheochromocytoma, hyperadrenocorticism should be ruled out at the time of medical workup. Other tests reported in humans include the clonidine suppression test, which should decrease serum catecholamine levels in normal patients but not in patients with a functional pheochromocytoma (because catecholamine release from the tumor is not neurally mediated). The administration of intravenous phentolamine, an α-adrenergic antagonist, to hypertensive patients will cause a decrease in blood pressure if 3 7
7,8
2
7
2
8
the hypertension is catecholamine mediated (close monitoring is vital). These tests have varying sensitivity and specificity, especially in the context of paroxysmal hypertension, and have not been evaluated thoroughly in veterinary patients. Provocation tests using metoclopramide, histamine, tyra¬ mine, and glucagon, all of which cause increased secretion of catecholamines from the tumor, are not recommended because of the potential for inducing acute hypertensive crises. For this reason, the use of metoclopramide as an antiemetic in patients with suspected pheochromocytoma may be contraindicated. Because hypertension and tachycardia may be paroxysmal, blood pressure and electrocardiogram (ECG) monitoring should be performed, but results may be low yield. Holter or continuous ECG monitoring may be necessary for the diagno sis of intermittent tachyarrhythmias. The results of a biopsy or fine-needle aspiration of adre nal tumor masses are not discussed at length in the litera ture. This may be partially due to the difficulty of safely obtaining samples, or because excisional biopsy is preferred. Gilson and others note a similarity in cytologic appearance between lymphosarcoma and pheochromocytoma when diagnosed from ascitic fluid in three dogs, so an adequate index of suspicion is necessary to prevent misdiagnosis. Impression smears of a pheochromocytoma may also appear similar to a round cell tumor. In addition, it is difficult to characterize relative malignancy on the basis of histopatho logic evaluation, so it may be difficult to accurately predict tumor behavior on the basis of biopsy specimens. Any tumor that demonstrates invasion of adjacent structures should be considered malignant. 2
2
7
5
7
TREATMENT
anesthetic premedication and induction. Long-lasting α-adren ergic antagonists such as acepromazine may complicate intraoperative or postoperative treatment and should be avoided, especially if the animal has been pretreated with phe¬ noxybenzamine. A safe induction protocol includes an opioid, such as oxymorphone, hydromorphone, or fentanyl (minimal histamine release), combined with a benzodiazepine and pro¬ pofol or etomidate to facilitate endotracheal intubation. Inhal ant agents such as isoflurane or sevoflurane are preferred to halothane, which sensitizes the myocardium to catechol¬ amine-induced arrhythmias. Desflurane can cause sympathetic stimulation and should be avoided. There are no contraindica tions to the use of nitrous oxide in humans undergoing surgery for pheochromocytoma. Inhalant agents may be supplemen ted with balanced anesthetic techniques using potent opioids such as fentanyl, administered as a constant rate infusion (0.7 to 2 μg/kg/min). 23
Intraoperative monitoring must include ECG and arterial blood pressure (preferably direct), as well as central venous pressure to estimate intravascular volume. Pulmonary arterial catheterization will give information about cardiac output and systemic vascular resistance that may help to tailor fluid and drug therapy during and after surgery; however, placement of these catheters may be associated with increased morbidity (see Chapter 50, Pulmonary Artery Catheterization). During anesthesia, treatment with short-acting β-blocking drugs such as esmolol (0.1 to 0.5 mg/kg IV followed by 0.5 to 2 μg/kg/min IV), or vasodilators such as nitroprusside (0.2 to 10 μg/kg/min IV), may be necessary to maintain normal hemodynamics (see Chapters 178 and 191, Antihypertensives and β-Blockers, respectively). Some human reports advocate magnesium sulfate for vasodilation during surgery for pheo chromocytoma. Supraventricular tachycardia (SVT) is a common arrhythmia during surgery, although bradycardia with atrioventricular block and ventricular premature com plexes have also been seen. Lidocaine may be used to treat ventricular arrhythmias (see Chapter 190, Antiarrhythmic Agents). Before surgery, blood type and crossmatch to multiple units of packed red blood cells or fresh whole blood should be performed in case of severe intraoperative hemor rhage. Blood pressure during anesthesia in the hypertensive animal should be maintained at levels close to its resting blood pressure to prevent renal hypoperfusion, and urine output should be measured intraoperatively. If a venotomy is anticipated for removal of a thrombus, external cooling of the patient may be of benefit to protect tissues during intraoperative interruption of blood flow and ischemia. Surgical manipulation of the tumor may cause catechol amine release. Alternatively, removal of the tumor may result in cardiovascular collapse from lack of catecholamines, requiring supplementation with sympathomimetic drugs such as phenylephrine (0.5 to 10 μg/kg/min IV) or norepi nephrine (0.1 to 3 μg/kg/min IV) (see Chapter 176, Vasoac tive Catecholamines). 23
24
Definitive treatment for pheochromocytoma is surgical exci sion. Surgery is often complicated, and may necessitate vena caval venotomy or nephrectomy to fully remove or debulk the tumor. A recent study found an overall mortality rate of 22% after removal of adrenal tumors in dogs, which was not correlated with vena caval invasion or tumor type. A thorough abdominal exploration is recommended during surgery to identify gross metastatic disease. In a study of 61 dogs, 15% showed metastasis and 39% had locally inva sive tumors. In this study, concurrent neoplasia of various cellular origins was identified in 54% of the dogs. Noncompetitive α-adrenergic blockade with phenoxyben¬ zamine (0.5 to 2.5 mg/kg PO ql2h) should be instituted at least 1 week before anesthesia for surgical resection of the tumor. This may help to blunt hypertensive episodes during anesthesia, although high dosages may be necessary. In humans, preoperative α-adrenergic blockade decreased perioperative mortality associated with resection of pheo chromocytoma from 13% to 45% to 0 to 3%. α-Methylpara-tyrosine competitively inhibits tyrosine hydroxylase, interfering with catecholamine biosynthesis. It may be a useful drug for patients with pheochromocytoma, although there are limited reports of its use in dogs or cats, none of which had a pheochromocytoma. Chronic sympathetic stimulation and vasoconstriction may result in intravascular volume depletion, which should be assessed and corrected before the induction of anesthesia. Anticholinergic drugs that cause tachycardia and barbitu rate agents that may cause ventricular arrhythmias in the presence of excess catecholamines should be avoided for 17
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16
Postoperatively, hypertension may or may not resolve, even with full excision of the tumor. If bilateral adrenalectomy has been performed, supplementation with glucocorticoids and mineralocorticoids will be necessary. Postoperative hypoten sion or cardiovascular collapse is possible, and a decreased sensitivity to catecholamines from chronic stimulation may require noncatecholamine pressors such as vasopressin to maintain adequate blood pressure. Blood glucose should be monitored postoperatively, because the removal of sympa thetic stimulation may cause hypoglycemia. 7
25
Functional adrenocortical tumors may be associated with pulmonary thromboembolic disease; however, the associa tion in the context of pheochromocytoma is unclear. If an animal is suspected to be hypercoagulable, postoperative anticoagulation with heparin may be indicated. In animals with symptomatic pheochromocytomas that are nonresectable or metastatic, in which surgical resection is not likely to be successful, medical treatment with phenox¬ ybenzamine, oral β-blockers, or other antiarrhythmic agents is indicated to alleviate some clinical signs. β-Blockers should not be administered without concurrent α-blockade, because the loss of β -receptor-mediated vasodilation may exacerbate hypertension. Other therapy directed more specifically toward the clinical signs (e.g., diuretics to treat ascites) may also be indicated. Chemotherapeutic or radiotherapeutic treatment of pheochromocytoma in small ani mals has not been reported; however, it has been unrewarding in human medicine. 2
51% (20 of 39) dogs experienced postoperative complications after resection of adrenal tumors. These included ventricular tachyarrhythmias, dyspnea, disseminated intravascular coag ulopathy, abdominal incisional dehiscence, internal hemor rhage, and vomiting. One dog in this group experienced refractory hypertension after removal of a pheochromocy toma. Tumor type (adrenocortical versus pheochromocy toma) or presence of caval thrombi was not related to complications. Seven of eleven dogs with pheochromocytoma experienced perioperative morbidity after resection of the tumor. In the limited studies available, recurrence of primary tumor or of metastatic disease is rare. In the nine dogs that survived surgical resection of a pheochromocytoma in the study by Kyles and colleagues recurrence of clinical signs or tumor-related death was not reported, with a median follow-up time of 9 months (range from 1 to 36 months). 16
16
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5
PROGNOSIS
SUGGESTED FURTHER R E A D I N G *
Extensive information on prognosis after surgical resection or medical treatment of pheochromocytoma is not available. According to the studies that have been published, larger tumors with invasion of neighboring structures may indicate a poorer prognosis. Gilson reported that factors such as neu rologic deficits, weight loss, and abdominal distention may be associated with a poorer prognosis in dogs. In humans, histopathologic analysis which shows multiploidy (e.g., aneu¬ ploidy or tetraploidy) in the nuclear D N A of the tumor cells has been associated with poorer prognosis. With complete resection and uneventful recovery from surgery, even dogs with vena caval thrombi may experience significant survival, reported from 18 months to 3 years. ' ' Many dogs, however, experience significant complications during the first 24 to 72 hours postoperatively. In one study, 7
26
Barthez PY, Marks SL, Woo J, et al: Pheochromocytoma in dogs: 61 cases (1984-1995), / Vet Intern Med 11:272, 1997. Veterinary retrospective study on incidence of pheochromocytoma in dogs, with a review of clinical signs and coexisting conditions. Kinney MAO, Narr BJ, Warner MA: Perioperative management of pheo chromocytoma, / Cardiothorac Vase Anesth 16:359, 2002. An excellent human review of anesthetic management of pheochromocytoma. Kyles A, Feldman E, De Cock H, et al: Surgical management of adrenal gland tumor with and without associated tumor thrombi in 40 dogs (1994-2001), 1 Am Vet Med Assoc 223:654, 2003. Excellent article describing advanced surgical and anesthetic management of dogs with adrenal masses. Rosenstein DS: Diagnostic imaging in canine pheochromocytoma, Vet Radiol Ultrasound 41:499, 2000. Article that discusses various imaging modalities for the adrenal mass.
2 8 16
16
*See the CD-ROM for a complete list of references.
Chapter 75 RELATIVE ADRENAL INSUFFICIENCY Jamie M. Burkitt,
D V M , DACVECC
KEY POINTS • Cortisol is an important hormone involved in modulation of inflammation and regulation of vascular tone. • Relative adrenal insufficiency (RAI) is common in humans with sepsis and other types of critical illness. • Human patients with RAI have poor vascular responsiveness and worse survival than those with normal hypothalamic-pituitary¬ adrenal axis (HPA) function. • The best method for diagnosing RAI is unknown. • Low dosages of hydrocortisone improve pressor responsiveness and survival in humans with RAI and septic shock. • RAI likely occurs in a subpopulation of critically ill dogs and cats. • Appropriate methods for the diagnosis and management of RAI in dogs and cats are unknown.
illness-associated RAI usually have normal to elevated basal serum Cortisol concentration, but a blunted Cortisol response to an A C T H stimulation test. Therefore their adrenal dysfunction truly is relative—it is believed that although the adrenal glands can make and release Cortisol, the quantity is inadequate for the degree of physiologic stress. Following recovery from sepsis, HPA axis dysfunction resolves. 10
ASSOCIATED PRIMARY ILLNESSES Patients with relative adrenal insufficiency (RAI) include humans with severe sepsis and septic shock, ' " severe hepatic disease, acute myocardial infarction, and hemor rhagic shock. It is important to note that although many illnesses are associated with RAI, all humans who have RAI are critically ill; RAI has not been documented in patients with localized infections, mild to moderate hepatopathy, or stable heart disease. 1 6
11
9
12
13
INTRODUCTION Cortisol is a hormone released by the adrenal glands in small amounts in a circadian rhythm, and in larger amounts during times of physiologic stress. It has many important homeostatic functions including regulation of carbohydrate, lipid, and pro tein metabolism; immune system modulation; ensuring proper production of catecholamines and function of adrenergic receptors; and stabilizing cell membranes. A classic example demonstrating the importance of Cortisol function is the patient with glucocorticoid-only hypoadrenocorticism. Patients with minimal endogenous corticosteroid production show clinical signs of gastrointestinal disturbance, weight loss, and collapse, particularly in stressful situations. These patients can be treated successfully with glucocorticoid supplementation. Serum Cortisol concentration is determined by the hor monal cascade and negative feedback mechanisms of the hypothalamic-pituitary-adrenal (HPA) axis. The hypothala mus produces corticotropin-releasing hormone (CRH), which stimulates the anterior pituitary to release adrenocorticotropic hormone (ACTH). A C T H in circulation stimulates the zona fasciculata and zona reticularis of the adrenal gland to produce and release Cortisol. Cortisol has negative feedback action on both the hypothalamic release of C R H and the pituitary release of A C T H . Thus, when circulating Cortisol concentration is low, C R H and A C T H will increase, stimulating the adrenal glands to produce more Cortisol. The increased serum Cortisol concentration inhibits the release of more C R H and A C T H . Research over the past decade has shown that abnormalities of HPA axis function are common in human patients with severe sepsis and septic shock, conditions that frequently carry a mortality rate of 50% or more in both human and veterinary medicine. Many well-conceived and well-performed clinical studies have found RAI, also called critical illness-related corti costeroid insufficiency (CIRCI), in up to 77% of human patients with severe sepsis and septic shock. ' " Unlike patients with classic hypoadrenocorticism, those with critical 1-5
1 5
9
SUSPECTED PATHOPHYSIOLOGY The underlying mechanisms of RAI are unknown. Studies have suggested that the inflammatory cytokines interleukin6 ' or tumor necrosis factor, ' or corticostatin peptides produced by immune cells may interfere with HPA axis function. Also, there have been reports of RAI associated with adrenal hemorrhage in critically ill humans. ' Adrenal hypoperfusion and microvascular disease from disseminated intravascular coagulation may contribute. Even if glucocorti coids are produced in adequate amounts in critically ill patients, they may not be able to exert their effects. There is evidence that corticosteroid receptor numbers may be decreased in patients with hemorrhagic and septic shock. Cytokines may cause corticosteroid receptor dysfunction. 14
15
16 17
18
19 20
21
22
SPECIES AFFECTED It is widely accepted that RAI occurs in critically ill humans but strong evidence of RAI does not yet exist in veterinary medicine. One study of 20 dogs sequentially admitted to a veterinary intensive care unit failed to find HPA axis abnormalities in any patients, although another study in critically ill septic dogs found a 48% incidence of R A I . A study in cats admitted to an intensive care unit did not demonstrate RAI in septic cats, but did find HPA axis abnormalities in cats with neoplasia. Another study showed a decreased response to exogenous A C T H in septic cats compared with a group of normal cats. Thus it appears that RAI probably occurs in some subpopula¬ tions of critically ill dogs and cats. Clinical evidence in other species is unavailable. 23
24
25
26
CLINICAL MANIFESTATIONS The most common clinical abnormality associated with RAI in humans with septic shock is hypotension refractory to fluid loading. Studies have shown that RAI is associated with decreased pressor responsiveness in human patients that is reversed with glucocorticoid administration. In vitro stud ies have shown that smooth muscle adrenergic receptor expression is modulated by glucocorticoids. ' One human clinical study showed that myocardial adrenergic receptor down-regulation in shock could be reversed by glucocorti coids. Another study investigating the phenylephrine¬ mean arterial pressure relationship in humans with septic shock showed that physiologic dosages of hydrocortisone normalized vasomotor response to the drug, underscoring the clinical importance of glucocorticoids in smooth muscle response to catecholamines. 27
28 29
30
31
Human patients with RAI may be more likely to die than those with similar illness severity and an intact HPA axis. " Preliminary data from a study in septic dogs suggests that those with RAI may be more likely to die than those with nor mal HPA function. 32
34
24
the stimulated value, which yields the δ-cortisol value. In humans, a 8-cortisol concentration of less than 250 nmol/L (90% cocaine) and the less pure
water-soluble hydrochloride salt (12% to 60%). It is rapidly absorbed across all mucosal surfaces and has a short half-life (duration of action of 30 minutes when given intravenously). Originally used by natives of South America to reduce fatigue while working at high altitudes, it has been abused for over a century in Western countries for its psychomotor stimulant effects. When given intravenously to experimental dogs, con vulsions began at a mean dosage of 11.8 mg/kg. The mean lethal dose in the same study was 21 mg/kg. Cocaine inhibits presynaptic neuronal reuptake of norepi nephrine, dopamine, and serotonin, thus increasing synaptic and circulating levels of these hormones. It also blocks fast sodium channels (like other type I antiarrhythmic agents), slowing conduction during phase 0 of the action potential, thereby blocking cell conduction. Cocaine therefore has local anesthetic activity; enhances sympathetic transmission caus ing tachycardia, cardiac arrhythmias, and increased arterial pressure; and has central effects of excitement and euphoria.
Outcome and Prognosis Animals presented with mild clinical signs have a good prog nosis with supportive care and intensive monitoring. Patients with severe cardiac and neurologic abnormalities, or those that are hyperthermic, have a more guarded prognosis.
5
Case Management Animals will usually be presented to a veterinarian with clini cal signs of restlessness, excitement, and hyperesthesia that may progress to seizures in cases with severe intoxications. The patient may vomit as a result of stimulation of the area postrema in the medulla (chemoreceptor trigger zone). Initial respiratory stimulation may progress to respiratory depression. Although bradycardia is reported as an early clinical sign, most animals will typically be tachycardic and hypertensive because of the sympathomimetic effects of cocaine. This hyperdynamic state may result in hyperthermia, hypoglycemia, and a lactic acidosis. Confirmation can me made with a urine illicit drug screen (see Color Plate 81-1). Decontamination strategies will have a small role because of the rapid absorption of cocaine. Goals of therapy include maintenance of normal ventilation, reduction of CNS activity, treatment of cardiac arrhythmias, resolution of hyperthermia (see Chapter 167, Heat Stroke), and correction of metabolic and acid-base derangements. Control of seizures and anxiety can usually be achieved with benzodiazepines. A n electrocar diogram is important to identify arrhythmias. Cardiac effects of cocaine are dose dependent and include sinus bradycardia and ventricular premature contractions at lower doses, and supraventricular or ventricular tachycardia at higher plasma levels. Benzodiazepines are effective for reducing sympathetic outflow from the CNS and therefore reducing sympatheticinduced arrhythmias. However, they have no effect on the myocardial sodium channel blockade that predominates in the pathophysiology of cocaine-induced ventricular arrhyth mias. Advanced Cardiac Life Support (ACLS) guidelines pub lished in 2001 recommend sodium bicarbonate or lidocaine as the first-line therapy for cocaine-related ventricular tachycar dia/ventricular fibrillation, whereas propranolol was contrain dicated. Sodium bicarbonate improves electrocardiographic changes and myocardial function secondary to experimental cocaine toxicity in dogs. It is not known if the effects of sodium bicarbonate are due to a change in sodium load or sec ondary to an increase in p H . There is still much controversy as to the use of lidocaine in the treatment of cocaine-induced arrhythmias because of fear of lowering the seizure threshold and potentiating cocaine toxicity. 6
7
8
Chlorpromazine and haloperidol may antagonize the effects of cocaine by antagonizing or blocking catecholamines.
OPIOIDS Pharmacology The term opioid refers to any synthetic or naturally occurring substance that produces morphine-like effects and is blocked by the opioid antagonist naloxone. The term opiate, although commonly used interchangeably with opioid, applies only to synthetic morphine-like drugs with a nonpeptide structure. Opium is an extract of the juice of the poppy plant Papa¬ ver somniferum and has been used for thousands of years to induce euphoria, sleep, and analgesia and to stop diarrhea. Small animals may suffer from opioid intoxication second ary to veterinary administration (e.g., morphine, metha done, hydromorphone, fentanyl), ingestion of prescribed opioids (e.g., fentanyl patches, codeine), or ingestion of rec reational opioids (e.g., diacetylmorphine [heroin]). Opioids have effects at G-protein-linked opioid receptors (μ, δ, and k) predominantly found in the CNS and G l tract. Neuronal excitability is reduced secondary to increased membrane potassium conductance and inhibition of calcium entry, with central cholinergic, serotoninergic, adrenergic, and dopaminergic systems all being affected. Opioids are used clinically for their analgesic properties, but commonly seen side effects of euphoria/dysphoria, respiratory depres sion, nausea/emesis, bradycardia, pupillary constriction, and decreased G l motility are seen with routine clinical use and secondary to intoxication. 9
Case Management Animals may be presented to the veterinarian with a known his tory of opioid ingestion (e.g., fentanyl patch belonging to a per son or animal) or iatrogenic opioid overdose. Some owners may not be aware of intoxication or may not volunteer this information. Animals may look nauseous or be vomiting, hav ing diarrhea, panting, or hypoventilating (evidenced by increased partial pressure of arterial carbon dioxide), and/or be ataxic, depressed, or even comatose. Pupils will be con stricted initially (dogs only; cats develop mydriasis), but if respi ratory depression and neurologic signs are severe, they may become dilated secondary to hypoxia. Despite central respira tory depression, cardiovascular function is relatively spared. A tentative diagnosis can be made with a urine illicit drug screen or following to a positive response to a naloxone response test. Treatment is based on G l decontamination, reversal of the opioid-induced effects with the antagonist, naloxone, and supportive care. Apomorphine can be administered if there are no contraindications to emesis induction. Although a chemically related compound, apomorphine does not bind to opioid receptors and exerts its emetic effects through dopamine agonism. Repeated doses of activated charcoal should also be given. Signs of opioid intoxication can be reversed with the antagonist naloxone. A n initial dose of 0.01 mg/kg IV should be given and the response noted. Several doses may be
necessary before signs improve. Depending on the half-life of the opioid, repeated doses or a constant rate infusion may be required to prevent renarcotization. Supportive care is important until the patient has normal neurologic, ventilatory, hemodynamic, and thermoregulatory function. If the patient is hypoxemic, supplemental oxygen should be provided. If a gag reflex is absent or the patient is hypercapnic despite opioid reversal with naloxone, endotra cheal intubation and mechanical ventilation are indicated.
Outcome and Prognosis Rapid recognition of opioid intoxication with appropriate sup portive care and reversal with naloxone will improve the prog nosis. If intervention for a patient is delayed, and the patient is severely hypoxemic or has been subjected to prolonged hyp oxemia, the prognosis is more guarded. A positive response to therapy is the best prognostic indicator in these cases.
PHENCYCLIDINE
contraindications, emesis should be induced. This should be followed by administration of repeated doses of acti vated charcoal and a cathartic, because there is extensive enterohepatic recirculation of PCP. Induction of anesthesia followed by intubation and gastric lavage should be consid ered in severely affected animals. Animals with mild signs should be kept quiet in a cool, dark area with minimal stimulation and anxiety controlled with benzodiazepines. Respiratory, hemodynamic, neurologic, and thermoregulatory care are essential in these patients and in animals with more severe clinical signs. Treatment of animals with severe neurologic signs is based on controlling seizures with benzodiazepines and attempting to maintain cerebral perfusion pressure and oxy gen delivery (see Chapter 100, Intracranial Hypertension). Strategies include the administration of mannitol to reduce cerebral edema, elevation of the patient's head at a 15-degree to 30-degree incline, prevention of jugular compression, and maintenance of normocapnia. Mechanical ventilation may be necessary if an animal is hypoventilating. Strategies to ensure normoglycemia and prevent hyperthermia should also be employed.
Pharmacology Phencyclidine (PCP) (5% to 90% pure) and ketamine are dissociative anesthetic agents that are used commonly as rec reational drugs. PCP was developed as a human intravenous anesthetic but was found to have too many psychomimetic effects following recovery and is now no longer used for this purpose. Ketamine is a closely related agent that is not used commonly as an anesthetic agent in humans, but is used fre quently in veterinary patients and human pediatric patients. Dissociative anesthetics noncompetitively antagonize N methyl-D-aspartate-operated calcium channels. They also act on the 5-receptor that is believed to mediate the effects of dysphoria and the hallucinations produced by certain opioids. PCP is rapidly absorbed. Clinical signs from the experimental intoxication of a conscious dog with 1 mg/kg IV of PCP included increased motor activity, jaw snapping, tremors, rigidity, nystagmus, seizures, and opisthotonus before death. Cardiovascular signs such as tachycardia and hypertension may be seen along with hyperthermia. In severe cases, respiratory depression can occur. 10
Case Management Patients may be presented following recent ingestion of PCP or may already have clinical signs related to the exposure. If clinical signs are minimal and there are no
Outcome and Prognosis With appropriate supportive care, animals presented with mild clinical signs generally return to a normal state within hours of arrival. Dogs with severe neurologic, cardiovascular, or respiratory dysfunction have a more guarded prognosis, but aggressive and appropriate supportive care will increase patient survival.
SUGGESTED
FURTHER
READING*
Catravas JD, Waters IW: Acute cocaine intoxication in the conscious dog: Studies on the mechanism of lethality, / Pharmacol Exp Ther 217:350, 1981. Experimental study of cocaine administration to conscious dogs. Coadministra tion of diazepam, propanolol, and pimozide, as well as the effect of a decreased ambient temperature, evaluated also. Janczyk P, Donaldson CW, Gwaltney S: Two hundred and thirteen cases of marijuana toxicoses in dogs, Vet Hum Toxicol 46:19, 2004. Large retrospective case series of marijuana in dogs. Rang HP, Dale M M , Ritter J M , Moore PK: Analgesic drugs. In Rang HP, Dale M M , Ritter I M , Moore PK, editor: Pharmacology, ed 5, Edinburgh, 2003, Churchill Livingstone. An excellent review of opioid pharmacology. *See the C D - R O M for a complete list of references.
Chapter 82 RODENTICIDES Andrew J. Brown,
MA,
vetMB, M R C V S ,
DACVECC
• Lori S. Waddell,
DVM, DACVECC
ANTICOAGULANT RODENTICIDES
KEY POINTS • Rodenticide intoxication is common in the dog and seen occasionally in the cat. • The clinician must identify which rodenticide has been consumed. • Unless contraindicated, decontamination techniques should be performed immediately following acute ingestion. • Anticoagulant rodenticide exposure will most commonly cause body cavity or pulmonary parenchymal bleeding. • Treatment of patients with rodenticide-induced coagulopathy consists of fresh frozen plasma to correct the coagulopathy, vitamin K to enable production of active coagulation factors, and supportive care. • Coagulopathy due to anticoagulant rodenticide exposure has an excellent prognosis if treated appropriately. • Bromethalin intoxication leads to cerebral edema and severe neurologic signs, and is associated with a poor prognosis. • Cholecalciferol intoxication results in hypercalcemia. This can lead to soft tissue mineralization, acute renal failure, and cardiac arrhythmias. • Zinc phosphide and strychnine are restricted-use pesticides. Intoxication is therefore uncommon, although secondary intoxication from the ingestion of poisoned rodents is possible.
Pathophysiology and Clinical Signs Animals that consume a sufficient amount of an anticoagulant rodenticide develop clinical signs secondary to a coagulopathy. Activation of coagulation factors II, VII, IX, and X (the vitamin K-dependent factors) requires reduced vitamin K (hydroqui¬ none) for posttranslational γ-carboxylation. Activation of these factors leads to oxidation of reduced vitamin K to inactive epox ide. The enzyme vitamin K reductase catalyzes the conversion of inactive epoxide back to active hydroquinone. Anticoagulation rodenticides antagonize the action of vitamin K epoxide reduc tase, so levels of hydroquinone decrease. Activation of the vita min K-dependent coagulation factors cannot occur (Figure 821) and levels of active factors II, VII, IX, and X decrease. Depleted levels of these factors will result in a coagulopathy and associated clinical signs. Coagulopathies typically are characterized by lung and body cavity bleeding, but bleeding at other sites such as the joints and trachea have been reported. Potentially fatal hemo rrhage in the central nervous system (CNS) is always possible.
INTRODUCTION
Case Management Acute Ingestion
Rodenticide ingestion is a common intoxication in dogs. Anticoagulant rodenticide intoxications are most frequently presented to the emergency veterinarian, but bromethalin and cholecalciferol are also seen. It is essential that the cor rect rodenticide be identified; treatment for the wrong intox ication could lead to the death of the animal. Owners should be encouraged to bring in rodenticide packaging for identifi cation of the active ingredient. Animal Poison Control Cen ter can give excellent advice to aid in identification of the rodenticide as well as treatment of these patients. In most cases the ingestion has been witnessed and the dog or cat is taken immediately to the emergency clinic before the onset of clinical signs. Other animals will present with signs of intoxication. Presenting complaints and clinical signs will vary with the type of rodenticide ingested. Careful questioning of the owner should be performed during the history. Asking, "Is there any rat poison on your property?" rather than "Is there any chance that your dog has gotten into rat poison?" will often result in a more useful response. The goal of treatment depends on how soon after ingestion the animal is presented. Decontamination of the animal to prevent rodenticide absorption is key following acute inges tion, whereas alternative treatment and supportive care are needed for patients that have clinical evidence of intoxication. The mechanism of action, pathologic consequences, and published lethal dose of common rodenticides are shown in Table 82-1.
Animals will most commonly present to the emergency clinician following a recent witnessed ingestion of rodenticide. The most common anticoagulants described in a retrospective study are brodifacoum (80%), diphacinone (18.7%), and chlor¬ ophacinone (2.7%). If a patient presents within 4 hours of ingestion and there is no contraindication to emesis (seizures, depression) then this should be implemented immediately with apomorphine or hydrogen peroxide (dogs). Cats are preferably given xylazine for induction of emesis. Activated charcoal should also be administered to adsorb remaining rodenticide in the gastrointestinal (Gl) tract. Dogs that ingest rodenticide typically are not fastidious eaters and will likely eat a charcoal and dog food slurry mix. Sodium sulfate (250 mg/kg in dogs and cats) or a 70% sorbitol solution (1 to 2 ml/kg) may be administered as a cathartic (see Chapter 77, Approach to Poi soning and Drug Overdose).
1
2
A prothrombin time (PT) should be obtained for all patients 48 hours after ingestion. The PT is a measure of the extrinsic pathway, including factor VII. Factor VII has the shortest half-life of all the vitamin K1-dependent coagulation factors (6.2 hours), and as a result the PT will be prolonged before the activated partial thromboplastin time (aPTT) and before the development of clinical signs. Forty-eight hours is sufficient time for factor VII levels to be depleted, resulting in a prolongation of the PT, but not enough time for depletion of the other factors that would result in clinical bleeding. If the PT is prolonged 48 hours
Table 82-1
Mechanism of Action, Pathologic Consequences, and Lethal Dose of Rodenticides Lethal Dose (mg/kg)
Rodenticide
Class
Mechanism of Action
Pathologic Consequences
Dog
Cat
Brodifacoum
Second-generation hydroxycoumarin
Inhibition of vitamin K epoxide reductase
Clinical bleeding due to coagulopathy
0.2 to 4
25
Bromadiolone
Second-generation hydroxycoumarin
Inhibition of vitamin K epoxide reductase
Clinical bleeding due to coagulopathy
11 to 15
>25
Chlorophacinone
Indandione
Inhibition of vitamin K epoxide reductase
Clinical bleeding due to coagulopathy
NK
NK
Diphacinone
Indandione
Inhibition of vitamin K epoxide reductase
Clinical bleeding due to coagulopathy
0.9 to 8
15
Warfarin
First-generation hydroxycoumarin
Inhibition of vitamin K epoxide reductase
Clinical bleeding due to coagulopathy
20 to 300
5 to 30
Cholecalciferol
Cholecalciferol
Increased gastrointestinal absorption and decreased renal calcium loss
Hypercalcemia leading to acute renal failure
1.5 to 8
NK
Bromethalin
Bromethalin
Uncoupling of oxidative phosphorylation
Neurologic signs from intramyelinic edema
2.5 to 5
0.5 to 1.5
NK, Not known.
Figure 82-1
Mechanism of action of anticoagulant rodenticides.
after ingestion, oral vitamin K (also known as phytonadione) should be started at a dosage of 2.5 mg/kg pO ql2h. Most anti coagulant rodenticides are now second-generation products, and treatment should therefore be continued for 4 weeks. Forty-eight hours after the last dose of vitamin K, a PT should be rechecked to ensure that an adequate course of therapy has been given. If the PT is still prolonged, vitamin K therapy should be continued for an additional 1 to 2 months. One other option is to treat empirically with vitamin K for 4 weeks and then check the PT 48 hours after the last dose. Because of the cost of vitamin K1, checking the PT 48 hours after ingestion generally is preferred. 2
1
Coagulopathies If the patient has evidence of clinical bleeding, presenting complaints may include lethargy, anorexia, dyspnea, hemop tysis, and/or lameness. Physical examination will typically show abnormalities consistent with the location of the bleed. Auscultation may reveal dull lung sounds if there is pleural 3
effusion, or dull heart sounds due to pericardial effusion. Episcleral hemorrhage or subcutaneous hematomas may also be seen. Palpation of the abdomen, kidneys, or joints may be painful. Differential diagnoses for animals with a severe co agulopathy include anticoagulant rodenticide intoxication, disseminated intravascular coagulation (secondary to the sys temic inflammatory response), severe thrombocytopenia, hemophilia, and liver failure. A minimum database may be consistent with acute hemor rhage (low total solids with low or normal packed cell vol ume). Blood gas analysis may reveal a metabolic acidosis (rule out increased lactate secondary to decreased perfusion) and an elevated alveolar-arteriolar gradient if there is pleural or parenchymal hemorrhage. A blood smear should be evalu ated for erythrocyte morphology and adequacy of platelets. Patients with anticoagulant rodenticide intoxication are often severely thrombocytopenic; this is thought to be a result of profound consumption secondary to the massive hemorrhage that can occur. Every patient with evidence of severe bleeding should be evaluated for objective measures of coagulation. Anticoagulant rodenticides will induce a prolongation of the PT before the aPTT. The aPTT will become prolonged as factors II, IX, and X are depleted and from consumption of other factors once bleeding has occurred. The activated clotting time also reflects the intrinsic pathway and will therefore not be prolonged until factor depletion is severe. If a patient has a greater elevation in the PT relative to the increase in aPTT, then anticoagulant rodenticide intoxica tion is likely. Similarly, anticoagulant rodenticide intoxica tion is unlikely in a patient with a severe prolongation of the aPTT and a mild prolongation of the PT. If both the PT and the aPTT are severely prolonged, then a diagnosis of anticoagulant rodenticide intoxication is more difficult. The PIVKA (proteins induced by vitamin K antagonism) was previously thought to be a more specific test for diagnosing anticoagulant rodenticide intoxication. However, it can be elevated with other disease processes, particularly severe liver disease and/or malabsorption and maldigestion syndromes. One study found that performing a PT and a PIVKA sim ultaneously added no additional diagnostic information. 4
Definitive diagnosis is possible with anticoagulation rodenti cide screens utilizing spectrophotometry (available at veteri nary laboratories), which can quantitatively demonstrate the presence of the toxin in whole blood. The concentration of rodenticide detected does not correspond with the severity of the change in PT, aPTT, or platelets. Although it takes 3 to 5 days to obtain results of this screen, the clinician can obtain a definitive diagnosis of anticoagulant rodenticide intoxication and learn the type of rodenticide ingested. This is especially use ful when the owner is adamant that there has been no exposure to rodenticide. Unless the patient is receiving Coumadin thera peutically, there is no possibility of a false-positive test result. Radiography may reveal loss of body cavity detail, and effusion may be seen on thoracic and abdominal ultrasonog raphy. If no pleural hemorrhage is present, a patchy to dif fuse pulmonary alveolar to interstitial pattern consistent with alveolar hemorrhage may be noted. Treatment of the symptomatic patient is based on correcting the coagulopathy, providing exogenous vitamin K1 for regener ation of coagulation factors, and supportive care. Clotting fac tors in the form of fresh frozen plasma (typically 10 to 20 ml/ kg) or fresh whole blood should be administered to the patient until clotting times have normalized and the hematocrit is greater than 24%. Dyspneic patients will require oxygen therapy, and the hemorrhagic pleural effusion may become so severe that they require thoracentesis. This ideally should be performed after correction of the coagulopathy, but will depend ultimately on the clinical status of the animal. Pericardiocen tesis may also become necessary in animals with hemorrhagic pericardial effusion, but only in extremely critical cases. Exoge nous vitamin K1 should be administered at an initial dosage of 5 mg/kg SC using a small-gauge needle. There is a high fre quency of anaphylaxis following intravenous administration of vitamin K1, so this route is not recommended. There is better bioavailability of vitamin K1 when ingested, so therapy should be switched from subcutaneous to the oral route as soon as pos sible. Oral vitamin K should be administered at 2.5 mg/kg PO with food ql2h for 4 weeks, and a recheck PT performed 48 hours following cessation of therapy (as described earlier in the section Acute Ingestion). Supportive care, including cor recting the anemia and supplying oxygen therapy, will be neces sary while the blood is resorbed and clinical signs resolve. 2
Outcome Patients with a witnessed anticoagulant rodenticide ingestion that are rapidly treated by induction of emesis, activated char coal, and a PT performed 48 hours after ingestion have an excellent prognosis. Those patients with a severe coagulopathy and clinical evidence of bleeding also carry an excellent prog nosis when treated aggressively and appropriately. ' Of all the causes of a coagulopathy, anticoagulant rodenticide intoxica tion has the best prognosis. In an abstract, 98.6% (74 of 75) of dogs that had a positive anticoagulant rodenticide screen sur vived, emphasizing the importance of a timely and accurate diagnosis and treatment. 2 5
2
CHOLECALCIFEROL Pathophysiology and Clinical Signs Intoxication from cholecalciferol rodenticide results in hyper calcemia and associated clinical signs. Following ingestion of
the bait, cholecalciferol (vitamin D ) is rapidly absorbed and transported to the liver by specific binding proteins. It is first converted within the hepatocytes to 25-hydroxycholecalciferol and then to 1,25-dihydroxycholecalciferol within the kidney, which increases G l absorption of calcium, reduces renal excre tion of calcium, and increases resorption of calcium from the bone. The primary pathologic effects of the hypercalcemia are acute renal failure and cardiac arrhythmias (see Chapter 56, Calcium Disorders). Clinical signs can develop between 4 and 36 hours after ingestion. Initial signs are related to the hypercalcemia, and include polyuria and polydipsia (through inhibition of ADH), lethargy, anorexia, and vomiting. Acute renal failure develops secondary to the hypercalcemia. Dehydration quickly ensues because of decreased fluid intake and increased G l and renal losses. Cardiac arrhythmias will often be present because of mineralization of the heart or changes in the ratio of intracellu¬ lar-to-extracellular ion concentrations and an increase in the depolarization threshold. 3
Case Management Acute Ingestion Many patients present for treatment following recent wit nessed ingestion of the rodenticide. As with acute anticoag ulant ingestion, G l decontamination strategies should be performed unless there is a contraindication to doing so (see Chapter 77, Approach to Poisoning and Drug Over dose). A serum calcium level should be checked 48 hours after acute ingestion.
Hypercalcemia In patients with hypercalcemia, cholecalciferol intoxication should always be considered and owners questioned accord ingly. Other differential diagnoses for increased ionized calcium levels include hypercalcemia of malignancy, hypoadrenocorti cism, chronic renal failure, primary hyperparathyroidism, osteolytic bone disease, and ingestion of vitamin D ointments (psoriasis creams) or supplements. Physical examination may reveal depression, weakness, dehydration, and cardiac arrhyth mias. Blood work will reveal severe hypercalcemia (total and ionized), and hyperphosphatemia. As the toxicosis progresses, hyperproteinemia, azotemia, hyperkalemia, and metabolic aci dosis may also develop. Histopathology commonly reveals dif fuse soft tissue mineralization. Therapy for hypercalcemic patients is directed toward reducing blood calcium levels and preventing acute renal failure. Intravenous isotonic saline (0.9% NaCl) should be administered to correct dehydration and provide moderate volume expansion. The high sodium concentration of 0.9% NaCl (154 mEq/L) will induce a calciuresis. Renal cal cium loss will also be enhanced by furosemide, glucocorti coids, and salmon calcitonin. However, furosemide should be administered only after fluid deficits are corrected and glucocorticoids given only after other diagnoses of hypercal cemia have been excluded. In addition to inducing a calciur esis, salmon calcitonin inhibits osteoclast activity and thus reduces the resorption of calcium from bones. However, there is a risk of anaphylaxis with salmon calcitonin therapy. Pamidronate disodium is a bisphosphonate that also inhibits osteoclastic bone resorption and reduces calcium concentra tions within 48 hours of administration (see Chapters 56 and 135, Calcium Disorders and Acute Renal Failure, respectively). 6
Outcome Dogs with cholecalciferol intoxication and mild to no azote mia have a fair to good prognosis with aggressive medical therapy; in four published case reports, four out of six dogs survived. Three cats with hypercalcemia associated with cholecalciferol toxicity were reported to have survived in one published case series. Once hypercalcemia and acute renal failure have developed, prognosis is poor. Rapid and aggressive therapy to reduce the calcium concentration and prevent soft tissue mineralization will lead to a better chance of survival. 6-9
10
12
Outcome
BROMETHALIN Pathophysiology and Clinical Signs The toxic effects of bromethalin are due to the uncoupling of oxidative phosphorylation with a resultant decrease in aden osine triphosphate (ATP) production. This decrease in cellu lar energy will lead to an inability of the ATP-dependent membrane transport pumps to function. The nonfunction ing Na ,K -ATPase transport pump will lead to a buildup of intracellular sodium, which will cause water to move into the cell. Cells of many organs can be affected, but clinical signs are predominantly associated with cerebral edema and the resultant elevated intracranial pressure. Clinical signs and their onset vary with the dose ingested. Ingestion of doses larger than the L D (the dose of the drug that will cause death in 50% of experimental animals; dogs 4.7 mg/kg and cats 1.8 mg/kg) results in severe muscle tre mors, hyperthermia, extreme hyperexcitability, and focal or generalized seizures within 24 hours. Clinical signs with lower doses may manifest between 1 and 3 days; signs include hind limb ataxia, paresis or paralysis, and CNS depression. +
only a theoretical benefit, glucocorticoid use in animals with bromethalin intoxication cannot be recommended. Unfortunately, a definitive diagnosis can be made only postmortem. Histopathologic examination of the cerebrum, cerebellum, brainstem, and spinal cord may support a diag nosis of bromethalin intoxication. Diffuse white matter vacuolation (spongy degeneration) with microgliosis is described consistently. Gas chromatography with electron capture can be used to detect bromethalin in samples of kid ney, liver, fat, or brain.
+
5 0
Case Management Acute Ingestion Animals that are presented following acute ingestion require immediate and aggressive decontamination. This will include emesis induction or general anesthesia, intubation, and gas tric lavage if the patient is unable to protect its airway and is at risk of aspiration. Repeated doses of activated charcoal should be administered (3 to 5 g/kg q6-8h) for 48 hours because of enterohepatic circulation of the toxin. Sodium sulfate (250 mg/kg in dogs and cats) or a 70% sorbitol solu tion (1 to 2 ml/kg) may be administered as a cathartic (see Chapter 77, Approach to Poisoning and Drug Overdose).
Neurologic Complications Treatment of animals with neurologic signs is based on sei zure control and supportive care. Attempts to maintain cere bral perfusion pressure and oxygen delivery should be made. These strategies include the administration of mannitol to reduce cerebral edema, elevation of the head at a 15-degree to 30-degree incline, prevention of jugular compression, and maintenance of normocapnia. Strategies to ensure normogly¬ cemia and prevent hyperthermia should also be considered. Treatment of bromethalin-induced neurologic signs with glu cocorticoids has commonly been cited. However, there is no evidence supporting this recommendation. Considering the known side effects of steroids, including hyperglycemia, and 11
Animals with severe signs have a very poor prognosis. To the authors' knowledge, there are no reports of dogs ingesting more than 5 mg/kg bromethalin, developing neurologic signs, and surviving. However, there is a report of a dog that survived after ingesting a lower dose of bromethalin (70%), overwhelming the adaptive response. A study was performed comparing the clinical signs of dogs subjected to inhaled carbon monoxide with dogs bled to a hematocrit of approximately 25% and subsequent volume replacement with crystalloid and colloid fluids or 1,7,18
Direct Mechanisms Direct cellular toxicity can be due to carbon monoxide bind ing to the heme proteins myoglobin and cytochrome a in the electron transport chain of mitochondria. Carbon mon oxide binds to myoglobin in cardiac and skeletal muscle, potentially causing decreased contractile function of the muscle cells. Oxygen has a greater affinity for myoglobin than carbon monoxide, however, and pathologic effects of carbon monoxide binding to myoglobin are thought to be minimal unless there is associated tissue hypoxia. Tissue hypoxia may be caused by the effects of carbon monoxide on oxygen delivery, depression of the CNS with resultant apnea, and decreased effective cellular respiration due to binding of carbon monoxide to cytochrome a3 Myocardial depression occurs as a direct result of mitochondrial dysfunc tion and may result in decreased cardiac output, contributing further to tissue hypoxia. " 3
4,20
7
2
Indirect Mechanisms There is a growing body of evidence demonstrating indirect mechanisms through which carbon monoxide toxicity results in changes that lead to cellular toxicity, particularly within the brain. These changes include sequestration of leuko cytes, increased nitric oxide (NO) production, reperfu¬ sion injury, lipid peroxidation, and direct neurotoxicity from carbon monoxide activity as the a neurotransmitter. It has been demonstrated experimentally that carbon mon oxide activates polymorphonuclear leukocytes (PMNLs), resulting in diapedesis and leukoencephalopathy. The activated neutrophils can contribute to tissue damage by producing reactive oxygen species, releasing proteolytic enzymes, and obstructing capillaries as the PMNLs accumulate. NO levels increase during exposure to high levels of carbon monoxide as a result of increased N O release from platelets and production in neuronal tissue. N O may have both a protective and dam aging role in carbon monoxide toxicity. NO decreases PMNL adhesion to endothelium, and a transient rise in nitric oxide may protect brain tissue initially, although tailing levels may be responsible for the delayed neurologic sequelae seen in some cases. The combination of N O and superoxide (one of the reactive oxygen species produced in activated PMNLs and other cells during reperfusion), however, results in peroxynitrite pro duction, a key player in lipid peroxidation. Lipid peroxidation is a process characterized by conversion of membrane lipids to reactive species and propagation of oxidative damage, culmi nating in severely damaged or destroyed cell membranes. Thus elevated carbon monoxide levels set up a chain reaction resulting in direct tissue damage, reperfusion injury, lipid per oxidation, cellular dysfunction, and ultimately cell death within the brain. ' 7
7,21,22
1,7
1,7,23
6,7
7
24
21
7,22
21
24
24
Figure 87-2 Oxygen saturation curves of hemoglobin, carboxyhemoglobin, and myoglobin. Note the leftward shift of the carboxyhemoglobin curve denoting a decreased release of oxygen to the tissues. (From Berne RM et al, editors: Physiology, ed 5, St Louis, 2005, Mosby.)
7 23
The role of endogenous carbon monoxide as a neurotrans mitter and the potential implications of exogenous carbon monoxide overstimulating certain neural functions are being explored. An altered ratio of carbon monoxide and N O may exaggerate neurologic malfunction. 6,7
7
1,2
incidence of DNS varies but is approximately 10% to 30%. Incidence of DNS increases to 25% to 50% in patients who suf fered loss of consciousness or with COHb levels over 25%. Approximately 50% to 75% of humans who suffer from DNS recover within 1 year. ' Risk factors for DNS include age (older), duration of unresponsiveness, and history of illness. ' Hypoxia alone is considered unlikely to cause these changes. ' The precise mechanism of DNS is unclear, but contributing factors are thought to include a compromise of autoregulation of brain blood flow resulting in hypoxia, fol lowed by oxidative damage and lipid peroxidation. ' ' Delayed neurologic sequelae have been reported in animals following smoke inhalation and carbon monoxide intoxication. ' ' Clinical signs range from an ataxic gait to inability to ambulate, depressed to stuporous mentation, and dysacousis (deafness). ' One retrospective analysis of 11 dogs with neurologic signs associated with smoke inhala tion noted a 46% occurrence of initial improvement in clin ical signs followed by acute recurrence of neurologic dysfunction 2 to 6 days after the insult. 25
1 2
2 10
Narcotizing Effect
7 10
The mechanism of CNS depression in patients with carbon monoxide exposure is still essentially unknown. It has been established experimentally that there is a decrease in oxygen consumption by the brain, an observation thought to be associated with the narcotizing effect of carbon monoxide. Cerebral vasodilation due to elevated carbon monoxide levels may cause cerebral hyperemia, increased intracranial pressure, and edema. Carbon monoxide affects neural func tion through its actions as a neurotransmitter and causes derangements in dopaminergic and serotonergic neural pathways. These changes are theoretically involved in the mentation changes associated with carbon monoxide exposure. 18
1
7
1 2 7
2 10 26
2 10
26
DIAGNOSIS CLINICAL SIGNS Initial Clinical Signs The clinical signs of carbon monoxide toxicity initially reflect the gas's effect on the CNS. These are lethargy, depres sion, headache, confusion, syncope, seizures, unconscious ness, and death. ' Concurrent signs reported at the onset of toxicity also include tachypnea, tachycardia, nausea, vomiting, and cherry red mucous membranes. ' Arrhyth mias may occur as a result of myocardial toxicity. The clas sic cherry red mucous membranes are indicative of the color of COHb and reported to occur only rarely in humans. ' Hyperemic mucous membranes were reported in 7 of 24 dogs and 2 of 17 cats in retrospective analyses of smoke inhalation. ' Unfortunately, COHb levels in these cases were not available, making it difficult to determine whether or not hyperemic mucous membranes represented elevated COHb or vasodilation from other causes. Hypotension is reported to occur rarely in experimental cases of carbon monoxide toxicity. If carbon monoxide toxicity occurs concurrently with smoke inhalation, symptoms may include those refer able to direct respiratory system damage such as dyspnea, cyanosis, and upper airway obstruction. 1 2
1 2
1
1 2
8 9
23
Severity of signs ranges from mild to severe and does not correlate consistently with COHb levels. Generally, however, COHb levels over 15% result in overt signs of toxicity such as tachypnea and headache, over 30% in neurologic dysfunc tion, and levels 50% or more typically result in loss of con sciousness that can progress to apnea and death. Increased duration of exposure to elevated levels of carbon monoxide contributes to morbidity. 1
4
1
Initial sign of carbon monoxide toxicity such as depression, tachypnea, and tachycardia can be nonspecific, particularly if they are mild. Historical information and clinical suspi cion are therefore vital to the diagnosis in small animals.
Co-oximetry Definitive diagnosis of carbon monoxide toxicity involves direct measurement of C O H b levels. This is performed with a co-oximeter, a machine used to measure hemoglobin content, oxygen saturation, percentage of COHb, and per centage of methemoglobin. Arterial samples are ideal for analysis of acid-base status and partial pressure of oxygen, but venous samples are adequate for determination of C O H b levels. In some cases, particularly if the animal received supple mental oxygen during transport, the COHb level may have fallen and may even be normal at the time of presentation. Diagnosis in these cases is based on clinical signs and a his tory suggestive of carbon monoxide toxicity. 2
1
Pulse Oximetry It has been well documented that pulse oximetry is inaccu rate in cases of carbon monoxide toxicity and will be falsely elevated, a phenomenon known as the pulse oximetry gap. ' ' The principle of pulse oximetry is based on mea surement of the ratio of light absorbed by tissues at a red wavelength (660 nm) to that at an infrared wavelength (940 nm). This absorption ratio reflects the arterial oxygen saturation through calibration curves that have been previ ously established. These calibration curves, however, do not account for variant hemoglobin species such as COHb and measure only oxyhemoglobin and deoxyhemoglobin. COHb and oxyhemoglobin have similar light absorptions at the red wavelength and are therefore indistinguishable by the pulse oximeter. However, the COHb cannot achieve an oxygen saturation of greater than 50%, resulting in a falsely normal pulse oximetry reading when the actual percentage of oxyhemoglobin is low. The pulse oximetry 1 2 27
27
27
Delayed Neurologic Sequelae A syndrome known as delayed neuropsychiatric syndrome (DNS) has been described in humans who have suffered car bon monoxide toxicity. Clinical signs develop 3 to 240 days following the toxic episode and include cognitive and per sonality changes, incontinence, dementia, parkinsonism, gait disturbance, hearing loss, and psychosis. ' ' The reported 1 2 10
27
gap is defined as the difference between percentage of satura tion measured by a pulse oximeter and the actual oxyhemo globin saturation. A retrospective analysis of human patients with carbon monoxide toxicity demonstrated a correlation between the pulse oximetry gap and COHb levels. There fore, if a blood gas analyzer that uses spectrophotometry is available to measure oxygen saturation, the percentage of COHb can be approximated throughout treatment with repeated measurements of oxygen saturation using a blood gas machine and routine pulse oximetry. 27
and duration of hypoxia has become the goal of treatment to prevent DNS. Hyperbaric oxygen (HBO) therapy is used in severe human cases of carbon monoxide toxicity because it may decrease the incidence of D N S . H B O is useful because it increases the amount of dissolved oxygen in the blood, so that the half-life of carbon monoxide is shorter than with normobaric oxygen therapy, and less carbon monoxide binds to heme proteins because the oxygen competes for binding sites. The half-life of carbon monoxide when breathing hyperbaric oxygen at 2 atmospheres of pressure is only 15 to 30 minutes. Data on the beneficial effects of HBO are conflicting, and it may offer no significant benefit over normobaric oxygen therapy. ' A prospective, randomized clinical trial comparing the effects of hyperbaric and normobaric oxygen therapy demonstrated a reduced frequency of occurrence of DNS by 46% in patients treated with hyperbaric oxygen. 2
25
25
1
Blood Gas Analysis
1 25
Blood gas analysis is useful in cases of carbon monoxide toxicity to evaluate patients for metabolic acidosis, suggesting decreased perfusion, a respiratory acidosis or alkalosis indicative of hypo ventilation or hyperventilation, respectively, and arterial partial pressure of oxygen (PaO ) measurements. One must keep in mind, however, that the oxygen-hemoglobin dissociation curve has been shifted down and to the left (see Figures 87-1 and 87-2), so PaO does not reflect typical oxyhemoglobin levels but rather the amount of oxygen dissolved in the blood. One of the main indications for measuring PaO levels in these patients is to assess the efficacy of oxygen therapy in maintaining supranormal PaO levels to decrease the half-life of carbon monoxide (see Oxygen Therapy). Lactate levels may also be useful in asses sing tissue oxygenation. 2
2
2
2
Neurologic Evaluation Once the diagnosis of carbon monoxide toxicity has been established, a full baseline neurologic examination and fre quent reevaluation should be performed to determine the appropriate aggressiveness of treatment (see Treatment) and track progression of neurologic sequelae.
25
In veterinary patients, H B O is not a practical option. Therefore therapy with 100% oxygen to maximize PaO using an oxygen cage or intubation and mechanical ventila tion in those with significant pulmonary pathology is recommended until the COHb is normal (20%) can cause cellular hypoxia and shock. • Clinical methemoglobinemia occurs when erythrocyte defense systems are overwhelmed and cannot reduce metHb back to hemoglobin fast enough to keep up with the oxidative damage MeTHbreductase deficiency is a rare condition in small animals that leads to inefficient reduction of metHb in the body, but may or may not lead to clinical signs of methemoglobinemia. • Substances that can cause clinical methemoglobinemia in small animals include acetaminophen, topical benzocaine formulations, phenazopyridine (a urinary tract analgesic), nitrites, nitrates, and skunk musk. • Many substances that cause methemoglobinemia can also cause the body to form clinically significant numbers of Heinz bodies (HzBs), aggregations of denatured hemoglobin that can lead to red blood cell destruction and anemia. • Treatment for methemoglobinemia involves augmentation of endogenous glutathione with N-acetylcysteine (NAC), antioxidant therapy, increased clearance or decreased metabolism of a toxin, blood transfusion if required, and supportive care. 3+
V M D , DACVECC
electron to or from another molecule. Protective mechanisms that prevent or reverse oxidative damage include proteins that act as free radical scavengers and reducing agents that can remove the unpaired electron from an oxidized molecule. Erythrocytes are especially vulnerable to oxidative damage because they carry oxygen, are exposed to various chemicals in plasma, and have no nucleus or mitochondria. ' The lack of cellular organelles renders the membrane the deformability necessary to navigate capillary beds, but results in a cell that is incapable of producing proteins or performing efficient energy production. They therefore have a finite number of cell proteins and are reliant on anaerobic respira tion to generate energy and reducing agents. Oxidants con tinuously generated in vivo include hydrogen peroxide ( H O ) , superoxide free radicals ( 0 ) , and hydroxyl radi cals ( O H ) (Box 88-1). Hemoglobin can undergo autoox¬ idation as an electron is pulled off the hemoglobin onto an oxygen molecule, resulting in the generation of metHb and O . Free radicals may also extract electrons by oxidizing deoxyhemoglobin. In contrast oxidant toxins can donate an electron to oxyhemoglobin, creating metHb and hydro gen peroxide (Box 88-1). 1 3
1
1
-
2
2
2
1,3,4
-
1 , 3
2
3
3
INTRODUCTION Hemoglobin, the molecule that confers gas-carrying capacity to erythrocytes, is composed of four polypeptide chains (globins); each is attached to a heme molecule. ' Heme is made up of a tetrapyrrole with a central iron molecule. ' The iron molecule must be maintained in the ferrous (Fe ) state in order for the hemoglobin to bind oxygen. " MetHb is an inactive form of hemoglobin created when the iron molecule of hemoglobin is oxidized to the ferric (Fe ) state because of oxidative damage within the red blood cell. It gives the red blood cell a darker brown color and results in dusky cyanotic or chocolate-colored mucous membranes. ' MetHb increases the affinity for oxygen in the remaining ferrous moieties of the hemoglobin molecule, decreasing release of oxygen to the tissues and shifting the oxy hemoglobin dissociation curve to the left. ' Approximately 0.5% to 3% of hemoglobin is oxidized to metHb q24h in nor mal animals. There are numerous mechanisms to prevent oxidative injury in erythrocytes, however, and metHb is reduced back to functional hemoglobin rapidly such that metHb accounts for less than 1% of total hemoglobin in normal adults. ' Exogenous substances that overwhelm the antioxidant defenses, or a congenital or acquired abnormality within the adaptive response, can result in elevated levels of metHb. 1 2
1 2
2+
1
4
3+
1-4
1 2
5 6
2-4
2 3
PATHOPHYSIOLOGY Oxidation in the Erythrocyte Reactive species derived from oxygen can cause oxidative dam age within the body by transferring or extracting an unpaired
Despite their limited capacity to produce energy and pro teins, erythrocytes have many mechanisms to protect them selves from oxidative damage. These include superoxide dismutase, catalase, glutathione peroxidase, glutathione, and metHb reductase (cytochrome b reductase) (see Box 88-1). Glutathione is a tripeptide produced in erythrocytes and com posed of glutamic acid, cysteine, and glycine and contains an easily oxidizable sulfhydryl (SH) group. It is a powerful antiox idant that operates as a free radical scavenger. Reducing agents such as nicotinamide adenine dinucleotide phosphate (NADPH) and nicotinamide adenine dinucleotide (NADH) are instrumental in reducing oxidized glutathione and metHb back to functional molecules (see Box 88-1). 1,3
5
3
1,3,4
Heinz Bodies Heinz bodies (HzBs) are aggregates of denatured precipi tated hemoglobin within erythrocytes that form as hemoglo bin that has undergone oxidative damage is metabolized. Oxidation of the SH groups of hemoglobin, either through autooxidation, free radical extraction of an electron, or oxi dant toxin donation of an electron, causes conformational changes in the globin chains that results in precipitation of the denatured globin. Aggregates of denatured globin and metabolized metHb clump into HzBs and continue to coalesce until visible, pale structures can be seen within the red blood cell cytoplasm (see Color Plate 88-2, B). The com plete sequence of events necessary for HzB formation is still being elucidated, but it is thought that formation of metHb is necessary for the development of HzBs. Feline hemoglo bin is more susceptible to oxidative damage because it has 1-4
3,4
4
3
Box 88-1
products, phenazopyridine (a urinary tract analgesic) products, nitrites, nitrates, skunk musk, and metHb reductase defi ciency. ' Agents that have resulted in metHb in humans and may be used in veterinary medicine include dapsone, nitroglyc erin, and nitroprusside. Regardless of the toxic agent, metHb is often formed within minutes to hours of exposure. Sub stances that cause metHb production are likely to cause HzB production and potentially hemolytic anemia in the days fol lowing the exposure. Numerous substances that cause an increase in HzBs are thought to cause some degree of methemo globinemia, but associated clinical signs are typically attribut able to a hemolytic anemia secondary to the HzBs rather than the metHb. These substances include Allium plants (onions and garlic), propylene glycol, zinc, methylene blue, crude oils, naphthalene (ingredient in moth balls), repeated use of propofol in cats, phenothiazine, phenylhydrazine, methionine (a urinary acidifier) in cats, menadione (vitamin K ) in dogs, and copper (particularly in animals with copper storage dis eases). ' Depending on the individual patients' metabolism, the dose, and the period over which it was ingested, these sub stances will cause varying degrees of HzB formation, and ane mia does not usually occur until HzB formation is moderate to severe.
Chemical Reactions Resulting in Free Radical Formation, Their Removal, and Methemoglobin Reduction
10
3 4
11
Free Radical Formation -
Superoxide anion: O + e Ferric production: F e + H O
-
O
2
2
2 +
2
Fe
2
3 +
+ OH- + O H
Mechanisms of Free Radical Removal -
+
Superoxide dismutase reaction: 2O + 2 H —> H O + O Catalase reaction: O + H O -> O + OH + O H 2
2
-
2
2
-
2
2
2
2
Glutathione Peroxide and Glutathione Reductase Reactions H O + 2 G S H ^ 2 H 0 + GSSG GSSG + H + N A D P H ^ 2 G S H + N A D P + 2
2
2
+
12
9
Methemoglobin Reduction MetHb-Fe
3+
W HbFe
2 +
+ 0
3
2
N A D H / A > NAD+
3 4
Modified from Engelking LR: Textbook of veterinary physiological chemis try, Jackson Hole, WY, 2004, Teton NewMedia. CAT, Catalase; GP, glutathione peroxidase; GR, glutathione reductase; GSH, glutathione; GSSG, oxidized glutathione; HbFe , ferrous hemo globin; MR, methemoglobin reductase; N A D , nicotinamide adenine dinucleotide; NADH, nicotinamide adenine dinucleotide; NADPH, nic otinamide adenine dinucleotide phosphate; SOD, superoxide dismutase. 2+
Acetaminophen
eight SH groups on the globin part of the molecule rather than four, as the canine counterpart does. ' ' ' HzBs have an affinity for membrane proteins. Binding of a HzB to these proteins causes disruption of anion transport, decreased membrane deformability, and aggregations of mem brane protein complexes that may act as autoantibodies. ' Numerous HzBs can disrupt the membrane sufficiently to result in "ghost" cells, empty red blood cells with just a cell membrane and HzB remaining, which are associated with oxidationinduced intravascular hemolysis. More commonly, however, erythrocytes that have undergone oxidative damage are removed by the mononuclear phagocyte system, particularly within the spleen. Rigid cells or cells with large HzBs protruding from the surface will become lodged in the narrow openings between splenic endothelial cells and undergo phagocytosis by the splenic macrophages. In most animals, the spleen can perform pitting functions and remove the HzBs from the erythrocyte. Feline spleens, however, have an ultrastructural variation and impaired ability to catch and remove oxidized red blood cells. As a result of the combination of more SH groups available for oxidation on feline hemoglobin and the unique spleen in this species, healthy cats often have notable HzBs in circulation (with reports up to 96%). The reasons that some cats undergo hemolysis with HzB percentages lower than 96% but other cats will have no clin ical signs with most of their erythrocytes affected are still unknown. ' It is clear, however, that various agents induce oxi dative damage in different ways and to varying extents, and the nature of the damage, the amount of affected hemoglobin within a cell, and individual variations seem to determine whether a given cat will develop clinically significant hemolysis. 3 4 7 8
4
4 7
7
7
3
3
9
9
7 9
7
SPECIFIC CAUSES OF ERYTHROCYTE OXIDATION Methemoglobinemia has been documented in small animals in association with acetaminophen ingestion, topical benzocaine
Acetaminophen (Tylenol) (see Chapter 79, Acetaminophen) is an analgesic and antipyretic drug that is used widely in human medicine. ' It is present in many pain and cold medications. Although considered safe in humans, this drug can be toxic to small animals, causing acute hepatoxicity in dogs and life-threatening methemoglobinemia in cats. ' Most phenacetin, a component of over-the-counter drug for mulations, is metabolized rapidly to acetaminophen and could result in toxicity in small animals. A dose of as little as 10 mg/kg of acetaminophen is toxic for cats, and 150 to 200 mg/kg is toxic for dogs. Unfortunately, the vast major ity of acetaminophen toxicities in small animals are due to intentional administration by the owner in an attempt to treat pain or malaise in their pets. ' Acetaminophen is metabolized in the liver via one of three pathways: (1) it is conjugated to a sulfate compound by a phe nol sulfotransferase, (2) it is conjugated to a glucuronide com pound by a uridine diphosphate-glucuronosyl transferase, or (3) it can be transformed and oxidized by the cyto chrome P-450 system which converts it to the reactive inter mediate N-acetyl-P-benzoquinone-imine (NAPQI). The toxicity of acetaminophen is due to N A P Q I . ' The glucuro nide and sulfate conjugations are nontoxic and are excreted in the bile and urine in most species other than the cat. ' Glutathione reacts with NAPQI to form a nonreactive mole cule, mercapturic acid, which is excreted in the urine. Low doses of acetaminophen are readily metabolized to nontoxic products, but higher doses can overwhelm the sulfate and glu curonide conjugate systems of the liver and deplete glutathione stores. Ultimately, the toxic metabolite NAPQI builds up and unmetabolized acetaminophen accumulates. Thus the half-life of acetaminophen becomes longer with higher dosages. 5 8
5
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5
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8
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Cats are very limited in the degree of glucuronide conjuga tion that they can perform, because they lack a specific form of the enzyme glucuronyl transferase needed to conjugate acet aminophen. ' Unfortunately, cats also have a somewhat lim ited sulfate binding capacity, so glutathione stores are depleted and NAPQI accumulates. ' Cats are estimated to have one tenth of the capacity to eliminate acetaminophen compared to 5 8
5 8
5
dogs. NAPQI oxidizes hepatic proteins, resulting in hepatocel lular damage. Once glutathione stores are depleted in erythro cytes, NAPQI causes intracellular oxidative damage, converting hemoglobin to metHb and oxidizing SH groups on hemoglobin, leading to the formation of HzBs. Methemoglobinemia becomes overt when metHb reductase and necessary reducing equivalents (i.e., NADH) become depleted in erythrocytes. Fol lowing the acute episode of metHb production, HzBs begin to form and aggregate into larger structures, eventually causing enough changes in the erythrocyte to trigger hemolysis. Although cats tend to develop metHb and HzB anemia and dogs undergo a significant hepatic insult with acetaminophen toxic ity, there is much individual variation, and many animals have evidence of both. The prognosis for acetaminophen toxicity is guarded, with evidence in both veterinary and human literature that time from ingestion to treatment is the most important fac tor in determining morbidity and survival.
Box 88-1) and therefore have elevated blood levels (18% to 41%), mild to moderate cyanosis of the mucous membranes (present in 100% of cases), and may suffer from exercise intolerance (present in 0.6 n m / L i n dogs; >0.3 n m / L in cats). Antibodies are detectable in 80% to 90% of dogs with acquired disease. Intercostal muscle biopsy may also be used to identify acetylcholine receptor antibodies at the N M J . If a more immediate diagnosis is necessary, edropho n i u m response testing may be performed. Edrophonium (0.1 to 0.2 mg/kg IV) results i n dramatic improvement i n gait for 1 to 2 minutes i n some animals with myasthenia gravis (anecdotal evidence suggests that improve ment is rarely seen i n cases of acute fulminating myasthenia gravis). Pretreatment with atropine (0.02 mg/kg IV) is recom mended to decrease salivation, defection, urination, bronchial secretion, and bronchoconstriction that may occur following edrophonium administration. The animal may require oxygen and endotracheal intubation i f severe dyspnea develops. Electrodiagnostic testing may also be performed. A 10% or greater decremental response o f the fourth or fifth compound action potential recorded from the interosseous muscle following repetitive stimulation of the tibial or ulnar nerve at 3 H z may be found. 22
23
Animals affected with generalized myasthenia gravis may be treated with oral pyridostigmine bromide (0.2 to 2 mg/kg q8-12h; I V infusions of 0.01 to 0.03 mg/kg/hr have also been used). Intramuscular neostigmine b r o m i d e or methylsulfate (0.04 mg/kg q6-8h) may be given to animals w i t h significant dysphagia and regurgitation. A l o w dosage is begun and titrated upward over 2 to 3 days u n t i l clinical signs resolve or signs of overdose occur (bradycardia, diar rhea, salivation, dyspnea, miosis, and recurrence of weak ness). W h e n these signs occur, the dosage is decreased u n t i l they are no longer present. The animals should be kept w a r m and exercise l i m i t e d . A l t h o u g h appendicular muscle weakness frequently resolves w i t h this care, pharyn geal, laryngeal, and esophageal dysfunction may continue for weeks.
In animals with focal and generalized myasthenia gravis i n w h o m dysphagia and megaesophagus are marked, p y r i dostigmine or neostigmine is given; however, management o f these patients must include feeding the animal from a raised height and keeping the head elevated for 10 minutes afterward to facilitate passage o f food into the stomach. Frequently a gastrostomy tube is necessary to provide nutri tional support until dysphagia and regurgitation resolve. Frequent auscultation and radiographs o f the thorax are recommended to determine whether aspiration pneumonia is present. If so, a transtracheal wash is performed and broad-spectrum antibiotics are given (see Chapter 23, A s p i ration Pneumonitis and Pneumonia). Aminoglycoside anti biotics should be avoided (see Aminoglycoside Intoxication later i n this chapter). Treatment o f acquired myasthenia gravis w i t h prednisone is controversial because it may result i n a rapid worsening o f clinical signs i n affected humans. In addition, the i m m u n o suppressive effects o f steroid therapy may lead to rapid respiratory deterioration i n patients w i t h aspiration pneu monia. Anecdotally, the addition o f prednisone to neo stigmine improves pharyngeal dysfunction sooner than cholinesterase inhibitors alone. A starting dosage o f 0.5 mg/kg/day increased to 2 mg/kg q24h over 1 week has been suggested. Prednisone should be started only i n the hospital, where the animal can be monitored for sudden deterioration and for aspiration pneumonia. Additionally, treatment with azathioprine (2 mg/kg P O q l 2 - 2 4 h , decrease dosage after 3 to 6 months) and mycophenolate mofetil (10 to 20 mg/kg P O or I V q l 2 h ) has proven useful and may m i n i m i z e side effects o f steroid a d m i n i s t r a t i o n . ' 24
25
The acquired disease is usually a temporary state and may resolve over many months o f supportive care. The most c o m m o n cause o f death or euthanasia is aspiration and pneumonia. In nine cases o f acute, fulminating myasthenia gravis reported i n the literature, eight died or were eutha nized because o f respiratory failure and aspiration despite anticholinesterase inhibitor therapy i n some cases. ' Plas mapheresis and intravenous y-globulins may, i n the future, prove useful i n treating acute, fulminating disease. 22
In approximately 15% of dogs with acquired myasthenia gravis, the disease is related to a thymoma. In these cases, thymectomy may resolve clinical signs. Other inciting causes include osteogenic sarcoma, biliary carcinoma, and reaction to exogenous antigens. One paper describes an association between hypothyroidism and myasthenia gravis i n dogs and suggests that testing for hypothyroidism be performed i n cases o f the latter. T h y r o i d supplementation should be instituted i f necessary. 26
Aminoglycoside
Intoxication
Animals may have a history o f recent parenteral aminoglyco side exposure. Affected animals are tetraparetic and clinical signs generally resolve following discontinuation of amino glycosides. It is important to note that clinical signs due to many o f the diseases listed in this chapter may worsen fol lowing therapy w i t h aminoglycosides.
SUGGESTED FURTHER READING* Braund K G : Braund's clinical neurology in small animals: Localization, diag nosis and treatment, online publication, 2005, International Veterinary Information Service; http://www.ivis.org. Accessed March 21, 2006. An online text that is updated continually to provide information on newly described neurologic disorders. De Lahunta A: Veterinary neuroanatomy and clinical neurology, ed 2, Phila delphia, 1983, Saunders. The most complete text available on both veterinary neuroanatomy and neurol ogy. A thoughtful and complex read suitable for those with a strong interest in veterinary neurology. Evans J, Levesque D, Shelton G D : Canine inflammatory myopathies: a clinicopathologic review of 200 cases, 7 Vet Intern Med 18:679, 2004. A comprehensive retrospective study on 200 affected dogs examining signaT ment, clinical signs, clinicopathologic findings, electrophysiologic findings, and histopathology used to differentiate various focal and generalized inflammatory myopathies. Kapatkin AS, Vite C H : Neurosurgical emergencies, Vet Clin North Am Small Anim Pract 30:627, 2000. A brief review that describes cranial, spinal, and peripheral nerve disease and their therapy in small animals.
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*See the C D - R O M for a complete list of references.
Chapter 102 TETANUS Simon R. Piatt,
B V M & S , D A C V I M (Neurology),
DECVN, MRCVS
KEY POINTS • Tetanus is the result of a bacterial infection by Clostridium
tetani
following a skin wound, surgery, or even parturition. • The clinical signs are due to the effects of an exotoxin produced by the bacillus that prevents neurotransmitter
1
release.
• C o m m o n signs include spasms of the masticatory, pharyngeal, and facial muscles, but the whole body can be involved. •
1
Definitive diagnosis is difficult in many cases unless serum antibodies can be associated with the bacterial toxin.
• Treatment is initiated immediately on suspicion of the disease based on clinical signs. • Tetanus antitoxin can prevent further deterioration of the patient from unbound toxin at time of treatment, but improvement relies on regrowth of axons and nerve terminals. •
Under anaerobic conditions found i n necrotic or infected tissue, the tetanus bacillus secretes two exotoxins: tetanospasmin and tetanolysin. Tetanolysin is capable of locally damaging otherwise viable tissue surrounding the infection and optimizing the conditions for bacterial multiplication. Tetanospasmin leads to the clinical syndrome of tetanus. This toxin may constitute more than 5% of the weight of the organism. It is a two-chain polypeptide of 150,000 daltons that is initially inactive, made up of a light and a heavy chain. The light chain acts presynpatically to prevent neurotransmitter release from affected neurons. Tetanospasmin binds to the membranes of the local motor nerve terminals. If toxin load is high, some may enter the bloodstream from where it diffuses to b i n d to nerve terminals throughout the body, and may even enter the central nervous system ( C N S ) through an intact blood-brain barrier. The toxin is then internalized and trans ported intraaxonally and i n a retrograde fashion to the cell body at a speed o f 75 to 250 m m per day. ' Transport occurs first i n motor and later in sensory and autonomic nerves. Further ret rograde intraneural transport occurs with toxin spreading to the brain stem i n a bilateral fashion, up the spinal cord. This passage includes retrograde transfer across synaptic clefts by a mechanism that is unclear.
Broad-spectrum anaerobic antibiotics, wound cleansing, muscle relaxants, and sedatives are the important constituents of medical management.
• A quiet environment and intensive nursing care are essential for the success of treatment regimens.
1 2
ETIOLOGY Tetanus is caused by the neurotoxins released by Clostridium tetani, a motile, gram-positive, nonencapsulated, anaerobic, spore-forming bacterium. The toxin is produced during veg etative growth of the organism in a suitable environment. The deoxyribonucleic acid for this toxin is contained i n a plasmid and is antigenically homogenous. The organism's resistant spores are ubiquitous, with a natural habitat i n moist fertile soil; however, they can survive indefinitely i n dusty indoor environments. Resistance of the spores has been proven to boiling water and an autoclave temperature of 120°C for up to 20 minutes. However, the vegetative phase of this bacterium is susceptible to chemical and phys ical inactivation. Organisms can be isolated from the feces o f dogs, cats, and humans, but presence of the organism does not indicate infection because not all strains possess the plasmid. 1
2
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Cats and dogs are considered to be relatively resistant to infection by the bacterium, especially when compared with horses and humans. In part the resistance i n these species is due to the inability of the toxin to penetrate and b i n d to nervous tissue. 2
It is after internalization i n inhibitory neurons that the light chain becomes activated; at this stage the toxin is no longer accessible for neutralization by antitoxin. ' It pre vents neurotransmitter release by cleaving and inactivating synaptobrevin, a membrane or "docking" protein necessary for the export of intracellular vesicles containing the neuro transmitter. In addition to disrupting docking proteins, the toxin may lead to cross-linking of synaptic vesicles to the cytoskeleton, further preventing neurotransmitter release. The toxin predominantly affects inhibitory interneurons, inhibiting release o f glycine and y-aminobutyric acid ( G A B A ) . ' Interneurons inhibiting oc-motor neurons are first affected, and the motor neurons lose inhibitory control. The disinhibitory effect o n the motor neuron may cause d i m i n u t i o n o f function at the neuromuscular junction, so the clinical effect is dissimilar to that of the related botulin u m toxin. Medullary and hypothalamic centers may also be affected. Disinhibited autonomic discharge leads to distur bances i n autonomic control, with sympathetic overactivity and excessive plasma catecholamine levels. 6
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Neuronal binding of toxin is thought to be irreversible. Recovery requires the growth of new nerve terminals, which explains the long duration o f tetanus. 10
PATHOGENESIS Tetanus develops when spores are introduced into wounds or penetrating injuries. M o s t cases develop after skin wounds, but infection can follow parturition or ovariohys terectomy. " 3
5
CLINICAL P R E S E N T A T I O N Clinical signs can take up to 3 weeks from the onset of infection to be apparent, although most cases exhibit
11
symptoms within 5 to 12 days. The clinical signs initially can be localized or generalized, with the former possibly being more c o m m o n i n dogs and cats. A study of 38 dogs with tetanus revealed that ocular and facial changes were the most c o m m o n initial signs. Localized signs begin proxi mal to the site of introduction o f the infection and can include single muscle rigidity, entire l i m b rigidity, and facial muscle spasms. The clinical signs may progress with more extensive muscle involvement. Generalized signs include a stiff gait affecting all limbs, increased muscle tone, dyspnea, an elevated tail and a "sawhorse stance," although the animal may become uncomfortable standing with such excessive muscle activity. At least 50% of dogs w i l l progress w i t h i n a median of 4 days (range 0 to 14 days) to recumbency with severe muscle spasms. 12
Involvement o f the head can lead to spasms o f the masti catory and pharyngeal muscles, causing trismus (lockjaw) and dysphagia. This can be functionally exacerbated by increased salivation, increased bronchial secretions, and increased respiratory rate resulting from involvement of the parasympathetic and somatic cranial nerve nuclei. Regurgi tation and gastroesophageal reflux can result rarely from esophageal hiatal hernia and megaesophagus, which may lead to aspiration pneumonia when combined with the pro blems described earlier. Excessive contraction of the facial muscles causes erect ears and a wrinkled forehead (Color Plate 102-1), and gives the animal a characteristic sneering of the lips known as risus sardonicus, or the sardonic grin (Color Plate 1022)7 Additionally, the patient can exhibit protrusion o f the third eyelid and enophthalmos, resulting from retraction of the globe from hypertonus o f the extraocular muscles. Reflex muscle spasms can occur i n animals w i t h generalized tetanus or intracranial involvement; these may be painful and resemble seizure activity, affecting agonist and antago nist muscle groups together. Severe progression o f signs can cause recumbency, opisthotonus, seizure-like activity, respiratory paralysis, and central respiratory arrest, poten tially causing death i f not rapidly recognized and managed. Death was reported i n 18% of dogs ( 7 o f 3 8 ) i n one retrospec tive study, and 6 of these dogs demonstrated concurrent autonomic signs. 13
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causing a m i l d , generalized form of the disease to progress to a crisis situation.
DIAGNOSIS The patient history and clinical signs are usually sufficient to make a presumptive diagnosis of tetanus. If general anesthe sia is used for diagnostic tests such as cerebrospinal fluid acquisition, the muscle spasms can be reduced but rarely are abolished. Intubation may be difficult in patients with trismus, and a stylet-assisted intubation should be antici pated i n severely affected animals (see Supportive Intensive Care). A complete blood count may suggest an infectious pro cess from a w o u n d , whereas serum biochemistry (with the exception of muscle enzymes) and cerebrospinal fluid analy sis findings are n o r m a l . Muscle enzymes may be elevated in patients with tetanus because of the persistent muscle spas ticity. Radiographs may be helpful to identify involvement of the esophagus, diaphragm, and secondary changes in the lungs resulting from aspiration pneumonia. Electrodiagnostic abnormalities of tetanus are nonspecific and consist of prolonged electric discharges following needle insertion on electromyography; nerve conduction velocities are n o r m a l . Measurement of serum antibodies to tetanospasmin can be performed by some laboratories and may be used for a definitive diagnosis. Values need to be compared with those of control animals. Attempts to isolate C. tetani from wounds often fails because of the l o w concentration of organisms and the requirement for strict anaerobic culture conditions at 37°C for at least 2 weeks. Performing a G r a m stain on a smear from an open w o u n d may identify gram-positive rods and darkstaining spheric endospores, but the morphology of the bacterium is similar to that of many other bacteria. 12
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It is possible to see an effect o n the autonomic system evi denced by episodes of bradycardia and tachycardia, hyperten sion, marked vasoconstriction, and p y r e x i a . ' A study of 38 dogs with tetanus revealed that 37% demonstrated abnorm alities of blood pressure or rectal temperature, or both, consis tent with autonomic disturbance. In the m i l d generalized cases, autonomic involvement may be manifested by dysuria and urinary retention, constipation, and gaseous distention. In humans, "autonomic storms" occur, causing marked car diovascular instability, severe hypertension alternating with profound hypotension, and even recurrent cardiac arrest. During these "storms," plasma catecholamine levels are raised up to 10-fold, similar to levels seen i n animals with a pheochromocytoma. 12,14
15
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A neurologic examination of these patients can reveal normal initiation of a response to postural reaction testing but a stiff and reduced motor response. Myotatic reflexes are generally accentuated and flexor reflexes depressed, but both may be difficult to assess because of the extreme rigid ity of the limbs. A l t h o u g h a complete neurologic examina tion is always ideal, it should be emphasized that animals can become very sensitive to tactile, visual, or auditory stim ulation that can exacerbate clinical signs, occasionally 2
TREATMENT Treatment strategies involve three principles: organisms present i n the body should be destroyed to prevent further toxin release; toxin present i n the body outside of the C N S should be neutralized; and the effects of the toxin already i n the C N S should be m i n i m i z e d .
Neutralization of Unbound Toxin A n t i t o x i n neutralizes any toxin that is unbound to the C N S or is yet to be formed. Therefore the timing of administra tion i n relation to the onset of the disease is essential to its efficacy. The antitoxin used can be either antitetanus equine serum or h u m a n tetanus i m m u n e globulin. The latter may be more likely to produce reactions i f given intravenously. Early intervention has been recommended as a matter of routine, but there are no studies objectively evaluating anti toxin use in dogs or cats, and its efficacy in cases with no evidence of a recent w o u n d is unknown. 16
The recommended dosage of equine antitoxin for dogs and cats is 100 to 1000 U / k g (maximum 20,000) IV, SC, or I M . Intra venous administration is preferred to intramuscular or subcuta neous administration. However, intravenous use of antitoxin is associated with a high incidence of anaphylaxis. To reduce 2
2
this risk, a test dose (0.1 to 0.2 m l of 1:10.000 solution) should be administered intradermally 15 to 30 minutes before the intrave nous dose. A wheal at the site of injection may indicate that an anaphylactic reaction will develop. Epinephrine (0.1 ml/kg IV of the 1:10,000 dilution), glucocorticoids, and an antihistamine should be readily available in case of an adverse reaction (or even given on a prophylactic basis). Repeated doses of antitoxin are more likely to cause adverse reactions and are not recommended or necessary because therapeutic levels persist for approximately 14 days. Intramuscular injection at and proximal to the w o u n d site (1000 U ) may be helpful in localized forms of tetanus. Although intrathecal administration of antitoxin has not been proven to be effective, experimental studies have suggested that it may be of use i n dogs, reducing both the morbidity and mortality i n affected patients. It is considered potentially advantageous, because it need not penetrate the blood-brain barrier when given intrathecally and may partially neutralize bound toxin. However, because o f the lack o f thorough clini cal evaluation and risks associated with administration, the intrathecal route should be reserved for severely affected cases. 2
2
16
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I M , IV, or P O q6-12h) is the drug of choice, although acetylpromazine (0.005 to 0.05 mg/kg I V q2h as needed [maxi m u m 3 mg i n any dog]) is a useful substitute. W i t h severe signs such as generalized tonic-clonic seizure activity, generalized body stiffness, and opisthotonus, barbitu rate or propofol infusions may be necessary, but cardio vascular parameters should be monitored closely and careful consideration should be given as to whether the patient should be intubated and placed on positive-pressure ventilation. Seda tion with propofol has been shown to assist with muscle spasm and rigidity control i n humans, without the use of neuromus cular blocking drugs. Neuromuscular blocking agents may be an option for the most severely affected veterinary patients, but assisted ventilation is imperative. 17
Narcotics and parasympatholytics such as atropine should be used w i t h caution. In severe h u m a n forms of tetanus, atropine infusions have helped to control autonomic dysfunction. 18
2
Removal of Source of Infection Any obvious wounds should be radically debrided after the administration of antitoxin. Flushing the w o u n d with hydro gen peroxide increases oxygen tension, w h i c h inhibits anaer obic organisms, although w o u n d healing may also be impaired (see Chapter 157, W o u n d Management). Antibiotics are essential to kill vegetative C. tetani organ isms and thereby reduce the amount of circulating toxin. Although local administration of antibiotics at a w o u n d site has been advised, parenteral administration is recommended more routinely. Classically, penicillin G has been the man agement of choice, either intravenously as an aqueous potas sium or sodium salt or intramuscularly as the procaine salt (20,000 to 100,000 U / k g q6-12h for 10 days i n both cats and dogs). However, metronidazole (10 mg/kg P O or I V q8h for 10 days) has been shown to be superior to penicillin G in clinical tetanus because it achieves bactericidal therapeu tic concentrations i n anaerobic tissues. Other options include clindamycin (10 mg/kg P O , IV, or I M q8-12h) and tetracycline (22 mg/kg P O or I V q 8 h ) . 2
2
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2
Control of Rigidity and Spasms See Anesthesia and Pain Management section and Chapter 184, Narcotic Agonists and Antagonists, for more details on specific therapies. Prevention of unnecessary stimulation is mandatory, but the mainstay of treatment is sedation with a benzodiazepine. Benzodiazepines augment G A B A agonism at the G A B A receptor. Diazepam (0.5 to 1 mg/kg P O q8h in dogs [maxi mum 10 mg], 0.25 to 0.5 mg/kg i n cats [maximum 5 m g ] , or a continuous intravenous infusion of 0.1 to 1 mg/kg/hr in dogs and cats) or clorazepate (0.5 to 1 mg/kg P O q8h i n dogs; 0.2 to 0.5 mg/kg P O ql2-24h i n cats) can be used i n this regard, although both may cause oversedation i n some patients. a
Additional sedation can be provided by anticonvulsants, particularly phenobarbital (1 to 4 mg/kg P O or I V q l 2 h or I M q6h), which further enhances GABAergic activity. Phenothiazines appear to be highly effective i n controlling the hyperexcitable state; chlorpromazine (0.5 to 2 mg/kg
Supportive Intensive Care Intensive nursing care is essential for successful treatment of patients w i t h tetanus. The dog or cat should be isolated i n a dark and quiet environment, with cotton wool balls placed i n the external ear canals (Color Plate 102-3). M i n i m a l handling is optimal, and all treatments should therefore be coordinated to occur together at set times through the day. A recent study of 10 dogs with tetanus documented the complications that occurred i n these dogs during treatment; these included aspi ration pneumonia, upper respiratory tract obstruction requir ing tracheostomy, and coxofemoral luxation. 1
Weight loss and dehydration are c o m m o n i n patients w i t h tetanus resulting from poor prehending, mastication, and swallowing capabilities, reduced gastrointestinal function i n the presence of autonomic dysfunction, increased metabolic rate, and hyperthermia from the muscular activity and pro longed critical illness. N u t r i t i o n and fluid therapy should therefore be established as early as possible. Enteral nutrition may be associated w i t h a lower incidence of complications and is cheaper than parenteral nutrition, but the latter may be necessary i n select cases. The risk of v o m i t i n g and subsequent aspiration pneumonia must be considered when making this decision (see Chapters 13 and 14, Enteral N u t r i tion and Parenteral N u t r i t i o n , respectively). Percutaneous gastrostomy may prevent the complications associated w i t h nasogastric tube feeding, particularly the stress that may be associated with an indwelling intranasal tube. Gastrostomy- or gastrojejunostomy-assisted feeding can also reduce the risk of aspiration pneumonia, a potential complication i n dogs w i t h severe forms o f tetanus and those that are recumbent for a prolonged period. If airway constriction due to laryngeal spasms, a buildup of saliva or tracheal secretions, or the need for artificial ventila tion are concerns, tracheostomy usually is performed after intubation (see Chapter 18, Tracheostomy). A stylet may be inserted into the airway and the endotracheal tube fed over the stylet for intubation of dogs w i t h severe laryngospasm. A tracheostomy requires meticulous care to prevent introduc tion of infection, but it w i l l allow intermittent tracheal suction to be performed with little stress to the animal. Oxygen sup plementation may be administered via tracheostomy flowby, intratracheally, or with mechanical ventilation. Urinary and fecal retention occur i n some patients with hypertonic anal and urinary sphincters. A n indwelling
urinary catheter may be beneficial i n these patients, although the urine should be analyzed regularly for evidence o f infection. Pressure sores or decubital ulcers should be prevented with appropriate soft or padded bedding and frequent turn ing and physiotherapy. However, the balance between fre quent physiotherapy and isolated rest is difficult to achieve, and pharmacologic sedation may be necessary before physical manipulation is possible i n some patients.
administration and either progression o f signs or survival. A prospective trial w i l l be necessary i n the future to further investigate the value o f these therapeutic options. A full recovery may not be possible i n at least 15% o f dogs that sur vive, but continued improvement may be seen for 3 to 5 months.
PROGNOSIS
Braund KG: Neurotoxin disorders. In Braund KG, editor: Clinical neurology in small animals: localization, diagnosis and treatment, Ithaca, NY, 2003, International Veterinary Information Service. Comprehensive veterinary neurology on-line text that is heavily referenced hut practically written. Coleman ES: Clostridial neurotoxins: tetanus and botulism, Comp Cont Educ Small Anim Pract 20:1089, 1998. Excellent and easy-to-read review of tetanus in dogs and cats; interesting path ophysiologic comparisons made between it and botulism. Greene C E : Tetanus. In Greene C E , editor: Infectious diseases of the dog and cat, ed 3, St Louis, 2006, Saunders. A comprehensive, well-referenced chapter covering the aspects of tetanus in companion animals
Most patients that recover will show some improvement within 7 days, unless autonomic abnormalities are noted, which are poor prognostic indicators. M e d i a n length o f hospitalization has been reported to be 13 days (range 6 to 42 days). One study estimated the mortality rate to be approximately 18% i n affected dogs. Dogs with surgical wounds manifest a more severe clinical course than those with external wounds, and young dogs are also more likely to develop more severe treat ment. There is no documented association between earlier w o u n d treatment, antibiotic administration, or antitoxin
11
SUGGESTED FURTHER READING*
"See the C D - R O M for a complete list of references.
Chapter 103 HEPATIC ENCEPHALOPATHY David Holt, BVSC, DACVS
K E Y POINTS • Hepatic encephalopathy (HE) is associated with moderate to severe liver insufficiency and may be secondary to a portosystemic shunt(s), end-stage liver disease, or congenital urea cycle enzyme deficiencies. • The pathophysiology of HE is complex and incompletely understood; however, the importance of elevated levels of ammonia in the blood have been reemphasized. • Clinical signs may include depression, dementia, stupor, coma, muscle tremors, motor abnormalities, excessive salivation, and focal or generalized seizures. • Medical treatment includes strategies to minimize ammonia absorption from the intestine and control seizure activity, if present. •
Definitive therapy involves correcting underlying causes, such as surgical treatment of a portosystemic shunt.
hepatic failure is an important cause o f H E in humans but is seen less c o m m o n l y i n veterinary medicine. Congenital urea cycle enzyme deficiencies may also lead to H E .
CAUSES In dogs and cats, congenital extrahepatic or intrahepatic portalto-systemic venous communications are the most frequent cause of H E ; up to 95% of affected animals demonstrate neuro logic clinical signs. These communications are generally via a single vessel, but multiple extrahepatic and intrahepatic con genital portosystemic shunts have been reported. Hepatic arte riovenous malformations cause portal hypertension, multiple extrahepatic portosystemic shunts, and ascites, and may cause symptoms of H E . In young dogs, hepatic microvascular dyspla sia and, rarely, congenital urea cycle deficiencies can also cause clinical signs o f H E . In older animals, portosystemic shunts develop secondary to portal hypertension that results from chronic liver disease. In cats, hepatic lipidosis often is associated with symptoms o f H E . Other causes o f chronic and acute hepatic failure that can result in symptoms of H E are discussed in Chapter 127, Hepatic Failure. 1
2
4
INTRODUCTION Hepatic encephalopathy ( H E ) comprises a spectrum o f neu rologic abnormalities associated w i t h moderate to severe liver insufficiency. In dogs and cats, it occurs most c o m m o n l y with portosystemic shunting o f blood. Fulminant
3
5
PATHOPHYSIOLOGY
concentrations in the cerebrospinal fluid are elevated i n dogs with H E and often are an accurate indicator o f the degree o f neurologic dysfunction i n humans with H E . Glutamine is exchanged across the blood-brain barrier for tryptophan, lead ing to increased levels o f tryptophan and tryptophan metabo lites i n the C N S (Figure 103-1). The tryptophan metabolites serotonin and quinolinate are important agonists o f inhibitory and excitatory neurotransmission, respectively, although the exact alterations i n both o f these systems i n patients with H E are complex and incompletely understood. Glutamine is also transported from astrocytes into neurons, where it is converted to glutamate. Overstimulation o f the N-methyl-D-aspartate receptors by both glutamate and ammonia can cause seizures and neurotoxicity, i n part as a result o f free radical formation. 8
In 1893, Marcel Nencki and Ivan Pavlov described the physi ologic consequences of a surgically created, end-to-side porta caval shunt (Eck fistula) and showed that clinical signs in this canine model worsened after a meat meal, linking H E to the concept o f "meat intoxication." Ever since this description, H E has been thought o f as a condition caused by gut-derived toxins that are not metabolized by a diseased or failing liver. Research over the last century has elaborated on this concept and demonstrated the complexity of this condition. However, recent work on several aspects o f H E including cerebrospinal fluid amino acid alterations, ' glutamate neurotoxicity, the generation of reactive oxygen species, and the mitochondrial permeability transition emphasizes the central role o f ele vated blood ammonia concentrations i n animals with H E . Other substances that are considered synergistic with ammo nia toxicity include mercaptans, free fatty acids, phenols, and bile salts (see Chapter 127, Hepatic Failure, Table 127-2 for a summary o f toxins implicated i n H E ) . 6
7 8
9
10
11
12
A m m o n i a is produced i n the intestinal tract as the end product o f amino acid, purine, and amine breakdown by bac teria, the metabolism o f glutamine by enterocytes, and the breakdown o f urea by bacterial urease. It is then absorbed into the portal b l o o d and rapidly converted to urea or gluta mine i n the normal liver. In animals w i t h portosystemic shunting of b l o o d or significant liver disease, high levels o f ammonia are present i n the systemic circulation. The perme ability of the blood-brain barrier to ammonia increases in ani mals with H E , and experimental studies suggest that H E coma is associated with brain ammonia concentrations i n the l o w millimolar range. These concentrations of ammonia decrease excitatory neurotransmission, i n part by down-regulating the N-methyl-D-aspartate (excitatory) receptors, yet at the same time block chloride extrusion from the postsynaptic neuron, decreasing inhibitory neurotransmission. 13
14
9
15
The brain has no urea cycle; consequently, ammonia i n the central nervous system (CNS) is removed by transamination of glutamate into glutamine i n astrocytes. Glutamine 16
Figure 103-1
9
7
17
y - A m i n o b u t y r i c acid ( G A B A ) is the most important inhib itory neurotransmitter i n the C N S , and alterations of G A B A neurotransmission have been proposed as an important c o m ponent o f H E . In spite o f several different observations i m p l i cating "increased G A B A e r g i c tone" in H E , studies have excluded the possibility o f increased amounts o f G A B A i n the C N S and changes i n the number o f G A B A receptors or affinity o f the receptor for its ligands i n patients with H E . It is likely that i f increased G A B A neurotransmission exists in animals with H E , it is due to increased brain concentrations of endogenous G A B A ligands, including endogenous benzo diazepines and neurosteroids. Increased levels o f endogenous benzodiazepine receptor ligands have been found i n the portal b l o o d and systemic circulation o f some dogs with portosyste mic shunts. Elevated levels of ammonia and manganese (also seen in liver disease) increase expression of the peripheral-type benzodiazepine receptor, a heterooligomeric protein complex on the outer mitochondrial membrane o f astrocytes. Activa tion o f the peripheral-type benzodiazepine receptor increases mitochondrial cholesterol uptake and the synthesis o f neuro steroids that may then act o n G A B A receptors. 1 8
19
20
There is also evidence that amino acid imbalances play a role in patients with H E . Dogs with portocaval shunts have a decreased ratio o f branched chain (valine, leucine, isoleucine) to aromatic (phenylalanine, tyrosine, tryptophan)
Diagram of the proposed effect of ammonia on tryptophan metabolism. Ammonia is metabolized to glutamine, which shares an antiport transport mechanism across the blood-brain barrier with tryptophan. A n increase in tryptophan transport leads to an increased flux through the serotonin and quinolinic acid pathways.
21
amino acids. Because these classes o f amino acids compete for transport across the blood-brain barrier, the increased relative concentration o f the aromatic amino acids means that they will be preferentially transported. This leads to an increased synthesis o f false neurotransmitters and a reduc tion i n the synthesis o f dopamine and norepinephrine. C o m a was induced i n n o r m a l dogs infused with the aro matic amino acids tryptophan and phenylalanine; addition of the branched chain amino acids to the infusion prevented 22
coma.
CLINICAL SIGNS The clinical signs associated with H E are often subtle and episodic initially. A new puppy may be mildly lethargic or depressed and first-time owners may not recognize this as abnormal behavior. Other clinical signs may include disor ientation, personality change, stupor, pacing, head pressing, "star gazing," amaurotic blindness, coma, and occasionally seizures. In general, signs o f C N S depression predominate over signs associated w i t h hyperexcitability. In cats, ptyalism is c o m m o n , and is often the only clinical sign associated with H E . In dogs, polydipsia and polyuria are also c o m m o n clinical findings, presumed secondary to hypercortisolemia and the subsequent partial inhibition o f vasopressin's action on the renal tubules. Clinical signs of gastrointestinal (GI) (vomiting, anorexia) and urinary tract (stranguria and hema turia secondary to a m m o n i u m biurate calculi) disease can also occur i n animals with portosystemic shunting o f blood. Although these signs are not unique to H E per se, it is i m p o r tant that they alert the veterinarian to investigate the possibil ity o f moderate to severe liver disease. 23
Clinical signs H E can be precipitated or worsened by the ingestion o f a high-protein meal, G I bleeding, systemic infec tion, and several medications, including narcotics and other anesthetic agents. Other precipitating factors include electrolyte imbalances (hyponatremia, hypokalemia), hypoglycemia, aci dosis or alkalosis, and constipation.
DIAGNOSIS The diagnosis o f H E is made when an animal has clinical signs compatible w i t h the c o n d i t i o n and alterations on a biochemical panel and liver function tests confirming m o d erate to severe liver disease (see Chapter 127, Hepatic Fail ure). A t the same time, none of the clinical signs described are specific for H E and other potential diagnoses, i n c l u d i n g other metabolic disorders, t o x i n or drug ingestion, and intra cranial lesions, should be excluded. Routine laboratory anal ysis (complete b l o o d count, biochemical profile, urinalysis) and liver function testing are often indicated. Possible liver function tests include preprandial and postprandial serum a m m o n i a or bile acid levels, a m m o n i a tolerance test (may potentiate seizure activity and therefore us contraindicated i n patients w i t h H E ) , and sulfobromophthalein dye reten tion test. It is important to note that samples for b l o o d a m m o n i a concentrations are useful only i f processed i m mediately. Canine samples for b l o o d a m m o n i a determina tion that are stored frozen for any length o f time give erroneous results. A d d i t i o n a l diagnostic testing that might be necessary include rectal portal scintigraphy and liver histopathology. 24
TREATMENT See Chapter 127, Hepatic Failure, Table 127-3 for a summary of treatments. Animals that have or develop focal or generalized seizures w i l l require immediate intervention to stop them (see Chap ters 98 and 186, Seizures and Status Epilepticus and Anticon vulsants, respectively). The use o f diazepam (Valium) is controversial because of the possibility of endogenous benzo diazepine agents (see Pathophysiology earlier in this chapter). The dosage is typically 0.5 mg/kg IV. Alternatively, the seizure activity may be managed with propofol (0.5 to 1 mg kg IV bolus, then 0.05 to 0.1 mg/kg/min constant rate infusion). M a n n i t o l therapy may also prove beneficial i f cerebral edema is present (0.5 to 1 g/kg I V over 30 minutes). Potassium bromide can be administered i n an attempt to prevent further seizure activity by loading the animal initially with 400 to 600 mg/kg q24h divided into 4 doses on day 1, then mainte nance therapy at 40 mg/kg q24h P O or rectally. Sodium bromide has been suggested as a parenteral antiepileptic for mulation i n dogs and cats, although there are few data to sup port its clinical use. The drug is generally administered at 15% of the potassium bromide dosage, including the loading dose on day 1. Phenobarbital may also be used as a parenteral antie pileptic, and a loading dose is typically given on day 1 at 16 mg/ kg I V divided into 4 doses, followed by 2 to 4 mg/kg I V q l 2 h thereafter. Both the bromide drugs and phenobarbital may lead to excessive sedation, and close monitoring is therefore essential. In animals with hepatic coma or seizures, any predispos ing factor should be treated. For example, i n the case of benzodiazepine sedation, flumazenil (0.02 mg/kg IV) is administered. Intubation o f comatose animals or those recovering from seizure activity may be necessary to protect the airway from aspiration and to maintain ventilation. IV fluids are often necessary, but the animal's serum albumin, glucose, electrolyte, and acid-base status should be evaluated carefully before and during administration. Affected animals are often hypoproteinemic and hypoglycemic; alkalosis increases ammonia diffusion into the C N S and hypokalemia stimulates renal ammonia production. C o l l o i d administra tion (synthetic or fresh frozen plasma) and potassium and glucose supplementation are often necessary. Should a trans fusion be necessary, fresh whole b l o o d or packed red blood cells are used, because storage of red blood cell products increases the ammonia concentration. A lactulose enema is administered to prevent ammonia production in, and absorption from, the colon. Lactulose (P-galactosidofructose) is a nonabsorbable disaccharide that exerts an osmotic cathar tic action. In addition, intestinal bacteria hydrolyze lactuloseproducing organic acids that lower colonic p H . Acidification traps ammonia i n its N H form, preventing absorption by nonionic diffusion, and also results i n the net movement of ammonia from the b l o o d into the bowel lumen. 25
+
4
Fulminant hepatic failure is u n c o m m o n i n animals but may be fatal. Death i n humans with fulminant hepatic failure is often associated with cerebral edema, hemorrhage, and sepsis. Therapy is similar to that described for hepatic coma and seizures. Assisted ventilation is used to prevent hypoven tilation and m i n i m i z e changes i n intracranial pressure. Twenty-five percent mannitol (0.5 to 1 g/kg IV) is adminis tered to m i n i m i z e cerebral edema. Glucose is supplemented as necessary. Animals with fulminant hepatic failure may be
coagulopathic, and fresh frozen plasma (10 to 20 m l / k g I V ) is administered to supplement coagulation factors, i f needed. Bacterial cultures (blood, urine) are obtained a n d broadspectrum antibiotics are administered i n animals with sus pected bacterial sepsis (see Chapter 106, Sepsis). General treatment goals for stable animals w i t h H E or those that have been stabilized after treatment for emergent conditions include reducing a m m o n i a levels, decreasing G A B A , and lowering endogenous benzodiazepines. Clinical signs o f H E can typically be treated with diet modification, oral administration o f lactulose, and antibiotic therapy. The diet should be moderately protein restricted (14% to 17% protein o n a dry matter basis i n dogs; 30% to 35% pro tein i n cats) and high i n carbohydrates. The protein should be o f high quality and have a high level o f branched chain amino acids. The diet should be a low-residue, easily digest ible food to minimize the amount o f material reaching the colon. It must contain adequate amounts o f arginine for cats, because this is an essential amino acid that is necessary for the urea cycle. Lactulose is an osmotic cathartic that increases transit time through the GI tract, thereby decreasing the availability of glutamine sources (ingested and endogenous) for metab olism. The p H o f the intestinal contents is also reduced, which decreases the numbers o f urease-producing colonic bacteria and traps a m m o n i a w i t h i n the G I tract as a m m o nium ions. Lactulose (1 to 3 ml/10 kg q6-8h) is administered orally or rectally (diluted to 30% with warm water and retained for 30 minutes), and the dosage rate and interval are titrated to produce two to four moderately soft stools daily. Antibiotics are administered to decrease numbers o f urease-producing bacteria i n the intestines. Neomycin sulfate (20 mg/kg P O q6-8h) is generally considered nonabsorbable, but it should be avoided i n animals w i t h concurrent renal dis ease. Metronidazole (10 to 20 mg/kg P O or I V q l 2 h ) is a rea sonable alternative, but neurotoxicity may occur more commonly i n animals with hepatic disease. Rifaximin is a commonly used antibiotic for the treatment o f H E i n humans, but its use i n small animals is limited at this time. The effect o f long-term antibiotic therapy o n the intestinal flora o f dogs and cats is not clear. Because the therapeutic effect o f lactulose depends o n its metabolism by colonic bac teria, the benefit o f combined lactulose and antibiotic therapy is open to question i n small animals. Although the two treat ments often are considered synergistic, oral neomycin inhibits lactulose metabolism i n 25% to 30% o f human patients. Enemas have also been used to decrease the colonic bac terial numbers and substrates. The following types o f enemas have been recommended: • W a r m water enemas at 10 m l / k g q4-6h until signs improve • Lactulose enemas at 5 to 15 m l diluted 1:3 w i t h w a r m water and administered q6-8h • Neomycin enemas at 15 to 20 m l o f 1% solution q8-12h • Metronidazole enemas at 7.5 mg/kg (systemic dose) mixed with water q l 2 h • Povidone-iodine (Betadine) enemas given b y diluting 1:10 with warm water and giving 10 m l / k g q8h and flushing out with w a r m water after 10 to 15 minutes • Activated charcoal enemas using the l i q u i d suspension q8h (can be administered and retained i n crisis)
• Vinegar enemas made by diluting the vinegar 1:4 with w a r m water and administering at 10 m l / k g q8h Other therapies that have been studied i n humans but not companion animals include ornithine aspartate, intestinal repopulation with lactose fermenting, non-urease-containing bacteria, zinc supplementation, branched chain amino acid solutions, a n d flumazenil a n d levodopa administration. Inhibitors o f the glutamine synthetase enzyme and serotonin receptor antagonists have been associated with a high rate of side effects and are not used for treatment o f clinical H E i n humans. 26
In cases o f H E secondary to portosystemic shunting o f blood, correcting the portosystemic shunt surgically often resolves the clinical signs o f H E permanently i n dogs. In cats, a variable percentage may have residual or recurrent neurolo gic signs. Treatment o f extrahepatic shunts usually involves either complete suture ligation or placement o f either an ameroid ring or cellophane band to occlude the shunting vessel more slowly. Intrahepatic shunts are treated either sur gically or with interventional radiographic techniques. A l l o f these procedures require general anesthesia; the metabolism of anesthetic agents and their effects o n the C N S are far from clear i n animals with H E . A l t h o u g h controlled clinical trials are lacking, general o p i n i o n favors a period o f medical treat ment to stabilize animals w i t h H E before anesthesia induction. 27
A n i m a l s w i t h liver insufficiency c o m m o n l y experience clinical or subclinical G I hemorrhage, and the digested b l o o d serves as another protein source protein that may cause o r contribute to H E . It is therefore recommended that these animals receive G I protectant therapy (see Chapter 181, Gastrointestinal Protectants). Drugs such as famoti dine (0.25 to 1 m g / k g P O or I V q l 2 - 2 4 h ) , omeprazole (0.5 to 1 mg/kg/day P O q l 2 h ) , misoprostol (2 to 3 ug/kg P O q8h), and sucralfate (0.25 to 1 g/25 kg P O q6-8h) are c o m m o n l y used.
SUGGESTED FURTHER READING* Albrecht J, Jones EA: Hepatic encephalopathy: Molecular mechanisms underlying the clinical syndrome, / Neurol Sci 170:138, 1999. A comprehensive review of the current concepts of molecular changes thought to occur in the central nervous system in HE. Aronson LR, Gacad R C , Kaminsky-Russet K, et al: Endogenous benzodiaze pine activity in the peripheral and portal blood of dogs with congenital portosystemic shunts, Vet Surg 26:189, 1997. Article describing that endogenous benzodiazepine levels are elevated in the portal and systemic circulation in some dogs with spontaneous portosystemic shunts. Butterworth RF: Neurotransmitter dysfunction in hepatic encephalopathy: new approaches and new findings, Metab Brain Dis 16:55, 2001. A review of CNS changes in HE that discusses the potential roles of manganese, the "peripheral-type" benzodiazepine receptor, and neurosteroids. Butterworth J, Gregory CR, Aronson LR: Selective alterations of cerebrospi nal fluid amino acids in dogs with congenital portosystemic shunts, Metab Brain Dis 12:299, 1997. Describes abnormal concentrations of glutamate and glutamine in the cerebro spinal fluid of dogs with spontaneously occurring portosystemic shunts. Dimski DS: Ammonia metabolism and the urea cycle: functional and clini cal implications, / Vet Intern Med 8:73, 1994. A review of ammonia metabolism and the urea cycle. Konsenko E, Venediktova N , Kaminsky Y, et al: Sources of oxygen radicals in brain in acute ammonia intoxication in vivo, Brain Res 981:193, 2003. Describes the formation of potentially toxic oxygen free radicals induced by ammonia in an experimental rat model of HE. *See the C D - R O M for a complete list of references.
Chapter 104 VESTIBULAR DISEASE Simon R. Piatt,
BVM&S, D A C V I M (Neurology), DECVN,
K E Y POINTS
MRCVS
Nerve Pathways to the Extraocular Muscles
• Patients with vestibular disease have dysfunction of the vestibular system and are often presented for treatment on an acute emergency basis.
Two neurons make up the pathway responsible for the sen sory input o f the head to the cerebral cortex (Figure 104-1).
• The vestibular system is comprised of a peripheral component within the structures of the inner ear and central components in the brain stem and cerebellum.
Neuron 1
• The c o m m o n clinical signs of vestibular disease include head tilt, ataxia, and nystagmus. • Peripheral vestibular disease can be accompanied by Horner's syndrome and facial nerve paresis. • Central vestibular disease typically is accompanied by loss of proprioceptive and motor function, in addition to multiple cranial nerve deficits and mentation changes. • The differential diagnosis for the cause of vestibular disease depends o n the localization of the lesion to the peripheral or central components. • Treatment of vestibular disease is determined by the underlying etiology, but supportive care is extremely important to the speed of individual patient compensation.
INTRODUCTION Dogs and cats have the ability to control posture and move ments o f the body and eyes relative to the external environ ment. The vestibular system mediates these activities through a network o f receptors and neural elements. Disease leading to dysfunction o f the vestibular system can lead to dramatic signs of disequilibrium. The investigation, treatment, and prognosis o f the cause o f the disequilibrium can differ depend ing on whether the peripheral or central components o f the system are affected. This chapter outlines the relevant anatomy o f the vestibular system and how this influences the clinical signs of its dysfunction, i n addition to the diseases that are most c o m m o n l y responsible for the acute onset o f clinical signs constituting an emergency.
N E U R O A N A T O M Y O F THE V E S T I B U L A R SYSTEM The vestibular system can be divided into peripheral compo nents located i n the inner ear and central nervous system (CNS) components. Three major C N S areas receive projections from the peripheral sensory receptors o f the vestibular system: the cerebral cortex, the spinal cord, and the cerebellum. The projection to the cerebral cortex incorporates extensions to the extraocular muscles.
The cell location for the first neuron is within the vestibular ganglion o f the eighth cranial or vestibulocochlear nerve, and the axon projects into the ipsilateral vestibular nuclei. These neurons receive input from the vestibular receptors i n the membranous labyrinth contained within a bony laby rinth i n the petrous temporal bone. The sensory neurons are incorporated into the vestibulocochlear nerve, which leaves the petrous temporal bone via the internal acoustic meatus, along with the facial nerve, and enters the medulla of the brain stem. 1
Neuron 2 The cell location for the second neuron is in the vestibular nuclei, w h i c h are situated i n the medulla oblongata. From these nuclei, axons travel i n the medial longitudinal fascicu lus w i t h i n the brain stem. The ascending axons within the fasciculus give off numerous side branches to the motor nuclei o f cranial nerves III, IV, and V I , thereby providing coordinated conjugated eyeball movements associated with changes i n position o f the head. Some axons project from the nuclei into the reticular formation and go on to provide afferents to the vomiting center located there. 1
Nerve Pathways to the Spinal Cord The vestibulospinal tract descends from the vestibular nuclei and projects mainly onto oc-neurons or extensor motor neu rons throughout the length o f the cord via interneurons i n the ventral grey c o l u m n . This pathway is strongly facilitatory to the ipsilateral alpha and gamma motor neurons to extensor muscles. 1
Nerve Pathways to the Cerebellum The vestibular nuclei project directly to the cortex of the ipsi lateral flocculonodular lobe (the flocculus o f the hemisphere and the nodulus o f the caudal vermis), as well as the fastigial nucleus o f the cerebellum. The return pathway from a cere bellar nucleus to the vestibular nuclei is also ipsilateral; this is an extremely large projection, providing the cerebellum with a strong influence over the activity o f the vestibular nuclei. These pathways between the cerebellum and the vestibular nuclei travel i n the caudal cerebellar peduncle. 1
Table 104-1 Neurologic Examination Findings in Animals With Peripheral and Central Vestibular Dysfunction Clinical Signs
Peripheral V e s t i b u l a r Disease
Central Vestibular Disease
H e a d tilt
T o w a r d t h e lesion
T o w a r d t h e lesion. or a w a y f r o m t h e lesion w i t h paradoxical disease
Spontaneous nystagmus
H o r i z o n t a l or rotatory w i t h t h e fast phase a w a y f r o m t h e side of t h e lesion
Horizontal, rotatory, vertical a n d or positional w i t h t h e fast phase t o w a r d or
Rarely p o s i t i o n a l
away from the lesion
F i g u r e 104-1 Diagrammatic overview of the neuroanatomy of the vestibular system. (From Piatt S, Olby N, editors: Manual of canine and feline neurology, ed 3, Gloucester, 2004, British Small Animal Veterinary Association.)
Paresis a n d proprioceptive deficits
None
Commonly ipsilateral t o t h e lesion
Mentation
Normal to disoriented
Depressed, stuporous, o b t u n d e d , or comatose
C r a n i a l nerve deficits
Ipsilateral C N VII deficit
Ipsilateral C N V , VII, IX, X, a n d XII
Horner's syndrome
C o m m o n ipsilateral t o t h e lesion
Uncommon
Head tremors
None
Can occur with concurrent cerebellar dysfunction
Circling
I n f r e q u e n t but can b e seen t o w a r d t h e side of t h e lesion
Usually t o w a r d t h e side o f t h e lesion
CLINICAL SIGNS Unilateral vestibular disease produces asymmetric signs, often on or toward the side of the disease. The most c o m m o n clinical signs of vestibular disease are head tilt, nystagmus, and ataxia; these may be single entities or a combination of signs. The primary aim of the neurologic examination is to determine i f these vestibular signs are due to a peri pheral vestibular system (inner ear) disease or a central vestibular system (brain stem and cerebellum, or both) dis ease. Localization of the disease determines the most appro priate diagnostic tests, the differential diagnoses, and the prognosis. 2
The essential determination of whether these signs are due to a peripheral or central disease may be possible by the identification of associated neurologic signs that are present only with central disease. Signs of central vestibular syndrome suggest damage to the brain stem and are not present in patients with inner ear disease unless there has been extension of the inner ear disease into the brain stem, such as can be seen with otitis media, otitis interna, and neoplasia. 2
3
Specific Signs of Vestibular Dysfunction Signs of vestibular dysfunction are outlined in Table 104-1.
Head Tilt Loss of equilibrium is most commonly represented clinically as a head tilt that may be present with either central or periph eral vestibular disease. The head tilt is always toward the side
CN, Cranial nerve.
o f the lesion with peripheral disease but may be toward either side with central disease. W h e n the head tilt is opposite to the side of the lesion, it is termed paradoxical. This can be seen with lesions of the flocculonodular lobe of the cerebellum or the supramedullary part of the caudal cerebellar peduncle, with sparing o f the vestibular nuclei in the rostral medulla; the head tilt often is accompanied by ipsilateral cerebellar signs, paresis, and proprioceptive deficits. Bilateral peripheral vestibular disease does not produce asymmetric lesions such as a head tilt. A characteristic side-to-side head movement is seen instead. 1
3
Nystagmus Pathologic or spontaneous nystagmus is an involuntary rhythmic oscillation of both eyes, occurs when the head is still, and is a sign of altered vestibular input to the neurons that innervate the extraocular eye muscles. This is in con trast to physiologic nystagmus, which can be induced in nor mal animals. Pathologic nystagmus may be horizontal, rotatory, or vertical. Vertical nystagmus implies a central ves tibular lesion but it is not a definitive localizing sign. If nys tagmus of any direction is induced only when the head is placed in an unusual position, it is known as positional nys tagmus, which may be more c o m m o n with, but not specific for, central disease; this term may also refer to nystagmus that changes its predominant direction with altered head positions. 2
2
Nystagmus occurs with the fast phase away from the damaged side and w i t h the slow phase c o m m o n l y directed toward the affected side. In acute and or aggressive nystag mus, the eyelids may be seen to contract at a rate correspond ing to that o f the nystagmus. Nystagmus may disappear w i t h chronicity o f the underlying lesion, particularly w i t h periph eral disease, but its presence usually indicates an active disease process w i t h i n the vestibular apparatus. Animals with bilateral vestibular disease do not have pathologic or physiologic nystagmus.
muscles, reduced jaw tone, facial paralysis, tongue weakness, and loss o f the swallow or gag reflex.
Circling, Leaning, and Falling W i t h unilateral vestibular dysfunction, dogs or cats may exhibit an ipsilateral reduction i n extensor tone, and contra lateral hypertonicity, causing them to lean, fall, and circle toward the side of the lesion. Falling may occur when the animal shakes its head i f there is aural irritation. 2
4
Ataxia Ataxia is a failure o f muscular coordination or an irregularity of muscle action. It is generally associated with a cerebellar, vestibular, or proprioceptive pathway abnormality. Animals with vestibular dysfunction assume a wide-based stance and may lean or drift toward the side o f a lesion i f the dysequilibrium is not too severe. 4
Signs That M a y Be Associated With Vestibular Dysfunction Facial Paresis, Paralysis, and Hemifacial Spasm Cranial nerve V I I , the facial nerve, is c o m m o n l y involved i n the same disease processes that cause peripheral vestibular disease. The resulting signs are those o f facial paresis, paral ysis or, more rarely, spasm.
Decerebellate
Posturing
In severe forms o f central vestibular dysfunction, the under lying disease may also cause decerebellate posturing or rigid ity; this is characterized by opisthotonus with thoracic limb extension, n o r m a l mentation, and flexion of the pelvic l i m b s . This posture can occur intermittently and be accompanied by vertical nystagmus, the combination being confused by owners as some type of seizure activity. Dorsiflexion o f the neck will sometimes elicit this posture. 3
Vomiting The v o m i t i n g center is located w i t h i n the reticular substance of the medulla, and there are direct connections to it from the vestibular nuclei. Vomiting may be seen i n animals affected acutely by vestibular disease. 1
2
5
Horner's
Syndrome
Horner's syndrome (miosis, ptosis, enophthalmos, and pro trusion of the third eyelid) of the ipsilateral eye may be present with either middle or inner ear disease causing peripheral vestibular dysfunction. This association is seen because the vagosympathetic trunk synapses i n the cranial cervical gan glion deep to the tympanic bulla. Horner's syndrome rarely is associated w i t h central vestibular disease.
DIFFERENTIAL D I A G N O S I S O F A C U T E VESTIBULAR D I S E A S E Tables 104-2 and 104-3 outline the overall etiology and infectious etiologies, respectively o f acute vestibular disease.
6
1
Hemiparesis
or
Tetraparesis
Paresis suggests abnormal neurologic function (weakness) without complete paralysis, w h i c h implies that some v o l u n tary m o t i o n remains. L o c o m o t i o n is thought to be initiated in the brain stem o f animals, so paresis usually is seen w i t h any lesion within the neuraxis caudal to the level o f the red nucleus i n the m i d b r a i n . W i t h unilateral focal central ves tibular diseases, paresis o f the ipsilateral limbs (hemiparesis) may be seen i f the motor pathways i n the medulla oblongata are also affected. A large lesion or multifocal lesions may cause an asymmetric tetraparesis. Paresis does not occur w i t h peripheral vestibular disease. 3
D I A G N O S T I C A P P R O A C H T O THE A N I M A L WITH A C U T E VESTIBULAR D I S E A S E The approach to an animal w i t h vestibular disease can depend o n whether a peripheral or central lesion is sus pected (Figure 104-2). To determine this, a complete history and a thorough physical and neurologic examination are essential. The following tests can be performed i n sequence, advanc ing i n expense and invasive nature until satisfactory informa tion is acquired. A l l o f the tests may be necessary i f central disease is suspected, whereas cerebrospinal fluid (CSF) anal ysis and advanced imaging may not be necessary i f peripheral disease is responsible for the vestibular dysfunction.
Altered Mental State
Minimum Database
Disorders causing central vestibular dysfunction may be accompanied by altered mentation. The reticular activating system o f the brain stem facilitates the alert and awake state in animals. Damage to this area may cause the animal to become disoriented, stuporous, or comatose. A l t h o u g h pe ripheral vestibular disease w i l l not cause stupor or coma, it may cause disorientation, w h i c h can make the assessment of the animal's mental status difficult.
Hematology, a comprehensive serum biochemistry, thyroid function analysis, urinalysis with culture and sensitivity, thoracic radiographs, and abdominal ultrasonography or radiographs should be analyzed in all cases o f acute vestibular dysfunction to evaluate the patient for multisystemic or concur rent disease.
1
3
Multiple
Cranial Nerve
Dysfunction
Central vestibular syndrome may be accompanied by other cranial nerve dysfunction as well. Clinical signs can include ipsilateral facial hypalgesia, atrophy of the masticatory
Otoscopy and Pharynx Examination General anesthesia is necessary to thoroughly examine the ears and pharynx for abnormalities such as exudates and soft tissue masses. Both ears should be examined with an oto scope. The tympanum should be examined for color, texture,
Table 104-2 Etiologies of Peripheral and Central Vestibular Diseases 1
Table 104-3 Infectious and Inflammatory Central Nervous System Disorders That May Cause Vestibular Dysfunction 1
Specific Diseases Disease Mechanism
Peripheral Disease
Degenerative
Central Disease
Class o f E t i o l o g i c Agent
Disease
Cerebellar cortical
Viral
Feline infectious peritonitis
abiotrophy
Feline i m m u n o d e f i c i e n c y virus
Lysosomal s t o r a g e diseases Anomalous
Nutritional
Rabies
Hydrocephalus
C o n g e n i t a l vestibular disease
Pseudorabies
Intracranial intraarachnoid cysts
—
Neoplasia
Feline l e u k e m i a virus
Thiamine deficiency
S q u a m o u s cell c a r c i n o m a
Meningioma
Fibrosarcoma
Oligodendroglioma
Osteosarcoma
Medulloblastoma
C e r u m i n o u s g l a n d or sebaceous g l a n d adenocarcinoma
Lymphoma Extension of m i d d l e ear
B o r n a disease virus D i s t e m p e r virus Protozoal
Toxoplasmosis, neosporosis Encephalitozoonosis
Bacterial
Aerobes Anaerobes
Rickettsial
Rickettsia Ehrlichia
Fungal
rickettsii spp
Cryptococcosis Blastomycosis
neoplasia
Histoplasmosis
Metastasis
Coccidioidomycosis Inflammatory or infectious
Bacterial otitis interna or labyrinthitis
See T a b l e 104-3
Aspergillosis Phaeohyphomycosis
Cryptococcosis Parasitic
N a s o p h a r y n g e a l polyps (cuterebral larval migration)
Angiostrongylus
vasorum
C u t e r e b r a l larval myiasis Dirofilaria immitis
—
Idiopathic
Idiopathic vestibular syndrome
Toxic
Aminoglycosides
Metronidazole
Eosinophilic meningoencephalitis
Furosemide
Lead
Granulomatous meningoencephalitis
Agent unknown
N e c r o t i z i n g m e n i n g o e n c e p h a l i t i s (Pug, M a l t e s e Terrier)
Chlorhexidine 10% Fipronil s o l u t i o n (aural administration) Traumatic
Nonsuppurative meningoencephalomyelitis ( p r e s u m e d viral)
Iatrogenic: External m i d d l e ear f l u s h i n g or bulla o s t e o t o m y
Head trauma
Myringotomy
Bulla fracture or hemorrhage Infarction or hemorrhage
Vascular
N e c r o t i z i n g l e u k o e n c e p h a l i t i s (Yorkshire Terrier)
Feline ischemic encephalopathy C u t e r e b r a l larval migration
Myringotomy is the deliberate puncture or incision o f an intact, although not necessarily healthy, tympanic mem brane. Needle puncture and subsequent aspiration through the ventrocaudal part of the tympanic membrane allows for collection of fluid from the tympanic cavity for cytologic examination and microbial culture and sensitivity testing. 8
Brain Stem Auditory Evoked Potentials and integrity; it is usually dark gray or brown in cases o f oti tis. A n intact tympanum does not rule out otitis media, and diagnosing otitis media on the sole basis of a ruptured tym panum is also unreliable. 5
Radiography Radiography is useful for evaluating the osseous tympanic bulla. Skull radiographs should be performed under general anesthesia to achieve adequate positioning. This may not always be possible, particularly in the trauma patient. Lat eral, dorsoventral, or ventrodorsal, lateral-20 degree ventral-laterodorsal oblique, and rostral-30 degree ventralcaudodorsal open-mouth oblique radiographs are advised for the assessment of tympanic bulla. 7
Brain stem auditory evoked potentials testing, also known as brain stem auditory evoked response testing, can be used to assess the integrity and function of the peripheral and cen tral auditory pathways, which allows for indirect evaluation of the vestibular pathways because of their close association. Brain stem auditory evoked potentials are recordings of sound-evoked electrical changes in portions of the auditory pathway between the cochlea and the auditory cortex. Because of the level of patient cooperation required, sedation or a light plane of general anesthesia is often needed for this test to be performed and interpreted properly. 4
9
Cerebrospinal Fluid Analysis CSF analysis is a useful adjunctive test for determining the cause of central vestibular disease, although results are rarely specific. Although serum and CSF antibody titers have been used
Figure 104-2 Algorithm detailing the approach to the patient with acute vestibular disease. CNS, Central nervous system; CSF, cerebrospinal; CT, computed tomography; MRI, magnetic resonance imaging. previously to diagnose infectious diseases, polymerase chain reaction analysis o f CSF can now be performed in specialized laboratories to evaluate for the presence o f infectious antigens rather than antibody titers. The risk of iatrogenic C N S trauma or cerebellar herniation following cisterna magna puncture with space-occupying lesions should not be underestimated. It is preferable to obtain advanced imaging studies o f the brain (see Advanced Imaging section next i n this chapter) before performing CSF tap, especially i f a caudal fossa lesion is suspected. 10
be less helpful because o f the artifacts relating to the density o f the petrous temporal bones surrounding the medulla (e.g., beam hardening). M R I o f the peripheral and central vestibular systems pro vides excellent multiplanar soft tissue resolution when com pared with C T . The improved soft tissue contrast provided by this modality allows better assessment of neoplastic and inflammatory conditions that result i n vestibular dysfunction (Figure 104-3). A typical M R I study consists o f Tl-weighted, T2-weighted, and proton density-weighted transverse images made before contrast m e d i u m administration. Postcontrast sequences have been recommended i f a mass is present in the tympanic bulla or the external ear canal. 11
1 1
11
Advanced Imaging C o m p u t e d tomography ( C T ) and magnetic resonance imag ing ( M R I ) have revolutionized the diagnosis o f vestibular diseases. C T evaluation o f the peripheral vestibular system is particularly useful i f radiographs have not determined an underlying cause, i f nasopharyngeal polyps and neoplasia are considerations, or i f the animal is a potential surgical candidate. C T evaluation for central vestibular diseases may
T R E A T M E N T A N D PROGNOSIS The damaged vestibular system can compensate over time w i t h central reprogramming o f eye movements and postural responses, as well as reliance on visual and other sensory
Supportive care can be essential, especially because these animals are frequently anorexic; feeding tubes and fluid ther apy can be vital initially until the patient can self-maintain. Vomiting, salivation, and nausea associated with vestibular disease can be treated with antiemetic medications. Drugs c o m m o n l y used include the phenothiazinc derivative chlorpromazine (0.2 to 0.5 mg/kg SC q8h), serotonin receptor antagonists dolasetron (0.6 t o l mg/kg S C , IV, or P O q24h) and ondansetron (0.1 to 0.1 mg/kg P O q l 2 - 2 4 h or 0.1 to 0.5 mg/kg IV slowly q6-12h), metoclopramide, an antidopaminergic serotonin receptor antagonist and chemoreceptor trigger zone inhibitor (0.1 to 0.5 mg/kg IV, S C , or P O q6h or as an I V infusion o f 1.1 to 2.2 mg/kg q24h), or the antihistamines diphenhydramine (2 to 4 mg/kg P O or I M q8h) and meclizine (12.5 mg P O q24h) (see Chapter 182, Antiemetics). 2
SUGGESTED FURTHER READING*
Figure 104-3 Transverse T2-weighted fluid-attenuated inversion re covery magnetic resonance study of a 4-year-old mixed breed dog with central vestibular disease and multiple cranial nerve involvement. A large irregular lesion hyperintense to the surrounding brain stem is identified (arrows). Pathologic examination confirmed granulomatous meningoencephalomyelitis.
Bagley RS: Recognition and localization of intracranial disease, Vet Clin North Am Small Anim Pract 26:667, 1996. A review chapter that documents the symptoms expected with lesions in the various regions of the intracranial neuroanatomy. Cook IB: Neurologic evaluation of the ear. Vet Clin North Am Small Anim Pract 34:425, 2004. An article that reviews neurologic dysfunction commonly associated with dis eases of the ear and differentiating these symptoms from central disease. Thomas WB: Vestibular dysfunction, Vet Clin North Am Small Anim Pract 30:227, 2000.
2
input that replaces lost vestibular input. If the underlying disease process can be targeted, the prognosis for a func tional recovery can be good. Residual signs, such as a head tilt, are always possible. Recurrences can occur at times o f stress, recurrent disease, or following anesthesia.
A comprehensive review of vestibular disease in dogs and cats. 'See the C D - R O M for a complete list of references.
Chapter 105 CEREBROSPINAL FLUID SAMPLING Beverly K. Sturges, D V M ,
DACVIM
(Neurology)
KEY POINTS • Cerebrospinal fluid (CSF) analysis can rapidly provide information that may be useful in making a diagnosis, deciding on a treatment protocol or further diagnostic tests, and monitoring response of central nervous system (CNS) disease to medical treatment. • The most c o m m o n indication for CSF analysis in the emergency or intensive care unit setting is suspicion of infectious or inflammatory disease of the C N S . • In collecting CSF, correct patient positioning and a good understanding of regional anatomy are essential. • CSF findings uncommonly yield a definitive diagnosis and should be interpreted in light of the patient history, neurologic signs, and other diagnostic results. In addition, they may be normal in spite of significant CNS disease. • Risks versus benefits of a CSF collection should be considered carefully in patients with elevated intracranial pressure. • CSF cell counts and cytology study may be done in-house with minimal investment in equipment and will give the emergency clinician the most useful information for making a diagnosis.
INTRODUCTION Cerebrospinal fluid (CSF) collection and analysis may pro vide rapid information to the clinician investigating a disease affecting the central nervous system ( C N S ) . It is particu larly useful for confirming the presence of inflammatory and infectious diseases affecting the brain, spinal cord, or nerve roots, especially when the meninges are involved.'" However, C S F analysis should be considered only after an accurate history, physical, and neurologic examination has localized a lesion to the C N S and a logical list of differential diagnoses has been considered carefully. In most situa tions, the results of a C S F analysis provide the clinician with a "piece of the puzzle" that must be used in conjunction with the results of other diagnostic tests, especially magnetic reso nance imaging ( M R I ) , to arrive at a correct diagnosis. 1 , 2
F i g u r e 105-1 Cerebrospinal fluid (CSF) pathway and location of cis ternal puncture. CSF, secreted by the choroid plexus (dark blue), flows through the ventricular system (medium blue) from rostral to caudal: lat eral ventricles, third ventricle, mesencephalic aqueduct, and fourth ven tricle. From there, most of the CSF exits via the lateral apertures of the fourth ventricle and flows cranially and caudally in the subarachnoid space around the brain and spinal cord (light blue). The remainder of CSF flows caudally down the central canal of the spinal cord. CSF from the cranial subarachnoid space enters the venous system via arachnoid villi. Cisternal puncture is performed by placing a needle in the dorsal subarachnoid space at the craniocervical junction. This space usually becomes accessible when the head is ventroflexed.
3
Absorption o f C S F occurs primarily through the arachnoid villi that penetrate the major dural venous sinuses in the cranium. 4
1,2
C E R E B R O S P I N A L FLUID F O R M A T I O N A N D FUNCTIONS
INDICATIONS FOR C E R E B R O S P I N A L FLUID C O L L E C T I O N A N D A N A L Y S I S C S F analysis is indicated when a patient has neurologic signs consistent with disease affecting the C N S , including the brain, spinal cord, and nerve roots.'" Advanced imaging (e.g., M R I , computed tomography [CT]) before C S F collec tion is usually recommended, whenever possible, to help define the underlying neurologic disease. It gives valuable information relating to the exact location of the lesion, the amount and distribution of associated edema, and any struc tural evidence of intracranial hypertension ( I C H ) . However, regardless of findings on advanced imaging, animals that are showing rapid neurologic deterioration are most likely to benefit from a diagnostic C S F analysis. C o m m o n indications for C S F collection in the emergency or critical care setting include the following: 3
The presence of C S F in the subarachnoid space reduces mechanical trauma to the nervous tissue and serves to remove the products of brain metabolism (Figure 105-1). It is also an intracerebral transport m e d i u m for nutrients, neu roendocrine substances, and neurotransmitters. Most C S F is formed by the choroid plexus in the ventricles via ultrafiltra tion of plasma and the active transport of selected substances across the blood-brain barrier. The C S F flows caudally through the ventricular system; the majority exits via the fourth ventricle to circulate cranially around the brain and caudally around the spinal cord in the subarachnoid spaces. 4
4
4
5
l . Suspected infectious or inflammatory disease affecting the C N S . Conditions causing meningitis, encephalitis, and 6
myelitis are often moderate to severe i n nature by the time these animals are showing neurologic signs and CSF analysis should be done as soon as possible. It is always preferable to collect C S F before treating with med ications that may influence the content and, subsequently, the interpretation o f the findings. 2. Suspected neoplastic disease affecting the C N S . ' W i t h the exception o f C N S lymphoma, C S F findings alone are rarely specific for neoplastic disease. However, an analysis is often done to rule out the possibility o f inflammatory disease that may also be o n the differential list, especially if advanced imaging is not available. 3. Animals having cluster or continuous seizures i n which underlying infectious or inflammatory disease or neopla sia is likely. 4. Acute, ascending lower motor neuron signs. Because the prognosis and treatment vary widely depending o n the underlying cause o f these signs, C S F findings may help to differentiate diseases such as acute polyradiculopathy from infectious, inflammatory, or neoplastic disease (e.g., l y m p h o m a ) . CSF analysis occasionally may be indicated to m o n i t o r short-term response to treatment when an obvious response to therapy is not evident or cannot be monitored. This may be especially applicable to animals that are systemically i l l , heavily sedated, or being mechanically ventilated. C S F evalu ation, or "the C B C o f the C N S , " may be particularly helpful in guiding the clinician i n further treatment and prognosis in such cases. 1 , 2
6
1
1
1
CONTRAINDICATIONS A N D RISKS CSF collection requires general anesthesia, the risks o f which are inherently higher i n animals that might have elevated intracranial pressure ( I C P ) . ' Risks o f anesthesia are m i n i m i z e d by the following measures: 1. Using an anesthetic protocol that reduces I C P 2. Treating patients with mannitol, ventilation, and control of partial pressure o f arterial carbon dioxide before anesthetizing i f severe I C H is suspected (see Chapter 100, Intracranial Hypertension) The emergency clinician should also be aware of the fol lowing situations i n which the risks o f performing a C S F col lection are very likely to outweigh benefits, and therefore the procedure is not recommended ' : • Acute traumatic brain injury • Rodenticide toxicity, aspirin ingestion, serious coagulopathies • Severe, progressive I C H • Atlantoaxial luxation or cranial cervical fracture or luxation Although C S F analysis is one o f the easiest and most direct methods for evaluating the C N S , the p r o x i m i t y o f important neural structures makes it possible to penetrate these structures inadvertently during needle placement, espe cially i f there is pathology affecting the subarachnoid space. The most c o m m o n injury is trauma to the cerebellum, brainstem, or cervical spinal cord. It produces a vestibular syndrome that is apparent when the animal recovers from anesthesia. A rarer, but more serious, consequence is iatro genic trauma that produces apnea. Immediate treatment w i t h hyperosmolar therapy, mechanical ventilation, and possibly 3
1
5
2
1
1
1
glucocorticoids, may save the life o f the apneic patient. Patients with vestibular signs w i l l usually recover without treatment i n a few days to a couple weeks. The incidence o f these complications is rare i n the hands o f a careful, trained individual. In cases o f I C H , herniation o f the brain may occur from a rapid reduction o f I C P (e.g., pop-off valve effect), producing apnea and unresponsiveness. Usually mydriatic pupils are apparent even while the animal is still anesthetized. A l t h o u g h immediate aggressive treatment for I C H is i n d i cated, these animals have a grave prognosis. 1
C E R E B R O S P I N A L FLUID C O L L E C T I O N TECHNIQUES Preparation For C S F collection and examination it is necessary to puncture the subarachnoid space i n the cerebellomedullary cistern or i n the lower l u m b a r s p i n e . Small animals must be anesthetized to ensure complete i m m o b i l i t y . A p r o p o f o l infusion w i t h m i d a z o l a m or fentanyl, or both, provides excellent anesthesia for performing C S F collection i n patients w i t h I C H . The site must be shaved, surgically prepared, and draped w i t h a small fenestrated sterile drape. Sterile surgical gloves should be w o r n . A l l equipment should be assembled and ready to use before p o s i t i o n i n g the patient. The following items are necessary: 1 , 3 , 5 , 6
1. Sterile gloves and drape or sterile field 2. Disposable spinal needles w i t h stylets A 22-gauge, 1 Vi-inch spinal needle is used i n most cister nal punctures regardless o f size of the dog; it may also be used for cisternal puncture i n cats and for lumbar puncture i n small dogs and cats. A 22-gauge, 2 /2-inch spinal needle is occasionally neces sary for doing a cisternal puncture i n giant breed dogs or i n large breed dogs with heavy cervical musculature; it is also c o m m o n l y used i n lumbar punctures o f most dogs weighing more than 5 kg. A 22-gauge, 3'/2-inch spinal needle is used for lumbar punctures i n large and giant breed dogs. A 25-gauge, 1-inch spinal needle may be used i n small cats and toy breed dogs. These needles are more easily supported by the surrounding tissues i n very small animals, and the bevel o n the needle is less likely to cause trauma to the brain stem or spinal cord. H o w ever, C S F flow is considerably slower through this needle, w h i c h should be remembered when watching for the flash o f C S F i n the hub identifying the subarachnoid space. 1
3. Red-top glass b l o o d collection tubes (Vacutainers)
Cerebrospinal Fluid Collection Sites and Techniques CSF collection can be done from the cisterna magna, the lat eral ventricle (rarely), or the lumbar r e g i o n . ' W h e n focal C N S disease is suspected, C S F findings are more likely to be abnormal and representative o f the underlying pathology when they are collected caudal to the lesion. In multifocal or diffuse C N S disease, C S F collection at both cisternal and lumbar sites is recommended. 1,3,5
6
Cisternal
Puncture
Positioning The subarachnoid space enlarges to form the cerebellomedullary cistern i n the dorsal atlantooccipital region (see Figure 1 0 5 - 1 ) . ' ' This site is used when the patient's signs suggest brain or cranial cervical spinal cord disease. D u r i n g cis ternal puncture the neck is flexed and a patent airway must be maintained under anesthesia by use o f an endotracheal tube. The animal is placed i n lateral recumbency (right lateral is usu ally easiest for a right-handed person) and an area from the occipital protuberance to the level o f C3 is surgically prepared. 1
3,5
6
W i t h the assistant standing opposite the person doing the puncture, the neck is flexed moderately (90 to 100 degrees) at the cisternal region while holding the ears out o f the way. It is important to make sure that the midline o f the neck and the head (from the nose to the occiput) are per fectly parallel to the tabletop. If the neck sags, as is c o m m o n i n larger dogs, place a small pad under it. T h e n palpate the wings o f the atlas and make sure they are superimposed, eliminating axial rotation. Positioning is critical i n m a k i n g the puncture exactly o n midline.
Recheck landmarks and patient alignment and try another puncture. 2. If bloody CSF appears i n the hub, most likely the needle has traumatically ruptured vessels i n the pia. Replace the stylet for a minute, let any blood-tinged CSF flow out, and collect CSF after it clears. C S F that remains uniformly blood tinged may reflect hemorrhage w i t h i n the C N S . If the tip of the needle is hitting bone, determine i f it is hitting C I or the occipital bone. P u l l the needle out slightly and redi rect cranially or caudally along the sagittal plane. If bone is encountered repeatedly, it is best to start over with a new needle after rechecking landmarks and patient positioning. In cats and small dogs, 1 to 2 m l o f CSF can be safely col lected by free flow into a sterile glass tube; 6 m l or more may be collected i n larger dogs. " It is best not to aspirate fluid from the hub of the needle, because it may collapse the CSF space or initiate hemorrhage. Once enough CSF has been collected, remove the needle. Historically, the opening pressure o f the C S F was measured by attaching a stopcock and manometer to the needle before collecting fluid. H o w ever, this practice has largely been abandoned for safer, more accurate ways o f measuring C S F pressure and is not recom mended. If there is concern o f life-threatening I C H , it may be safer to attempt a lumbar puncture instead of a cisternal puncture. 1
3
1
5
Palpate all landmarks before inserting the needle: external occipital protuberance, spinous process o f C 2 vertebra, the dorsal arch o f C I vertebra (do this by slipping rostrally off of C 2 spine), and the wings o f the atlas. Either o f the follow ing methods for finding the correct point of insertion may be used: 1. Using the external occipital protuberance and the spine o f C2, the puncture is made o n midline halfway between the occiput and the cranial end of the spinous process. If the dorsal arch o f C I can be palpated, the puncture is made on the midline just cranial to it. 2. Using the wings o f the atlas, the puncture is made i n the center o f the triangle formed by the occiput and the wings of the atlas. W i t h either method, a natural indentation can usually be palpated o n midline where the needle is most likely to enter the subarachnoid space.
PRECAUTION: Especially important i n the emergency and critical care setting is to exercise caution when collecting CSF from patients with very high pressures from meningoenceph alitis, C N S edema, or an intracranial mass. In these cases it may be dangerous to remove or allow escape o f very much CSF. The sudden release o f pressure may lead to brain hernia tion. If CSF flows out o f the needle at a high rate, or i f flow is initially very good and then suddenly diminishes, a m i n i m a l amount o f CSF should be collected. Also, i n animals with sus pected I C H , extreme care should be taken not to severely flex the animal's head or place any compression o n jugular veins during CSF collection.
Lumbar
Puncture
Needle Insertion
Positioning
Place the spinal need perpendicular to the plane o f the verte bral c o l u m n and advance it slowly at a 90-degree angle through the skin and underlying tissues. Extremely tough skin, as i n cats, may need to be tented and penetrated before the landmarks are identified for puncture into deeper tissues. Every time a layer o f tissue is penetrated, detected by a sud den decrease of resistance at the needle tip, remove the stylet and observe the hub o f the needle for a few seconds for the appearance o f CSF. In small dogs and cats, the tissue planes are not as easily ascertained by feel and the stylet should be removed and checked every 1 to 2 m m . This prevents inad vertent penetration o f neural tissue. W h e n the dura is pene trated, resistance decreases and C S F appears i n the hub o f the needle when the stylet is removed. Occasionally a twitch may be seen or felt when the dura is penetrated, especially i f it is inflamed.
In animals with thoracic, lumbar, or sacral spinal cord dis ease, C S F should be collected from the lumbar region. ' Additionally, lumbar C S F is usually preferred i n animals with ascending lower motor neuron disease or suspected polyradiculopathies. Because o f the proximity of the punc ture site to the diseased cord and the craniocaudal flow of CSF, lumbar fluid is more likely than cisternal C S F to reflect the disease process. In animals that are too i l l to undergo general anesthesia or are comatose, a lumbar puncture (and occasionally a cisternal puncture) can be done with a local anesthetic and a tranquilizer i f needed.
Tips for Trouble-Shooting Puncture
Cerebrospinal
Fluid
1. If pure b l o o d drips from the hub, most likely the needle is slightly off midline and into the vertebral venous plexus, outside o f the dura. This poses no harm to the patient and the needle should be removed and discarded.
1
6
The technique of lumbar puncture for collection of CSF is the same as that used to place a needle for injection of con trast material into the subarachnoid space for myelography. CSF analysis should always be done before myelography to rule out meningitis or myelitis, because injecting contrast media when there is inflammation or infection may further damage an injured cord and possibly disseminate infection. If need be, after lumbar spinal needle placement and CSF collection, the patient can be kept under anesthesia with the needle i n place for the few minutes needed to do a cell count and differential; then the myelogram can be done i f marked inflammation is not present. The patient is
positioned i n lateral recumbency with the right side down (for a right-handed person). The lumbar spine may be gently flexed to open up the interarcuate space between L4-5 (large breed dogs preferred site), L5-6 (small breed dogs preferred site), or L6-7 (cats preferred site). A n area from the m i d lumbar to the sacral region is clipped and surgically prepped; sterile technique is used as described above. Palpating the spinous process caudal to the desired interarcuate space, insert the spinal needle through the skin at the caudal lateral edge o f the spinous process. W i t h the needle directed cranially and following the spinous process down, insert it until the vertebral arch is encoun tered. Then "walk" the needle cranially u n t i l the interarcu ate space is felt. Push the needle gently through the ligament and spinal canal u n t i l the floor o f spinal canal is encountered. The animal w i l l often twitch when the needle penetrates the dura. If spinal fluid is not seen i n the hub o f the needle w i t h i n a few seconds, the needle can be rotated or retracted slowly, or both, u n t i l the subarachnoid space is entered and fluid appears. F l u i d should be allowed to d r i p into the collection tube by free flow and not aspirated from the needle. If b l o o d is present i n the hub, the needle should be withdrawn and discarded and another puncture attempted at a different site. N O T E : Although the cauda equina is penetrated i n the process of performing the puncture, this usually produces no i l l effects.
Table 105-1 Characteristic
Normal Characteristics of CSF Findings in Normal CSF
Color
Colorless
Clarity
T r a n s p a r e n t , clear
Refractive i n d e x
1.3347 t o 1.3350
Protein concentration
Cisternal: 6 weeks) therapy is generally indicated. C o m b i n a t i o n therapy is recommended for cases of infective necrotizing fasciitis (see section on Empiric Antibiotic Strategies later i n chapter), endocarditis, or when polymicrobial infections are suspected. 15
t
s
15
2
11
15
19
2
2
Streptococcal toxic shock syndrome (STTS), with or without necrotizing fasciitis, is recognized as an emerging syndrome i n dogs (see Chapter 115, Necrotizing Soft Tissue Infections). ' The most c o m m o n infection i n animals w i t h STTS appears to be the lung, with affected dogs suffering from acute or peracute suppurative bronchopneumonia. Some case histories have included failed attempts to treat patients with enrofloxacin and nonsteroidal antiinflamma tory agents. ' Cases of STTS-associated septicemia are often fatal, whereas most dogs w i t h necrotizing fasciitis 10
15
15
19
10
15
ENTEROCOCCAL INFECTIONS Enterococcus species are facultative anaerobic cocci that dem onstrate intrinsic and acquired resistance to multiple antibio tics. Enterococci (previously group D streptococci), as the name implies, are commensal bacteria that inhabit the alimen tary tract of animals and h u m a n s . ' ' Enterococcal infec tions were previously considered rare, and not especially virulent, i n companion animals. They typically are recovered from mixed infections i n w h i c h it is difficult to assess their role; they are assumed to be commensal organisms "along for the ride" w i t h other more virulent organisms such as anae robes and gram-negative enteric bacteria. Such a priori assumptions can no longer be made, because pathogenic and drug-resistant enterococci are recovered increasingly from hospitalized patients. ' Similarly, the presence and expression of virulence genes i n some enterococcal species implies that these organisms are an important consideration i n the treat ment of serious gram-positive i n f e c t i o n s . ' ' ' ' 8
4
10
14
14
3 4
3
4
7
14
15
Postoperative w o u n d and urogenital infections are seen most commonly; however, enterococcal cholangiohepatitis, peritonitis, vegetative endocarditis, mastitis, and b l o o d borne infections have been reported i n companion ani mals. ' M a n y enterococci are intrinsically resistant to numerous antibiotics, and the development of M D R entero cocci is thought to result from both inappropriate antibiotic usage and poor infection control measures i n hospitalized patients. " ' ' The vast majority of clinical isolates belong to the species Enterococcus faecalis, although E. faecium remains the species that exhibits a disproportionately greater resistance to multiple antibiotics. ' 4
15
2
4
8
10
7
8
E. faecium is largely of interest because of increasing resis tance to vancomycin, which u n t i l recently was effective for almost all penicillin-resistant enterococci. Strains that remain sensitive to vancomycin may be resistant to a wide range o f drugs that are c o m m o n l y selected for empiric treat ment of intensive care patients. ' A l t h o u g h the veterinary literature is sparse, there are recent and serious concerns of acquired antibiotic resistance by E. faecalis and E. faecium. There is a lack of host specificity among various bacterial strains that suggests that cross-colonization of resistant strains may occur from one species to another. ' ' E. faecium often possesses inherent and acquired resistance to many 10
7 8
7
8
22
drug classes, including the fluoroquinolones, clindamycin, macrolides, and potentiated sulfonamides. ' Unlike most streptococci, the enterococci are often inhibited, but not killed, by penicillins and are generally resistant to cephalos porins. Moreover, although enterococci do not intrinsically produce B-lactamases, production o f these enzymes by the bacteria may be induced by exposure to B-lactamase inhibitor drugs. As such, it is of no benefit to prescribe amoxicillinclavulanate or ampicillin-sulbactam i f the pathogen is sensitive to the aminopenicillin alone. 7 8
2
O f the 52 E. faecium isolates obtained from clinical patients at the Ryan Veterinary Hospital of the University of Pennsyl vania, 71% were resistant to ampicillin (S. Rankin, personal communication). One o f the few effective modes of therapy takes advantage of antibiotic synergy; penicillins alone only arrest their growth and aminoglycosides are without effect except at very high concentrations, but the combination of both drugs effectively kills the organism. This high-dosage synergy approach is among the most effective pharmacologic means to clear infection and, unless there is compelling evi dence that other potentially safer antibiotic regimens are effec tive both i n vivo and i n vitro, the combination o f gentamicin plus a cell wall-active agent (generally ampicillin) remains a gold standard for critically ill veterinary patients. 4
22
Unfortunately, some enterococci are becoming resistant to aminoglycosides, even when coadministered with ampicil l i n , leaving the clinician with few alternatives to eradicate the infection. In some cases, the only effective drugs are glycopeptides, such as vancomycin, but this drug should be viewed as an absolute last resort. ' Vancomycin has a nar row spectrum and is potentially nephrotoxic (see Chapter 200, Miscellaneous Antibiotics). Clinical experience with vancomycin is limited i n veterinary medicine. 4
4 8
1
O f approximately 35 species of staphylococcal organisms, 3 are o f clinical importance i n companion animals: Staphylo coccus aureus, Staphylococcus intermedius, and Staphylococcus schleiferi subspecies coagulans. ' ' S. intermedius is the leading pyogenic bacterium of dogs. Although it is recog nized as the most c o m m o n etiologic agent of bacterial skin and ear infections, it is may also cause systemic infections including arthritis, osteomyelitis, cystitis, mastitis, and bac teremia. ' Sites of infection are similar i n cats, although reports of disseminated disease are less numerous. Infections with strains of S. intermedius that are resistant to virtually all P-lactam agents are becoming more com m o n . Approximately 40% of S. intermedius strains isolated from dogs are simultaneously resistant to three or more anti biotics. Antibiotic resistance patterns have emerged for pyo derma and systemic infections caused by S. schleiferi as well. A l t h o u g h this bacterium appears to be a less frequent cause of disseminated infections, results of clinical studies reveal that tissue tropism and antimicrobial susceptibility data are not predictable for this relatively novel species. S. aureus, however, is well established as a significant communityacquired and nosocomial pathogen i n humans, and infection with methicillin-resistant S. aureus ( M R S A ) is an ominous development in veterinary m e d i c i n e . ' ' ' ' 9 l0 2i
10
5
5
9
9
5
3
6
6
11
12
10,12
6 11
10
1112
12
23
2
3
9
18
23
Pathogenic staphylococci may affect any organ system and are responsible for community-acquired and nosoco mial infections. Pyogenic staphylococcal infections occur most c o m m o n l y in the skin, eyes, ears, and respiratory and genitourinary tracts. Osteomyelitis, meningoencephalitis, bacteremia, and endocarditis have also been r e p o r t e d . ' 12
12
18
9
24
25
25
6
24
5
The broad distribution of staphylococci as n o r m a l flora o f domestic animals is perhaps the most important epide miologic factor i n staphylococcal i n f e c t i o n s . ' ' ' These organisms are generally not inherently invasive and colo nize intact epithelium o f healthy animals without causing disease. ' Subsequently, isolation of these bacteria may signify the presence of transient contaminants or long-term colonization o f epithelial surfaces. ' Disease pathogenesis and lesion development are i n c o m pletely understood, but likely involve a breach of the host's mucosal barrier or other means of immunocompromise, i n conjunction with numerous bacterial virulence factors such as staphylococcal toxins and enzymes that permit them to withstand phagocytosis by neutrophils. " For many years, production of coagulase by staphylococci has been associated with virulence and tissue tropism, and almost all infections i n humans, dogs, and cats were caused by coagulase-positive spe cies, with coagulase-negative staphylococci viewed invariably as c o n t a m i n a n t s . ' M o r e recent studies have implicated coagulase-negative staphylococci as a cause of significant infection i n humans and companion a n i m a l s . ' ' ' '
6
N o t all S. aureus organisms are methicillin resistant. Moreover, other staphylococcal species may be classified as methicillin resistant. Determination o f methicillin resistance is based o n i n vitro resistance to o x a c i l l i n . If staphylococci are resistant to oxacillin, they are considered resistant to all other B-lactams, including cephalosporins and amoxicillinclavulanate, regardless of the results of i n vitro susceptibility testing. A l t h o u g h dogs and cats are not natural reservoirs of S. aureus, they can become colonized, i n all likelihood from h u m a n s . ' Once colonized, pets may clear the organism, go o n to develop infection, or remain asymptomatic carriers for an indeterminate p e r i o d . ' 6
STAPHYLOCOCCAL INFECTIONS
10
24
Virulent M D R staphylococcal infections are isolated most commonly from hospitalized patients, or patients that have a history of antibiotic use. Surgical wound, bronchopulmon ary, and genitourinary tract infections caused by M R S A are documented more commonly, although any body system is susceptible to infection by these opportunistic bacteria. Staphylococcal resistance to P-lactam agents is due to the possession of a plasmid-encoded P-lactamase, or the pres ence o f a chromosomal element that contains the gene that encodes for a penicillin-resistant P B P s . ' ' ' Infected animals should be isolated, and barrier contact pre cautions should be used when handling patients, food bowls, bandages, and all associated materials. Handwashing between patients is imperative. Such guidelines must be enforced (1) to minimize the risk of patient-to-patient spread of resistant clones and (2) to limit the likelihood of animal-to-human transmission. There is increasing evidence that interspecies transmission o f M R S A occurs and that it may be emerging as an important zoonotic and veterinary disease. ' ' 6
6
9
1 2
2 4
5 6 25
In h u m a n hospitals, transmission occurs mainly via the transiently colonized hands of health care workers. Colo nized veterinary personnel are thought to be the most likely vectors of M R S A in veterinary h o s p i t a l s . ' ' A l l personnel i n contact with patients should be advised of appropriate precautions once M R S A infection is c o n f i r m e d . ' Like other staphylococci, M R S A can survive for long periods on inanimate objects such as bedding and cages, and it is rela tively resistant to heat. Thus it is difficult to eliminate once 6
24
25
9
25
introduced to the hospital environment. M R S A infections, although serious, most often remain treatable, albeit b y a small number o f antibiotics. ' ' Because M R S A may be transmitted between animals and humans, owners o f infected or colonized animals should be informed o f this potential. However, veterinarians are discouraged from making any recommendations regarding the diagnosis or treatment o f M R S A , or any disease, i n humans. Treatment o f deep or disseminated staphylococcal infec tion requires systemic therapy. ' D r u g choices should be based o n i n vitro susceptibility testing i n combination w i t h other factors (e.g., drug penetration, site o f infection). H i s torically, uncomplicated methicillin-susceptible staphylococ cal infections are predictably responsive to p-lactam and (3lactamase inhibitor combination drugs and first-generation cephalosporins. These are drugs o f first choice for routine infections when staphylococcal infection is suspected. C l i n d a mycin, azithromycin, potentiated sulfonamides, tetracycline, gentamicin, and the fluoroquinolones are frequently, although not uniformly, effective for treating most staphylo coccal infections. ' ' This level of confidence cannot extend to hospitalized patients with risk factors for M D R , such as those with a history o f antibiotic use, indwelling devices, exposure to nosocomial pathogens, and protracted hospital stays. 5
6
25
6
10
12
Table 108-1 Antibiotics Used to Treat Gram-Positive Infections Drug
Dosage
Amikacin
15 to 20mg/kg IV q24h
Ampicillin
22 mg/kg IV q6-8h
Ampicillin-sulbactam
22 mg/kg IV q8h
Azithromycin
5 to 10 mg/kg IV q24h
Cefazolin
22 mg/kg IV q6-8h
Cefotetan
30 mg/kg IV q8h
Cefoxitin
30 mg/kg IV q6-8h
Chloramphenicol
25 to 50 mg/kg IV q8h (dogs) 15 to 20 mg/kg IVq12h (cats)
Clindamycin
10 mg/kg IV q8-12h
Enrofloxacin
12.5 to 20 mg/kg IV q24h (dogs) 5 mg/kg IV q24h (cats)
Gentamicin
6.6 mg/kg IV q24h
Imipenem-cilastatin
5 to 10 mg/kg IV q6-8h
12
1
10
26
Meropenem
8 to 12 mg/kg IV q8-12h
Ticarcillin-clavulanate
50 mg/kg IV q6-8h
Vancomycin
15 mg/kg IV q8h (dogs) 10 to 15 mg/kg IV q8h (cats)
12
Culture and susceptibility testing is imperative for such patients, regardless o f the drug being considered for ther apy. The proliferation o f methicillin resistance i n S. aureus, S. schleiferi, and S. intermedius suggests that empiric therapy guidelines require revision, because resistance to many non-B-lactam antibiotics occurs i n these genera as w e l l . ' Significantly, methicillin-resistant S. intermedius and M R S A are increasingly resistant to fluoroquinolones and macrolides. Commercial veterinary laboratories should test all P-lactam-resistant staphylococci for susceptibility to chloramphenicol, clindamycin, tetracycline, and potentiated sulfonamides. Preliminary reports should be available w i t h i n 2 days for standard aerobic cultures submitted under appro priate c o n d i t i o n s . Duration o f therapy depends o n the site o f infection and comorbid conditions that may impair host defenses or delay healing. W h e n tolerated, therapy extends 2 weeks beyond the resolution o f clinical signs o f infection. 12
2
9
1,2,9,12
10,12
Although vancomycin and linezolid remain the only effective antibiotics for M D R strains i n human health care settings, these drugs should be used only i n exceptional circumstances i n veterinary medicine. It is argued that their use should restricted i n dogs and cats, because avoidance of antibiotic use is a valid strategy to curtail antibiotic resistance. Consultation with a microbiologist or clinical pharmacologist is strongly recommended before determin ing that therapy with either o f these drugs is indicated for a given patient. 12
EMPIRIC ANTIBIOTIC STRATEGIES In the critically i l l patient, broad-spectrum empiric anti microbial therapy is warranted when the pathogen is not known or when polymicrobial infection is suspected (Table 108-1). Wright-Giemsa and gram-stained cytologic preparations o f aspirates or impression smears should be examined to evaluate the morphologic and staining charac teristics of bacterial pathogens.
IV, Intravenous.
Clinicians should be familiar w i t h the gram-positive pathogens associated w i t h severe infections i n their hospital and choose therapy based o n the prevalence and susceptibil ity patterns o f these bacteria, a n d the site(s) o f infection. Once culture a n d susceptibility data are available, therapy is streamlined to ensure eradication o f the pathogen without promoting resistance secondary to inappropriate antibiotic treatment. A l t h o u g h bacterial resistance to previously effective antibiotics is an ever-increasing concern i n patients with gram-positive infections, first-choice recommendations i n critically i l l veterinary patients still include a first-generation cephalosporin (e.g., cefazolin), aminopenicillin, or a P-lactam and P-lactamase inhibitor combination (e.g., ampicillinsulbactam). The first-generation cephalosporins have a simi lar spectrum o f activity to ampicillin, w i t h the notable differ ence that P-lactamase-producing staphylococci often remain susceptible to the cephalosporins. However, methicillinresistant coagulase-positive staphylococci are resistant to all cephalosporins. 12
1
Sulbactam, like clavulanic acid, is an inhibitor o f P-lactamases. These drugs have weak antibacterial activity by them selves, but show extraordinary synergism when administered with ampicillin, amoxicillin, or ticarcillin, because they irre versibly b i n d the P-lactamase enzymes o f many resistant bacteria. ' The aminopenicillins and first-generation cepha losporins have relatively short half-lives, and i n the absence of renal impairment they should be administered every 6 hours to take advantage o f the well-described pharmacodynamic properties o f most p-lactam agents. This recommendation is particularly relevant for patients w i t h altered volumes o f distribution (i.e., patients o n intravenous fluids, parenteral nutrition or b l o o d products, and those with vascular leak or third-spacing syndromes). 1
1
11
Alterations i n drug clearance can occur rapidly, and the clinician must consider these and other pharmacokinetic principles when determining dosages o f all antibiotics so that the desired pharmacodynamic effects can be reached. A notable exception to the above therapeutic recommen dations occurs when there is documentation of a new infec tion i n a patient that is already receiving one of these drugs. Similarly, critically i l l patients with a history o f antibiotic therapy or polymicrobial infection may be treated appro priately w i t h broader-spectrum antibiotics, such as a carbapenem, alone or i n conjunction with an aminoglycoside or fluoroquinolone, while culture and susceptibility results are pending. Both fluoroquinolones and aminoglycosides remain effec tive treatment for some staphylococci. Neither drug class is predictably active against streptococci. They do, however provide very good coverage for gram-negative pathogens that may be contributing to patient morbidity. These agents generally are administered once daily at the upper end of the dosage range. Enrofloxacin should not be administered at high dosages to cats, because its administration has been associated with temporary or permanent blindness i n domestic felids. A m o n g the aminoglycosides, gentamicin is generally more effective than amikacin for staphylococcal infections. Both are associated w i t h potential renal dysfunction, but they frequently are prescribed without incident for shortterm therapy (20) has been reported with G I hem orrhage, especially when it occurs i n the upper G I tract. This phenomenon has been explained by volume depletion and intestinal absorption o f proteins, including digested blood, into the circulatory system. Large bowel hemorrhage is reported to have little effect on B U N levels. ' However, as diseases result ing i n increased protein metabolism (fever, burns, infections, starvation, and administration o f glucocorticoids) may also result i n an increased BUN-to-creatinine ratio, they should be considered before concluding that G I hemorrhage is the cause. ' It should also be noted that many dogs with GI hem orrhage do not have an elevation i n the B U N concentration. 4
1 4
15
15
15
16
1 15
1
In equivocal cases of G I hemorrhage a fecal occult blood test, most o f which rely o n the peroxidase activity o f hemoglobin, may be performed. Although it may be helpful for detecting occult G I hemorrhage, diets containing red meat or having high peroxidase activity, such as fish, fruits, or vegetables, can cause false-positive results. The presence o f peroxidase-producing bacteria within the GI tract may also cause false-positive results. These factors must be considered when interpreting positive chemical-based fecal occult b l o o d test results. 17
17
It has been recommended that animals be fed a meat-free diet for at least 72 hours before a fecal occult b l o o d test. O n the other hand, a negative fecal occult b l o o d test result does rule out significant GI hemorrhage. W h e n significant gastric hem orrhage is suspected but not confirmed, passage of a nasogastric tube and aspiration o f the stomach contents may confirm and help localize the site o f GI hemorrhage, although the procedure may cause discomfort and false-negative results have been reported. ' 18
2
11
16
Tests to Help Identify Underlying Causes Once G I hemorrhage is confirmed or suspected, a search for an underlying cause should be pursued. This often includes a coagulation profile, complete b l o o d count, routine b i o chemistry profile, electrolytes, adrenocorticotropic hormone stimulation testing, imaging, and endoscopy as indicated. The coagulation profile may identify coagulopathies such as rodenticide intoxication or clotting factor deficiencies. It may also detect prolonged bleeding times that are not
the direct cause o f GI hemorrhage but that significantly exacerbate b l o o d loss. The platelet count is important, because immune-mediated thrombocytopenia is a common cause o f moderate to severe GI hemorrhage i n dogs. A n elevated hematocrit i n a patient with acute hemorrhagic diarrhea and a relatively n o r m a l plasma protein concentra tion is suggestive o f hemorrhagic gastroenteritis. Given that hepatic and renal disease are reported causes of GI ulceration and hemorrhage, particular attention should be paid to the biochemical markers reflective of these diseases (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and bilirubin i n cases o f hepatic disease; and urea, creatinine, and phosphorus i n cases o f renal dis ease). Because hypoadrenocorticism has been reported as a cause o f severe G I hemorrhage i n the dog, electrolyte levels should be evaluated and an adrenocorticotropic hormone ( A C T H ) stimulation test performed i f another cause for GI hemorrhage cannot be f o u n d . Fecal smears, cultures, and parvovirus testing may be indicated i f infectious disease is sus pected. Measurement o f gastrin levels is recommended in cases o f recurrent GI ulceration and i n cases that fail to respond to medical therapy. 1
18
19
4
Radiographs may detect foreign bodies, masses, or free air i n the peritoneal cavity. Pneumoperitoneum is suggestive of G I perforation i n a patient that has not undergone recent abdominal surgery. Although contrast radiographs may iden tify mucosal defects as a cause of GI hemorrhage, they generally have been replaced by ultrasonography and endoscopy. ' Ultrasonography often w i l l identify foreign bodies and masses, and may help to identify concurrent GI perforation when present. ' The use o f ultrasonography to identify ulcers i n dogs has been described. It allows evaluation of the intestinal wall structure and thickness and can detect the presence o f a defect or crater. W h e n used serially, it may help determine changes i n response to therapy and has suggested the need for surgery i n some instances. Ultrasonography has also been reported i n the assessment of cats w i t h GI ulceration. 4 16
20
21
21
21
3
Endoscopy is considered the most sensitive test to evalu ate upper G I tract hemorrhage and ulcers, although patients must be optimally resuscitated before the procedure. ' It often provides a diagnosis, helps assess prognosis, and may have therapeutic benefits (i.e., foreign body retrieval). In addition to allowing direct visualization o f the mucosa, it permits biopsies for histology and culture, which may be required to identify lesions and infectious diseases (i.e., neoplasia, inflammatory bowel disease, protothecosis). The disadvantages o f endoscopy include the need for anesthesia, its limitation to the proximal GI tract and colon, the poten tial to exacerbate G I hemorrhage, and the possibility of causing iatrogenic ulcer perforation. 7
16
14
If the above diagnostic procedures fail to identify the cause o f significant ongoing G I hemorrhage, abdominal exploratory surgery, scintigraphy using technetium-labeled red b l o o d cells, and arteriography should be consid ered. ' ' Scintigraphy has been demonstrated to aid in localization o f GI hemorrhage i n dogs, and arteriography may help identity GI vascular anomalies. ' ' 2
16
18
2
9
18
TREATMENT The treatment priority i n patients with GI hemorrhage is to stabilize the cardiovascular system, control ongoing
hemorrhage, treat existing ulcers, prevent bacterial transloca tion, and to identify and address the underlying cause. The i n i tial priority is to rapidly identify and reverse any signs o f shock (see Chapters 10 and 65, Shock and Shock Fluids and F l u i d Challenge, respectively). Depending on the duration and extent o f b l o o d loss, administration o f packed red b l o o d cells, whole blood, or oxyglobin may be indicated. In the patient w i t h severe acute GI hemorrhage, this is often implemented as part o f the initial resuscitation protocol. In patients that do not display initial signs of shock, determining when a b l o o d transfusion should be given is less clearly defined. The decision to trans fuse all patients at a specified hematocrit remains controversial. The hematocrit at which a patient requires a transfusion will vary depending o n the degree and rate o f b l o o d loss, hemodynamic status, initial and subsequent hematocrits, presence of concurrent illness, and severity o f clinical signs. If the patient displays clinical signs attributable to a decrease i n oxygen delivery (i.e., tachycardia, hyperlactatemia, tachypnea) or i f serial measurements reveal a decreasing hematocrit after initiating therapy, a b l o o d transfusion is indicated. 22
22
If GI hemorrhage is the result o f a primary coagulopathy or is exacerbated by a secondary coagulopathy (i.e., disseminated intravascular coagulation, hepatic failure, shock, or d i l u t i o n with aggressive fluid therapy), fresh frozen plasma should be considered. In patients with persistent G I hemorrhage as a result o f thrombocytopenia, vincristine may increase the release of platelets from the bone marrow, although the func tion o f these platelets has been questioned. 23
Iced saline gastric lavage has been suggested as a therapy to decrease GI hemorrhage ' ; however, the current consensus i n the human literature is that it be avoided. Iced saline gastric lavage has not been proven to slow hemorrhage, is k n o w n to cause discomfort, and can rapidly lower core body tempera ture, which was demonstrated to prolong bleeding i n an experimental canine study. ' Animals with hematemesis and melena should be treated for G I ulcers until proven otherwise. Medications k n o w n to cause ulcers should be discontinued (i.e., N S A I D S ) . Given the association between GI hemorrhage and steroids i n dogs, unless they are considered essential to therapy (i.e., hypo adrenocorticism, immune-mediated diseases), they should also be discontinued. It is reasonable to administer GI protectants before confirming the cause o f GI hemorrhage, given that ulcers are the most c o m m o n cause o f G I hemorrhage i n dogs and cats, and GI protectants have a wide safety margin. In addition, intraluminal gastric acid neutralization may slow GI hemorrhage by promoting mucosal homeostasis. ' C o m m o n l y used GI protectants include acid suppressants such as histamine-2 receptor antagonists (cimetidine, raniti dine, famotidine) and proton p u m p inhibitors (omeprazole, pantoprazole), mucosal binding agents such as sucralfate, and synthetic prostaglandins such as misoprostol. There are no veterinary studies to conclude which gastroprotectants or combination o f gastroprotectants are most efficacious i n the management o f GI ulcers. However, a study demon strated that famotidine (0.5 mg/kg I V q l 2 h ) , omeprazole (1 mg/kg P O q24h), and pantoprazole (1 mg/kg I V q24h) sig nificantly suppressed gastric acid secretion i n dogs, but ranit idine (2 mg/kg I V q24h) failed to show significant gastric acid suppression at the dosage evaluated. 5 6
6
14
7
24
24
A l t h o u g h histamine-2 antagonists, p r o t o n p u m p i n h i b i tors, sucralfate, and m i s o p r o s t o l have been administered concurrently, most cases o f suspected G I ulceration are managed w i t h either a histamine-2 antagonist or p r o t o n p u m p i n h i b i t o r and sucralfate. ' In cases o f N S A I D toxicity, m i s o p r o s t o l may provide additional benefit. In deciding w h i c h medications to use, consideration should be given to the route o f drug administration because absorption o f medications administered orally i n critically i l l patients has been questioned, and many dogs w i t h G I hemorrhage are v o m i t i n g , w h i c h may further limit the utility o f oral medications. In patients that have persistent v o m i t i n g , antiemetics can be used. M e t o c l o p r a m i d e , given as a constant intravenous infusion (1 to 2 m g / k g q24h), is often tried initially. Cases refractory to metoclopramide may benefit f r o m a d d i t i o n a l antiemetics such as odansetron. Because many causes o f G I hemorrhage are asso ciated w i t h discomfort and p a i n , analgesics such as an o p i o i d s h o u l d be considered. 4
14
In cases w i t h significant GI hemorrhage, broad-spectrum antibiotics (i.e., a penicillin and an aminoglycoside or fluoroquinolone, or a combination o f a cephalosporin, metronidazole, and an aminoglycoside or fluoroquinolone) are warranted because o f the risk o f G I mucosal barrier compromise and bacterial translocation. Ideally, samples for culture and sensitivity (i.e., urine and blood) should be collected before starting antibiotic therapy. M o s t cases o f G I hemorrhage can be managed medically. In cases o f severe G I ulceration and hemorrhage refractory to medical treatment, endoscopic hemostasis may be beneficial. Ulcer hemostasis has been described by injecting epinephrine or 98% alcohol through an endoscope sclerot o m y needle into the base o f an u l c e r . ' The m i n i m a l l y invasive use o f Endoclips or endoscopic thermal, electric, and laser cautery has been described to control G I hemor rhage secondary to vascular anomalies and ulcers i n humans and may be applicable to veterinary medicine. ' Surgery can be avoided i n most cases, but is indicated for preexisting surgi cal disease (foreign body, tumor, septic abdomen) i n patients at risk o f exsanguination or perforation (based on endoscopy or serial sonographic evaluation), or if the patient fails to respond to medical therapy. 7
25
7
11
Because o f the large number o f disease conditions that can result i n G I hemorrhage, therapy directed toward correcting the underlying cause is variable (i.e., surgery for foreign bodies or tumors, steroids for hypoadrenocorti cism, immunosuppressives for immune-mediated t h r o m bocytopenia, discontinuation o f N S A I D s ) . In considering the underlying cause, it is important to consider related or unrelated coagulation abnormalities (i.e., liver disease causing ulceration and a clotting factor deficiency) and to address concurrent diseases that may exacerbate G I hemor rhage (i.e., uremia i n a patient o n N S A I D s ) .
PROGNOSIS M a n y cases o f G I hemorrhage are self-limiting and the prog nosis varies w i t h the underlying cause. In cases o f moderate to severe GI hemorrhage requiring a b l o o d transfusion, the prognosis is reportedly fair to poor, w i t h a mortality rate of 29% to 4 5 % . 1
One of the few publications investigating causes ofGI hemorrhage in veterina patients and an excellent paper addressing causes and management patients with severe acute GI hemorrhage. Liptak JM, Hunt GB, Barrs VRD, et al: Gastroduodenal ulceration in cats: Eight cases and a review of the literature, / Feline Med Surg 4:27-42, 2002. Washabau RJ: Acute gastrointestinal hemorrhage. Part I. Approach to A small study with a good review of the literature concerning GI ulcers in cats. patients, Comp Cont Educ Pract Vet 1:1317, 1996. Stanton ME, Ronald BM: Gastroduodenal ulceration in dogs: retrospective In conjunction with reference that follows, one of the most complete review study of 43 cases and literature review, / Vet Intern Med 3:238, 1989. acute GI hemorrhage published in the veterinary literature. A nice retrospective study and review of GI ulceration in dogs, including Washabau the RJ: Acute gastrointestinal hemorrhage. Part II. Causes and ther apy, Comp Cont Educ Pract Vet 1:1327, 1996. pathophysiology of ulcer development in dogs with various underlying diseases. In conjunction with preceding reference, one of the most complete review Waldrop JE, Rozanski EA, Freeman LM, et al: Packed red blood cell transfu acute GI hemorrhage published in the veterinary literature. sions in dogs with gastrointestinal hemorrhage: 55 cases (1999-2001), / Am Anim Hosp Assoc 39:523, 2003. *See the CD-ROM for a complete list of references. SUGGESTED FURTHER READING*
Chapter 131 VOMITING AND REGURGITATION Peter S. Chapman,
BVetMed,
DECVIM-CA, MRCVS
KEY POINTS • It is important to differentiate between vomiting and regurgitation before proceeding with further diagnostic testing or therapy. • Idiopathic megaesophagus is the most common cause of persistent regurgitation in the adult dog. Myasthenia gravis is the most common cause of secondary megaesophagus, accounting for 20% to 30% of all cases. • Aspiration pneumonia is the most important cause of morbidity in the regurgitating patient. • The multitude of differential diagnoses for vomiting can be subdivided into primary gastrointestinal and other causes. • Abdominal radiographs should be obtained in all patients with acute vomiting. Abdominal ultrasonography may be a more useful imaging modality in patients with chronic vomiting.
regurgitating animals may stretch and arch their necks, m i m i c k i n g abdominal contractions, and the response to pain from an inflamed or ulcerated esophagus may resemble the classic signs o f nausea. It is important to distinguish true bile from the froth and saliva that animals w i t h esophageal disease may regur gitate. A l t h o u g h relatively nonspecific, a further factor that may assist i n the definition o f the problem is the fre quency o f the episodes. A n i m a l s w i t h esophageal disease may regurgitate saliva as frequently as hourly, yet remain bright and systemically healthy. A v o m i t i n g animal is unlikely to sustain this frequency o f v o m i t i n g without becoming unwell.
DIFFERENTIATION OF VOMITING AND REGURGITATION
REGURGITATION
Before formulating a diagnostic and therapeutic plan, it is important to define the patient's clinical problem. M o s t importantly, v o m i t i n g and regurgitation must be distin guished; pet owners may not differentiate between the two problems, but the diagnostic investigations and treatment options w i l l differ significantly. Occasionally pet owners w i l l describe the harsh coughing and retching o f canine infectious tracheobronchitis as v o m i t i n g . In most cases the problem can be defined accurately after taking a thorough history. Historic findings likely to assist i n the differentiation between v o m i t i n g and regurgitation are presented i n Table 131-1. P r e m o n i t o r y signs, active abdominal contrac tions, and bile are the characteristics that are most useful for making a diagnosis i n vomiting animals and that are u n c o m m o n l y seen i n regurgitating patients. However,
Regurgitation is the passive ejection o f food, water, or saliva associated w i t h esophageal or, less commonly, pharyngeal disease.
Definition
Clinical Consequences of Regurgitation The most significant clinical complication of regurgitation is aspiration pneumonia. Any patient with persistent regurgita tion is at risk of aspiration pneumonia, and measures to reduce its occurrence should be instigated. Aspiration pneumonia is the most likely indication for hospitalization and intensive treatment of regurgitating patients. In the absence of aspiration pneumonia or other disease, most patients are able to maintain good hydration, although persistent regurgitation of undi gested food may lead to marked weight loss.
Table 131-1 Comparison of the Key Features of Vomiting and Regurgitation Vomiting Premonitory symptoms (nausea) often seen (hypersalivation. depression, discomfort)
Box 131-1
Important Differential Diagnoses for Regurgitation
Regurgitation
Pharyngeal Disease
No premonitory symptoms
Cricopharyngeal achalasia Focal or generalized neuromuscular disease Foreign body Neoplasia
Active abdominal contractions Passive ejection of food
Esophageal Disease
May occur at any time
Typically occurs shortly after ingestion of food
Hypomotility: megaesophagus
Digested food
Undigested food, may conform to the cylindric shape of the esophagus
Bile may be present
No bile
Differential Diagnoses
Congenital Idiopathic (primary) Secondary • Myasthenia gravis (20% to 30% of cases) • Generalized neuromuscular disease • Hypoadrenocorticism • Lead toxicity • Hypothyroidism
Inflammation: esophagitis Regurgitation is associated with esophageal or pharyngeal disease. It is more common i n dogs than i n cats. In most cases the problem is localized to the esophagus or pharynx, but it is sometimes a manifestation of systemic disease. C o m m o n differ ential diagnoses are provided i n Box 131-1. Idiopathic megaeso phagus is the most c o m m o n cause o f regurgitation i n the adult dog, and most middle-aged to older patients with uncompli cated regurgitation prove to have this disease. However, it should be noted that focal myasthenia gravis is a significant cause of megaesophagus i n the absence of other neurologic signs.
Drug: chemical-induced Gastroesophageal reflux • General anesthesia • Hiatal hernia • Idiopathic Lupus myositis Spirocerca lupi infection
1
M a n y other concurrent diseases have been reported as causes o f megaesophagus but epidemiologic evidence o f an association is lacking. It is reasonable to exclude these diseases from the differential diagnosis i f other clinical and clinicopathologic changes are lacking and the problem list is limited to regurgitation. 2
Diagnostic Approach History Important historic information includes access to drugs or caustic substances and recent drug therapy or anesthesia that may have precipitated esophagitis. M o s t cases o f druginduced esophagitis are as a result o f doxycycline adminis tration, but many drugs have the potential to cause this side effect. Animals with esophagitis may also show signs o f apparent esophageal discomfort, such as pain o n swallowing (odynophagia), repeated swallowing attempts, lip smacking, and arching o f the neck. These signs are seen less often i n patients with megaesophagus, most o f which regurgitate without premonitory signs and show no odynophagia. Most animals that do not have odynophagia maintain a good appetite and will often attempt to eat the regurgitated ingesta. Other systemic signs such as lethargy, anorexia, vomiting, and diarrhea are not seen w i t h uncomplicated esophageal disease and suggest a concurrent disease process or an underlying cause for the esophageal disease. C o u g h i n g or a sudden deterioration i n the patient's clinical status should alert the clinician to the possibility o f aspiration pneumonia.
Physical Examination The physical examination should include a thorough oral examination and palpation of the neck. Abnormalities i n the neck may include masses, palpable esophageal dilation, or pain. In some cases, palpation o f the esophagus may elicit
Mechanical obstruction Esophageal stricture Foreign body Neoplasia Vascular ring anomalies Extraluminal compression (e.g., mediastinal mass) Hiatal hernia Gastroesophageal intussusception
regurgitation or discomfort. A n y crackles i n the lung fields should be noted, but these should be differentiated from sounds o f fluid i n the esophagus.
Clinical Pathology Routine hematology and biochemistry may show evidence o f an underlying cause o f megaesophagus. Results are unre markable i n most patients with uncomplicated idiopathic megaesophagus.
Diagnostic Imaging Thoracic radiography is the most important and useful imaging modality for evaluating patients with regurgitation. Plain radiographs will be diagnostic i n most cases o f megaesophagus and foreign body obstruction. Plain radiographs may also show evidence o f secondary aspiration pneumonia or mediastinal masses. Two lateral radiographs and an orthogonal view should be obtained to evaluate all lung fields. If plain radiographs do not show any abnormalities, contrast studies or endoscopy may be indicated. A b d o m i n a l ultrasonography rarely provides useful information i n animals with regurgitation.
Further Diagnostic Testing Serum should be submitted for acetylcholine receptor antibody assay o n all patients with megaesophagus. Additional tests to consider based o n clinical suspicion include an adrenocortico tropic hormone stimulation test, serology for antinuclear anti body, serum creatine phosphokinase activity, electromyography
and nerve conduction velocity, and muscle and nerve biopsy. Evidence for an association with hypothyroidism is lacking, but thyroid function (thyroid stimulating hormone assay, thy roid stimulating hormone stimulation, free and total thyroid hormone levels) testing may be warranted i n individual patients with other suspicious signs. Most patients with megaesopha gus secondary to hypoadrenocorticism will have electrolyte changes and other systemic signs. 2
General Treatment Guidelines Most animals with regurgitation are stable and well hydrated and do not require therapy before a definitive diagnosis is made. In the absence o f concurrent disease, these patients can be treated o n an outpatient basis and do not require hospitalization. Empiric treatment w i t h a histamine-2 recep tor antagonist, prostaglandin analog, or proton p u m p inhib itor, with or without the addition o f sucralfate, may be warranted (see Chapter 181, Gastrointestinal Protectants). Bethanechol stimulates esophageal contractions i n some affected dogs and may be a useful prokinetic agent i n those with megaesophagus. S m o o t h muscle prokinetic agents such as metoclopramide and cisapride are not effective on the striated muscle o f the canine esophageal body. Animals with secondary aspiration pneumonia require more intensive therapy and monitoring. These patients should be started on broad-spectrum antibiotics (see Chapter 23, Aspira tion Pneumonitis and Pneumonia) and may require supplemen tal oxygen (see Chapter 19, Oxygen Therapy). Prolonged or repeated courses of antibiotics may be required and, when possi ble, airway samples should be collected for cytology and culture before initiating antibiotic therapy. If regurgitating animals require hospitalization, the priority should be to prevent aspira tion pneumonia by feeding a high-calorie diet i n small frequent meals from an elevated or upright position, and dietary consis tency should be tailored to the animal. Although intuitively a firm diet would appear to reduce the risk o f aspiration, many patients will have less frequent regurgitation when fed a more liq uid ration. Animals that cannot maintain adequate nutritional balance with oral intake should be fed using a temporary or per manent gastrostomy tube (see Chapter 13, Enteral Nutrition).
Prognosis Animals with congenital idiopathic megaesophagus have a fair prognosis. W i t h adequate attention to caloric needs and pre vention o f aspiration pneumonia, many animals w i l l develop improved esophageal motility over months. Pet owners must be committed to a prolonged period o f physical therapy and nutritional support. The m o r b i d i t y and mortality o f acquired idiopathic megaesophagus continues to be unacceptably high.
VOMITING Definition V o m i t i n g is the forceful ejection o f upper gastrointestinal (GI) tract contents and may occur as a result o f gastric, intestinal, or systemic disease.
from the G I tract transmit impulses to the v o m i t i n g center when stimulated by inflammation or overdistention. The v o m i t i n g center also receives stimulation from within the brain; the vestibular system, cerebrum, and chemoreceptor trigger zone all provide input to the v o m i t i n g center. The latter is a specialized region, lacking an intact blood-brain barrier, that is located o n the floor o f the fourth ventricle. The chemoreceptor trigger zone is sensitive to several c o m m o n drugs and toxins. The pathways involved in v o m i t i n g and the receptors involved are shown schemati cally i n Figure 131-1. Sufficient stimulation o f the vomiting center results in the initiation o f vomiting. A period o f intestinal antiperistalsis is followed by a highly coordinated sequence o f events, beginning w i t h a deep inspiration and ending with a strong simultaneous contraction o f the diaphragm and abdominal wall musculature and relaxation o f the lower esophageal sphincter.
Clinical Consequences of Vomiting The principal deleterious consequence o f vomiting is dehy dration as a result of fluid loss i n the vomitus and a reduced fluid intake. The loss o f G I contents compounded by dehy dration may lead to electrolyte and acid-base disturbances. A hypochloremic metabolic alkalosis, primarily resulting from the loss o f gastric contents rich i n hydrogen and chlo ride ions, w i t h or without a contraction alkalosis, is the most c o m m o n finding i n dogs with GI foreign bodies, regardless of their location. Patients with more chronic vomiting may be more prone to developing metabolic acidosis as a result o f dehydration, and mixed acid-base disorders may be seen. Hypokalemia is the most c o m m o n electrolyte dis turbance i n vomiting patients. Aspiration pneumonia is a less c o m m o n complication o f vomiting than it is o f regurgi tation because reflex closure of the glottis occurs during emesis. It is a greater risk i n animals with impaired laryngeal function, typically a result o f primary laryngeal disease or a reduced state o f consciousness. 4
Differential Diagnoses There are many differential diagnoses for vomiting, and to assist i n the investigation and treatment it can be useful to subdivide these. One c o m m o n subdivision is between those diseases i n which the primary pathology is GI and those in w h i c h the primary pathology is extragastrointestinal. It can also be useful to distinguish between those diseases that are more likely to cause acute vomiting and those that are more likely to cause chronic vomiting. The most c o m m o n and important differential diagnoses for vomiting are shown in Box 131-2. It is worthwhile to note that for the extragas trointestinal causes o f vomiting, other systemic signs such as polydipsia or weight loss are likely to be present. Thus an animal that is vomiting but lacks other signs is more likely to have primary G I disease, and an animal that vomits only occasionally and yet has marked systemic signs is more likely to have an extragastrointestinal problem.
Physiology of Vomiting
Diagnostic Approach History
The v o m i t i n g reflex is mediated by the v o m i t i n g center i n the m e d u l l a . Vagal and sympathetic afferent pathways
A description of the character of the vomiting should be obtained and, as described above, should be distinguished
3
Figure 131-1 Schematic representation of the receptors and pathways involved in vomiting. 7, Pathway more important in dogs; 2, pathway more important in cats. Receptors: D, dopaminergic; H, histaminergic; M, acetylcholine (muscarinic); NK, neurokinin; 5-HT, serotonin; a, a-adrenergic; to, benzodiazepine; ENK, enkephalinergic opioid; MOT, motilin; NMDA, glutamate.
from regurgitation. It is important to determine the approx imate frequency and duration o f v o m i t i n g because the chronicity and severity of signs w i l l aid i n formulating a diagnostic and treatment plan. Fresh b l o o d or digested b l o o d ("coffee grounds") is suggestive o f gastric ulceration, but bleeding is also often seen i n acute infectious conditions such as the hemorrhagic gastroenteritis syndrome. Other important information from the patient's history includes vaccination status, travel history, medication history, dietary indiscretion or recent diet changes, drug or toxin exposure, and any possibility o f foreign body ingestion. As noted above, systemic signs should raise the possibility o f an extragastrointestinal cause for the vomiting.
Physical Examination Vital signs and a thorough physical examination are i m p o r tant for the vomiting patient. The most important part o f the physical examination is a thorough palpation o f the abdomen. Attention should be paid to any abdominal pain or discomfort and the presence o f any palpable effusion, organ distention, masses, or foreign bodies. The m o u t h should be examined for evidence o f systemic disease (uremic or ketotic odor, ulcers) or a linear foreign body. In cats, the thyroid gland should be palpated to check for a goiter. A rec tal examination should be performed for additional infor mation (hematochezia, worms, prostatomegaly with or without pain), and an examination o f the central nervous system may be indicated in difficult cases. Assessment o f hydration and hemodynamic status w i l l aid i n formulating an appropriate treatment plan.
Clinical Pathology A full hematology and biochemistry panel should formed i n any persistently v o m i t i n g patient. In most with an extragastrointestinal cause, there w i l l be abnormalities in the biochemistry panel results.
be per animals notable Normal
biochemical and hematologic parameters are more strongly suggestive o f primary G I disease. The hematology and bio chemistry panels also allow evaluation o f abnormalities in electrolytes and acid-base status, w h i c h may be complica tions o f protracted vomiting. A sample for urinalysis should be obtained at the earliest opportunity to aid w i t h the differ entiation o f prerenal and renal azotemia. A fecal sample should be submitted for zinc sulfate flotation i n all cases, and also for selective bacterial culture or analyses i n patients with acute vomiting. Further testing should be performed based o n clinical suspicions.
Diagnostic Imaging Radiography and abdominal ultrasonography are vital in the investigation o f vomiting. The preferred diagnostic imag ing modality depends on the nature o f the complaint. In the acutely v o m i t i n g patient, abdominal radiographs are generally preferred over ultrasonography because they have adequate sensitivity and greater specificity for detecting intestinal obstruction. As such, they can be used to help determine whether medical or surgical management o f the case is more appropriate. The role o f abdominal ultrasonog raphy in the acutely v o m i t i n g patient is more limited; it may be useful i n the evaluation o f neoplastic obstructions and other abdominal organs i f an extragastrointestinal cause o f the v o m i t i n g is suspected. If radiography and ultrasonogra phy are equivocal and G I obstruction is still suspected, administration o f b a r i u m and sequential abdominal radio graphs may be helpful. In patients w i t h chronic vomiting, the likelihood o f intesti nal obstruction is m u c h less than i n patients who are v o m i t i n g acutely, and abdominal radiography has a lower diagnostic yield. A b d o m i n a l ultrasonography is generally preferred i n these patients. It allows an evaluation o f the intestinal wall thickness and layering along with a thorough evaluation o f the extraintestinal structures. It therefore proves very useful
Box 131-2 Important Differential Diagnoses for Vomiting Gastrointestinal Obstruction Foreign body* Intussusception* Neoplasia Torsion or volvulus
esophageal disease i f the history has led to an incorrect identification o f the primary problem as vomiting, they aid i n the detection o f neoplastic involvement i n the thorax, and they may show evidence o f aspiration pneumonia.
General Treatment Guidelines
Dietary Allergy " Intolerance Indiscretion* 1
1
Infectious Viral (parvovirus)* Parasitic "
The important factors to consider when treating a vomiting patient are: (1) treatment of the underlying cause, (2) treatment and prevention and electrolyte and acid-base disturbances, and (3) symptomatic control o f further vomiting, when appropri ate. Fluid therapy and antiemetic drugs are discussed i n Chap ters 55, 56, 181, 182, Potassium Disorders, Calcium Disorders, Gastrointestinal Protectants, and Antiemetics, respectively. The general recommendation is to withhold food for 24 to 48 hours after the last episode of vomiting. The rationale for this is to avoid stimulating further vomiting, to avoid the develop ment o f food aversions i n nauseated patients, and to reduce the risk o f aspiration pneumonia. 5
1
Bacterial (salmonellosis)* Other Neoplasia^ Inflammatory bowel disease^ Gastrointestinal ulceration NSAID-induced Uremic gastritis Liver disease Idiopathic Extragastrointestinal Uremia Pancreatitis* Diabetic ketoacidosis* Liver disease Peritonitis* Pyometra* Prostatitis Drug or toxin induced* Hypoadrenocorticism Hyperthyroidism Vestibular disease Heartworm disease (cats) 1
*More commonly acute. More commonly chronic. NSA1D, Nonsteroidal antiinflammatory drug. 1
i n helping to decide whether medical management, endoscopy, or surgery w o u l d be most appropriate. Thoracic radiographs should also be obtained i n v o m i t i n g patients. Their role is multifold. They may show evidence o f
Food should always be withheld from any patient with suspected G I obstruction or any patient whose signs worsen after feeding. However, some vomiting patients may have a significantly quicker recovery when early enteral nutrition is instigated, and dogmatic enforcement o f starvation may be unnecessary for some canine and feline patients. Animals with persistent vomiting may not be good candidates for feeding tubes, and parenteral nutrition may be necessary (see Chapter 14, Parenteral Nutrition). 6
SUGGESTED FURTHER READING*
Gaynor AR, Shofer FS, Washabau RJ: Risk factors for acquired megaesopha gus in dogs, J Am Vet Med Assoc 211:1406, 1997. A retrospective, case-control study that is the only epidemiologic investigation the risk factors for canine megaesophagus, which include peripheral neuropa thies, laryngeal paralysis, myasthenia gravis, and esophagitis. No association found between hypothyroidism and megaesophagus. Washabau RJ: Gastrointestinal motility disorders and gastrointestinal proki netic therapy, Vet Clin North Am Small Anim Pract 33:1007, 2003. A review of gastrointestinal motility disorders that provides a brief summary of the pathogenesis, clinical signs, and treatment of canine idiopathic megaesophagus. Webb C, Twedt DC: Canine gastritis, Vet Clin North Am Small Anim Pract 33:969, 2003. An extensive review article that discusses the pathogenesis, investigation, an treatment of gastric inflammation. Discusses a wide range of conditions, reflecting the diverse causes of vomiting in canine patients. *See the CD-ROM for a complete list of references.
Chapter 132 DIARRHEA Daniel Z. Hume, DVM,
DACVIM, DACVECC •
Mark P. Rondeau,
KEY POINTS • Diarrhea is a common clinical finding in critically ill animals. • Diarrhea can lead to abnormalities in nutrient, acid-base, and electrolyte balance. • Diarrhea may result from iatrogenic causes, primary gastrointestinal diseases, or other disease processes.
INTRODUCTION Diarrhea is a very c o m m o n clinical sign observed i n critically ill canine and feline patients. Diarrhea is defined as an increase i n fecal mass caused by an increase i n fecal water or solid content. This is usually associated w i t h an increase in frequency, fluidity, or volume o f feces. In a 20-kg dog, approximately 2.5 L of fluid enters the d u o d e n u m each day, and about 98% o f the fluid entering the intestine is absorbed. Diarrhea i n the critical care setting is often over looked and overshadowed by the primary disease process. However, diarrhea can lead to severe aberrations i n nutrient, acid-base, fluid, and electrolyte balance. W i t h o u t proper attention it can lead to the deterioration o f the patient's con dition. Diarrhea may be associated with patient discomfort, local dermatitis, catheter or catheter site infections, and potentially bacterial translocation i f the integrity o f the intes tinal mucosa is altered. Consideration o f the most likely cause is important because it allows the clinician to decide which diagnostic modalities are indicated for proper investi gation of the diarrhea. Three broad etiologic categories may be used when considering diarrhea: iatrogenic causes, p r i mary gastrointestinal (GI) causes, and other diseases second arily causing diarrhea. 1
PATHOPHYSIOLOGIC MECHANISMS OF DIARRHEA There are several categorization schemes for diarrhea, with great overlap among the classifications. One o f the most commonly used classification schemes arranges the patho physiologic mechanisms underlying diarrhea as follows: osmotic diarrhea, secretory diarrhea, diarrhea resulting from altered permeability, and diarrhea resulting from deranged motility. Osmotic diarrhea is caused by the presence o f excess luminal osmoles, leading to fluid retention and fluid draw into the intestinal lumen. M o s t causes o f a diarrhea have an osmotic component. Secretory diarrhea is caused by a net increase i n intestinal fluid secretion. This results from either an absolute increase
DVM, DACVIM
in intestinal secretion or a relative increase caused by a decrease i n intestinal absorption. N o r m a l intestinal physiology and systemic health are dependent o n the semipermeable nature o f the intestinal mucosa. Nutrients, electrolytes, and fluid are absorbed and secreted, and the mucosa and i m m u n e system o f the intestine inhibit translocation of bacteria and bacterial toxins. However, microscopic and macroscopic damage to either the epithelial cells or epithelial cell junctions can lead to altered intestinal permeability. N o t only are vital substances lost into the intes tinal lumen, but the altered permeability leaves the intestine vulnerable to translocation o f potentially fatal bacteria and their products. Alterations i n intestinal motility are probably the least understood o f the causes o f diarrhea. M o t i l i t y alterations lead ing to diarrhea include either increased peristaltic contractions or decreased segmental contractions. Even within this classifi cation scheme, significant overlap occurs among the groups. In animals w i t h primary GI causes o f diarrhea, historical questions may provide evidence that allows anatomic locali zation o f the disease to either the small or large bowel. This differentiation w i l l allow a more accurate formation o f differential diagnoses and subsequent diagnostic testing. Historical and clinical differences usually noted between small and large bowel diarrhea are illustrated i n Table 132-1. 1
IATROGENIC CAUSES OF DIARRHEA Iatrogenic causes o f diarrhea are likely more c o m m o n than is realized and should be ruled out to facilitate clinical improvement. Diarrhea is a c o m m o n side effect o f several classes o f drugs used i n critically i l l patients (Box 132-1). A n t i m i c r o b i a l agents may cause diarrhea as a direct result of drug formulation or properties, or as a result o f altera tions i n intestinal microbacterial flora. M o s t o f the chemotherapeutic agents have direct toxic effects against the rapidly dividing cells o f the intestinal crypts, leading to v i l lous blunting and altered absorption. Other classes o f drugs such as antiarrhythmic agents, lactulose, and proton p u m p inhibitors may also be associated with diarrhea. Acute or abrupt changes i n the diet are not u n c o m m o n i n hospitalized or critically i l l patients. Anorexic animals are often coaxed to eat w i t h canned diets and other potentially novel foods. Enteral tube feeding is c o m m o n l y employed i n critically i l l patients. The osmotic and caloric properties o f these diets may exceed the digestive and absorptive capacities of the intestine and lead to osmotic diarrhea. Furthermore, prolonged quiescence o f the intestine from either anorexia or parenteral nutrition can lead to villous atrophy and decreased absorptive function when enteral feeding is initiated.
2
Table 132-1 Differentiation of Diarrhea Based on Anatomic Location Characteristic
Small Bowel
Large Bowel
Mucus
Uncommon
Common
Hematochezia
Uncommon
May be present
Stool volume
Increased to normal
Normal to decreased
Melena
May be present
Absent
Frequency
May be increased to normal
Increased
Urgency
Uncommon
Common
Tenesmus
Uncommon
Common
intolerance) to a dietary substance. Although true food allergies are rare, food intolerance is probably one of the more c o m m o n causes of acute diarrhea i n the small animal patient. Intolerance can result from dietary indiscretion or gluttony, but often the exact cause is unknown. The resultant diarrhea is short term and self-limiting. Infectious disease is a c o m m o n cause of diarrhea i n canine and feline patients. Gastrointestinal (GI) parasitism (e.g., Ancylostoma, Toxocara spp, Toxascaris, Trichuris) is another c o m m o n cause of diarrhea, but is rarely associated with debil itation except i n young or small patients. The exact role of various infectious bacterial organisms as the cause of diarrhea is controversial. G I disease and diarrhea may be associated with a variety of bacteria, including Salmonella spp, Cam pylobacter spp, enteropathogenic Escherichia coli, Clostridium difficile, and Clostridium perfringens. ' Although diarrhea has been associated with clostridial organisms i n the dog and cat, " the direct role remains unclear given that C. diffi cile toxin and C. perfringens enterotoxin can be demon strated i n the feces of animals with normal stool quality and no clinical G I signs. ' 3 4
Box 132-1
Medications Commonly Associated With Diarrhea 17
18
Antimicrobial Agents Gastrointestinal Medications Histamine-2 blockers Misoprostol Proton pump inhibitors Oral antacids Chemotherapeutic Agents Cardiac Medications Quinidine Procainamide Digoxin Antihypertensive Agents (3-Blockers ACE inhibitors Immunomodulatory Agents Azathioprine Cyclophosphamide Cyclosporine Endocrine Medications Mitotane Trilostane Methimazole Acarbose NSAIDs Miscellaneous Agents Amitriptyline Parasiticides Bethanechol Clomipramine Colchicine Acetazolamide ACE, Angiotensin-converting enzyme; NSAIDs, nonsteroidal antiinflammatory drugs.
PRIMARY GASTROINTESTINAL CAUSES OF DIARRHEA Adverse reactions to foods can result from i m m u n o l o g i c reactions (food allergy) or n o n i m m u n o l o g i c reactions (food
3
5
6 7
Systemic viral infections such as canine parvovirus and feline panleukopenia are c o m m o n l y associated with diar rhea. Feline panleukopenia and canine parvovirus are caused by similar, but not identical, nonenveloped D N A parvo viruses. ' Transmission occurs via oronasal exposure and the organism subsequently spreads to the bone marrow, l y m p h o i d organs, and intestinal crypts, leading to a peripheral leukopenia and intestinal villus blunting and collapse. ' Fungal (Histoplasma, Pythium, Cryptococcus spp), algal (Prototheca), protozoal {Tritrichomonas foetus, Giardia, Cryptosporidium, Isospora spp), and rickettsial (Neorickettsia spp) gastroenteritis may be seen depending o n the geographic location and husbandry of the patient. Intussusceptions may occur secondary to infectious or idiopathic causes, and may lead to severe diarrhea. The role of small intestinal bacterial overgrowth (SIBO) or antibiotic-responsive diarrhea ( A R D ) is a controversial subject i n small animal veterinary gastroenterology. Debate exists not only regarding whether the disease occurs as a pri mary condition, but also i n how it should be defined and how it is best diagnosed. Some authors have divided the dis ease into either secondary SIBO i n the cases i n which an accompanying or primary intestinal disease can be identi fied, or idiopathic A R D i n the cases in which no underlying disease can be f o u n d . Examples of secondary SIBO can be seen with exocrine pancreatic insufficiency and inflamma tory bowel disease (IBD). The exact etiology of A R D has yet to be identified, but local intestinal immunodeficiency may play a role i n the pathogenesis. 8
9
8 9
10
11
Neoplastic disease may also lead to diarrhea in small animals patients; GI adenocarcinoma, alimentary lymphosarcoma, mast cell tumor, and G I stromal tumors are examples. These tumors may cause significant intestinal protein and blood loss. IBD is one of the more c o m m o n causes of chronic diarrhea in cats and dogs. Loss of local i m m u n e tolerance to normal dietary and bacterial components leads to up-regulation of i m m u n e and inflammatory responses and establishment of an inflammatory focus within the intestine. Infiltration with inflammatory cells leads to thickening of the intestinal absorp tive surface and decreased absorptive capacity. There are dif ferent types o f I B D i n the dog and cat, and classification is based o n the primary type of inflammatory cell infiltrate. Lymphocytic-plasmacytic is the most c o m m o n form of IBD,
but eosinophilic and granulomatous forms may also be diag nosed. Prolonged or extensive bowel disease can lead to severe metabolic derangements, including panhypoproteinemia and hypocholesterolemia. The diagnosis of I B D is based on histo pathologic evidence of moderate to severe GI inflammation coupled with the exclusion of an underlying cause of the inflammation. Lymphangiectasia can occur as a primary disease (Yor kshire Terrier, Norwegian L u n d e h u n d , and Maltese Terrier) or secondary to other infiltrative processes such as I B D . Alterations of intestinal lymphatic permeability leads to leakage of protein-rich and fat-rich chyle into the intestinal lumen and loss of these dietary components into the feces. Resultant clinical signs include chronic diarrhea and severe weight loss.
EXTRAGASTROINTESTINAL DISEASES CAUSING DIARRHEA Diarrhea may occur i n dogs and cats w i t h hepatobiliary disease for several reasons. Concurrent inflammatory GI disease may be seen i n the dog and is c o m m o n i n the c a t . " End-stage cirrhosis may be associated w i t h elevated portal hydrostatic pressures, and functional hepatic failure may lead to hypoalbuminemia and G I wall edema. B o t h of these conditions often lead to altered absorptive proper ties of the gut. Diseases affecting the biliary tree may also hinder delivery of bile salts to the intestine, leading to fat maldigestion. 12
14
Diarrhea is c o m m o n l y seen as a sequela of pancreatic disease. Exocrine pancreatic insufficiency may result from pancreatic acinar atrophy (dogs more commonly) or chronic pancreatitis (cats more commonly). Lack of exocrine pancre atic function leads to maldigestion and malabsorption of dietary substrates and culminates in diarrhea and weight loss. Both acute and chronic pancreatitis may also lead to diarrhea. Pancreatic inflammation may cause local inflammation of the duodenum and colon, interfere with pancreatic acinar secretion, and result i n decreased bile salt delivery to the small intestine via obstruction of biliary flow. Congestive heart failure, particularly right-sided failure, can lead to intestinal and hepatic venous congestion and ascites. Congestion of the splanchnic vasculature may lead to altered absorptive capacities of the intestine. Several endocrine disorders may be associated w i t h diar rhea. Diarrhea is noted in some cats with hyperthyroidism. The diarrhea i n these cases may be a result of increased food intake as well as intestinal hypermotility. Waxing and waning GI signs are seen frequently i n dogs and less c o m m o n l y i n cats with hypoadrenocorticism. Cortisol is vital for mainte nance of normal GI function, motility, and integrity, as well as vascular tone and subsequent perfusion. The lack of mineralocorticoids may be associated with alterations i n electrolyte balance, leading to altered GI motility and absorption. Diarrhea is an u n c o m m o n l y reported clinical sign associated with hypothyroidism. Various other diseases may be associated w i t h diarrhea. Idiopathic noncirrhotic portal hypertension may interfere with absorption w i t h i n the intestinal tract. The role of hypoalbuminemia as a direct cause o f diarrhea is debated. The decreased oncotic draw resulting from hypoalbumine mia leads to alterations i n Starling forces and decreased absorption of fluid across the intestinal lumen.
Hemorrhagic diarrhea is seen c o m m o n l y i n critically i l l patients suffering from or following resuscitation from var ious causes o f cardiovascular shock, such as following an episode of heat-induced illness. G I complications are c o m m o n i n animals w i t h acute and chronic renal disease, but diarrhea is not c o m m o n l y reported. Systemic infections (including sepsis) may secondarily affect the G I tract and cause diarrhea. Experimental canine studies have shown that bacterial endotoxin impairs colonic water and sodium absorption and increases small and large intestinal motility, at least partially explaining the diarrhea noted i n septic patients. 15,16
DIAGNOSTIC EVALUATION The diagnostic evaluation o f diarrhea is best guided by the historical, clinicopathologic, and physical examination find ings. The physical condition of the patient and the duration and clinical course o f the diarrhea w i l l help determine h o w aggressive the clinician should be i n attempting to find a cause. Results of a complete b l o o d count, serum chemistry profile, and urinalysis are indicated i n all critically i l l patients and often help to delineate between GI and n o n - G I causes of diar rhea. Based o n these findings, additional tests may be needed to screen for hyperthyroidism, hypoadrenocorticism, or occult liver disease. Fecal flotation (including zinc sulfate for Giardia) and direct cytologic examination of the feces is recommended i n most cases. A l t h o u g h cytologic examination of the feces may help indirectly to point toward a particular pathogen, isolation or amplification of toxin or enterotoxin may provide a more specific diagnosis i n the case of clostridial infection. Bacterial culture {Salmonella, Campylobacter, enteropathogenic E. coli), enterotoxin screening (Clostrid ium), and enzyme-linked immunosorbent assay (ELISA) (par vovirus) of the feces may be indicated when an infectious cause is suspected. Specific tests for other infectious agents may also be indicated depending on the geographic location and husbandry of the patient. Exfoliative rectal cytology may be useful i n diagnosing fungal, algal, inflammatory, and neo plastic diseases. Trypsin-like immunoreactivity testing is i n d i cated i n any patient with suspected exocrine pancreatic insufficiency. Folate and cobalamin testing may be helpful i n animals suffering from SIBO. A l t h o u g h abdominal radio graphs are of limited value i n animals primarily affected w i t h diarrhea, abdominal ultrasound is often indicated and useful for assessing integrity, architecture, and thickness of the G I system and other abdominal organs. Lastly, G I endoscopy or exploratory laparotomy is often needed for direct visualiza tion of the intestinal tract and procurement o f diagnostic samples.
TREATMENT Iatrogenic causes of diarrhea should be considered i n all patients, especially those i n w h i c h diarrhea was not part of the presenting complaint. If the diarrhea is severe, therapeutic medications may need to be discontinued or modified. A l t h o u g h diarrhea is c o m m o n l y associated w i t h enteral feed ing, the diet formulation may need to be altered if the diarrhea is severe or adversely affecting the patient's quality o f life. Treatment of diarrhea associated w i t h primary GI diseases or diseases secondarily causing diarrhea is best achieved after
careful diagnostic evaluation o f the underlying cause. After a definitive diagnosis has been achieved, direct treatment can be initiated. Rarely, medications directed toward symptom atic treatment o f the diarrhea are used (see Chapter 181, Gastrointestinal Protectants). Intestinal transit time is effec tively a result o f the balance between propulsive peristalsis and segmental contractions. C o n t r a r y to historical belief, diarrhea rarely results from increased peristalsis, but more c o m m o n l y is the result o f decreased segmental contractions. Anticholinergic agents generally are contraindicated because they decrease both propulsive peristalsis and segmental contractions and predispose the patient to ileus. Conversely, opioid-containing medications such as loperamide, diphe noxylate, and o p i u m tincture can decrease propulsive contrac tions and increase segmental contractions, as well as increasing water and fluid absorption. These medications may be i n d i cated i n some cases of diarrhea i n which infectious causes have been excluded. K a o l i n , pectin, and bismuth subsalicylate are used occasionally for symptomatic treatment. Symptomatic therapy is rarely indicated because treatment o f the primary disease process provides the best means for eliminating diar rhea. Indications for symptomatic therapy include diarrhea that adversely affects the patient's quality o f life, causes severe fecal scalding o f the skin, or predisposes to secondary infec tion (e.g., urinary or intravenous catheter infections i n recum bent animals). 1
Table 132-2 Formulary of Commonly used Drugs for the Treatment of Diarrhea in Small Animals Drug
Canine
Feline
Prednisone
1 to 2 mg/kg PO q12h
1 to 4 mg/kg POq12h
Budesonide
15 kg: 3 mg PO q24h
Azathioprine
2 mg/kg PO q24h
Not routinely used
Chlorambucil
Not routinely used
2 mg/m PO q48h
Sulfasalazine
10 to 15 mg/kg PO q8-12h
10 to 20 mg/kg PO q24h
Metronidazole
10 to 15 mg/kg PO q12h
10 to 15 mg/kg PO q12h
1
1
Oxytetracycline 22 mg/kg PO q8h
10 to 15 mg/kg PO q8h
Tylosin
10 to 20 mg/kg PO q8-12h
10 to 20 mg/kg PO q8-12h
Erythromycin
10 to 20 mg/kg PO q8h 10 to 20 mg/kg PO q8h
Enrofloxacin
10 to 20 mg/kg PO q24h
1
In animals with IBD, treatment often is tailored to the i n d i vidual patient given severity o f the clinical signs and histopath ologic lesions. Dogs and cats with intermittent clinical signs, good body condition, and m i l d histologic lesions may respond to dietary therapy alone. The rationale behind dietary therapy in the treatment o f I B D is that the Joss o f immunologic toler ance to n o r m a l dietary proteins and subsequent GI inflamma tion may be one o f the pathophysiologic mechanisms behind the disorder. Dietary therapy for I B D usually relies o n either a novel protein diet or a diet using a hydrolyzed protein source. Animals with some degree o f lymphangiectasia may benefit from a low-fat diet. However, most animals w i t h moderate to severe disease w i l l need some degree o f i m m u n o m o d u l a t i o n to obtain clinical remission. Glucocorticoids (prednisone, predniso lone, and dexamethasone) are the mainstay o f i m m u n o modulatory therapy. There has been interest i n the locally active steroid, budesonide. This drug undergoes significant first-pass metabolism, thereby l i m i t i n g systemic absorption and potentially lessening the side effects compared to gluco corticoids. Azathioprine, chlorambucil, or other i m m u n o modulating agents may be needed i n dogs with refractory disease or those unable to tolerate glucocorticoids. A m i n o salicylates (sulfasalazine, mesalamine) can be used i n dogs w i t h primarily large bowel disease. Metronidazole is often used for both its antimicrobial and antiinflammatory effects. Antibiotic therapy may be useful i n many other diarrheal diseases o f dogs and cats (Table 132-2). Primary (idiopathic) or secondary A R D w i l l often respond well to antimicrobial
2
5 mg/kg PO q24h
PO, Per os.
agents. Those most often used include metronidazole, oxy tetracycline, and tylosin. The drug of choice for treatment of Campylobacter spp is the macrolide erythromycin. H o w ever, its use is associated w i t h GI side effects (typically vomiting and/or diarrhea). Other antimicrobial drugs that may be considered include enrofloxacin, tetracyclines, chlor amphenicol, cefoxitin, and tylosin. Animals with diarrhea of suspected clostridial origin may be treated with metronida zole, ampicillin, macrolides, or tetracyclines. 4
4
SUGGESTED FURTHER READING*
Cave NJ, Marks SL, Kass PH, et al: Evaluation of a routine diagnostic fecal panel for dogs with diarrhea, J Am Vet Med Assoc 221:52, 2002. A case-controlled study examining the diagnostic yield of fecal panels in evaluation of canine diarrhea. Greene CE: Enteric bacterial infections. In Greene CE: Infectious disease of the dog and cat, ed 3, St Louis, 2006, Saunders. The most detailed reference available focusing on small animal infectio disease. Hall EJ, German AJ: Disease of the small intestine. In Ettinger SJ, Feldman EC, editors: Textbook of veterinary internal medicine, St Louis, 2005, Saunders. Up-to-date chapter reviewing common diseases of the canine and feline sm intestine. *See the CD-ROM for a complete list of references.
Chapter 133 PERITONITIS Susan W. Volk,
VMD,
PhD,
DACVS
KEY POINTS • Peritonitis is inflammation of the peritoneal cavity and is most commonly the result of gastrointestinal rupture, perforation, or dehiscence in small animals. • Clinical signs in patients with peritonitis may be mild to severe and are often nonspecific. • Abdominocentesis is the diagnostic method of choice for confirming peritonitis. • Abdominal fluid cytology that reveals degenerative neutrophils and intracellular bacteria confirms a diagnosis of septic peritonitis and is an indication for emergency surgical exploration of the abdomen. • Open peritoneal drainage or closed suction drainage should be considered for cases of septic peritonitis in which the source of contamination cannot be controlled completely or if significant contamination or inflammation remains following surgical debridement and lavage. • Prognosis is guarded in patients with peritonitis. Reported survival rates are highly variable and dependent on the etiology and presence of infection.
INTRODUCTION Peritonitis is defined as inflammation of the peritoneal cavity and may be classified according to the underlying etiology (primary or secondary), extent (localized or generalized), or the presence of infectious agents (septic or nonseptic). Primary peritonitis refers to a spontaneous inflammatory condition i n the absence of underlying intraabdominal pathology. Secondary peritonitis occurs more c o m m o n l y and is the consequence of a preexisting aseptic or septic pathologic, intraabdominal condition. Secondary septic peritonitis is the more c o m m o n form i n the dog and cat, most commonly resulting from leakage of gastrointestinal (GI) contents from a compromised GI tract. Because of the multitude of conditions that may lead to peritonitis, the types of clinical signs and their severity are varied. Hematogenous dissemination o f infectious agents has been postulated as the mechanism of development o f primary peritonitis and is likely facilitated by impaired host immune defenses. The most c o m m o n form of primary peri tonitis is the effusive form of feline infectious peritonitis, caused by feline coronavirus, which should be included on any differential diagnosis list for cats w i t h peritoneal effusion. Other infectious agents reported to have caused primary peritonitis i n dogs and cats include Salmonella typhimurium, Chlamydia psittaci, Clostridium limosum, Mesocestoides spp, Blastomyces spp, and Candida spp. Inflammation of the abdominal cavity in the absence of infectious pathogens (aseptic peritonitis) most commonly occurs i n response to exposure of the peritoneum to sterile fluids (i.e., gastric, biliary, or urine), pancreatic enzymes, or
foreign material. Aseptic bile and urine cause m i n i m a l perito neal inflammation, and gastric fluid and pancreatic enzyme leakage lead to a more intense peritoneal reaction. Both micro scopic and macroscopic foreign material, including surgical glove powder, surgical materials (suture, cotton swabs, surgical sponges), hair, and impaled objects (sticks, plant material, metal) may elicit a granulomatous response. To minimize iatro genic causes of aseptic peritonitis, it is recommended that the surgeons rinse or wipe surgical gloves with sterile saline or use powder-free gloves, perform a surgical sponge count before opening and closing a celiotomy, and use surgical sponges with radiopaque markers. M o r e commonly, secondary peritonitis can be identified as a septic process, w i t h the most frequent source of infec tion being the G I tract. Leakage of G I contents may occur through stomach and intestinal walls that have been com promised by ulceration, foreign body obstruction, neoplasia, trauma, ischemic damage, or dehiscence of a previous surgi cal incision. Spontaneous gastroduodenal perforation may be associated w i t h nonsteroidal antiinflammatory drug administration but may also be seen w i t h corticosteroid administration, neoplastic and nonneoplastic G I infiltrative disease, gastrinoma, and hepatic disease. ' GI linear foreign bodies i n dogs have been reported to lead to the develop ment of peritonitis i n 4 1 % of cases, higher than that previ ously reported for cats. Dehiscence occurs in 7% to 16% of postoperative patients requiring intestinal enterotomy or anastomosis, w i t h mortality rates of 75% to 85% i n this population. One study identified dogs as being at high risk for leakage following intestinal anastomosis i f they had two or more of the following conditions: preoperative peri tonitis, intestinal foreign body, and a serum albumin concen tration of 2.5 g/dl or less. Other causes of septic peritonitis can be found i n Box 133-1. 1 2
3
4
CLINICAL SIGNS Historical information may provide clues regarding the underlying cause of peritonitis. Previous and current mala dies and surgical procedures (including neutering), current medications (particularly those w h i c h may predispose to GI ulceration), and duration of current clinical signs should be investigated. Owners should be questioned specifically regarding potential for trauma exposure and foreign body ingestion. Clinical signs o f dogs and cats with peritonitis vary in both type and intensity and may reflect the underlying dis ease process. Peritoneal effusion is a consistent finding but may be difficult to appreciate on physical examination i f a small volume of fluid is present, and may even be difficult to detect sonographically i n animals exhibiting dehydration.
Box 133-1
Differential Diagnoses of Septic Peritonitis
Primary Feline coronavirus (feline infectious peritonitis)
hematologic finding, although a n o r m a l or low neutrophil count may be present. It is anticipated that animals recovering without incident from G I surgery may also have a transient inflammatory leukogram; however, the overall peripheral white b l o o d cell counts typically fall w i t h i n nor mal l i m i t s . A n increasingly left-shifted neutrophilia (or neutropenia) paired w i t h clinical signs o f peritonitis may raise the clinician's index o f suspicion for postoperative intestinal dehiscence (which typically occurs 3 to 5 days postoperatively). 6
Salmonella typhimurium Chlamydia psittaci Clostridium limosum Mesocestoides spp Blastomyces spp Candidiasis spp Secondary Penetrating abdominal wounds Surgical peritoneal contamination Peritoneal dialysis Gastrointestinal conditions Gastric rupture secondary to GDV, neoplasia, perforating ulcer Intestinal leakage Perforating foreign body, ulcer, or neoplasia Bacterial translocation secondary to obstruction (foreign body, neoplasia, intussusception, or bowel incarceration) Dehiscence of intestinal surgical wound Ischemic intestinal injury Hepatobiliary condition Liver abscess Liver lobe torsion with abscess formation Ruptured biliary tract with bacterobilia Pancreatitis or pancreatic abscess Hemolymphatic conditions Splenic abscess Splenic torsion with anaerobic bacterial colonization Mesenteric lymph node abscess formation Urogenital conditions Renal abscess Septic uroabdomen Pyometra (ruptured or with mural bacterial translocation) Uterine torsion Prostatic abscess formation GDV, Gastric dilatation-volvulus.
A b d o m i n a l pain may be appreciated o n palpation, w i t h a small number o f dogs exhibiting the "prayer position" i n an attempt to relieve abdominal discomfort. In a retrospective study focusing o n cats w i t h septic peritonitis, only 62% exhibited pain o n palpation o f the a b d o m e n . M o s t animals with septic peritonitis are systemically i l l and exhibit nonspe cific clinical signs such as anorexia, v o m i t i n g , mental depres sion, and lethargy. It should be noted that animals w i t h uroperitoneum may continue to urinate w i t h a concurrent leakage into the peritoneal cavity. These patients may arrive in progressive states o f hypovolemic and cardiovascular shock, with either injected or pale mucous membranes, pro longed capillary refill time, tachycardia with weak pulses, and with either hyperthermia or hypothermia reflecting poor peripheral perfusion. A significant number o f cats (16%) with septic peritonitis exhibited bradycardia (see Chapter 106, Sepsis). 5
5
DIAGNOSTIC TESTS Patients with suspected or confirmed peritonitis should have routine hematologic, biochemical, and coagulation analyses. A marked neutrophilia with a left shift is the predominant
Furthermore, acid-base and electrolyte abnormalities may be noted. Hyperkalemia may indicate uroperitoneum, par ticularly i f trauma or urinary tract dysfunction has been noted historically. Hypoproteinemia may be a result of the loss o f protein w i t h i n the peritoneal cavity. Patients with a concurrent septic process may be hypoglycemic. Hepatic enzymes, creatinine, and b l o o d urea nitrogen may be ele vated, indicating p r i m a r y dysfunction o f these organs or per haps reflecting states o f decreased perfusion or dehydration. The serum o f patients with bile peritonitis may be icteric if the total b i l i r u b i n is elevated. Patients w i t h suspected peritonitis should be evaluated for peritoneal effusion. Little or no fluid may be detected initially i f patients arrive early i n the disease process or before fluid resuscitation i f they are dehydrated. Large volumes o f effusion may be obtained v i a b l i n d abdomino centesis or, alternatively, v i a ultrasonographic guidance. Single paracentesis attempts are successful i n only 20% of patients w i t h l o w volumes o f peritoneal effusion (3 ml/kg) and i n o n l y 80% w i t h larger volumes (10 ml/kg). Ultra sonographic guidance w i l l facilitate the retrieval o f smaller volumes o f peritoneal fluid. If single-site sampling is negative for fluid, four-quadrant sampling should be performed. A diagnostic peritoneal lavage should be performed when peritonitis is suspected despite the absence o f detect able effusion or when a m i n i m a l volume o f effusion makes it difficult to obtain a sample. Diagnostic peritoneal lavage ideally is performed using a peritoneal dialysis catheter but can also be performed using an over-the-needle, large-bore (14 to 16 gauge) catheter. The technique is performed by infusion o f 22 m l / k g o f a warmed, sterile isotonic saline solution through the catheter inserted i n an aseptically prepared site just caudal to the umbilicus and retrieval of a sample for analysis and culture and sensitivity. It is important to remember that the lavage solution w i l l dilute the sample and therefore may alter the analysis. A repeated diagnostic peritoneal lavage may increase accuracy o f the technique when results o f the first procedure are equivocal (see Chapter 156, Diagnostic Peritoneal Lavage). Leukocyte counts i n peritoneal fluid are normally less than 500 cells/u.1. White blood cell counts between 1000 and 2000 cells/ul indicate m i l d to moderate inflammation, and a higher peritoneal fluid leukocytosis suggests marked peritonitis. ' However, cell counts i n peritoneal lavage fluid obtained from postoperative patients undergoing intestinal resection and anastomosis may also show evidence of signif icant inflammation i n the absence o f surgical complications. In the patient that has undergone a celiotomy, 7000 to 9000 cells/u.1 suggests m i l d to moderate peritonitis. In these patients, intracellular bacteria or increasing inflammation (numbers o f neutrophils or morphologic features o f toxicity in these cells) observed i n serial samples correlated with clin ical findings may prove more useful than single leukocyte 6
7
underlying etiology of peritonitis, in addition to its use in localizing and aiding retrieval of peritoneal effusion. In the case of a confirmed uroabdomen, preoperative contrast radi ography (excretory urography or cystourethrography) is recommended to localize the site o f urine leakage and aid in surgical planning. It should be noted that all patients should be hemodynamically and medically stabilized before diagnostic imaging is carried out.
Figure 133-1 Lateral abdominal radiograph showing free peritoneal gas and possibly ingesta free within the abdomen. Pneumoperitoneum without a history of recent surgery or open-needle abdominocentesis indicates the need for abdominal exploratory. This cat was diagnosed with a ruptured gastric mass during surgery.
counts in abdominocentesis samples when deciding whether reoperation is indicated. It is also of note that dogs receiving antibiotics may have no observable bacteria in peritoneal fluid samples, despite having peritoneal contamination. In addition to the presence of bacteria and a high nucle ated cell count, the glucose concentration of abdominal effu sion is a useful predictor of bacterial peritonitis in dogs. A concentration difference of more than 20 mg/dl between paired samples for blood and peritoneal fluid glucose is a reli able predictor of a bacterial peritonitis. Additionally, a bloodto-fluid lactate difference less than 2 m m o l / L was predictive of septic peritonitis in dogs but has not been as useful in cats. ' Intravenous administration of dextrose or the pres ence of a hemoperitoneum may decrease the accuracy of this test. 8 9
Samples for aerobic and anaerobic cultures should be obtained at the time of initial sampling so that additional samples are not required after confirming the presence of a septic process and initiating antibiotic therapy. The diagnosis of uroperitoneum in dogs can be made i f the peritoneal fluid creatinine or potassium concentration exceeds that of the serum creatinine (>2:1) or potassium concentration ( > l . 4 : l ) . Similarly, biliary rupture will lead to a bilirubin concentration that is higher in the peritoneal fluid than in the serum. In addition, bile pigment or crystals may be visible on cytologic examination of the peritoneal effusion in animals with bile peritonitis (Color Plate 133-1). These changes may not be seen in patients with bile peritonitis secondary to a ruptured gallbladder mucocele because the gelatinous bile often fails to disperse throughout the abdomen. l H
Plain radiographs may reveal a focal or generalized loss of detail that is otherwise known as the ground glass appear ance. A pneumoperitoneum (Figure 133-1) suggests per foration of a hollow viscous organ, penetrating trauma (including recent abdominal surgery) or, less commonly, the presence of gas-producing anaerobic bacteria. Intestinal tract obstruction or bowel plication should be ruled out. Prostatomegaly in male dogs and evidence of uterine disten tion in female dogs should be noted. Thoracic radiographs should be performed to rule out concurrent illness (infec tious, neoplastic, or traumatic). The presence of bicavitary effusions increased the mortality rate of patients 3.3-fold compared with that of patients with peritoneal effusions alone." Ultrasonography may be useful for defining the
TREATMENT Medical Stabilization The goals for animals with septic peritonitis are to identify and address the source of contamination in order to resolve the infection and treat the systemic consequences of such infection (i.e., fluid and electrolyte abnormalities and hypoperfusion). Before surgical intervention, a decision must be made whether additional hemodynamic and med ical stabilization is indicated before proceeding, or whether this additional time and continued contamination of the abdominal cavity will result in further clinical decline that outweighs the benefits of further medical treatment. The goals of medical treatment are to restore normal fluid and electrolyte balance and minimize ongoing contamina tion. Fluid resuscitation is initiated after obtaining pretherapy blood samples for a m i n i m u m database (packed cell volume, total solids, Azostix, dextrose), hematology, serum chemistry, and coagulation evaluation. Urine should be col lected, if possible, for analysis with or without culture and sensitivity testing. Shock doses o f crystalloids (90 ml/kg in the dog, 50 ml/kg in the cat) or a combination o f isotonic crystalloids (20 to 40 ml/kg) and synthetic colloids (hydroxyethyl starch 10 to 20 ml/kg in the dog or 5 to 10 ml/kg in the cat; or 7% to 7.5% hypertonic saline in 6% dextran70, 3 to 5 ml/kg IV over 5 to 15 minutes) should be adminis tered to effect (see Chapter 65, Shock Fluids and Fluid C h a l lenge). Because significant amounts of protein are lost into the peritoneal cavity, plasma and/or albumin administration may also be warranted. Electrolytes and glucose should be supplemented i f indicated (see Chapters 55 and 69, Potas sium Disorders and Hypoglycemia, respectively). After appropriate volume resuscitation, vasopressor therapy may be necessary to further alleviate hypotension. A urinary cath eter may aid in diversion of infected urine in the case of a ruptured bladder or proximal urethra and allow for the nec essary correction of any metabolic derangements (typically hyperkalemia and acidosis) (see Chapters 55 and 59, Potas sium Disorders and Acid-Base Disturbances) before surgery. Broad-spectrum antibiotic therapy should be initiated immediately after confirming the diagnosis of a septic perito nitis (see Chapters 108 and 109, Gram-Positive Infections and Gram-Negative Infections, respectively). Escherichia coli, Clostridium spp, and Enterococcus spp are c o m m o n iso lates. A second-generation cephalosporin such as cefoxitin (30 mg/kg IV q6-8h) may be used as a single agent or c o m bination antibiotic therapy such as ampicillin or cefazolin (22 mg/kg IV q8h) administered concurrently with either enrofloxacin (10 to 20 mg/kg I V q 2 4 h [dog], 5 mg/kgq24h [cat]) or an aminoglycoside (amikacin 15 mg/kg IV q24h or gentamicin 6.6 mg/kg IV q24h). In the event that extended anaerobic coverage is necessary, metronidazole (10 mg/kg IV ql2h) can
be used. Aminoglycosides should be avoided unless renal insufficiency has been ruled out and the patient is well hydrated. It is advisable to tailor antibiotic therapy to the results of culture and sensitivity testing when they become available.
Surgical Treatment The goals o f surgical treatment for septic peritonitis include resolving the cause o f the infection, d i m i n i s h i n g the infec tious and foreign material load, and promoting patient recovery with enteral feeding, i f indicated. A ventral midline celiotomy from x i p h o i d to pubis allows a thorough explor atory laparotomy to determine the underlying cause. M o n o filament suture material is advocated i n an animal with a septic process, and surgical gut is avoided because o f its shortened half-life i n this environment. Placement o f nonab sorbable suture material or mesh w i t h i n the abdominal cav ity is not recommended i n cases o f septic peritonitis because either material may serve as a nidus for infection. If possible, the surgeon should isolate the offending organ from the rest o f the abdomen w i t h laparotomy sponges to prevent further contamination during correction o f the problem. Surgical treatment is tailored to the individual case and the underlying cause of the septic peritonitis. If a G I leakage is being treated, adjunctive procedures such as serosal patching or omental wrapping o f the repaired site are recommended to reduce the incidence o f postoperative intestinal leakage or dehiscence. A l t h o u g h heavily contaminated or necrotic omen t u m may necessitate partial omentectomy, preservation o f as m u c h o m e n t u m as possible is advised to promote drainage of the peritoneal cavity. In addition, surgical applications o f the o m e n t u m relate to its immunogenic, angiogenic, and adhesive properties and include intracapsular prostatic o m e n talization for prostatic abscess f o r m a t i o n , pancreatic abscess omentalization, omentalization o f enterotomy or intestinal resection and anastomosis sites, and around gastrostomy or enterostomy tube sites. Because enteral nutrition directly nourishes enterocytes and decreases bacterial translocation across the intestinal wall, feeding tube placement (gastrostomy or jejunostomy) should be considered during initial surgical exploration. 12
13
After addressing the underlying cause to prevent further contamination o f the peritoneum, the infectious and foreign material load must be diminished through a combination o f debridement and lavage. Localized peritonitis should be treated with lavage o f the affected area only, to m i n i m i z e dis semination o f the infection. A thorough lavage o f the entire abdominal cavity with body-temperature sterile isotonic fluid is essential i f peritonitis is generalized. The addition o f anti septics and antibiotics to lavage fluid is not beneficial and may actually be detrimental by inducing a superimposed chemical peritonitis. Lavage o f the abdominal cavity is continued until the retrieved fluid is clear. A l l lavage fluid should be retrieved because fluid accumulation i n the abdom inal cavity impairs bacterial opsonization and clearance. 14
If debridement and lavage can resolve gross foreign mate rial or G I spillage and the source o f contamination can be controlled, the abdomen should be closed primarily because potential complications are associated with open abdominal drainage and closed suction drains. A l l patients w i t h abdom inal drainage are susceptible to superinfection w i t h nosoco mial bacteria and are subject to massive fluid and protein losses.
Open peritoneal drainage is accomplished with a simple con tinuous pattern o f nonabsorbable suture material in the rectus abdominus muscle, loosely enough to allow drainage through a gap of 1 to 6 c m in the body wall (Color Plate 133-2). A preassembled, sterile bandage comprised o f a nonadherent contact layer, laparotomy sponges or gauze pads, roll cotton or surgical towels, roll gauze, and an outer water-impermeable layer is placed to absorb fluid and protect the abdominal con tents from the environment. Initially this bandage is replaced twice during the first 24 hours and daily thereafter, although the amount o f drainage produced by an individual patient may dictate more frequent changes. A sterile-gloved finger may need to be inserted through the incision to break down adhesions and to allow thorough drainage of the peritoneal cav ity. Alternatively, patients with severely contaminated tissues may be placed under general anesthesia and the abdomen explored and lavaged daily before reapplying the bandage. The quantity o f fluid can be estimated by the difference in weight of the bandage before application and after removal. Abdominal closure typically can be performed 3 to 5 days following the ini tial surgery. The placement of a urinary catheter and collection system helps to limit contamination of the bandage and under lying exposed tissues. Alternatively, the abdomen may be closed primarily and drainage accomplished w i t h closed suction (Jackson-Pratt) d r a i n s . Closed suction drainage has been advocated for treatment o f generalized peritonitis because it has several advantages over open a b d o m i n a l drainage, including a decreased risk o f nosocomial infection, less intensive nursing care and bandaging requirements, decreased risk for evisceration, and the need for only one surgical proce d u r e . Disadvantages are that the drains may induce some fluid p r o d u c t i o n and may become occluded, although in one study active drainage was maintained for up to 8 days w i t h this technique i n 30 dogs and 10 cats. Additionally, closed suction drains allow daily quantitative and qualita tive assessment o f retrieved fluid for assessing the resolu tion o f peritonitis. Typically, one drain placed between the liver and diaphragm is sufficient for small dogs and cats, and two drains are more appropriate for larger dogs (the fenestrated p o r t i o n o f second drain is placed in the caudal abdomen along the ventral b o d y wall). The drain tubes exit the b o d y wall through a paramedian stab incision and are sutured to the a b d o m i n a l skin w i t h a pursestring and Chinese finger-trap sutures ( C o l o r Plate 133-3). 15
15
15
After routine closure o f the abdomen, the suction reser voir bulb is attached to the tubing with vacuum applied. A protective abdominal bandage is placed with sterile contact material around the tube-skin interface and is changed daily to allow assessment o f this site. Fluid collected within the bulbs is emptied using aseptic technique, and the volume is recorded every 4 to 6 hours, or more frequently i f needed. Drains are removed by applying gentle traction at a time when the volume o f fluid production has decreased signifi cantly and cytologic analysis suggests resolution of the peri tonitis (decreasing numbers o f nondegenerative neutrophils i n the absence o f bacteria). A sterile bandage is again reap plied to cover the drain exit site until the following day.
Postoperative Care Postoperative care for patients with peritonitis is typically intense because these patients are critically i l l and subject to a variety o f complications. Aggressive fluid therapy is a 7
necessity, particularly i n patients w i t h continued fluid losses from abdominal drainage. Electrolytes and acid-base status should be assessed routinely during the postoperative period and corrected as needed. Because anemia and hypoproteinemia are c o m m o n complications i n these patients, b l o o d component therapy and synthetic colloidal support are often necessary, with a goal o f maintaining a packed cell volume greater than 24%, serum protein over 3.5 g/dl, and colloid osmotic pressure higher than 15 m m H g . Proper nutrition w i l l provide a source o f protein that is greatly needed i n these patients. Failing to meet nutritional demands, either with parenteral or enteral nutrition, may contribute to impaired w o u n d healing and i m m u n e defenses. Enteral feeding is preferred over parenteral feeding but may be stymied by the anorectic patient unless G I feed ing tubes were placed during the original surgery. If this was not done, nasoesophageal tubes can be placed i n patients unable to tolerate more anesthesia or esophagostomy tubes in those that can. Animals with refractory vomiting typically require parenteral nutrition. Postoperative hypotension m a y b e treated w i t h vasopressor therapy, but only after addressing any underlying hypovole mia (see Chapter 176, Vasoactive Catecholamines). Proper analgesia is required to ensure patient comfort and to d i m i n ish the negative cardiovascular effects associated with overac tive sympathetic stimulation (see Chapter 164, Analgesia and Constant Rate Infusions). Other complications, including car diac arrhythmias, disseminated intravascular coagulation, and systemic inflammatory response syndrome can be found i n other chapters (see Chapters 11 and 107, Systemic Inflamma tory Response Syndrome and Septic Shock, respectively).
PROGNOSIS The prognosis for animals with peritonitis depends o n the underlying etiology and whether or not infection is present. Studies i n which patients have benefited from advances i n crit ical care management cite overall survival rates o f 50% to 7 0 % . ' ' ' Cats were reported to have a lower survival rate than dogs i n two studies ' ; however, another study focusing o n 51 cats with septic peritonitis found a 70% survival i n animals i n 4
16
1
5
w h i c h treatment was pursued. Poor prognostic indicators for animals with septic peritonitis have included refractory hypo tension, cardiovascular collapse, disseminated intravascular coagulation, and respiratory disease. ' M o r t a l i t y rates i n patients w i t h septic peritonitis secondary to G I leakage have been reported to vary between 30% and 8 5 % . ' ' ' ' Bacte rial contamination was highly associated with mortality i n animals w i t h bile peritonitis i n one study, and only 27% (3 o f 11) o f animals w i t h septic biliary effusion survived com pared with 100% (6 o f 6) w i t h aseptic effusions. Cats with uroperitoneum have an overall survival rate or 6 2 % , whereas the survival rate i n dogs is slightly lower at 4 3 % to 5 6 . 2 % . Survival rates appear to be similar i n patients with septic peri tonitis treated with p r i m a r y closure, open peritoneal drainage, or closed suction d r a i n a g e . ' 15
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SUGGESTED FURTHER READING*
Costello MF, Drobatz KJ, Aronson LR, King LG: Underlying cause, patho physiologic abnormalities, and response to treatment in cats with septic peritonitis: 51 cases (1990-2001), / Am Vet Med Assoc 225:897, 2004. Clinical presentation, treatment, and outcome of 51 cats with septic peritoniti studied to provide useful information regarding underlying cause, patho physiologic abnormalities, and response to treatment in this species. This i the first focused examination of this condition in cats; previous studies had focused on dogs or a combined population of dogs and cats. Evans KL, Smeak DD, Biller DS: Gastrointestinal linearforeignbodies in 32 dogs: a retrospective evaluation and feline comparison, J Am Anim Hosp Assoc 30:445, 1994. Retrospective study evaluating case records of 32 dogs with gastrointestinal li ear foreign bodies treated surgically to assess clinical signs, laboratory abnormalities, radiographic signs, surgical procedures, and complications. Peritonitis evident in 41% of cases, increasing the probability of death (both found to occur at nearly twice the rate previously described for feline patient with this condition). Lascelles BDX, Blikslager AT, Fox SM, Reece D: Gastrointestinal tract perfo ration in dogs treated with a selective cyclooxygenase-2 inhibitor: 29 cases (2002-2003), / Am Vet Med Assoc 227:1112, 2005. A retrospective study examining risk factors associated with gastrointestinal tract perforation in 29 dogs treated with a selective cyclooxygenase-2 inhib tor. Perforation attributable to a multitude offactors, prompting the authors to warn against using this type of medication outside of the recommended dosage and to avoid its use in close temporal association with other lessselective nonsteroidal antiinflammatory medications or steroids.
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*See the CD-ROM for a complete list of references.
Chapter 134 GASTRIC DILATATION-VOLVULUS AND BLOAT Susan W. Volk,
VMD, PhD, DACVS
KEY POINTS • Gastric dilatation-volvulus (GDV) is a life-threatening condition that requires aggressive emergency medical stabilization, surgical intervention, and intensive postoperative care to optimize management. • The pathogenesis of GDV is complex, with both genetic and environmental influences. • Distention and displacement of the stomach cause cardio respiratory dysfunction and gastrointestinal compromise. A cascade of pathophysiologic events further impairs these systems as well as the metabolic, hemolymphatic, renal, and central nervous systems. • Potential life-threatening postoperative complications include cardiac arrhythmias, persistent hypotension, disseminated intravascular coagulation, peritonitis, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. • Client education is key and promotes early intervention and decreased incidence of this condition through breeding and home treatment practices. • Despite often challenging case management, the overall survival rate for patients treated appropriately for GDV approaches 85%.
previously stated, this may occur i n the presence or absence of volvulus and, less commonly, volvulus may occur without significant dilatation. Rapid, significant gastric distention with gas and the ensuing cardiorespiratory dysfunction lead to the typical acute clinical picture, although some dogs may have chronic, subtle G I dysfunction. Multiple contributing factors have been identified and influence incidence within a genetically susceptible population. Although small dogs and cats can develop G D V , it is pre dominantly a syndrome o f the large and giant breed dogs. Certain breeds, including the Great Dane, Weimaraner, Saint Bernard, G o r d o n Setter, Irish Setter, and Standard Poodle, are at significantly increased risk. Furthermore, having a first-degree relative with a history of G D V was found to be a significant risk factor. It has been hypothesized that genetic predisposition to G D V may occur through inheri tance o f conformation, personality, or temperament that predisposes to the condition. Anatomic studies have shown a correlation between increased thoracic depth-to-width ratio and incidence o f G D V within certain breeds. It has been speculated that this conformation may inhibit eructa tion. Failure o f n o r m a l eructation and pyloric outflow mechanisms may be a prerequisite for gastric dilatation. Stretching o f gastric ligaments, as may occur with previous dilatation, large intraabdominal masses, or splenic torsion may facilitate development o f the c o n d i t i o n . ' 1
2
3,4
INTRODUCTION
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Acute gastric dilatation with or without volvulus is a life-threat ening condition that is classically described i n large or giant breed dogs with deep chests, and appears to occur more frequently i n older animals. Although there has been m u c h debate whether dilatation or volvulus occurs first i n the gastric dilatationvolvulus ( G D V ) syndrome, it is plausible that either may occur primarily as isolated cases of both conditions occur. Regardless of the sequence of events, once gastric distention and malpositioning occur, the compression of low-pressure (venous) intraab dominal vasculature leads to cardiovascular, respiratory, and gastrointestinal (GI) compromise. Impaired perfusion causes secondary compromise of multiple organs, the hemolymphatic system, and the metabolic system. Elements o f individual treat ment regimens remain controversial; however, treatment strate gies shown to yield the most successful outcomes combine aggressive emergency medical diagnostics and therapeutics with early surgical intervention and intensive postoperative critical care management. It is clear that an understanding of the etiol ogy, pathophysiology, and clinical features of this syndrome contribute to improved survival rates.
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Overeating, postprandial exercise, and food type have all been incriminated as causes o f G D V , but there remains a lack of evidence to support these assumptions. Based on the results by G l i c k m a n and colleagues examining nondietary risk factors for G D V i n 1637 large and giant breed dogs, feeding fewer meals per day or several small meals per day, moistening dry food before feeding, and restricting exercise or water intake immediately before or after eating were not associated with a decreased risk of G D V on multivariate analysis. In this large, prospective study, factors significantly associated w i t h increased risk were increasing age, having a first-degree relative with a history of G D V , eating faster (for large but not giant breeds of dogs), and having a raised feeding bowl. 2
A separate study documented that an episode of stress (e.g., boarding, traveling, a veterinary visit) occurred more fre quently during the period immediately before development of a G D V than i n a comparable disease-free population. The propensity to be influenced by a stressful event may be related to the personality o f a given individual. In a pros pective cohort study of 1914 dogs, the only breed-specific characteristic significantly associated with G D V was a negative correlation between owner-perceived happiness and incidence 8
PATHOGENESIS W h e n considering etiology, it is important to realize that several subpopulations o f dogs have gastric dilatation. As
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of G D V . However, other studies have suggested that fear ful or aggressive dogs may be at increased risk for develop ing G D V . ' The findings i n these studies and others may help decrease the incidence o f G D V by providing owners and breeders with guidelines for breeding and treatment practices. 2
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PATHOPHYSIOLOGY Gastric distention and displacement directly affect the cardio vascular, respiratory, and GI systems. Secondary effects o n these and other systems (i.e., metabolic, hemolymphatic, renal, and central nervous systems) ensue. Shock is the lifethreatening abnormality i n dogs with G D V , and an under standing of the cause of this state allows rational treatment. Severe gastric distention results i n compression o f the intraabdominal veins (caudal vena cava, portal vein, and splanchnic vasculature). This venous occlusion results i n decreased venous return and increased venous pressure (splanchnic pooling and portal hypertension). The combina tion diminishes cardiac output and systemic b l o o d pressure. The collateral circulation is unable to handle the venous return, leading to interstitial edema and loss o f intravascular volume, which further contribute to poor perfusion o f major organs. In addition, gastric distention prevents caudal displace ment of the diaphragm and therefore impedes normal respi ratory excursion. To compensate, respiratory rate and effort may increase. These efforts may become inadequate and eventually respiratory acidosis, due to impaired carbon diox ide clearance, might contribute further to the metabolic aci dosis that exists secondary to poor tissue perfusion (lactic acidosis). Aspiration pneumonia may further exacerbate this respiratory compromise. The increased intraluminal gastric pressures impair flow through the gastric wall vasculature and this, combined w i t h poor cardiac output, may lead to gastric necrosis. Avulsion, thrombosis, and stretching o f the short gastric arteries are common and may further contribute to diminished perfu sion of the stomach. Mucosal hemorrhage and necrosis are common. Susceptibility o f the mucosa to damage by hypo perfusion may be exacerbated by the acidic environment o f the gastric lumen and high metabolic demands. Decreased gastric perfusion results in serosal hemorrhage and edema of the stomach wall, which begins i n the fundus and spreads to the body of the stomach. Bacterial translocation from the stomach or other portions o f the poorly perfused intestinal tract may lead to septicemia. Severe compromise to the gas tric wall results in necrosis and perforation, w i t h resultant peritonitis. Cardiac arrhythmias, mainly ventricular i n origin, occur in approximately 40% o f patients with G D V . ' Several fac tors have been implicated i n the cause o f cardiac arrhyth mias. Coronary blood flow i n experimentally induced G D V is decreased by 5 0 % . Histologic lesions compatible w i t h myocardial ischemia are seen i n both experimental and spontaneous G D V and may establish ectopic foci o f electrical activity. Circulating cardiostimulatory substances such as epinephrine and cardioinhibitory substances such as myo cardial depressant factor have also been implicated i n the generation of arrhythmias. 1 0
hypoperfusion may result i n an increased production of lactic acid by anaerobic energy production, resulting i n a metabolic acidosis. Blood p H may be normalized by a concurrent meta bolic alkalosis caused by sequestration o f hydrogen and chlo ride ions i n the stomach lumen (causing a mixed acid-base disorder). Several pathophysiologic events may promote the development o f hypokalemia, including the administration of a large volume o f low-potassium fluids, sequestration o f potassium within the stomach or loss through vomiting or lavage, hyperchloremic metabolic alkalosis with transcellular shifting, activation of renin-angiotensin-aldosterone system, and catecholamine-induced shifting o f potassium into cells. B l o o d glucose levels may also fall i n the later stages of shock as energy demands cannot be met by the inefficient production o f adenosine triphosphate through anaerobic metabolism. Infarction o f splenic arteries and thrombosis o f splenic veins may occur, resulting i n splenic necrosis. Disseminated intravascular coagulation ( D I C ) is seen frequently i n dogs with G D V . C o n t r i b u t i n g factors include pooling o f b l o o d in the caudal vena cava, portal vein, or splanchnic circula tion, tissue hypoxia, acidosis, endotoxemia, and sepsis. 1 3
HISTORY AND CLINICAL SIGNS Affected dogs are often adult large, deep-chested breeds, although G D V i n small breed dogs and puppies as young as 1 m o n t h has been reported. Typically, the onset o f clinical signs is acute, with affected dogs appearing restless, u n c o m fortable, and anxious. M o s t affected dogs salivate and may retch or attempt to vomit. The owners may note the dis tended abdomen, although this may be difficult to appreci ate i n deep-chested, well-muscled, or obese individuals.
PHYSICAL EXAMINATION Physical examination parameters are manifestations o f the circulatory and respiratory compromise that results from acute gastric distention and displacement. Dogs often pre sent i n cardiovascular shock, w i t h depressed mentation, pale mucous membranes, prolonged capillary refill time, cool extremities, and rapid, weak pulses. Irregular cardiac rhythms and pulse deficits may be present. Tachypnea or dyspnea, or both, may reflect b o t h discomfort and a reduc tion i n tidal v o l u m e due to gastric distention. The abdo m e n can vary from unremarkable o n palpation, through distended and firm, to tympanic. Splenic congestion may lead to the finding o f splenomegaly. If presentation has been delayed, dogs can be collapsed and comatose.
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Acid-base and electrolyte imbalances are not seen consis tently i n dogs with G D V . Cellular hypoxia caused by systemic
DIAGNOSIS Complete b l o o d count may reveal evidence o f hemoconcentration and a stress leukogram. Platelet consumption and/or loss may lead to thrombocytopenia. The presence o f three or more abnormal hemostatic parameters (prolonged pro t h r o m b i n or activated partial thromboplastin time, hypofibrinogenemia, thrombocytopenia, elevated fibrin degradation products concentration, and antithrombin III depletion) correlates with gastric necrosis. Hepatocellular damage and biliary stasis may be evidenced by elevations i n alanine 13
Figure 134-1 The right lateral recumbent view is the radiographic view of choice for diagnosis of gastric dilatation-volvulus. In this view, the pylorus moves to a cranial position in a dog with gastric dilatationvolvulus and is separated by a soft tissue opacity from the body of the stomach In addition, in this example, enlargement of the spleen is evi dent and the serosal surfaces of the stomach, small intestine, and dia phragm are well defined, indicating a pneumoperitoneum.
transaminase and total bilirubin levels, respectively. Cardio vascular and renal compromise and hypovolemia may lead to elevations in blood urea nitrogen and creatinine. Potas sium may be elevated, normal, or low but is typically low for the reasons stated above. Plasma lactate concentration is an established predictor of gastric necrosis and survival in dogs with G D V . A b d o m i n a l radiography is used to differentiate simple gastric dilatation from dilatation with volvulus and to rule out other conditions. A l l dogs should be stabilized medically before radiographs are taken. The right lateral recumbent view is the view of c h o i c e . ' If possible, a dorsoventral view may also be taken to help delineate gastric position. Ventrodorsal positioning may lead to further cardiovascular compromise and may predispose to aspiration pneumonia should the patient regurgitate or vomit. The pylorus in a dog with G D V moves cranial to and is separated by a soft-tissue opacity from the body of the stomach (called reverse C, double bubble, or Popeye sign) in the lateral projection and to the left of midline on the dorsoventral view (Figure 134-1). In comparison, the pylorus lies ventral to the fundus and to the right of midline in a dog without volvulus. Although gastric pneumatosis (intramural gas) and pneumoperitoneum suggest gastric necrosis and possibly perforation, it is important to remember that gastric air may be introduced when a trocar is used in the emergency stabilization of the patient before radiographs are t a k e n . Chest radiographs may also be indicated in older animals that might have coexisting disease, animals with hyp oxemia, or patients suspected of having concurrent cardiacdisease. 1 4
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TREATMENT GOALS The most important goal of treatment is correction o f circulatory shock. Aggressive preoperative correction o f cardiovascular collapse before surgery has dramatically improved patient survival to an overall rate of approxi mately S3",,." " Following initial stabilization, treatment goals include decompression o f the stomach, differentiation 1
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of dilatation versus dilatation-volvulus, repositioning and pexying the stomach if volvulus exists, and early diagnosis and treatment of complications. Fluid resuscitation is initiated after placement of at least two large-bore (14 to 18 gauge) catheters in the cephalic or jugular veins. Blood samples can be obtained at this time for a m i n i m u m data base (packed cell volume, total solids, Azostix, and dex trose), hematology, serum chemistry, and coagulation evaluation. Shock doses of crystalloid fluids (90 ml/kg) or a combination of isotonic crystalloids (20 to 40 ml/kg) and synthetic colloids (hydroxyethyl starch 10 to 20 ml/kg; or 7% hypertonic saline in 6% dextran-70 5 ml/kg IV over 5 to 15 minutes) should be administered to effect (see Chap ter 65, Shock Fluids and Fluid Challenge). After appropriate volume resuscitation, vasopressor therapy may be necessary to further alleviate hypotension. During the initial examina tion and resuscitation, supplemental oxygen should be admi nistered, i f possible, to optimize oxygen saturation of hemoglobin. If available, continuous electrocardiographic (ECG) monitoring should be performed and arrhythmias (typically ventricular) treated i f they interfere with cardiac function and output. Broad-spectrum antibiotic therapy should be considered because these animals are at high risk for bacterial translocation from the GI tract to the bloodstream. Gastric decompression should be attempted only after cardiovascular resuscitation has begun. Decompression will further improve cardiorespiratory function; however, addi tional cardiovascular insult occurs with the rapid release of endotoxins and ischemic by-products (reperfusion injury). Gastric decompression usually can be accomplished with orogastric intubation (Color Plate 134-1). Sedation may be required and can be accomplished using a combina tion o f oxymorphone (0.1 mg/kg I V ) , buprenorphine (0.01 mg/kg IV) or butorphanol (0.2 to 0.4 mg/kg), and diazepam (0.2 to 0.25 mg/kg I V ) . Intubation may be desirable to protect the airway and prevent aspiration pneu m o n i a . The smooth-surfaced orogastric tube should be marked to a length of the distance from the nares to the cau dal edge of the last rib and the lubricated tube not passed beyond this point. In the event that the orogastric tube can not be passed easily, trocar insertion should be performed using a large-gauge, short needle or over-the-needle cathe ter in a region o f the left or right cranial, dorsolateral abdo men. This should be performed in an area that exhibits the greatest tympany and that has been clipped and aseptically prepared. C o n t i n u e d periodic assessment of physical parameters (heart rate, peripheral pulse pressure and quality, mucous membrane color, capillary refill time, and gastric disten tion) as well as laboratory data (packed cell volume, total solids, acid-base status, and electrolyte values) should be performed to ensure treatment remains tailored to the individual's response to therapy. As stated previously, only after cardiovascular stability is achieved should radio graphs be attempted. Immediate surgical intervention is indicated for animals with G D V . Dogs with gastric dilatation in the absence of volvulus (GD) typically do not require immediate surgical interven tion, although gastropexy is recommended for these patients to help prevent the development of G D V in the future. Conservative treatment in these patients is tailored to the individual patient and may consist of intravenous fluid therapy as described above and orogastric intubation as
needed. In addition, simethicone (2 to 4 mg/kg P O q6h) and metaclopramide (0.2 to 0.4 mg/kg S C q8h) m a y b e considered in order to decrease the amount o f gas and promote gastric emptying, respectively. It should be noted that even i n the absence of radiographic evidence of gastric volvulus, surgical exploration should be recommended for G D patients who are unresponsive to medical treatment (repeated bloating, persistent hypotension, and/or tachycardia).
SURGICAL TREATMENT The goals for surgery are to decompress and reposition the stomach, assess viability of the stomach and spleen, remove irreversibly compromised tissue, and create a permanent adhesion between the stomach and body wall to help prevent recurrence o f gastric volvulus. A large ventral midline i n c i sion is made, taking care not to damage abdominal viscera pushed up to the linea by gastric distention. Typically, the pylorus has moved from its normal position next to the right body wall toward the left body wall, in a clockwise direction. The rotation may be 90 to 360 degrees but most c o m m o n l y is 180 to 270 degrees. W i t h this type o f rotation, the greater omentum is found draped over the cranial abdominal organs. The stomach is decompressed by orogastric intubation (by the anesthetist with guidance by the surgeon) or via gastrocentesis and is rotated back into its n o r m a l position. The pylorus can be located by tracing the d u o d e n u m (identifiable by the attached pancreas) forward from the duodenocolic ligament. By gently bringing the pylorus back to the right o f midline using one hand and using the other hand to push the body o f the stomach dorsally, the stomach is derotated. A n orogastric tube may be used to completely decompress the stomach and empty ingesta. Gastrotomy is not recom mended for the removal of suspected food particles but is war ranted if potentially obstructive material is present w i t h i n the gastric lumen. Next, the stomach and the spleen should be assessed for viability and gastric resection or splenectomy performed as needed. The spleen should be removed only i f it has t h r o m bosed or been damaged by the gastric volvulus; it is rarely twisted otherwise. Partial gastrectomy is required when gastric necrosis has occurred, usually along the greater curvature. Gastric viability is assessed by examination of serosal color, palpation o f gastric wall thickness, and pres ervation o f arterial bleeding i f incised. Gray or black colora tion and palpable thinning o f the stomach are signs o f necrosis. Serosal coloration w i t h i n areas o f viable tissue may improve dramatically w i t h i n minutes o f decompression and repositioning. Gastric resection may be accomplished by preplacing stay sutures to m i n i m i z e or prevent additional abdominal contamination, followed by resection to bleeding tissue and closure. Whether hand-sewing or stapling (TA-90 or GIA-50) is used for closure, a second inverting suture line is recom m e n d e d . Invagination o f necrotic tissue has also been used to treat gastric necrosis. Because this technique does not require opening of the gastric lumen, it is technically less demanding and is theoretically less likely to result i n peritoneal contamination through gross spillage during partial gastrectomy or due to suture dehiscence; however, it should be noted that invaginated tissue may be prone to ulcer f o r m a t i o n . ' Although there are risks associated 17
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w i t h gastric resection and invagination, the devastating sequelae o f perforation and peritonitis resulting from necrotic tissue that is not excised make it advisable to remove or invaginate any gastric tissue o f questionable via bility. Gastric necrosis has been associated with the develop ment o f several life-threatening complications including peritonitis, disseminated intravascular coagulation, sepsis, and arrhythmias. A l t h o u g h two large retrospective studies examining postoperative outcome i n dogs surgically treated for G D V (295 and 166 cases) d i d not agree whether gastric resection was a risk factor for death, these studies both sug gest that w i t h aggressive preoperative and postoperative management, 70% to 74% o f dogs w i t h gastric resections may survive to d i s c h a r g e . ' ' 20
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M a n y procedures have been described to pexy the pyloric antral region o f the stomach to the right body wall. These include the tube, incisional, muscular flap, circumcostal, and belt loop gastropexies, as well as various modifications of the above. The a i m is to create a permanent adhesion between the antral region o f the stomach and the right body wall. A n incisional gastropexy is accomplished easily and quickly by making an incision about 5 c m long i n the trans verse abdominus muscle just caudal to the last rib, and a corresponding incision is made i n the seromuscular layer (taking care not to enter the gastric lumen). The orientation of the incisions reflects an attempt to preserve a relatively normal gastric position when the two edges o f each incision are sutured together using either polypropylene or polydioxanone. The pexy site should not be incorporated into the abdominal closure because the stomach could be damaged if cranial abdominal surgery is required at a future date. Although there is some variability i n strength o f the adhe sions formed using the various techniques when tested i n vitro, recurrence rates are similar for all the above tech niques when performed properly (percutaneous endoscopic gastrostomy tubes are not recommended because o f incon sistent adhesion f o r m a t i o n ) . The tube gastropexy may be associated with a higher m o r b i d i t y because o f premature tube removal and peristomal cellulitis; however, it may be useful for continued gastric decompression o f air and gastric secretions and for administration o f medications and n u t r i tional support to anorexic patients postoperatively. 21
The surgical technique used is probably less important than the surgeon's familiarity with one o f the established techniques and the surgeon's ability to perform it profi ciently and efficiently.
POSTOPERATIVE CARE The a i m o f postoperative management is to m a i n t a i n tissue perfusion. Because o f substantial fluid loss into the perito neal cavity and G I tract, reasonably h i g h fluid rates often are required for the first 48 to 72 hours. M u c o u s m e m brane color, capillary refill time, packed cell volume, total solid values, urine output, E C G , b l o o d pressure, and acid-base balance s h o u l d be m o n i t o r e d closely postopera tively. Dogs recovering well from surgery can be offered water first, and then a small amount o f food i f water is t o l erated o n the first or second day after surgery. These dogs can be weaned gradually off their intravenous fluids over 2 days. Because o f the high incidence o f gastric mucosal compromise, nonsteroidal antiinflammatory drugs are avoided, and histamine-2 receptor antagonists (ranitidine,
cimetidine, famotidine) and coating agents (sucralfate) should be considered. Cardiac arrhythmias often begin 12 to 24 hours after surgery. C o n t i n u o u s E C G m o n i t o r i n g is ideal. C o n t r i b u t ing factors include p o o r myocardial perfusion, electrolyte disturbances, acidosis, D I C , p a i n , and myocardial depres sant factor. If arrhythmias occur, these contributing factors should be sought and treated. A n t i a r r h y t h m i c therapy should be considered i f cardiac function is i m p a i r e d (poor pulse quality or pulse deficits) or i f serious electrical changes are evident (such as R o n T p h e n o m e n o n , m u l t i form ventricular premature contractions, or when sus tained ventricular tachycardia occurs w i t h a heart rate o f >180 beats/min), because this rate probably impairs ven tricular filling and therefore cardiac output) (see Chapters 46 and 47, Supraventricular Tachyarrhythmias and Ventricular Tachyarrhythmias, respectively). Reports have been conflicting as to whether the presence o f arrhythmias negatively affects the p r o g n o s i s . ' '
OWNER RECOMMENDATIONS
Perioperative risk factors significantly associated w i t h death before suture removal include hypotension at any time d u r i n g hospitalization, c o m b i n e d splenectomy and partial gastrectomy, peritonitis, sepsis, and D I C . Contri buting factors for the development o f D I C include p o o l i n g o f b l o o d i n portal circulation and caudal vena cava, sepsis, vascular thrombosis, endotoxemia, acidosis, tissue hypoxia, and splenic congestion. This c o n d i t i o n may persist into the postoperative period and require appropriate treatment w i t h fluids, plasma, and heparin (see Chapter 117, H y p e r coagulable States). Sepsis can occur d u r i n g the postopera tive p e r i o d . Gastric leakage must be ruled out; however, it is i m p o r t a n t to consider other culprits i n these patients such as aspiration p n e u m o n i a . The u n d e r l y i n g cause should be identified and w i l l help guide therapy. Systemic inflammatory response syndrome and m u l t i p l e organ dys function syndrome may occur i n critically i l l patients postoperatively (see Chapter 11, Systemic Inflammatory Response Syndrome).
SUGGESTED FURTHER READING*
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Based o n available information, veterinarians should discuss preventive strategies w i t h owners o f large and giant breed dogs. These w o u l d include not feeding dogs from a raised food b o w l and trying to ensure that large breed dogs eat more slowly (although this may be contraindicated in giant breed dogs). This may involve supervising feedings and separating dogs i n households with multiple pets to decrease competition at feeding time. O n the basis o f the findings of G l i c k m a n and colleagues , one o f the strongest recommen dations to prevent G D V is to remove from the breeding pools dogs that have a first-degree relative that has had a G D V . Prophylactic gastropexy, either laparoscopically or via a conventional approach, has been shown to reduce the life time probability of death due to G D V i n at-risk breeds and should therefore be offered to owners o f these dogs. " 2
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Brockman DJ, Holt DE, Washabau RJ: Pathogenesis of acute canine gastric dilatation-volvulus syndrome: is there a unifying hypothesis? Compen dium 22:1108, 2000. An excellent review of risk factors for GDV, proposing a unifying hypothesis to explain the pathogenesis. Glickman LT, Glickman NW, Schellenberg DB, et al: Multiple risk factors for the gastric dilatation-volvulus syndrome in dogs: a practitioner/owner case-control study, / Am Assoc Hosp Assoc 33:197, 1997. A retrospective risk factor analysis that determined extrinsic and intrinsic ris factors for the development of GDV in 101 dogs compared with their breed-matched, size-matched, and age-matched controls. Hedlund C, Fossum TW: Surgery of the digestive system. In Fossum TW, editor: Small animal surgery, St Louis, 2007, Mosby. Easy to follow, user-friendly surgical textbook that provides clear descriptio and helpful diagrams of the most commonly used gastropexy techniques, partial gastrectomy, and splenectomy. "See the CD-ROM for a complete list of references.
Part XIII UROGENITAL DISORDERS Chapter 135
ACUTE RENAL FAILURE
Chapter 136
CHRONIC RENAL FAILURE
Chapter 137
HEMODIALYSIS AND PERITONEAL DIALYSIS
Chapter 138
URINARY CATHETERIZATION
Chapter 139
PYOMETRA
Chapter 140
DYSTOCIA AND OBSTETRIC CRISES
Chapter 141
PARAPHIMOSIS AND PRIAPISM
Chapter 142
MASTITIS
Chapter 135 ACUTE RENAL FAILURE Catherine E. Langston, DVM, DACVIM
KEY POINTS • Therapeutic intervention during the initiation stage of acute renal failure (ARF) is more likely to be successful than treatment during the extension, maintenance, or recovery phases. • Prerenal failure is rapidly reversed, whereas animals with intrinsic parenchymal failure may take weeks to months to recover. Long standing prerenal ischemia can lead to intrinsic renal failure. • Careful attention to fluid balance, with accurate monitoring of urine output, fluid administration guided by intake and output, and frequent reassessment of the patient, is an important feature of treatment. • Anuric and oliguric ARF carry a worse prognosis than does polyuric ARF. • Polyuric ARF can be associated with extreme fluid losses from high urine output. • Mortality rates for ARF are high (ss60%).
progression to more severe injury, but changes i n glomerular filtration rate ( G F R ) and urine specific gravity are not appar ent at this stage. D u r i n g the extension phase, cellular injury progresses to cell death. The maintenance phase occurs when irreversible renal damage has occurred. Removal of the initiat ing cause at this stage does not alter the existing damage. The recovery phase may last weeks to months. 2
CLINICAL PRESENTATION History Listlessness, v o m i t i n g , diarrhea, and anorexia are c o m m o n historical findings. Oliguria, anuria, or polyuria may be reported. Compensatory polydipsia may be present or may be overshadowed by anorexia. Less c o m m o n historical findings include seizures, syncope, ataxia, and dyspnea. 3
INTRODUCTION Acute renal failure (ARF) is an abrupt decline i n filtration and excretory function o f the kidney, leading to retention o f uremic toxins and dysregulation o f fluid, electrolyte, and acidbase balance. A l t h o u g h anuria and oliguria are classic features of A R F , nonoliguric and polyuric A R F are c o m m o n and carry a better prognosis.
ETIOLOGY A R F can be categorized into prerenal, intrinsic renal parenchy mal, and postrenal causes. Prerenal causes include decreases i n renal b l o o d flow or perfusion or excessive vasoconstriction. Prerenal azotemia rapidly reverses when the inciting cause is eliminated. Intrinsic renal parenchymal causes include pro longed hemodynamic or ischemic events (extension of prerenal causes), infectious diseases, toxins, or systemic diseases w i t h renal manifestations. Box 135-1 lists substances with a nephro toxic potential. Postrenal failure is due to obstruction or diver sion o f urine flow, including urethral obstruction, bilateral ureteral obstruction or unilateral obstruction w i t h a nonfunc tional contralateral kidney, or urine leakage. Restoration o f urine flow rapidly resolves azotemia, although prolonged obstruction may lead to intrinsic parenchymal renal failure. Calcium oxalate nephroliths and ureteroliths are encountered i n cats with increasing frequency. This condition c o m m o n l y has many features o f A R F , although there is frequently a significant component of chronic renal damage.
Physical Examination Dehydration is c o m m o n . Other findings include uremic hali tosis, oral ulceration, tongue tip necrosis, scleral injection, tachycardia or bradycardia, hypothermia, and cutaneous bruis ing. A hallmark o f A R F is enlarged, painful kidneys. Melena or diarrhea may be present from uremic gastritis or enteritis. Signs of the primary ailment causing renal failure (e.g., disseminated D I C intravascular coagulation, vasculitis) may predominate.
DIAGNOSIS Laboratory Tests The urine specific gravity w i l l be isosthenuric (1.007 to 1.015). W i t h acute tubular necrosis (most of A R F ) , a urine dipstick may reveal glucosuria (without hyperglycemia), proteinuria, and microscopic hematuria. The urine p H is usually acidic, unless there is a concurrent bacterial urinary tract infection. U r i n e sediment examination may show white b l o o d cells, red b l o o d cells, and granular casts. C a l c i u m oxalate crystals i n large numbers are indicative o f ethylene glycol intoxication, although a few oxalate crystals may be present normally. U r i n e culture is important to document pyelonephritis and guide antimicrobial therapy.
PATHOPHYSIOLOGY
Hematocrit may be elevated from hemoconcentration or decreased from gastrointestinal (GI) b l o o d loss. Platelet count may be n o r m a l or low, although uremia induces a thrombocytopathy, prolonging the buccal mucosal bleeding time despite a normal coagulation profile.
A R F proceeds through four phases. The initiation phase is the period o f renal injury. Intervention at this phase may prevent
The severity o f azotemia depends o n disease and duration. The ratio o f b l o o d urea nitrogen to creatinine can be high from G I bleeding or dehydration, or it can
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Box 135-1 Substances With Nephrotoxic Potential 2
Therapeutic Agents
Diuretics
Antimicrobial
Angiotensin-enzyme converting inhibitors
Agents
Aminoglycosides Penicillins Nafcillin
Immunosuppressive
Cephalosporins Sulfonamides Fluoroquinolones Carbapenems Aztreonam Rifampin Tetracyclines Vancomycin Antifungal
Nontherapeutic Agents Heavy
Agents
Chemotherapy
Cisplatin and carboplatin Methotrexate Doxorubicin Azathioprine Adriamycin Antiviral
Metals
Mercury Uranium Lead Bismuth salts Chromium Arsenic Gold Cadmium Thallium Copper Silver Nickel Antimony
Amphotericin B Cancer
Drugs
Cyclosporine FK-506 Interleukin-2
Agents
Other Diagnostic Modalities
Endogenous
Acyclovir Foscarnet Antiprotozoal
Hemoglobin Myoglobin
Agents
Organic
Pentamidine Thiacetarsamide Trimethoprim-sulfamethoxazole Sulfadiazine Dapsone
Compounds
Ethylene glycol Carbon tetrachloride Chloroform Pesticides Herbicides Solvents
Miscellaneous Allopurinol Cimetidine Apomorphine Deferoxamine Streptokinase Dextran-40 Methoxyflurane Penicillamine Acetaminophen Tricyclic antidepressants e-Aminocaproic acid Lipid-lowering agents Nonsteroidal antiinflammatory drugs
Miscellaneous
Agents
Gallium nitrate Diphosphonate Mushrooms Grapes or raisins Calcium antagonists Snake venom Bee venom Lily Illicit drugs Radiocontrast agents
below i n early stages of A R F . Ionized calcium levels tend to be normal, but acute severe hyperphosphatemia can decrease total calcium as a result of the law of mass action. Ethylene gly col, however, may cause a profound ionized hypocalcemia, due to both severe hyperphosphatemia and chelation o f calcium by oxalate. A n i o n gap is high because o f retained organic and inorganic acids that the damaged kidney is unable to excrete. The anion gap is calculated by the formula: +
may be readily apparent, although obstructing ureteroliths may be below the limit o f resolution. A b d o m i n a l ultrasonogra phy usually shows normal or enlarged kidneys w i t h normal architecture. Bilateral pyelonephritis or obstruction character ized by renal pelvic dilation, or lymphosarcoma characterized by a diffusely thickened cortex, could cause ARF. W i t h ethylene glycol intoxication, oxalate crystal deposition i n the kidneys increases the echogenicity, making the kidneys hyperechoic, or "bright." A n intravenous pyelogram can aid i n the identification of pelvic, ureteral, and cystic disease processes, especially obstructions. In addition it can provide information regarding renal function. Difficulties associated w i t h pyelography include worsening o f A R F due to the hyperosmolarity of the contrast agent and inadequate study quality due to poor uptake o f con trast i n oliguric or anuric states. Antegrade pyelography may be a better choice for ureteroliths. Computed tomography or mag netic resonance imaging can add information about architec ture and obstruction but requires anesthesia.
Measurement o f G F R (e.g., iohexol clearance, endogenous creatinine clearance, scintigraphy) can be difficult or time consuming to perform, and some techniques are subject to limited availability. Because the renal function tends to change rapidly, these studies have limited applicability i n the initial treatment o f A R F . Ethylene glycol intoxication is an emergency situation that requires immediate specific ther apy, making accurate and timely diagnosis crucial, and a commercially available in-house test kit is available (see Chapter 78, Ethylene Glycol). Leptospirosis titers detect an antibody reaction to the organism or vaccine. There is considerable cross-reactivity among serovars. Titers may be negative w i t h i n the first 7 to 10 days; a fourfold rise after 2 to 4 weeks confirms infec tion. A single titer o f 1:800 or greater w i t h appropriate clin ical signs i n the absence o f recent vaccination (or titers to nonvaccinal serovars) is also suggestive. Cats are resistant to leptospirosis. A polymerase chain reaction assay on urine has been developed for rapid early diagnosis i n dogs. Sero logic tests for other infectious disease k n o w n to cause A R F , such as Rocky M o u n t a i n spotted fever (Rickettsia rickettsii), Ehrlichia canis, Lyme disease (Borrelia burgdorferi), Babesia, or Leishmania, may be useful i n certain areas or when there are other consistent clinical or pathologic signs, although a positive titer does not prove causality o f A R F . 4
A renal fine-needle aspirate can confirm the presence of lymphosarcoma but its absence cannot reliably be documen ted this way. The risk o f bleeding is low, but possible. Renal biopsy can be obtained v i a percutaneous ultrasonographically guided needle biopsy, laparoscopy, or surgical wedge biopsy through a keyhole incision i n the flank. A renal biopsy may confirm etiology (i.e., ethylene glycol toxicity, renal lymphosarcoma, or it may show acute tubular necrosis. The risk o f bleeding when uremia is severe is high because o f the thrombocytopathy.
+
A n i o n gap = ( N a + K ) - ( H C O ^ + C I " ) +
+
where N a = sodium, K = potassium, HCO3 = bicarbonate, and C l ~ = chloride. N o r m a l anion gap is 10 to 15 m E q / L .
TREATMENT Imaging Survey abdominal radiographs may show normal kidneys or renomegaly with normal shape. Nephroliths or ureteroliths
Treatment o f A R F involves therapy for azotemia, therapy for extrarenal manifestations, supportive care and, i n some cases, therapy specific to the underlying disease process.
Fluid Therapy Dehydration deficits should be replaced w i t h a balanced polyionic solution such as lactated Ringer's solution or Plasmalyte. Ultimately, the fluid choice must be guided by m o n itoring s o d i u m concentration because the degree o f free water loss relative to s o d i u m loss varies greatly i n patients with A R E The guiding principle i n treating a s o d i u m disor der is to reverse it at the same rate at which it developed, because rapid increases or decreases i n s o d i u m concentration may cause central nervous system ( C N S ) dysfunction. C o l l o i d a l support (hydroxyethyl starch [hetastarch], dextran, or plasma) may also be indicated. Determining the amount o f fluid to use i n A R F requires frequent reassessment o f the patient's status. The calculated amount for rehydration (percentage o f dehydration x body weight (kg) = fluid deficit i n liters) is usually administered over 4 to 24 hours. If the patient appears hydrated, give 5% o f body weight to account for undetectable dehydration. If the patient is anuric or oliguric, fluid administration should be guided by volume o f urine output. Patient output includes insensible loss (respiration, stool) plus urine output plus ongoing losses (vomiting, diarrhea, nasogastric suction ing, fluid exudation into wounds). Insensible loss is 22 m l / k g q24h. To measure urine output, use a urinary catheter and record volume produced at least every 6 hours. O n g o i n g losses, such as v o m i t i n g , diarrhea, and yield from gastric suction, can be measured but usually are estimated (see Chapter 204, U r i n e Output). To write treatment orders for intake and output using two intravenous catheters, the daily insensible loss is divided by 4 to determine the 6-hourly dose of intravenous fluid for one catheter. This fluid can be used to deliver any drugs that need to be given by constant rate infusion (CRI) (metoclopramide, lidocaine), being cognizant o f drug incompatibil ities. For the replacement fluid dosage, a volume based o n estimate o f the patient's needs is selected. The fluid rate is then recalculated every 6 hours. Use the previous 6-hour urine output volume plus an estimate o f losses during that period (vomiting and diarrhea) as the volume to deliver over the next quarterly dose i n the second catheter. This method avoids having to recalculate the dosage for the C R I infusion every 6 hours. If only one intravenous catheter is available, the amount o f medication to be administered by C R I over 6 hours is calculated. This amount is added to the fluid v o l ume required over the next 6 hours (6 hours o f insensible losses + previous 6-hour urine output). The total volume is divided by 6 to get the hourly rate for the C R I . A n anuric patient should receive fluid administration to replace insensible loss only. If the patient is overhydrated, even that is withheld. Overhydration i n an anuric patient or inability to induce diuresis i n an oliguric or anuric patient is a clear indication for some form o f dialysis, w h i c h is the only other effective therapeutic option. M o n i t o r i n g fluid status is an ongoing process that must be repeated throughout the day. M o n i t o r i n g skin turgor takes no special equipment, but the clinician should be wary of patients w i t h vasculitis or hypoproteinemia, who may be unable to retain fluid w i t h i n the vascular compartment. Body weight should be measured at least twice daily. Follow ing trends i n packed cell volume, total solids, and b l o o d pressure can give a relative indication o f volume status. C e n tral venous pressure measurement is useful i n oliguric patients, although the correlation between central venous
pressure and pulmonary vascular pressure (and development of pulmonary edema) is not perfect. Urine volume can be determined by a variety o f methods, including (1) urinary catheter and closed collection system, (2) collection o f naturally voided urine, (3) metabolic cage, (4) weighing cage bedding and litter pans (1 m l of urine = 1 g), and (5) using body weight to verify accuracy. Urine vol ume can be categorized as anuria (none to negligible amount), oliguria (2 ml/kg/hr).
Diuretics There is no evidence that diuretics improve the outcome of A R F , and some surmise that the ability to respond to diuret ics is a marker of less severe renal injury associated with a better prognosis. In humans, an increase i n urine output after diuretic administration delays referral for dialysis, per haps inappropriately. However, i n veterinary medicine where dialysis is not as readily available to control fluid vol ume, diuretic use that leads to increased urine output may enhance the ability to administer the volume of other medications or nourishment that are recommended (see Chapters 7 and 180, Oliguria and Diuretics, respectively). 5
Acid-Base and Electrolyte Balance A variety o f acid-base and electrolyte disturbances occur c o m m o n l y i n A R F . Hyperkalemia can be an immediately life-threatening electrolyte disorder. Renal excretion is the primary mechanism for removing potassium from the body. The increase i n extracellular potassium changes the electrical potential o f excitable cells. The myocardium is relatively resistant compared w i t h the conduction cells. Typical elec trocardiographic changes include bradycardia, tall spiked T waves, shortened Q T interval, wide Q R S complex, and a small, wide, or absent P wave. Severe hyperkalemia can lead to a sine wave, ventricular fibrillation, or standstill. Treatment consists o f insulin (0.5 U / k g regular insulin IV ) to translocate potassium intracellularly. It takes up to 30 m i n utes to have an effect. Dextrose induces endogenous insulin release i n nondiabetic patients and prevents hypoglycemia when insulin is administered. It is given at 0.5 g/kg IV or 1 to 2 g per unit o f insulin given and 1 to 2 g per unit i n the next dose o f intravenous fluids. Metabolic acidosis causes an extra cellular shift o f potassium as hydrogen ions increase intracellu larly. Correction o f metabolic acidosis with bicarbonate allows an intracellular shift of potassium as the hydrogen ions are com bined with bicarbonate and removed. The dosage o f sodium bicarbonate is based o n the base deficit or 2 mEq/kg IV. Cal c i u m gluconate 10% (0.5 to 1 ml/kg I V to effect, given slowly) can be used i n critical situations to restore membrane excitabil ity without decreasing potassium concentration. It has an effect in 10 minutes, which can buy time for potassium-lowering maneuvers to work. D u r i n g infusion the electrocardiogram must be monitored, and the infusion slowed or stopped i f the arrhythmia worsens. Dialysis is the only method that actually removes potassium from the body. Metabolic acidosis is a c o m m o n acid-base disturbance i n renal failure. D a i l y hydrogen i o n load is excreted with N H as N H j . W i t h renal failure, the kidneys are unable to excrete hydrogen ions and cannot reabsorb bicarbonate. There may be some contribution from lactic acidosis from dehydration and p o o r perfusion. Treatment with sodium bicarbonate 3
+
is geared toward causing acid ( H ) to combine w i t h bicarbonate H C 0 , which dissociates to water and carbon dioxide. If the lungs are unable to eliminate the carbon diox ide, the reaction does not proceed. Bicarbonate administra tion in this situation can increase the partial pressure o f carbon dioxide and can lead to paradoxical C N S acidosis. This is due to the ability o f carbon dioxide to diffuse into the C N S , where it can be converted back to acid. 3
Treatment is also contraindicated w i t h hypernatremia. Sodium bicarbonate therapy usually is reserved for patients with a p H less than 7.2 or bicarbonate level less than 12 m E q / L . The bicarbonate dosage can be calculated from the formula: 0.3 x body weight(kg) x base deficit = bicarbonate ( m E q / L ) where the base deficit = 24 — patient bicarbonate. Give one fourth to one third of the dose intravenously and an addi tional one fourth i n the intravenous fluids over the next 4 to 6 hours. Adjust any subsequent doses based o n serial blood gas determinations. Symptomatic hypocalcemia (tetany) occurs infrequently in patients with ARF. The m i n i m u m dose o f calcium gluco nate that controls clinical signs should be used to prevent precipitation with phosphorus. C a l c i u m gluconate 10% can be used at a dosage o f 0.5 to 1.5 m l / k g I V over 20 to 30 m i n utes. As when treating hyperkalemia, m o n i t o r the electrocar diogram during infusion.
Extrarenal Manifestations of Uremia Vomiting is c o m m o n w i t h A R F . Ranitidine (0.5 mg/kg I V q24h), famotidine (0.5 to 1 mg/kg I V q24h i n dogs, S C i n cats), and cimetidine (5 to 10 mg/kg I V slowly q8h i n dogs, q l 2 h i n cats) are histamine-2 ( H ) blockers that have been used to decrease gastric acid production. Famotidine can cause hemolysis when administered intravenously to cats. The dosage for H blockers i n renal failure is lower because these drugs are eliminated by renal clearance. 2
2
Omeprazole is a proton pump blocker that is absorbed i n the small intestine. If capsules must be split, the drug should be dis solved i n sodium bicarbonate to protect it from degradation i n the stomach. G I protectants help heal ulcers that have already formed. Sucralfate (0.25 to 1 g P O q6h) binds to the ulcerated surface, works best i n an acid environment, and should be given 2 hours before antacids. 6
Because uremic toxins directly affect the chemoreceptor trigger zone i n the C N S , causing nausea and vomiting, cen trally acting antiemetics occasionally are needed to control intractable vomiting i n the patient with A R F . M e t o c l o p r a mide (0.2 to 0.4 mg/kg S C q8h) is a central dopamine antag onist that is effective i n decreasing v o m i t i n g i n many cases. It should not be administered concurrently with dopamine. Phenothiazine derivatives such as chlorpromazine (0.2 to 0.5 mg/kg I M or S C q6-8h) and prochlorperazine (0.1 to 0.5 mg/kg I M or S C q8-12h) have hypotensive and sedative side effects. Experience w i t h serotonin antagonists such as ondansetron (0.1 to 0.3 mg/kg I V q8-12h) and dolasetron (0.5 mg/kg P O , SC, or I V q24h) is limited, but anecdotally favorable, although these drugs are expensive. Cisapride (0.1 to 0.5 mg/kg P O q8-12h) is used as a prokinetic agent to treat delayed gastric emptying. Bradycardia from increased vagal tone can worsen during a vomiting episode, leading to syncope or cardiac arrest. A n t i cholinergic medications such as glycopyrrolate (0.005 to
0.01 mg/kg I V o r I M , or 0.01 to 0.02 mg/kg S C q8- 12h) should be considered when this occurs. N u t r i t i o n a l support i n the early stages o f A R F decreases m o r b i d i t y i n h u m a n studies. Enteral feeding is often limited by the v o m i t i n g frequently seen with renal failure. However, for those patients i n w h i c h v o m i t i n g is not present or controlled pharmacologically, nasoesophageal, nasogastric, esophagostomy, or percutaneous endoscopic gastrostomy tubes can be used. If v o m i t i n g cannot be controlled, partial or total parenteral n u t r i t i o n should be a consideration. In patients who are anuric or oliguric, the volume instilled, whether enterally or parenterally, must be taken into consid eration and constitutes a relative contraindication unless there is a method o f fluid removal (i.e., dialysis). Phosphate binders (i.e., a l u m i n u m hydroxide, a l u m i n u m carbonate, calcium acetate) administered concurrently with enteral feedings may decrease phosphate absorption. Dialytic support may be the only effective treatment for uremia i n an oliguric or anuric patient or i n patients whose disease is refractory to conventional medical treat ment (see Chapter 137, Hemodialysis and Peritoneal Dialysis). Once diuresis has been established, polyuria can be quite profound. M o n i t o r i n g urine production to prevent inade quate fluid administration is necessary i n this situation, as well as with oliguria or anuria. Weaning these patients off of I V fluids is a crucial step. W h e n the azotemia has been controlled and the patient seems stable, the fluid dosage can be decreased by 10% to 20% per day. If the urine output diminishes by a corresponding degree and the azotemia does not return, continue tapering slowly. If the urine output does not diminish, the kidneys are unable to regulate fluid balance, and further reduction i n the fluid administered w i l l lead to dehydration. It can take weeks for the kidneys to regain the ability to control fluid volume, but a rule o f thumb is to taper fluids over the same length o f time it took to diurese them. Furosemide can be tapered by 2 5 % to 50% per day, with close m o n i t o r i n g to ensure continued adequate urine output.
Specific Treatments In many cases o f A R F , the exact etiology is not k n o w n i n i t i ally, and therapy is aimed at treating the uremia and its manifestations. However, some causes o f A R F have spe cific treatments. Penicillin G or ampicillin (22 mg/kg q6h) is the antibiotic o f choice for leptospiremia, although doxycycline is also effective i n the leptospiremic phase. The carrier state can be eliminated using doxycycline (5 mg/kg q l 2 h for 2 weeks). Antidotes for ethylene glycol (4 methylpyrazole [4-MP, Antizol-Vet] or alcohol) must be administered shortly after ingestion to be effective (see Chapter 78, Ethylene Glycol).
PROGNOSIS 7
Overall mortality from A R F i n dogs is about 6 0 % . In the dogs that survive, approximately 60% have chronic renal failure, and only 40% recover n o r m a l renal function. In cats, mortality is about 4 0 % to 50%, with approximately 50% o f survivors left w i t h chronic renal failure. Certain subsets o f patients have a better prognosis. Approximately 82% to 86% o f dogs with leptospirosis survived i n one 7
8
9
series. Patients w i t h polyuria have a better outcome than those w i t h oliguria or a n u r i a . ' 8
10
SUGGESTED FURTHER READING* Adin C A , Cowgill L D : Treatment and outcome of dogs with leptospirosis: 36 cases (1990-1998), / Am Vet Med Assoc 216:371, 2000. One of several articles on leptospirosis containing much clinically useful information.
Cowgill LD, Francey T: Acute uremia. In Ettinger SJ, Feldman EC, editor: Textbook of veterinary internal medicine, ed 6, Philadelphia, 2005, Saunders. An excellent comprehensive review of ARF. Worwag S, Langston CE: Retrospective, acute renal failure in cats: 25 cases (1997-2002), / Vet Intern Med 18:416, 2004. An abstract presenting outcome data and some predictors of outcome in cats with ARF from a variety of causes and seventy. *See the C D - R O M for a complete list of references.
Chapter 136 CHRONIC RENAL FAILURE Catherine E. Langston, DVM, DACVIM
KEY POINTS • Chronic renal disease or failure (CRF) is one of the most common reasons for older cats to be presented to the veterinarian, but is also commonly seen in dogs and in young animals. • Many drugs and therapies are available for treatment of CRF, but there is no cure. The goal of therapy is to slow progression and to improve the pet's sense of well-being (quality of life). • Dietary therapy decreases the number of uremic crises and decreases mortality. All pets with CRF should be encouraged to eat a renal diet if there are no contraindications (such as dietary allergies). • As uremia progresses and the number of uremic complications increases, the number of medications to control complications increases. The nursing care involved may require a substantial time commitment from the owner.
INTRODUCTION C h r o n i c renal failure ( C R F ) is a c o m m o n disease i n cats and dogs. Because each nephron works as a unit, i f the glomeru lus is damaged irreversibly, the associated tubule w i l l degen erate and vice versa. A s nephrons are lost, the remaining nephrons hypertrophy. A l t h o u g h initially adaptive, glomeru lar hypertension damages the nephron, leading to further nephron loss. After a certain amount o f damage has been sus tained, renal failure may be progressive despite resolution o f the initiating cause. A s the renal damage progresses, azotemia develops, and eventually signs o f uremia appear.
ETIOLOGY The chronic lymphoplasmacytic interstitial nephritis that we see commonly, especially i n older cats, is probably not a single entity, but the end result of any k i n d of renal insult. Differential diagnoses for C R F include tubulointerstitial nephritis, renal dysplasia (young animals), polycystic kidney disease (Persians,
other longhair cats, less frequent i n domestic shorthair cats), chronic pyelonephritis, nephrolithiasis or ureterolithiasis, infarction, lymphoma, glomerulonephritis, amyloidosis, and incomplete resolution of acute renal failure. 1
EPIDEMIOLOGY C R F can affect cats o f any age but is more c o m m o n i n older cats. The incidence approaches 15% i n cats over 15 years of age. Symptomatic cats tend to be older than asymptomatic cats (mean age 12.5 to 14.5 years versus 8.3 years). A l t h o u g h C R F occurs less c o m m o n l y i n dogs, the incidence also increases with age. 2
CLINICAL PRESENTATION Asymptomatic In some patients, m i l d and asymptomatic azotemia is discov ered incidentally, perhaps i n conjunction with geriatric or dental screening. The asymptomatic pet with very m i l d elevations i n blood urea nitrogen ( B U N ) or creatinine, that is maintaining body weight and appropriate hydration, may not need treat ment other than diet, although routine monitoring is indicated.
Symptomatic M i l d clinical sings may be present for months to years (espe cially polyuria, polydipsia, and weight loss) before examina tion. In pets presented for evaluation because o f early signs of renal failure, outpatient treatment is usually sufficient without the need for a hospital stay. A markedly dehydrated pet w i t h severe uremic syndrome that has decompensated w i l l likely need hospitalization for intensive therapy, includ ing intravenous fluid administration. Once the uremic
crisis is controlled, however, continued treatment at home will help delay another crisis. C o m m o n signs include polyuria and polydipsia, weight loss, anorexia, vomiting, lethargy or depression, halitosis, dys phagia or oral discomfort, and weakness. C o m m o n physical examination findings include t h i n body, dehydration, abnor mal kidney size or shape, heart m u r m u r , oral ulceration, gin givitis, halitosis, hypothermia, and pale mucous membranes. Severely affected animals may suffer from altered con sciousness, seizures, or bleeding problems, or be moribund.
DIAGNOSIS The combination o f historical and physical examination find ings frequently leads to a clinical suspicion o f CRF. Diagnostic evaluation can confirm the diagnosis, occasionally indicate the underlying cause, and detect uremic complications.
Laboratory Testing C o m m o n laboratory abnormalities include azotemia, hyper phosphatemia, hypokalemia, metabolic acidosis, and hypercal cemia or hypocalcemia, although the ionized calcium level usually is normal. Lack o f erythropoietin, a hematopoietic hormone, leads to a nonregenerative anemia. C h r o n i c inflammation or i r o n deficiency from chronic gastrointestinal (GI) b l o o d loss may contribute. Some animals have an acute anemia (that may be partially regenerative) from acute b l o o d loss from GI ulcera tion. The platelet count is usually normal, although platelet function may be impaired with uremia. A buccal mucosal bleeding time may be prolonged, but coagulation panel (prothrombin time and partial thromboplastin time) results are expected to be normal. Poorly concentrated urine (urine specific gravity < 1.035 i n cats, < 1.030 i n dogs) with azotemia i n the absence o f urinary obstruction defines CRF. Active urine sedimentation (white blood cells, red b l o o d cells, bacteria) may indicate urinary tract infection as a cause or consequence o f CRF. A positive urine culture result may indicate pyelonephritis, although a negative urine culture result does not eliminate pyelonephritis as a cause of CRF. Routine urine culture is recommended even in the absence of lower urinary tract signs or active urine sedi mentation because cats with C R F may have silent urinary tract infections. The urine protein-to-creatinine ratio is usually normal (60 m m H g ) despite therapy are candidates for mechanical ventilation. 1
Hypoxemia Oxygenating ability must be monitored closely during the postoperative period. If an animal has an arterial catheter, an arterial blood gas analysis with and without supplemental oxy gen should be performed to determine arterial oxygenation. If an arterial catheter is not available, noninvasive measures o f oxygenation such as pulse oximetry should be used until the patient's oxygen saturation exceeds 95%. If oxygenation is inadequate, supplemental oxygen should be administered by oxygen cage or h o o d or nasal, nasopharyngeal, or tracheal oxygen catheterization. 2
Hypoxemia, identified as a partial pressure o f arterial oxy gen less than 80 m m H g or an oxygen saturation o f less than 95%, is most commonly a result o f pulmonary parenchymal disease such as pulmonary edema, pulmonary contusions, pneumonia, atelectasis, or parenchymal dysfunction second ary to pleural space disease. In the patient breathing r o o m air, hypoventilation can cause hypoxemia that will resolve rapidly with oxygen administration. If hypoxemia is identi fied, it should prompt the clinician to evaluate the patient thoroughly and perform further diagnostic tests as indicated.
CIRCULATORY STATUS Hypotension Critical illness and anesthesia are both c o m m o n causes o f hypotension, making intensive b l o o d pressure m o n i t o r i n g essential during the postoperative period. Continuous direct arterial blood pressure monitoring is ideal i n the critically i l l patient; when it is unavailable, indirect measurement is done with an oscillometric and/or Doppler technique. Hypotension may be caused by hypovolemia, vasodilation, or decreased
myocardial contractility. Initial therapy generally is focused o n aggressive support o f intravascular volume. Measurement of central venous pressure can help guide this therapy. If primary myocardial disease is suspected, echocardiographic evaluation is indicated and positive inotropic drugs such as dobutamine may be required. Vasodilation is a potent cause o f hypotension that is unresponsive to fluid administration. It is most commonly a result o f anesthetic drug effects and/or a severe systemic inflammatory response during the postoperative period. Vasopressor drugs such as dopamine, norepinephrine, and vasopressin are usually required to support b l o o d pressure i n these patients. Bradyarrhythmias and tachyarrhythmias can also cause hypotension and should be treated appropriately. Electrocar diographic m o n i t o r i n g can be very useful i n the postopera tive patient for early detection o f dysrhythmias, as well as identification o f tachycardia that can be an early warning sign o f cardiovascular compromise, pain, or anxiety.
Oxygen Delivery Oxygen delivery is dependent o n arterial oxygenation, hemo globin concentration, and the ability o f the heart and circula tory system to deliver vital oxygen to end organs, including peripheral tissues. Factors that influence oxygen delivery include bradyarrhythmias or tachyarrhythmias, inadequate cir culating intravascular fluid volume, inadequate hemoglobin concentration or oxygen carrying capacity, inadequate hemo globin saturation o f oxygen, and peripheral vasoconstriction that increases vascular afterload, hypothermia, and depressed myocardial contractility. U n t i l anesthetic drugs have w o r n off or have been metabolized, inappropriate vasodilation with peripheral vasoconstriction, hypoventilation, and decreased myocardial contractility may also be present. Careful monitor ing o f cardiac rhythm, b l o o d pressure, hemoglobin concentra tion, oxygen saturation, and core body temperature should be performed until all have normalized.
PAIN VERSUS DYSPHORIA D u r i n g the immediate postoperative period, it is often diffi cult to accurately differentiate between pain and dysphoria. Recognition o f pain i n animals can be challenging because of interpatient and interspecies variations i n manifestations of clinical signs o f pain. Postoperative analgesia should be administered w i t h the intent that the animal should never be allowed to be i n pain. M u l t i m o d a l analgesia w i t h opioids, nonsteroidal antiin flammatory drugs, and intrapleural or local administration of anesthetic agents can be performed to m i n i m i z e patient discomfort and maximize analgesia without causing adverse side effects. It is still difficult to accurately assess whether an animal is i n pain, attention seeking, or dysphoric. Physical examination parameters such as heart rate and b l o o d pres sure can be increased w i t h pain, or they can be increased because o f anxiety, dysphoria, or an animal's need to urinate or defecate i n an area away from its immediate environment. 3
First, evaluate the surgical site for evidence o f pain on palpation. If present, administration o f additional analgesia may be necessary. If the animal's physical status is unchanged after additional anesthetic or analgesia, or i f it does not respond to a painful stimulus at the surgical site, consider
whether the animals vocalization or thrashing improves with soothing voice and attention from the caregiver. If this improves the animal's outward manifestation of apparent pain, consider that the animal may be seeking attention. Finally, place a urinary catheter or allow the animal to urinate or defecate i n an area away from its immediate environment, when possible, to eliminate this potential cause o f stress. If all else fails, administration o f an anxiolytic or partial reversal o f an opioid with an agonist-antagonist or antagonist may be useful in diagnosing and treating apparent clinical signs o f dysphoria.
HYPOTHERMIA Hypothermia is a postoperative complication that can inter fere with tissue offloading o f oxygen from hemoglobin, cardiac performance, elimination o f anesthetic wastes, coagulation, and w o u n d healing. ' Hypothermia can be prevented or m i n i m i z e d intraoperatively by using circulating w a r m water blankets, circulating warmed forced-air blankets, intrave nous fluid warmers, and lavage o f body cavities w i t h warmed sterile fluids. D u r i n g the immediate postoperative period, anesthetic drugs will interfere w i t h the body's n o r m a l physi ologic mechanisms that create shivering. 4
5
6
The accessories mentioned above can also be used post operatively to increase the animal's body temperature. Elec tric blankets and electric heating pads should never be used because o f the risk o f causing severe thermal burns. Once the animal's core body temperature has been increased to 99° F, active rewarming efforts should stop, to prevent acci dental hyperthermia. 7
6
partial thromboplastin time or prothrombin time, or both, disseminated intravascular coagulation should be suspected.
ACID-BASE AND ELECTROLYTE STATUS Acid-base, electrolyte, and glucose abnormalities are com m o n during the immediate postoperative period. The ani mal's acid-base and electrolyte status should be evaluated at least once every 12 to 24 hours and i n critical patients may be indicated every 2 to 4 hours. Fluid therapy should be tailored accordingly. Metabolic acidosis can be associated with decreased organ perfusion and usually can be corrected once intravascular circu lating volume and hypothermia have been corrected. Serial lac tate measurements can be performed as an indicator o f global organ perfusion and oxygen utilization. Serial elevations in peripheral lactate can be a poor prognostic indicator and sug gests a lack o f response to fluid and oxygen therapy. Severe met abolic acidosis with a p H less than 7.1 warrants aggressive intervention. Supplemental bicarbonate therapy may be indi cated i f therapy o f the primary disease process is ineffective. A base deficit can be determined, and the dosage of bicarbonate required can be calculated with the following formula: Bicarbonate deficit(mEq H C O ^ ) = B W x 0.4 x(24-HC0 -) k g
3
where B W is the patient's body weight i n kilograms. Gen erally, only one third to half o f this calculated dose is admi nistered. Alternatively, a more cautious approach to normalizing the patient's metabolic acidosis is to administer immediately one fourth o f the calculated bicarbonate dose, then administer the rest over a period o f 4 to 6 hours. k g
COAGULATION WOUND CARE AND BANDAGING Intravenous administration o f large volumes o f intravenous crystalloid or colloid fluids, b l o o d products, and hypother mia can all lead to coagulation abnormalities. Anticoagu lants used i n b l o o d products can b i n d w i t h calcium and lead to poor muscular responsiveness. In animals with refractory perianesthetic hypothermia and hypotension that have received b l o o d products, ionized calcium concentration should be measured, because hypocalcemia can interfere with arteriolar constriction and vascular tone. W h e n present, hypocalcemia can be corrected with intravenous administra tion o f calcium gluconate and careful infusion o f calciumcontaining crystalloids, such as lactated Ringer's solution. 8
9
True coagulopathies that have been documented by pro longed p r o t h r o m b i n time, activated partial thromboplastin time, or activated clotting time can be reversed partially w i t h administration o f activated clotting factors i n fresh frozen plasma. Significant thrombocytopenia can also cause a coa gulopathy, and patients w i t h platelet counts less than 10,000 cells/ul may require platelet administration. A l t h o u g h platelet concentrate and platelet-rich plasma exist, they usu ally must be ordered from a commercial b l o o d bank, so unfortunately are often not available during the immediate postoperative period. Serial measurements o f the animal's hematocrit can be performed to document and treat ongoing b l o o d loss and anemia. In animals whose serial coagulation profiles indicate worsening thrombocytopenia, elevations in fibrin degrada tion products or D-dimers, and rapid or prolonged activated
A n animal's wounds and bandages can be a source o f noso comial i n f e c t i o n . ' Further, a large percentage of nosoco mial infections are acquired from direct contact with the hands o f hospital personnel. Bandages should be checked frequently for evidence o f soilage or strike-through. Any bandage that becomes wet or soiled should be changed immediately. The surgical site or w o u n d should be checked at least once or twice daily for evidence of erythema, tender ness, pain, or drainage. Whenever a bandage is changed or the w o u n d site is evaluated, personnel should wash their hands carefully and wear gloves to protect the patient from a potential source o f infection. Catheter sites should be eval uated at least once daily for evidence of pain, thrombosis, erythema, or discharge. W h e n signs are present, the catheter should be removed and the catheter tip cultured for bacteria. 10
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NUTRITION Enterocytes will atrophy within 48 hours o f lack o f luminal nutrients. N u t r i t i o n a l support is one o f the most important aspects o f promoting healing. Inadequate enteral nutrition can delay w o u n d healing and promote bacterial transloca tion from the gastrointestinal tract, and thus increase patient morbidity, length o f hospital stay and, potentially, mortality. At the time o f surgery, an esophagostomy, gastrostomy, or jejunostomy tube should be placed i f an animal has been
inappetent, or is at risk for inappetence during the postoper ative p e r i o d . " A patient's daily caloric requirements (rest ing energy expenditure, or R E R ) can be calculated by the formula 12
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R E R i n kcal = (30 x B W ) + 70 k g
If enteral nutrition is impossible, parenteral nutrition can be provided through a central venous or intraosseous cathe ter. Supplemental feeding can be discontinued once the animal is able and willing to voluntarily consume its daily caloric requirements. 18
PATIENT CLEANLINESS Patient cleanliness is o f paramount importance during the postoperative period. Contamination o f surgical sites w i t h wound exudates, feces, urine, vomitus, or contaminants from the external environment can delay w o u n d healing and promote infection. Wounds and surgical sites should be covered to prevent contamination from the outside. Moisture or strike-through o f b l o o d or w o u n d exudates can promote wicking o f bacteria from the environment into the wound. A n y bandage with strike-through should be immediately changed and discarded. Immobile animals should have a urinary catheter i n place to prevent urination into bedding and urine scald. Bedding should be well pad ded, soft, clean, and dry to prevent urine scalding, pressure necrosis, and decubitus ulcers.
PATIENT IMMOBILIZATION AND PHYSICAL THERAPY Immobile animals are at particular risk for atelectasis, pneu monia, and decubitus ulcers. Nonambulatory or i m m o b i l e animals should be turned from side to side and placed i n sternal recumbency at least every 4 to 6 hours to promote adequate ventilation and prevent atelectasis i n the dependent lung. Padding around pressure points (elbows, shoulders, hips, and stifles) should be thick and adequate to prevent
pressure necrosis. Deep tissue massage and passive rangeof-motion exercises should be performed 3 to 4 times daily to prevent disuse atrophy and dependent edema. Whenever possible, visitation w i t h the animal's family and movement to the outdoors should be promoted to maintain the ani mal's mental well-being. Visits from caretakers i n off times, without providing any therapy other than company and ten der loving care, should also be included as part of the critical patient's daily treatment orders. 19
CONCLUSION Careful m o n i t o r i n g and assessment o f the critically ill patient is challenging during the immediate postoperative period. A l t h o u g h anesthetic recovery is critical, other criteria includ ing nutrition, cleanliness, and physical therapy are necessary to maximize the animal's well-being and promote w o u n d healing. Analgesia and sedation should be maximized with out causing dysphoria and agitation. W o u n d and bandage care is optimal i n preventing postoperative infection. Kirby's Rule o f T w e n t y is discussed i n Chapter 201, Daily Assess ment o f the Critically 111 Patient. This checklist can provide even the most astute clinician with a source o f potential c o m plications i n the postoperative critically ill patient. 19
SUGGESTED FURTHER R E A D I N G * Armstrong SR, Roberts BK, Aronsohn M : Perioperative hypothermia, / Vet Emerg Crit Care 15:32, 2005. Describes the pathophysiology, recognition, adverse consequences, and treat ment of perioperative hypothermia. Brady C A , King LG: Postoperative management of the emergency surgery small animal patient, Vet Clin North Am Small Anim Pract 30:681, 2000. Describes an approach to the critically ill postsurgical small animal patient, with special emphasis on recognition of systemic inflammatory response syndrome. Seim H B , Willard M D : Postoperative care of the surgical patient. In Fossum T W , editor: Small animal surgery, ed 2, St Louis, 2002, Mosby. Describes the postoperative care and considerations in the small animal patient, with particular emphasis on nutrition and placement of feeding tubes. "See the C D - R O M for a complete list of references.
Chapter 145 POSTCRANIOTOMY MANAGEMENT Rodney S. Bag ley,
D V M , D A C V I M (Neurology)
KEY POINTS
edema may evolve for up to 48 hours after injury and persist for a week or more. Physiologic monitoring during the hours to days following intracranial surgery should be performed on a frequent, i f not continual, basis. This type of m o n i t o r i n g c o m m o n l y includes assessment o f heart rate and rhythm, respiratory rate and character, blood pressure, b l o o d gases, oxygenation, urine production and, in some instances, I C P through objective means. The goal of such monitoring is to maintain adequate cerebral blood flow without compromising other organs. 2
• Imaging studies ideally are performed immediately following surgery, while the patient is still under anesthesia. • After anesthetic recovery, animals usually are monitored in a critical care area for signs of neurologic deterioration or other complications such as pneumonia for at least 48 hours. • Oral food and water are withheld until the animal regains swallowing function, which may take a number of days. • Maintaining cerebral blood flow is essential during the recovery phase following intracranial surgery. • Poor ventilation and increasing partial pressure of arterial carbon dioxide (PaC0 ), such as from obstruction or crimping of the endotracheal tube, can lead to disastrous increases in brain volume, terminal brain swelling, and subsequent herniation. 2
Cerebral b l o o d flow is maintained primarily through sup port o f systemic b l o o d pressure using fluid therapy and vasopressive drugs i f needed, at the same time preventing increases i n ICP. B l o o d gas measurements or capnometer use aids i n controlling respiration to prevent increases in P a C 0 and subsequent cerebral vasodilation. Capnometer measurements, however, are usually less accurate than direct blood gas measurements. 2
INTRODUCTION Intracranial surgery is employed most commonly for removal o f intracranial masses, biopsy o f intracranial lesions, placement of ventricular shunts, decompression and debridement o f intracranial tissues, and treatment o f increased intracranial pressure (ICP). Surgery may include removal o f sizable por tions o f the skull (craniotomy or craniectomy) or be limited to smaller burr holes for decompression and evacuation o f hematoma or stereotactic biopsy. Other indications for intra cranial surgery i n humans include seizures, chronic pain, and movement disorders.
POSTOPERATIVE MANAGEMENT
I C P is m o n i t o r e d objectively i n some situations; however, this type o f measurement is not performed routinely in animals. I C P m o n i t o r i n g has been described i n dogs and cats. " A n advantage with this measure is that trends toward increasing I C P can be recognized early and treated before lifethreatening increases o c c u r . A n objective measure o f ICP and b l o o d pressure also allows for calculation o f cerebral per fusion pressure ( C P P ) as a reflection o f cerebral b l o o d flow. Disadvantages to invasive I C P monitoring include added surgery time for implantation o f the monitoring system, expense, and the potential for iatrogenic brain damage from the monitoring system. U n t i l some of these disadvantages are overcome, I C P monitoring will probably not become routine for animals undergoing intracranial surgery. ' Newer, noninvasive techniques for measurement of the cere bral b l o o d flow such as transcranial Doppler ultrasonogra phy may provide an indirect measure o f I C R Similar procedures and information have been investigated in dogs and c a t s . '
Immediately following surgery, while the patient is still under anesthesia, is the ideal time to perform an anatomic imaging study such as magnetic resonance imaging. The degree o f lesion resection is assessed, as well as any intracranial c o m p l i cations associated w i t h the surgical procedure such as cerebral edema, parenchymal damage, or hemorrhage (hematoma). Immediate surgical decompression is indicated i f there is an expanding hematoma or i f brain compression is significant. After recovery from anesthesia, animals usually are m o n itored i n a critical care or intensive care area for signs o f neurologic deterioration for at least 48 hours. Animals should be kept i n a comfortable, well-padded, and quiet environment with m i n i m a l light stimulation. Cerebral
Neurologic parameters monitored include pupil size and responsiveness to light, level of consciousness, behavior, and the ability to move and walk. Cranial nerve abnormal ities may provide important clues to underlying intracranial injury or deterioration. Animals that have recovered from anesthesia are placed in a neutral or head-elevated position. Head elevation to 30 degrees above cardiac level decreases I C P primarily by facil itating venous drainage. " In humans it has been shown that C P P and cerebral b l o o d flow are maintained i n the 30-degree head elevation position and I C P is concurrently decreased. There continues, however, to be debate about the degree of benefit of head elevation in animals following intracranial surgery.
1
A consensus on the most appropriate postoperative m a n agement of animals after intracranial surgery is lacking. M a n y postoperative procedures are taken from similar exper iences i n humans. They are based o n information regarding pathophysiologic alterations i n the intracranial space and their treatments, as well as individual clinicians' anecdotal experiences.
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Oral food and water are withheld until the animal is fully alert. W i t h the combination o f intracranial depressant effects of surgical manipulation and anesthetic or anticonvulsant drug therapies, appropriate swallowing, which prevents aspi ration of oral contents, may take a number o f days to return, putting the patient at risk for aspiration o f oral contents (see Nonneurologic Complications later i n this chapter). Stools are monitored regularly for melena that might indicate gas trointestinal (GI) ulceration. If noted, an antiulcer medica tion (e.g., ranitidine) is administered concurrently because of the apparent increase i n G I ulcers in patients with neuro logic impairment.
Hydration Maintaining cerebral b l o o d flow is important during the recovery phase following intracranial surgery. Cerebral per fusion depends on systemic b l o o d flow and I C P and is expressed via the formula: CPP = M A B P - ICP where C P P = cerebral perfusion pressure, M A B P = mean arterial blood pressure. ' For C P P to remain constant, the effects of increased I C P on b l o o d flow to the brain must be reciprocated by increases i n systemic blood pressure. C P P is a determinant o f cerebral b l o o d flow but is not always equivalent. In many instances, however, C P P is a reasonable reflection o f cerebral blood flow. Following clinical assessment, fluid resuscitation or fluid maintenance usually is performed with appropriate crystal loids or colloids. They are administered intravenously to maintain appropriate b l o o d pressure and organ perfusion, including appropriate cerebral perfusion. The effects o f fluid therapy should be monitored carefully, because overhydra tion with isotonic fluids may perpetuate brain edema, and dehydration may predispose to intracranial b l o o d sludging and ischemia. M o n i t o r i n g o f systemic b l o o d pressure and central venous pressure may help to reestablish normovole mia. Implantation o f a central venous catheter should be performed cautiously i n an animal with increased ICP, because manipulation or occlusion o f the jugular vein for catheter placement may elevate ICP. Quick, efficient, and atraumatic jugular catheterization is a must in this situation. 19
20
Ventilation Cerebral vessels are directly responsive to P a C 0 concentra tions, with cerebral blood flow coupled to cerebral metabolic rate. The cerebral vessels have the ability to change diameter in response to P a C 0 (chemical autoregulation) and b l o o d pressure (pressure autoregulation) i n order to maintain a rel atively constant cerebral b l o o d flow. Cerebral vessels change diameter through perivascular changes in p H , occurring as a direct result of P a C 0 concentrations. As P a C 0 concentrations increase, cerebral vessels dilate to increase blood flow to the brain. Poor ventilation and increasing P a C 0 , such as from obstruction or c r i m p i n g o f the endotracheal tube, can lead to disastrous increases i n brain volume, terminal brain swelling, and subsequent h e r n i a t i o n . If autoregulation is intact, hyperventilation to decrease P a C 0 will cause cerebral vasoconstriction, decreased cerebral b l o o d volume, and subsequently decreased ICP. Unfortunately, cerebrovascular autoregulatory capability is negatively affected by a variety o f intracranial pathologies 2
2
2
2
2
21
2
including local acidosis, which is c o m m o n i n many hypoxic and ischemic brain areas. Animals often are hyperventi lated during intracranial surgical procedures to maintain P a C 0 i n the range between 28 and 32 m m H g , to prevent cerebral hypoxia from poor ventilation. D u r i n g the post operative period, ventilatory support may be indicated. Endotracheal intubation and ventilator support can be per formed under the influence o f barbiturate anesthesia or neuromuscular blockade. Appropriate ventilator manage ment is imperative. 21
2
W h e n ventilatory support is not immediately necessary or is not feasible, it is still important to recognize that decreased ventilatory effort or capacity may result i n increases in ICP. Preventing atelectasis by frequent (hourly) movement o f the animal from a lateral recumbent position may also be necessary.
Oxygenation A l o n g w i t h maintenance o f cerebral perfusion, maintenance of cerebral oxygenation is an important aspect o f treatment of acute intracranial injury. Nasal oxygen administration may be helpful i n an animal that has sustained trauma.
Sedation Sedation may be necessary i n animals requiring ventilatory management or when the animal is disoriented, at risk for further injury from excessive or uncoordinated movements, or i f demented and vocalizing excessively. Forced expiration i n these situations may result i n increases i n ICP. A n i n depth review o f sedative and anesthetic agents and their effects on the nervous system is beyond the scope o f this chapter and have been reviewed elsewhere. " The choice of these agents depends o n many factors, including ease o f administration, rapidity and ease o f induction and recovery, effects o n cerebral metabolism and b l o o d flow, alterations i n ICP, and familiarity o f the anesthetist w i t h the anesthetic agent. Effects o f anesthetic agents o n I C P have also been reviewed elsewhere. " 22
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Barbiturates can be used i n some instances to decrease cerebral metabolism, cerebral b l o o d flow, and subsequently I C P . Barbiturates may benefit brain b l o o d flow by causing vasoconstriction i n n o r m a l tissue and by shunting b l o o d to underperfused or ischemic areas. Other suggested benefits include decreases i n vasogenic edema, decreased oxygen metabolism, decreases i n intracellular calcium, and free rad ical scavenging. Arterial b l o o d pressure should be m o n i tored closely, however, because barbiturates can result i n hypotension, which may then decrease cerebral blood flow and increase cerebral ischemia. 26
26
Most inhalant anesthetic agents increase I C P as a result o f their vasodilatory effects on cerebral vessels and subsequent increase i n cerebral b l o o d flow. Halothane, for example, causes the largest degree o f cerebral vasodilation. Increases i n cerebral b l o o d flow can increase I C P because o f the asso ciated increase i n intracranial v o l u m e . Isoflurane is the most c o m m o n l y used maintenance anesthetic agent for intracranial surgery and has been used safely i n both clini cal and experimental studies involving intracranial surgery in dogs and cats. " Benzodiazepines may help, especially for short-term seizure control. Propofol is being used increasingly for anesthesia i n animals with intracranial abnormalities. " 27
28
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9
Pain Management
Antibiotics
Pain is controlled w i t h narcotics for at least 72 hours after surgery. M o r p h i n e , fentanyl, or codeine is used for this pur pose i n our hospital. A l t h o u g h these drugs have been shown to increase ICP, they are still used often for pain control i n humans following intracranial surgery. " The level o f pain associated with intracranial surgery may be less than that with other surgeries, but pain control is still mandatory. Obviously, there is a need to balance analgesia i n relation ship to ongoing intracranial physiologic derangements. Some animals are delirious after surgery and vocalize, w h i c h may be mistaken for a pain response. Excessive exposure to sound and light should be kept to a m i n i m u m to prevent further stimulation.
The necessity for preoperative and intraoperative antibi otics has been debated i n h u m a n neurosurgery; there is support for prophylactic antibiotic administration i n clean neurosurgical p r o c e d u r e s . ' Antibiotics most often are given for prolonged (>1.5 hour) procedures, i f contami nated b o d y cavities are to be opened (i.e., the nasal cavity), or i f contamination is more likely (excessive number of individuals involved i n surgery). Prophylactic antibiotics are usually first-generation cephalosporins (cephalothin 22 m g / k g I V q l . 5 h ) u n t i l the end o f the procedure. There is no information regarding the utility o f routine prophy lactic antibiotic administration following intracranial sur gery. Antibiotics are indicated, however, for the specific infections that have been documented and identified in these animals.
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38
39
43
44
Anticonvulsants M a n y animals requiring intracranial surgery have seizures. These animals are often receiving anticonvulsant medications before surgery, and the medication should be continued dur ing the postoperative period. If animals are not receiving anticonvulsants, and i f the risk o f seizures after surgery is significant, then anticonvulsant therapy should be begun before surgery. Anticonvulsant medications are used prophylactically i n humans following intracranial surgery when the seizure risk is high or i f any seizure w i l l have a detrimental effect. Routine use o f prophylactic anticonvulsant adminis tration, however, has been questioned i n some situations i n humans, primarily because of the low overall risk o f seizures after surgery and the medication side effects. ' 39
40 41
Ideally, medications should be begun preoperatively so that therapeutic levels are stabilized before surgery. If potas sium bromide is to be used, a longer period between initia tion o f the drug and surgery may be needed. Intravenous loading w i t h s o d i u m bromide has been described i f surgery needs to be performed i n a more expeditious manner. Because o f alterations i n cerebral b l o o d flow and systemic b l o o d levels, levels o f anticonvulsants may fluctuate widely during and after surgery (see C o m m o n Postoperative Complications later i n this chapter). 42
Physical Therapy After the acute effects o f brain injury are controlled, the goal is to allow time for brain healing and recovery o f function to occur. Smaller animals are often better candi dates for prolonged nursing care than are larger animals because o f the ease o f m a n i p u l a t i o n . G o o d nursing care includes preventing decubitus ulcers i n the recumbent ani mal and m o n i t o r i n g for secondary infections, mainly o f the p u l m o n a r y and urogenital systems. Recumbent ani mals s h o u l d be placed o n clean, soft bedding and turned frequently (ideally every h o u r ) . Physical therapy can begin as soon as possible. Physical therapy is individualized but may include supported or unsupported walking, passive flexion and extension o f the limbs, massage, or s w i m m i n g . A daily record o f physical therapy w i l l ensure that this therapy is not overlooked and allows for multiple i n d i v i duals, i n c l u d i n g the owner, to become involved i n the heal ing process. Massage and passive range of m o t i o n of the limbs is reason able even i n stuporous or comatose animals. Because severely impaired animals have little control over their movements, they may be predisposed to secondary musculoskeletal inju ries. Cautious manipulation o f comatose and stuporous ani mals is necessary to prevent iatrogenic injury. M o r e rigorous physical therapy is begun when the animal is alert.
Wound Management A stockinet or similar light bandage may be placed over the incision. Holes are cut i n the stockinet to allow the ears to be unrestricted. Gauze sponges may be placed under the stockinet to collect any discharge from the w o u n d . A m i l d l y compressive bandage helps decrease the chance of subcutaneous emphysema i f the frontal sinus has been opened. Rarely, i f an a n i m a l is excessively violent i n its movements, a helmet-type or similar protective device can be used to prevent additional injury. A n i m a l s w i t h excessive or violent movements s h o u l d be sedated w i t h diazepam (either bolus or constant infusion) or, i n some instances, even acepromazine. Incisions are examined daily for signs of inflammation. Oral food and water are withheld until the animal is fully alert. Unless the animal behaves normally and can walk, we do not give anything orally for up to 5 days after surgery to decrease the incidence o f aspiration pneumonia (see C o m m o n Postoperative Complications later i n this chapter).
COMMON POSTOPERATIVE COMPLICATIONS Postoperative complications following intracranial surgery include those involving damage or injury to the intracranial nervous system as well as systemic abnormalities. Iatrogenic injury to the brain often results i n intracranial signs that are present immediately u p o n recovery from anesthesia or evolve w i t h i n the following 48 to 72 hours. Intracranial hem orrhage, increasing cerebral edema, increasing ICP, and ischemia due to cerebrovascular disease are most often the causes of neurologic deterioration following surgery. As with all surgery, infectious complications are possible, but overall are rare. Seizures are possible even i f they were not present pre operatively. Seizures that occur during the immediate postoperative period are managed i n standard fashion. 40
Intravenous diazepam boluses are used acutely i f seizures occur. If the animal was receiving maintenance anticonvul sant medication before surgery, dosages are adjusted as nec essary. If recurrent seizure activity ensues, a constant infusion of diazepam may be needed. In the animal that has not been receiving anticonvulsants, maintenance is initiated. Seizures may suggest increasing I C P or poor cerebral perfusion and, i f prolonged or severe, may warrant repeat evaluation with an intracranial imaging study. 41
W i t h definitive surgical therapy, we have noted that some dogs seem overly sedated when receiving phenobarbital follow ing surgery. This usually becomes most apparent between 2 and 5 days after surgery. Serum phenobarbital levels have not been elevated suggesting that, either because o f alterations i n brain blood flow or cellular concentration of the antiepileptic medica tion, the effects of phenobarbital may be relatively more potent after surgery. Seemingly excessive sedation from a similar dos age of phenobarbital may last for 3 to 5 days, but it usually is self-limiting. If the sedative effects are excessive, the phenobar bital dosage may need to be decreased for a few days. Increasing I C P is a c o m m o n complication following intracranial surgical manipulation. Increases i n I C P may result from a variety o f secondary pathophysiologic sequelae. Treatment to lower I C P is indicated when increases occur.
Treatment of Increased Intracranial Pressure Treatment recommendations for increased I C P are taken p r i marily from those for management o f general brain injury (Box 145-1; see Chapter 100, Intracranial Hypertension).
Nonneurologic Complications As with all diseases, an understanding o f the pathophysiology associated with the disease is necessary when determining
Box 145-1 Treatment of Increased Intracranial Pressure Therapies With Established Efficacy Fluid resuscitation with isotonic fluids Diuretics Mannitol (0.25 to 1 g/kg IV)
Therapies With Possible but Unknown Efficacy Hypertonic saline (3% solution, 5.3 ml/kg IV; 23.4% solution, 0.7 mg/kg IV) Head elevation
the most appropriate treatment. Pathophysiologic alterations following intracranial surgery may occur for a variety o f reasons. Their scope and severity may be influenced by the underlying type, extent, and severity o f intracranial disease, iatrogenic brain injury d u r i n g the surgical manipulations, as well as systemic health apart from that o f the nervous system. Systemic pathophysiologic alterations such as changes i n b l o o d pressure, coagulation status, hydration, nutrition, and the function o f other organ systems require general critical care assessment and treatment and are beyond the scope o f this chapter. Appropriate and intensive critical care assess ment and management are imperative, because many of the complications that occur i n these animals do so during the immediate postoperative period. O f the nonneurologic complications following intracra nial surgery, pneumonia is the most c o m m o n . Numerous factors may contribute to the development o f pneumonia, but this is probably the result o f aspiration o f food or other digestive material. Megaesophagus seems to be a risk factor associated with p n e u m o n i a i n dogs following intracranial surgery. M a n y o f these dogs are also chronically i l l and i n overall debilitated states. M a n y dogs are receiving multiple drugs, including glucocorticoids and anticonvulsants. Glucocor ticoids, because of their immunosuppressive and catabolic effects, may contribute to development o f pneumonia. Often these dogs have dry mouths and oral disease that predisposes to alterations i n the microorganisms i n the m o u t h . Some dogs received perioperative or postoperative antibiotics, which could have altered the normal flora o f the m o u t h and pharynx or predisposed to superinfection. Some animals, although apparently able to gag reflexively, may not be effectively swallowing accumulated saliva or food and water. C o u g h i n g may also be suppressed. Finally, early feeding before adequate swallowing probably plays a role. A l t h o u g h all o f the causes o f pneumonia have not been clarified, this complication has severe enough conse quences to warrant concern. 4 5
A fever is usually a cardinal sign o f pneumonia i n these dogs. A n y dog w i t h a fever d u r i n g the postoperative period should be evaluated with a thoracic radiograph. Although not ideal nutritionally, nothing orally for up to 5 days following surgery may be the best way to prevent pneumonia from developing i n these animals. We have attempted to use various types o f percutaneous alimentation including gastro stomy, nasogastric, esophagostomy, and jejunostomy tubes i n these dogs without a significant decrease i n the incidence o f pneumonia. The most appropriate way to manage alimentation i n these dogs has not been established.
Furosemide (0.07 to 1 mg/kg IV) Hyperventilation Cerebrospinal fluid aspiration
SUGGESTED FURTHER R E A D I N G *
Craniotomy
Therapy With Unknown Efficacy and Potential Detrimental Effects
Bagley RS: Intracranial pressure in dogs and cats: physiology and treatment, Comp Cont Educ Pract Vet 18:605, 1996. An overview of ICP considerations in animals. Bagley RS: Pathophysiologic sequelae of intracranial disease, Vet Clin North Am Small Anim Pract 26:711, 1996. An overview of pathophysiologic alterations associated with intracranial disease. Cornick JL: Anesthetic management of patients with neurologic abnormal ities, Comp Cont Educ Pract Vet 14:163, 1992. A basic reference that discusses many of aspects of anesthesia in animals with intracranial abnormalities.
Glucocorticoids
*See the C D - R O M for a complete list of references.
Miscellaneous Drugs Deferoxamine mesylate Superoxide dismutase Allopurinol Opiate antagonists (naloxone) Thyrotropin-releasing hormone and calcium channel blockers
IV, Intravenous.
Chapter 146 PORTOSYSTEMIC SHUNT MANAGEMENT Margo Mehl,
D V M , DACVS
3
KEY POINTS • Clinical signs of portosystemic shunt (PSS) include neurologic, gastrointestinal, and urinary abnormalities, and can manifest as other signs such as prolonged recovery from anesthesia. • Intrahepatic PSS is more common in large breed dogs and extrahepatic PSS usually occurs in small dogs and cats. • The goal of preoperative PSS stabilization and medical treatment is to control clinical signs of hepatic encephalopathy and prevent progression of neurologic signs. • The treatment of choice is surgical attenuation of the shunting vessel. • Perioperative morbidity and mortality is higher with intrahepatic PSS repair than with surgical correction of extrahepatic PSS. • Serious postoperative complications of PSS include hemorrhage, hypoglycemia, seizures, and portal hypertension. • Several predictors of clinical outcome have been identified for surgical management of extrahepatic and intrahepatic PSS in dogs.
INTRODUCTION Portosystemic shunts (PSSs) are vascular anomalies that connect the portal circulation with the systemic circulation, diverting portal blood away from the liver. These vascular anomalies are categorized most c o m m o n l y as extrahepatic or intrahepatic shunts. Extrahepatic PSSs can be further categorized as congenital or acquired and often are described based o n the supplying and draining vessels, such as porta caval or portoazygos shunts. Intrahepatic PSSs usually are classified based o n the branch o f the portal vein supplying the shunt and divide intrahepatic PSSs into left-divisional, central-divisional, and right-divisional categories. Single extrahepatic PSSs are the most c o m m o n l y reported type i n dogs and cats; they are congenital and seen p r i m a r i l y i n small breed dogs. " C l i n i c a l signs are related to hepatic dysfunction, i n c l u d i n g gastrointestinal (GI) signs, central nervous system ( C N S ) disturbances, and urolithiasis. Some patients w i l l require intensive ther apy to stabilize them before surgical correction of the PSS. Postoperative complications can occur i n an unpre dictable and precipitous manner and can range i n severity from ascites to life-threatening hemodynamic and neuro logic abnormalities, m a k i n g these patients extremely chal lenging to treat after surgery. 1
prolonged recovery from a previous anesthesia. Preopera tive stabilization depends on the animal's status on arrival and often includes fluid therapy and anticonvulsant medications to stop the progression of neurologic signs. If a patient has m i l d clinical signs of hepatic encep halopathy and is stable, medical treatment may be initiated (i.e., low-protein diet, anticonvulsants, antibiotics, and cathartics). O n the other hand, i f a patient has moderate to severe signs of hepatic encephalopathy, more aggressive therapy is indicated. A major contributing factor to wors ening hepatic encephalopathy is hemorrhage into the GI tract, w h i c h acts as a large protein source for further a m m o n i a production. To reduce signs of hepatic encepha lopathy, immediate removal of any protein source within the G I tract with lactulose enemas is a priority. Ongoing a m m o n i a production and absorption should be prevented w i t h oral antibiotics and cathartics (see Chapter 103, Hepatoencephalopathy). GI signs i n patients with PSS often include vomiting and diarrhea, which can lead to fluid and electrolyte imbalances. These imbalances should be addressed before surgical correc tion of the PSS. Pica is reported frequently i n PSS patients, and as a result the patient may be vomiting secondary to a G I foreign body. Occasionally animals can have a urinary emergency secondary to PSS, such as a urethral obstruction. Initial treatment may include correcting fluid and electrolyte abnormalities followed by relief of the obstruction.
MEDICAL MANAGEMENT
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PREOPERATIVE STABILIZATION Animals with PSS c o m m o n l y will have neurologic abnorm alities, G I signs, urinary signs, and other signs such as
As long as portal blood flow is being shunted away from the liver, hepatic function w i l l continue to decline. Surgery offers the opportunity to redirect portal blood back to the liver. Medical management should be initiated before surgical cor rection o f the PSS i n animals with signs of hepatic encepha lopathy, and anticonvulsant therapy may be beneficial in PSS patients preoperatively. The benefit of preoperative anticon vulsant therapy was evaluated by Tisdall and others and showed that prophylactic anticonvulsants d i d not signifi cantly reduce the risk of postoperative neurologic signs, but may have reduced their severity. Therefore routine use of prophylactic anticonvulsant therapy i n all dogs with PSS may be warranted. There are several protocols for preopera tive anticonvulsant therapy and the authors' recommendation in dogs is potassium bromide at a loading dosage for 24 4
Table 146-1 Suggested Preoperative Anticonvulsant therapy in Dogs and Cats With PSSs Drug
Therapeutic Blood Levels
Canine and Feline Dosage
Phenobarbital 1 to 2mg/kg PO q12h
15 to 45 ng/ml
Potassium bromide
2 to 3 mg/ml when used as a sole agent 1 to 2 mg/ml when used in conjunction with phenobarbital
Loading dosage*: 100 mg/kg PO q6h x 4 doses (total dosage of 400 mg/kg in 24 hr) Maintenance dosage: 60 to 100 (canine) mg/ kg once a day
From Plumb DC. Plumb's veterinary drug handbook, ed 5, Stockholm, 2005. PharmaVet Inc. *A loading dose is recommended if therapeutic levels are required quickly. This is one of several protocols for potassium bromide loading. A maintenance dose given longer than 15 days in dogs will provide adequate blood levels as an alternative to giving the loading dose. These drugs can be associated with neurologic and respiratory depression and patients should be monitored accordingly. Loading doses of potassium bromide can cause gastrointestinal disturbances. PO, Per os, PSSs, portosystemic shunts. 22
hours (100 mg/kg P O q6h) or a maintenance dosage for a m i n i m u m of 2 weeks (40 mg/kg P O q24h) (Table 146-1). Feline patients with PSS have a high incidence o f neuro logic complications after surgery, ' so preoperative anticon vulsant therapy is often instituted. Potassium bromide has been associated with allergic airway disease i n cats; consequently the author uses phenobarbital (1 to 2 mg/kg P O q l 2 h ) and recommends confirming that the serum concentrations reach therapeutic levels before surgery (see Table 146-1). Because phenobarbital is metabolized i n the liver, animals with liver insufficiency may require lower dosages to achieve thera peutic levels. 5 6
The goal o f medical therapy is to decrease p r o d u c t i o n and absorption o f a m m o n i a , and management includes dietary modification, antibiotic therapy, and cathartics. Typically, a diet high i n carbohydrates and l o w i n protein will decrease the b u i l d i n g blocks for a m m o n i a p r o d u c t i o n . Dairy and vegetable protein sources are less likely to cause signs o f hepatic encephalopathy than are meat proteins. Antibiotics that concentrate i n the G I tract, such as amox icillin, neomycin, and metronidazole, w i l l reduce the n u m ber o f bacteria responsible for a m m o n i a p r o d u c t i o n . Cathartics, such as lactulose, w i l l shorten the transit time in the G I tract and trap a m m o n i u m ions i n the l u m e n , reducing its absorption. Acid-base imbalances, electrolyte abnormalities, and hypoglycemia should be identified and corrected before surgery. Hypoalbuminemia is a consistent finding i n patients with PSSs. Because their hypoalbuminemia is chronic, it generally is not associated with signs i n the stable patient and as such it does not warrant therapy. It will, however, be a concern i n the patient that requires significant fluid resuscitation, a c o m m o n requirement o f the preoperative PSS patient. Large volumes o f crystalloid fluid will cause hemodilution and worsen the hypoalbuminemia, making maintenance o f intravascular volume very difficult. Hemodynamically compromised hypoproteinemic patients generally require support o f serum colloid osmotic pressure ( C O P ) . Although synthetic colloids such as hetastarch are very
effective at increasing C O P , they interfere with coagulation. Because patients with PSSs tend to have coagulation deficits, synthetic colloids should be avoided or minimized. Plasma transfusions will support intravascular volume, help maintain COP, and provide coagulation factors. For this reason plasma can be an invaluable therapy i n the perioperative stabilization of the patient with a PSS. 7
SURGICAL OPTIONS The treatment o f choice is surgical attenuation of the shunting vessel. The traditional surgical technique involves placing a ligature around the anomalous vessel, w h i c h is gradually tightened while measuring portal pressure and observing the splanchnic viscera. If the ligature is too tight, there is sig nificant risk o f inducing portal hypertension, w h i c h is a severe and often fatal complication. Criteria for judging the safe degree o f PSS attenuation include an increase i n portal pressure w i t h temporary complete PSS attenuation o f no more than 10 c m H 0 . 1
8 1 1
2
Gradual, rather than acute, PSS occlusion has been advo cated as a safer surgical t e c h n i q u e . ' It is proposed that gradual occlusion allows the development o f the hepatic architecture i n response to the increased vascular supply, meanwhile avoiding fatal portal hypertension. The ameroid ring constrictor and the cellophane band are both designed to produce gradual vascular occlusion. Surgical access, localization, and attenuation o f an intra hepatic PSS can be challenging. A number o f techniques, both intravascular and extravascular, have been reported for accessing an intrahepatic PSS, some o f w h i c h require a caudal sternotomy. Intrahepatic PSSs are often large vessels shunting sizeable volumes o f portal b l o o d away from the liver, and there is a significant risk o f creating portal hyper tension w i t h excessive attenuation. Therefore most patients w i t h an intrahepatic PSS w i l l tolerate only partial PSS ligation. 12
13
POSTOPERATIVE MONITORING General critical care principles apply to the postoperative management o f patients w i t h PSSs, and close observation is extremely important because their status can deteriorate rapidly. O p t i m a l outcome occurs when clinicians identify life-threatening complications early and treat them aggressively. Several parameters should be monitored i n these patients after surgery, including arterial b l o o d pressure and heart and respiratory rates. These patients are often young, small breed dogs that can be hypothermic after surgery and benefit from continuous temperature m o n i t o r i n g and active rewarming. Box 146-1 provides a comprehensive list o f parameters for postoperative monitoring. H y p o v o l e m i a is a c o m m o n postoperative issue as a result of venous congestion o f the splanchnic viscera, G I losses, and hypoproteinemia, w h i c h may be more severe following intraoperative h e m o d i l u t i o n . C l i n i c a l signs o f hemody namic compromise such as evidence o f p o o r perfusion or systemic hypotension should be considered results o f hypo volemia unless proven otherwise. Central venous pressure m o n i t o r i n g may be advantageous to guide fluid therapy. W h e n choosing a fluid for volume resuscitation, it is
Box 146-1
Table 146-2 Recommended Treatment for Neurologic Dysfunction in Patients With PSSs
Recommended Clinicopathologic Parameters to Monitor in the Postoperative PSS Patient
Mode of Administration Canine and Feline Dosage
Clinical Parameters
Agent
Heart rate
Diazepam
Bolus CRI
0.2 to 2 mg/kg IV to effect 0.2 to 0.6 mg/kg/hr IV to effect
Midazolam
Bolus CRI
0.1 to 0.5 mg/kg IV to effect 0.1 to 0.3 mg/kg/hr IV to effect
Propofol
Bolus CRI
2 to 6 mg/kg IV to effect 0.1 to 0.6 mg/kg/min IV to effect
Respiratory rate Temperature Direct arterial pressure* Central venous pressure Electrocardiogram Urine output A b d o m i n a l circumference Intraabdominal pressure
Phenobarbital Bolus
Mentation and neurologic status
Laboratory Parameters
Maintenance
Packed cell volume
Pentobarbital Bolus
Total protein Glucose
CRI
Lactate
2 to 5 mg/kg IV, can repeat at 20-min intervals up to a total dosage of 20 mg/kg 2 to 4 mg/kg IV q12h 3 to 15 mg/kg IV SLOWLY to effect 0.5 to 5 mg/kg/hr to effect
From Plumb DC. Plumb's veterinary drug handbook, ed 5, Stockholm, 2005. PharmaVet Inc. NOTE: All of these drugs are associated with moderate to profound neurologic and respiratory depression. Intensive monitoring is essential; patients may require intubation and mechanical ventilation. CRI, Constant rate infusion; IV, intravenous; PSSs, portosystemic shunts.
Electrolytes Acid-base status *When direct arterial pressure is unavailable, indirect arterial pressure should be measured. PSS, Portosystemic shunt.
important to consider that these patients w i l l have both a low C O P and coagulation defects. As a result, plasma is often the fluid o f choice i n combination w i t h isotonic crystalloids. M o n i t o r i n g intraabdominal pressure with a urinary catheter can provide useful information and help detect lifethreatening portal hypertension (see Chapter 206, Intraabdom inal pressure). Clinicopathologic parameters to evaluate at reg ular intervals after surgery include packed cell volume, total protein, lactate, glucose, and electrolytes (Box 146-1). Severity and progression of abdominal distention can be monitored with serial measurements o f abdominal circumference using a mea suring tape or string. These patients may require a continuous electrocardiogram to detect cardiac arrhythmias. Tachycardia is frequently the first sign of hypovolemia i n these patients.
In patients with PSSs, portal venous blood is bypassing the liver, resulting i n reduced hepatic mass and decreased pro duction and activation o f coagulation factors. Therefore these patients often have abnormal coagulation and require plasma and other b l o o d products both during surgery and postoperatively. Clinical signs o f coagulopathy can range from m i n o r oozing from catheter and surgical sites to lifethreatening hemorrhage into body cavities (see Chapter 66, Transfusion Medicine). 7
Seizures can occur during the immediate postoperative period and have been reported up to 72 hours after surgery. In some dogs, neurologic signs such as vocalization, disorien tation, and ataxia are observed before seizures occur. M i l d signs o f partial seizures, such as disorientation, vocalization, salivation, or twitching, may resolve after administration of anticonvulsant therapy, whereas postoperative grand mal sei zures are associated with a high mortality rate. ' Manage ment recommendations include preventing hypoglycemia and other electrolyte abnormalities and treating seizure activ ity early. There are several recommendations for treating sei zure activity after surgical intervention for PSS in dogs, including a single agent or a combination o f the following intravenous agents: diazepam, phenobarbital, pentobarbital, and propofol (Table 146-2). Anticonvulsant therapy protocols i n PSS patients have not been evaluated scientifically, so there is not proven benefit o f one agent (or agents) over another. 14
15
POSTOPERATIVE COMPLICATIONS The three most important postoperative complications seen i n patients w i t h PSSs are portal hypertension, coagulopathy, and neurologic abnormalities. Portal hypertension occurs when the liver is unable to accommodate the increase i n portal b l o o d flow after closure o f the shunting vessel. This leads to venous congestion o f the abdominal organs normally drained by the portal system, w h i c h is associated w i t h hemodynamic c o m promise. Signs o f portal hypertension are abdominal pain, abdominal distention, melena, diarrhea, and systemic hypo tension. The degree o f portal hypertension can vary from m i n o r to moderate to severe. M o s t cases with m i n o r to m o d erate portal hypertension w i l l respond to fluid therapy, includ ing b l o o d products, and opioid-based pain management. Animals with severe portal hypertension that is not responsive to aggressive medical therapy may require emergency surgery to remove the occlusive device from the shunting vessel. The portal vein supplies the liver w i t h 50% o f its oxygen requirements and other essential hepatotrophic factors. 3
16
Controversy exists regarding what toxins are responsible for hepatic encephalopathy. It has been suggested that benzo diazepine receptor ligands play a role i n the pathogenesis of hepatic encephalopathy; unfortunately the impact this has on the administration o f exogenous benzodiazepines to patients with PSSs remains u n d e t e r m i n e d . ' Numerous benefits and risks are associated with anticonvulsant drugs in patients with neurologic signs after surgery. It has been sug gested that propofol stops seizure activity seen in the clinical patient but may not alter the electrical activity occurring in the brain. The impact this may have on the use o f propofol i n patients with postoperative neurologic dysfunction remains 17
18
unclear. Postoperatively, dogs and cats w i t h neurologic signs of partial or focal seizures should be treated aggressively to prevent the progression of clinical signs to grand mal seizures, which carry a grave prognosis. It is important to remember that many o f these therapies can cause loss o f the gag reflex, hypoventilation, and apnea, which may necessitate intubation and mechanical ventilation. Inadequate airway protection can lead to aspiration pneumo nia, which can have life-threatening consequences. Elevation of the partial pressure o f carbon dioxide that occurs with hypoventilation is associated with cerebral vasodilation, lead ing to increases i n intracranial pressure. This can be cata strophic i n the patient with preexisting neurologic disease such as hepatic encephalopathy.
PROGNOSIS A number of studies have reported the mortality rate asso ciated with surgical repair o f both extrahepatic and intrahe patic PSSs. The perioperative mortality rate for extrahepatic PSS repaired with a method for slow attenuation, cellophane banding, or ameroid ring constrictor placement has been reported to be between 5.5% and 7 . 1 % . ' Several factors that predict surgical mortality i n dogs with a single extrahe patic PSS treated by ameroid ring constrictor placement are postoperative complications and preoperative white b l o o d cell c o u n t . 1 8
1 9
18
Similarly, the mortality rate and predictive factors for sur gical mortality have been reported after surgical management of intrahepatic PSS. Papazoglou and others reported a 20
surgical mortality rate o f 12.5% i n 32 dogs with intrahepatic PSS repair, and several predictors for short-term outcome for dogs w i t h intrahepatic PSS included body weight, total protein, albumin, and b l o o d urea nitrogen concentrations. A number o f studies have reported higher surgical mortality rates for intrahepatic PSS than for extrahepatic PSS. Because intrahepatic PSSs are often larger vessels shunting a substan tial amount o f portal b l o o d around the liver, these patients are unlikely to live a n o r m a l lifespan without surgical intervention.
SUGGESTED FURTHER R E A D I N G * Mehl M L , Kyles A E , Hardie E M , et al: Evaluation of ameroid ring constric tors for treatment for single extrahepatic portosystemic shunts in dogs: 168 cases (1995-2001), J Am Vet Med Assoc 226:2020, 2005. A retrospective paper that identified predictive factors for postoperative death, continued shunting, and long-term outcome. Papzoglou L G , Monnet E , Seim II H B : Survival and prognostic indicators for dogs with intrahepatic portosystemic shunts: 32 cases (1990-2000), Vet Surg 31:561, 2002. A retrospective study evaluating predictive factors for long-term outcome in dogs with intrahepatic PSS and that determined PCV and TP were predic tive for long-term survival. Tobias T M : Portosystemic shunts and other hepatic vascular anomalies. In Slatter D H , editor: Textbook of small animal surgery, ed 3, Philadel phia, 2003, Saunders. A good review of hepatic vascular anatomy and embryonic development of the portal system. This chapter also provides a general overview of PSS diagnosis and treatment.
*See the C D - R O M for a complete list of references.
Chapter 147 PERITONEAL DRAINAGE TECHNIQUES Matthew W. Beal,
D V M , DACVECC
KEY POINTS • A variety of medical and surgical disease processes necessitate the evacuation of fluid from the peritoneal cavity. • When combined with source control, peritoneal drainage is a critical component in the management of chemical and septic peritonitis. • Peritoneal drainage techniques may be used to facilitate preoperative stabilization of the patient with life-threatening hyperkalemia and azotemia secondary to urinary tract disruption. • The peritoneal cavity may be drained initially using needle abdominocentesis or catheter abdominocentesis. When sustained drainage is indicated, a peritoneal dialysis catheter, closed suction drain, or open peritoneal drainage is employed.
INTRODUCTION
Box 147-1 Guidelines for Abdominal Drainage in Dogs and Cats With Septic Peritonitis Open Peritoneal Drainage Source control accomplished Severe generalized peritonitis Severe contamination that cannot be resolved completely with debridement and lavage Closed Suction Drainage Source control accomplished Moderate to severe generalized peritonitis Localized peritonitis Contamination that can be resolved through debridement and lavage Primary Closure
Sampling and evacuation o f fluid from the peritoneal cavity is a cornerstone o f both the diagnostic workup and various ther apeutic strategies for the treatment o f the dog or cat w i t h a n acute condition o f the abdomen and a host o f other medically and surgically managed disease processes. A number o f medi cal and surgical procedures may be used to facilitate peritoneal drainage and each has specific indications, contraindications, advantages, a n d disadvantages. A thorough knowledge o f peritoneal drainage strategies allows for appropriate medical and surgical decision making a n d w i l l maximize the likeli h o o d o f a positive clinical outcome.
INDICATIONS FOR PERITONEAL DRAINAGE Septic Peritonitis Septic peritonitis is b y far the most c o m m o n indication for sustained peritoneal drainage. It is generally accepted that the removal o f fluid that m a y contain infectious agents, inflammatory mediators, and foreign material (e.g., bile, ingesta) is beneficial to resolution o f the infection w i t h i n the peritoneal space. Furthermore, fluid w i t h i n an infected cavity may significantly impair h u m o r a l and cell-mediated i m m u n e mechanisms. Despite a lack o f prospective, randomized con trolled studies i n dogs and cats to definitively document decreased m o r b i d i t y and improved outcome when peritoneal drainage is established, open peritoneal drainage ( O P D ) or closed suction peritoneal drainage ( C S D ) is the standard o f care for generalized septic peritonitis. 1
Recommendations for abdominal drainage techniques i n dogs a n d cats with septic peritonitis may be found i n Box 147-1. In clinical practice, the author prefers to use C S D , even when criteria are met for primary closure. C S D
Source control accomplished Local or focal peritonitis of nongastrointestinal origin Minimal contamination that is resolved completely with debridement and lavage
allows not only for drainage o f abdominal fluid that may accumulate but also for sampling o f the abdominal fluid for cytologic analysis a n d confirmation that the inflamma tory reaction and infectious process are indeed subsiding. Detailed descriptions o f O P D and C S D techniques may be found later i n this chapter.
Chemical Peritonitis Uroperitoneum and bile peritonitis account for two common sources o f chemical peritonitis. A l t h o u g h most commonly sterile, both conditions may be associated w i t h sepsis. Cyto logic examination and biochemical analysis (glucose and lac tate) o f abdominal fluids may aid i n differentiating between sterile and septic processes. (Please see the preceding section for a discussion o f abdominal drainage i n dogs and cats with septic peritonitis.) Bile peritonitis is associated w i t h an intense inflammatory response. Bile salts are toxic to mesothelial cells i n the peri toneal cavity, and the presence o f bile alters host defense mechanisms and may reduce phagocytic abilities o f inflam matory cells i n the peritoneal space. " O P D is probably unnecessary i n sterile bile peritonitis and may predispose to nosocomial colonization o f the peritoneal cavity. The author has found C S D to be valuable for maintaining peritoneal cavity decompression and facilitating ongoing removal o f small bile particulate matter i n dogs w i t h sterile bile peritonitis. 2
3
Box 147-2 Possible Indications for Peritoneal Drainage •
Septic peritonitis
•
Bile peritonitis
•
Uroperitoneum
processes is not indicated i n the absence o f increased intraabdominal pressure or respiratory embarrassment.
TECHNIQUES FOR PERITONEAL DRAINAGE
•
Pancreatitis-associated peritonitis
•
Peritoneal dialysis
•
Increased intraabdominal pressure
•
A b d o m i n a l effusion compromising ventilation
•
Abdominal effusion compromising patient comfort
Peritoneal drainage plays important roles i n b o t h the preoperative and postoperative management o f the dog or cat w i t h uroperitoneum. In the preoperative setting, i n addition to standard therapeutic measures to manage hypovolemia and hyperkalemia (see Chapters 55 and 137, Potassium Disorders and Hemodialysis and Peritoneal Dialysis, respectively), a peritoneal dialysis catheter or other fenestrated catheter i n the peritoneal space w i l l facil itate the evacuation o f urine from the peritoneal cavity and the diversion o f urine that continues to leak from the dis rupted urinary tract u n t i l the patient is stable and surgical intervention can be performed. In the postoperative setting, because the likelihood o f large particulate debris in the peritoneal space concurrent w i t h uroperitoneum is unlikely, C S D (rather than O P D ) w i l l facilitate the evacua tion o f inflammatory exudates from the peritoneal cavity and should be necessary for only 1 to 3 days postopera tively i n dogs and cats w i t h moderate to severe generalized peritonitis.
Other Indications for Peritoneal Drainage Reliable cannulae for infusion and drainage o f fluid from the peritoneal space are critical to the practice o f peritoneal dial ysis. Two C S D catheters or other long-term peritoneal dialy sis catheters may be placed laparoscopically or through a small laparotomy incision. Renal biopsy might be performed during the procedure (see Chapter 137, Hemodialysis and Peritoneal Dialysis). Increased intraabdominal pressure has been documented in conditions including, but not limited to, portal hyperten sion, repair o f chronic diaphragmatic hernia, abdominal counterpressure bandages, hemoperitoneum, and gastric dilatation-volvulus. Elevated intraabdominal pressure has generalized deleterious effects on the cardiovascular system, primarily mediated through decreased venous return and subsequent decreases i n cardiac output. Local cardiovascular effects include decreased end-organ perfusion, both depen dent and independent o f the aforementioned effect o n car diac output. Increased intraabdominal pressure is also transmitted to the thoracic cavity v i a the diaphragm and may result i n hypoxemia and hypoventilation. Peritoneal drainage may be indicated for animals with intraabdominal pressures higher than 30 c m H 0 as measured with trans urethral techniques. Box 147-2 lists conditions for w h i c h peritoneal drainage might be employed. Routine drainage of peritoneal fluid accumulations due to right heart failure, liver disease, or other noninflammatory or noninfectious 4
2
4
*10.2 Fr 30-cm Polyurethane Thoracic Drainage Catheter, SurgiVet, Wauke sha, WI 53186.
Needle or Catheter Abdominocentesis A b d o m i n a l drainage via a hypodermic needle or over-theneedle catheter is a m i n i m a l l y invasive technique. However, it is very inefficient and does not allow for sustained abdom inal drainage. Additionally, clogging o f the needle or catheter with o m e n t u m or other visceral structures may preclude effective evacuation. This technique is more useful for sam pling o f abdominal fluid for diagnostic purposes or one-time decompression i n a patient exhibiting signs o f respiratory compromise or discomfort secondary to abdominal fluid accumulation. Necessary supplies include an 18- to 20-gauge hypo dermic needle or over-the-needle catheter o f a length appro priate for the anticipated thickness o f the body wall. If an over-the-needle catheter is used, a small 1- to 3 - m m side hole may be created using a N o . 11 scalpel blade approxi mately one fourth o f the way from the tip o f the catheter to the hub. The side hole increases the surface area for the retrieval o f fluid and makes occlusion o f the catheter with o m e n t u m less o f a problem. A d d i t i o n a l equipment w i l l include a 60-cc syringe, three-way stopcock, and intravenous extension tubing to attach to the needle or catheter. The author prefers to use a closed collection system to m i n i m i z e the likelihood o f contamination o f the peritoneal cavity and to m i n i m i z e the introduction o f air into the peritoneal space. The patient is positioned i n left lateral recumbency to allow the spleen to fall away from the proposed site o f needle insertion. The abdomen should be liberally clipped o f hair and aseptically prepared as i f for a surgical procedure and draped using a fenestrated paper or cloth drape. The pro posed insertion site is located 2 to 3 c m caudal to the u m b i l icus, either on or slightly to the left o f midline. Local infusion o f lidocaine hydrochloride may decrease patient discomfort i f drainage is likely to take an extended time. The needle should be inserted perpendicular to the surface of the body and advanced through the skin. The stopcock may then be opened and the syringe aspirated. The needle is then advanced i n 1- to 2 - m m increments and the syringe aspirated intermittently until fluid is retrieved. In cir cumstances i n which only a small volume o f peritoneal fluid is present, four-quadrant abdominocentesis may be per formed. Ultrasonography may be used to guide the sampling needle to very small-volume fluid accumulations. Samples should always be saved for cytologic analysis, culture (if i n d i cated), and chemical analysis, i f indicated (see Chapter 155, Abdominocentesis).
Paracentesis With a Fenestrated Catheter per the Mini-Laparotomy Method In contrast to abdominocentesis with a needle or over-theneedle catheter, use o f a catheter with multiple fenestrations '''Lidocaine HC1 Injectable St. loseph, M O 64503.
2%,
AmTech
Group,
Phoenix
Scientific,
will facilitate both rapid and sustained decompression of larger volume abdominal effusions (mini-laparotomy method). This technique might be used during stabilization o f a dog with bladder rupture and uroperitoneum i n preparation for surgical intervention. A number o f commercially available catheters may be used.* M a n y o f these are designed to be placed via a c o m pletely closed method using a trochar w i t h i n the catheter; however, it is the author's experience and recommendation that placing these catheters using a small laparotomy i n c i sion w i l l optimize the likelihood o f successful placement, as well as m i n i m i z i n g risk o f injury to intraabdominal organs that may occur during closed placement. The patient should be given sedatives and analgesics appropriate for the cardiovascular and respiratory status. First, the bladder should be emptied via catheterization or gentle expression. The patient should be prepared as described previously (Needle or Catheter Abdominocentesis). Local anesthesia techniques focusing o n the skin, subcutane ous tissues, and the body wall are critical to performing this procedure w i t h a m i n i m u m o f discomfort to the patient. Strict asepsis must be practiced. The patient should be placed i n dorsal recumbency, and a 1- to 2-cm skin incision should be made on the ventral midline approximately 2 c m caudal to the umbilicus. Blunt dissection to the linea alba should be performed using a hemostat. The linea should be grasped at both ends o f the incision using hemostats allowing for the creation o f tension and elevation o f the N o . 11 scalpel blade, a 3- to 4 - m m incision should be created in the linea. The catheter should be placed through a sepa rate skin incision 2 c m lateral to the insertion site. This cre ates a small subcutaneous tunnel, making the collection system less susceptible to contamination. W h e n using this technique i n the postoperative setting, the catheter should never be inserted through the laparotomy incision. If the catheter is o f a type i n w h i c h the trochar protrudes from the tip o f the catheter, it should be withdrawn to just inside the catheter. The trochar and catheter may then be inserted into the peritoneal cavity i n a dorsocaudal direction (toward the pelvic inlet). After the trochar and catheter are 2 to 3 c m inside the peritoneal cavity, the catheter may be advanced over the trochar. Dead space i n the subcutaneous tissues should be eliminated and the skin incision closed routinely. A purse-string and finger-trap suture should be used to secure the catheter to the body wall. A sterile dressing should be applied and changed as needed.
Paracentesis With a Fenestrated Catheter Using the Seldinger Technique A b d o m i n a l paracentesis may also be performed using a fene strated catheter placed via the Seldinger technique.^ The patient should be sedated and prepared as described previ ously, positioned i n dorsal recumbency, and the urinary bladder evacuated. Landmarks are similar to those described earlier or slightly off o f midline to avoid the r o u n d ligament of the bladder. Local anesthetic usage w i l l facilitate this pro cedure (see Chapter 63, Central Venous Catheterization). Once i n place, the catheter may be secured and dressed as
"10.2 Fr 30-cm Polyurethane Thoracic Drainage Catheter, SurgiVet, Wauke sha, WI 53186. ^enckhoff Acute Peritoneal Dialysis Catheters, Cook Medical, Bloomington, IN 47402-4195.
described i n the previous paragraph (Paracentesis W i t h a Fenestrated Catheter per the M i n i - L a p a r o t o m y Method).
Surgical Placement of Closed Suction Drains C S D has allowed surgeons to find a middle ground between the sometimes risky method o f primary closure o f the abdominal cavity and the labor-intensive method of providing O P D in the patient with acute, effusive, surgically treated abdominal disease (e.g., septic peritonitis). The author also uses closed suction drains via a limited laparotomy incision for peritoneal dialysis. Numerous types of closed suction drains exist, ranging from flat drains with multiple fenestrations to those that are fluted (Color Plate 147-1), a design that is resistant to obstruction by omentum, tissue, and cellular debris. Closed suction drains are placed as the last step before abdominal closure. In a cat or small dog, a single 10-Fr drain maybe placed i n a craniocaudal direction. In larger dogs, dual 10- or 15-Fr drains may be placed parallel to one another i n a craniocaudal direction, or with one drain located cranially and the other located more caudal. The drains may exit the skin 2 to 3 c m off of midline. 5
Some drains come swaged onto a steel trochar that is used to pass the drain tubing from the intraabdominal space to the drain exit site. The drains should never exit from the laparotomy incision. They should be secured with a pursestring suture at the exit point and continued into a fingertrap pattern. Once the abdomen is closed, the drains should be connected to the negative pressure reservoir(s) with anti reflux valve^).* The drain exit sites should be covered with sterile dressings and an abdominal bandage. The negative pressure reservoir may then be attached to the abdominal bandage. The sterile dressing and abdominal bandage should be replaced daily and the ostomy site and surgical incision evaluated for evidence o f infection. D r a i n reservoirs should be evacuated when they are full. D r a i n effluent should be evaluated daily or every 48 hours to ensure that the underlying disease process is resolving. The author prefers to collect these samples for cytologic analysis from the drain tubing rather than the reservoir. Routine precautions to prevent contamination o f the drain tubing or reservoir should be performed. The drains may be removed when the drainage declines to acceptable levels (5 to 7 m l / k g q24h), patient c o n d i t i o n is i m p r o v i n g , and cytologic characteristics o f the drain fluid show a resolving inflammatory response and no evidence of infection. The presence o f indwelling drains certainly places the patient at risk for hospital-acquired infection, but this hazard may be prevented by strict attention to aseptic technique while handling the drains and while changing the dressings. W h e n closed suction drains are used to perform peritoneal dialysis, one drain may be used for infusion and a second for drainage, or the drain tubing may be connected using a Y adap tor that allows both drains to be used for infusion and drainage (see Chapter 137, Hemodialysis and Peritoneal Dialysis).
Open Peritoneal Drainage Technique O P D was the original alternative to primary closure in patients with septic peritonitis. ' Once source control has been established and the abdominal cavity lavaged thor oughly, the O P D technique may be performed. In male dogs, the parapreputial aspect o f the ventral midline incision is 6
7
l - V a c , Johnson & Johnson Medical, Somerville, NJ 08876.
closed routinely. A urinary catheter should be placed i n all dogs to prevent urine from soiling the abdominal bandage and to help quantify urine output. The technique for providing O P D involves placement o f a monofilament suture (most often 2-0 or 0 polypropylene) i n the external rectus sheath as is routine for closure o f a ventral midline abdominal incision. However, the sutures are not pulled tight, leaving a gap for drainage o f approximately 2 to 4 c m . Sutures prevent evisceration during bandage changes (Color Plate 147-2). A sterile, nonadherent dressing* is then placed over the abdominal incision. This is followed by a large layer of highly absorbent sterile dressing ' and a sterile hand towel. The entire bandage is secured using cast padding,* stretchable roll gauze,^ and additional bandaging materials as needed. The external bandage material should extend far cranial and caudal to the abdominal incision to ensure that it will remain covered i n the event o f bandage migration. 1
The abdominal dressing should be changed a m i n i m u m of 1 to 2 times daily and always when strike-through is evi dent. Weighing the abdominal dressing before placement and after removal may help quantify fluid losses and thus help direct fluid therapy. D u r i n g bandage change, sterilegloved fingers may be inserted into the abdominal cavity between sutures to ensure that fibrin and abdominal organs are not precluding effective abdominal drainage. A b d o m i n a l fluid should be evaluated daily or every 48 hours. Once abdominal drainage has decreased and cytologic characteristics o f the drainage fluid show evidence o f resolv ing inflammatory response and no evidence o f infection, the abdomen may be closed. The author advocates reexploration and lavage o f the abdomen at the time o f closure. Aerobic and anaerobic cultures may be collected from the abdominal cavity. The subcutaneous and skin layers are debrided as needed, lavaged, and closed routinely. O P D may place the patient at risk for hospital-acquired infection, but this hazard may be prevented by strict attention to aseptic tech nique while performing dressing changes and handling the drainage system.
COMPLICATIONS OF PERITONEAL DRAINAGE Volume and Albumin Loss and Peritoneal Drainage Techniques A l l surgical procedures have inherent disadvantages and complications. A knowledge and expectation o f certain
*Adaptic, Johnson & Johnson Medical, Gargrave, Skipton, U K , BD23 3RX. STERIROLL, Franklin-Williams, Lexington, KY. 40502 Specialist Cast Padding, BSN Medical, Brierfield, England BB9 SNJ. Conform Stretch Bandages, Kendall, Mansfield, M A 02048. f
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complications inherent to peritoneal drainage techniques w i l l allow the clinician to anticipate and modulate these. A n y t i m e the peritoneum is evacuated o f fluid, there w i l l be volume loss as well as potential loss o f a l b u m i n and other proteins. Appreciation that abdominal fluid is i n flux w i t h the extracellular fluid volume and that significant volumes of fluid can be lost as a result o f ongoing drainage w i l l allow the clinician to replace fluid volumes and provide oncotic support as necessary. O n e advantage o f the C S D technique is easy quantifica tion o f volume loss. C o m p a r i n g the weight o f the dry O P D bandage w i t h its weight after removal can give an estimate of fluid losses through the O P D site. Close attention should be paid to total volume losses as well as patient albumin concentration, colloid oncotic pressure, and evidence o f peripheral edema when choosing a fluid therapy regimen. Early nutritional support should be strongly considered i n patients w i t h acute abdominal illness.
CONCLUSION A variety o f peritoneal drainage techniques are available to allow clinicians to provide one-time, intermittent, or sus tained drainage for patients requiring evacuation o f fluid from the peritoneal cavity. Attention to indications, contrain dications, and aseptic technique w i l l allow these techniques to be employed w i t h m i n i m a l complications.
SUGGESTED FURTHER R E A D I N G * Conzemius M G , Sammarco JL, Holt D E , et al: Clinical determination of preoperative and postoperative intra-abdominal pressures in dogs, Vet Surg 24:195, 1995. An excellent prospective evaluation of the effects of elective surgical procedures and clinical disease states associated with abdominal distention on intraab dominal pressure. Transurethral technique for measuring intraabdominal pressure described. Mueller M G , Ludwig L L , Barton LJ: Use of closed-suction drains to treat generalized peritonitis in dogs and cats: 40 cases (1997-1999), J Am Vet Med Assoc 219:789, 2001. The only veterinary study detailing a case series of dogs and cats with septic peritonitis in which closed suction drains were used to maintain abdominal decompression during the postoperative period. Describes technique for CSD placement. Descriptive only, limited by its retrospective nature. *See the C D - R O M for a complete list of references.
Chapter 148 POSTTHORACOTOMY MANAGEMENT Eric Monnet,
D V M , PhD, DACVS, DECVS
KEY POINTS • Postoperative management of the patient after thoracotomy requires intensive monitoring of pulmonary and cardiovascular function. • Optimization of oxygen delivery is the primary goal during the postoperative period. • Hypoxemia, hypotension, and arrhythmias are very common after thoracotomy. • Aggressive pain control to improve comfort and ventilation is essential.
Residual pneumothorax and fluid accumulation during the postoperative period can also contribute to hemodynamic compromise. These effects are aggravated by fluid losses dur ing surgery. Volume loading the patient before surgery with crystalloid or colloid fluids to a central venous pressure of 6 to 7 c m H 0 w i l l help prevent the reduction i n cardiac output. Volume loading has to be performed with caution in the patient w i t h cardiac disease, and monitoring of central venous pressure is advised to guide this therapy. 2
Hypothermia INTRODUCTION Thoracotomy is a c o m m o n surgical procedure performed to manage cardiac conditions, lung pathology, pleural effusion of various origins, esophageal disease, and mediastinal dis ease. Intercostal thoracotomy and median sternotomy are the most c o m m o n approaches used i n veterinary medicine. Penetration o f the pleural space induces tremendous changes in p u l m o n a r y and cardiovascular physiology that can impact patient recovery. These patients require intensive m o n i t o r i n g with an emphasis o n evaluation o f p u l m o n a r y function and hemodynamics.
POSTOPERATIVE CONSEQUENCES OF THORACOTOMY
PHYSIOLOGIC EFFECTS OF THORACOTOMY O p e n i n g the thoracic cavity results i n disruption o f the subatmospheric pleural pressure. Consequently lung collapse occurs (atelectasis) and venous return is impaired, compromis ing cardiac output. " 1
O p e n i n g o f the thoracic cavity with a median sternotomy or an intercostal approach results i n a significant drop i n the patient's body temperature because o f the increase i n the surface area exposed to r o o m air. The longer the surgery, the more pronounced the reduction i n temperature will be. This effect is even more significant i n younger and smaller animals. Hypothermia causes severe cardiovascular, respira tory, electrolyte, acid-base, and coagulation abnormalities. Continuous temperature monitoring and active rewarming techniques are required during both the intraoperative and postoperative periods.
After thoracotomy, hypoxemia, residual pneumothorax, pleu ral effusion, and pain need to be corrected to help the patient restore normal p u l m o n a r y and cardiovascular physiology. 5
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Atelectasis Loss o f subatmospheric pleural pressure causes atelectasis, which can be further aggravated by manipulation and retraction of the lungs during the surgical procedure. Atelectasis results i n hypoxemia because there are regions o f ventilation-perfusion mismatch and shunt. Hypoxemia due to atelectasis and shunt w i l l not respond well to oxygen supplementation. Use of positive end-expiratory pressure at the end of the surgery and before the thoracic cavity is closed will help correct the atelectasis and may help relieve postoperative hypoxemia. 4
Hypoxemia Hypoxemia is a c o m m o n problem after thoracic surgery. Hypoxemia during the recovery period is primarily a conse quence o f atelectasis that develops during the procedure. It can be aggravated during the postoperative period by lateral recumbency o f the patient and pleural space disease. In lat eral recumbency, the dependent lung is collapsed under the weight o f the heart and any fluid accumulation. Ventilation is distributed mostly to the nondependent lung, and gravity distributes b l o o d flow to the dependent lung that is not well ventilated. Therefore the ventilation-perfusion mismatch is worsened. It is very important to turn these patients regu larly to reduce the ventilation-perfusion mismatch. 6
Reduction of Venous Return W i t h the loss o f subatmospheric intrapleural pressure, the large intrathoracic veins have a tendency to collapse, w h i c h can cause a reduction i n venous return and cardiac output.
Pleural Space Disease Residual pneumothorax and accumulation o f pleural effu sion contribute to hypoxemia because they interfere with
lung reexpansion. Thoracostomy tube placement is para mount, and chest tube management is an important aspect of postoperative care. Pneumothorax may be a result o f incomplete evacuation o f the pleural space at the end o f the surgical procedure, or it can be secondary to a p u l m o nary lesion as a result o f the surgery or the p r i m a r y disease process. M i l d to moderate pleural effusion is not u n c o m m o n following thoracotomy. Fluid is frequently hemorrhagic i n nature, and the volume of fluid production w i l l vary w i t h the nature of the procedure. Large volumes o f frank b l o o d (confirmed by a fluid packed cell volume equal to or greater than the peripheral packed cell volume) is o f concern, and a surgical consultation should be sought.
Pain Thoracotomy is a painful procedure because o f the retrac tion o f the rib cage. Pain will prevent full excursion o f the thoracic wall, which will impair ventilation and further encourage atelectasis. Therefore pain can contribute to hypoxemia. Pain is also associated with catecholamine release, contributing to vasoconstriction, reduction o f tissue perfu sion, tachycardia, and arrhythmias. Pain management helps reduce the incidence o f tachycardia and arrhythmias during the postoperative period. Consequently, pain management is an essential component o f the postoperative care o f these patients. However, pain medications, especially opioids, can have a significant depressant effect o n the respiratory center. Therefore a good balance between pain control and effec tive respiratory function is required. Short-acting opioids like fentanyl are recommended, because their effect can be adjusted quickly to patient needs. Intercostal nerve blocks at the end o f an intercostal thoracotomy are highly recommended. Injection o f lidocaine and bupivacaine i n the interpleural space is another very efficient technique to control postoperative pain without affecting ventila t i o n . E p i d u r a l analgesia has also been reported as an effi cient technique to control pain without interfering w i t h ventilation (see Chapter 164, Analgesia and Constant Rate Infusions). 3,7
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electrocardiographic m o n i t o r i n g o f these patients during the postoperative period is recommended. General criteria have been established for management o f ventricular arrhythmias. Usually, sustained ventricular tachycardia w i t h a rate above 160 beats/min, m u l t i f o r m ventricular prema ture contractions, and the R on T phenomenon are all con sidered indications for medical management i n an effort to prevent deterioration into ventricular fibrillation. The most c o m m o n antiarrhythmic drug used to correct ventricular arrhythmias is lidocaine. A bolus o f 1 to 2 mg/kg is given to test the response o f the patient and is followed by a constant rate infusion o f 25 to 100 |xg/kg/min. Hypokalemia can impair the effectiveness o f lidocaine and should be trea ted aggressively w i t h potassium supplementation. Magne sium chloride can also be used to manage ventricular arrhythmias i n dogs at the dosage o f 0.75 m E q / k g / I V q24h intravenously (see Chapter 47, Ventricular Tachyarrhyth mias). Pain medication and oxygen therapy are optimized to augment arrhythmia management, because catechol amine release and endocardial ischemia contribute to ven tricular tachycardia.
Hypotension Hypotension is a c o m m o n complication after thoracotomy, and b l o o d pressure m o n i t o r i n g is essential. Continuous direct arterial b l o o d pressure m o n i t o r i n g via an indwelling arterial catheter is ideal, but indirect oscillometric or D o p pler m o n i t o r i n g is acceptable. The most c o m m o n cause of hypotension is hypovolemia. Hypotension can result from reduced cardiac function or severe vasodilation due to severe systemic inflammatory response syndrome and sepsis. Crys talloid fluid therapy w i t h or without synthetic colloid administration is an essential aspect o f postoperative care (see Chapter 65, Shock Fluids and Fluid Challenge). In addi tion, b l o o d products should be administered as required to maintain hematocrit and coagulation parameters in the opti mal ranges. Central venous pressure monitoring can help optimize fluid therapy and is recommended i n cases o f per sistent hypotension. Central venous pressure should be maintained between 3 and 5 c m H 0 i n the patient without cardiac disease. If the patient has cardiac disease such as mitral valve regurgitation or cardiomyopathy, it is important to prevent volume overload. 2
POSTTHORACOTOMY MONITORING Lactate During the postoperative period it is important to m o n i t o r cardiac and pulmonary f u n c t i o n . The goal o f postoper ative care is to optimize oxygen delivery, w h i c h is a function of cardiac output and arterial oxygen content. Heart rate, arterial blood pressure, central venous pressure, and urine production are monitored constantly for the first 24 hours after surgery. Arterial b l o o d gas analyses are performed to follow the progression o f ventilation and hypoxemia, and to guide oxygen supplementation. Hematocrit and total pro tein concentrations are optimized to allow better oxygen delivery. 6,11,12
Cardiovascular Function Arrhythmias Ventricular arrhythmias are very c o m m o n after thoracic surgery, especially cardiac surgery. Hypoxemia, pain, m a n i pulation of the heart, and surgical trauma to the myocar d i u m contribute to arrhythmias. Consequently, continuous
Elevated b l o o d lactate levels i n the postoperative patient are a reliable indicator o f poor tissue oxygen delivery. M e a surement o f b l o o d lactate concentration should be per formed regularly (every 2 to 4 hours) during the immediate postoperative period. The normal lactate level is less than 2 m m o l / L . Increased levels should prompt an evaluation o f perfusion and oxygenation indexes and appropriate therapy instituted.
Respiratory Function Hypoxemia Hypoxemia after thoracic surgery is c o m m o n l y due to hypo ventilation and atelectasis, although underlying pulmonary pathology and aspiration pneumonia can also be present. Residual gas anesthetic, residual pneumothorax, pleural effusion, and pain are factors that c o m m o n l y affect respira tory function. For this reason m o n i t o r i n g o f oxygenating ability during the recovery period is essential, and oxygen
administration should be provided as indicated. Intermittent arterial b l o o d gas analysis is recommended. Continuous or intermittent pulse oximetry can be used i n conjunction w i t h arterial b l o o d gas analysis to detect acute deteriorations i n patient oxygenating ability. In the absence o f arterial b l o o d gas measurement, pulse oximetry must be relied on, but the limitations o f this m o n i t o r i n g device should be recognized. Hypoxemia is defined as a partial pressure o f oxygen i n the arterial b l o o d ( P a 0 ) of less than 80 m m H g , w h i c h is equivalent to a saturation o f 95%. A P a 0 less than 60 m m H g is considered severe hypoxemia (oxygen saturation of 90%). It is important to m a i n t a i n the P a 0 above 60 m m H g because below this level h e m o g l o b i n saturation decreases precipitously, leading to significant compromise o f oxygen delivery. Supplemental oxygen should be administered as needed to maintain the saturation above 95% (above 90% as an absolute m i n i m u m ) . Oxygen can be delivered by a mask, a nasal cannula, or by placing the patient i n an oxygen cage. If the P a 0 cannot be kept above 60 m m H g despite therapy, mechanical ventilation is indicated. T h o r a c i c radio graphs to definitively rule out pleural space disease should be considered before initiating mechanical ventilation. 2
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Ventilation Ventilation is best evaluated by the partial pressure o f carbon dioxide i n arterial or venous blood. If the partial pressure o f carbon dioxide is higher than 45 m m H g , alveolar ventila tion is inadequate. If hypoventilation develops, the thora costomy drain should be checked to eliminate residual pneumothorax or fluid accumulation i n the pleural space. Analgesia is indicated i n an attempt to allow a better excur sion o f the thoracic wall without c o m p r o m i s i n g ventilation via depression of the respiratory centers. If hypoventilation is thought to be due to excessive narcotic drug administra tion, reversal w i t h naloxone or partial reversal w i t h butorphanol should be considered. If significant hypoventilation persists (partial pressure o f carbon dioxide >60 m m Hg) despite medical therapy, mechanical ventilation is indicated.
Thoracostomy Tube Thoracostomy tube management is a vital aspect o f care for the postthoracotomy patient. The tube entry site should be
clean and kept covered w i t h a sterile dressing. The chest tube should be secured i n two places to lessen the chance o f inad vertently dislodging it, and it should be sealed securely with both three-way stopcock and a tube clamp (see Chapter 32, Thoracostomy Tube Placement and Drainage). It is generally recommended to aspirate the chest tube every hour for the first 4 hours postoperatively and then every 4 hours thereafter. In some cases of severe pleural space disease, continuous suction via a 3-chamber apparatus may be indicated. It is important to turn the patient regularly (every 2 to 4 hours) to reduce the development o f atelectasis and to improve fluid drainage from the pleural space. If a patient develops hypoxemia, the chest tube should be aspirated immediately. If tube aspiration is unproductive, dislodgement o f the chest tube and progressive pleural space disease should be ruled out as a possible cause o f the hypoxemia. If tube aspiration is productive, the patient should be observed for an improvement i n respiratory rate and effort and arte rial b l o o d gases measured to ensure the hypoxemia is corrected.
Temperature Because these patients are prone to hypothermia, continuous or regular intermittent temperature monitoring is required. D u r i n g the immediate postoperative period, active warming should be instituted until the patient's temperature reaches 99.5° F. Use o f blankets and active warming should be guided by the animal's temperature for the rest o f the recov ery period.
SUGGESTED FURTHER R E A D I N G * Tucker A : Respiratory pathophysiology. In Slatter D, editor: Textbook of small animal surgery, Philadelphia, 2003, Saunders. Excellent review of pulmonary physiology applied to the surgical patient. Wagner A E , Gaynor IS, Dunlop CI, et al: Monitoring adequacy of ventila tion by capnometry during thoracotomy in dogs, / Am Vet Med Assoc 212:377, 1998. Excellent manuscript to describe modification of pulmonary physiology during thoracotomy; illustrates an augmentation of dead-space ventilation. *See the C D - R O M for a complete list of references.
Chapter 149 POST-CARDIAC SURGERY MANAGEMENT E. Christopher Orton,
DVM, PhD, DACVS
KEY POINTS • Impaired cardiac function in the form of inadequate cardiac output or elevated end-diastolic pressure, or both, is often present in patients that have undergone cardiac surgery. • Overzealous administration of crystalloid fluids should be avoided in animals undergoing cardiac surgery. • Inadequate cardiac output after cardiac surgery is suggested by resting blood lactate levels greater than 2.5 mmol/L or oxygen extraction ratio over 40%. • Cardiac function in animals undergoing cardiac surgery should be supported with inotropic and vasoactive drugs. • Ventricular tachycardia and atrial fibrillation are the most important arrhythmias occurring in animals after cardiac surgery.
INTRODUCTION Cardiac function is impaired when cardiac output is inade quate despite adequate ventricular end-diastolic pressure or when adequate cardiac output is maintained at the expense of elevated ventricular end-diastolic pressure. Generally ani mals undergoing cardiac surgery have varying degrees o f impaired cardiac function before surgery. Superimposed on this preexisting cardiac insufficiency are the detrimental effects that general anesthesia and thoracic surgery have o n cardiopulmonary function. A positive element is that the cardiac repair should improve cardiac function. A guiding principle o f cardiac surgery is that it should not be underta ken unless the prospect for improved cardiac function is sig nificant. Nevertheless, these patients do require some special considerations for supportive care during the period immediately after surgery. 1
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FLUID THERAPY Fluid therapy after cardiac surgery often presents a dilemma. O n the one hand, most animals benefit from some degree o f volume loading during and after surgery to counteract the nega tive effects of anesthesia and surgery o n cardiovascular function. This would include animals with preexisting cardiac insuffi ciency. O n the other hand, patients often enter cardiac surgery with varying degrees o f heart failure, and like any animal with heart failure, will not tolerate large loads of crystalloid fluids. The goal of fluid therapy i n these patients is to maintain a vascular volume adequate to support cardiac function without worsening or precipitating congestive heart failure. Assessments o f vascular volume include body weight, cen tral venous pressure ( C V P ) , and pulmonary wedge pressure. The latter is ideal for animals w i t h left-sided cardiac insuffi ciency but is not generally available. Thus body weight, C V P , and good clinical judgment are the best guides to fluid
therapy. Preoperative body weight and C V P serve as good guidelines for the postoperative period i f the animal was sta ble entering surgery. In general, a C V P o f 4 to 8 c m H 0 (3 to 7 m m Hg) is a reasonable therapeutic target. It is impor tant to realize that animals w i t h cardiac insufficiency are more likely to be volume overloaded than hypovolemic after cardiac surgery. 2
Overzealous fluid therapy is detrimental and inappropriate. As a general rule, animals should not receive higher than mainte nance rates of crystalloid fluids after cardiac surgery. In fact, ani mals may be trying to excrete excess body water and sodium if the cardiac repair has substantially improved cardiac function. These animals may benefit from having little or no crystalloid fluid therapy. If blood volume is inadequate or there is ongoing loss of volume due to surgical bleeding, then volume replacement should take the form o f colloid-type fluids such as fresh whole blood, plasma, washed red blood cells, or albumin. The hemato crit, plasma total solids, total protein, and colloid osmotic pres sure serve as guides for the type of colloid fluid administered. Animals should be monitored closely for evidence of pulmonary or systemic congestion after cardiac surgery. If congestion devel ops, intravenous furosemide (2 mg/kg bolus or 0.25 mg/kg/hr constant rate infusion [CRI]) is indicated.
CARDIAC OUTPUT A n i m a l s should be monitored for adequacy o f cardiac out put after cardiac surgery. Inadequate cardiac output is sug gested by a resting b l o o d lactate concentration greater than 2.5 m m o l / L , m i x e d venous oxygen saturation less than 70%, or oxygen extraction ratio o f over 4 0 % . L o w mean systemic arterial pressure suggests the possibility of, but does not con firm, inadequate cardiac output. Moderate hypotension (mean arterial pressure o f 60 to 75 m m Hg) w i t h evidence of generalized vasodilation (i.e., p i n k mucous membranes) and without evidence o f inadequate cardiac output is well tolerated and does not generally require therapy to augment cardiac output. O n the other hand, hypotension i n a patient w i t h generalized vasoconstriction (i.e., white mucous m e m branes, cold extremities) suggests that cardiac output may be inadequate. 3
A n i m a l s w i t h evidence o f inadequate cardiac output w i t h or without concurrent hypotension should receive support ive therapy to improve cardiac output. H y p o v o l e m i a should be corrected, i f present, but aggressive volume loading is not appropriate for animals w i t h cardiac insufficiency. Thera peutic support o f cardiac output takes the form o f drugs or drug combinations w i t h inotropic and vasomotor effects. The choice o f drugs is influenced by several factors, includ ing the magnitude and chronicity o f myocardial failure, mean arterial pressure, and renal function (Table 149-1). 4
• Dobutamine, a synthetic analog with predominant P-agonist activity, is administered when inotropic support of the myocardium is desired. Stimulation o f peripheral |3 receptors promotes vasodilation and can contribute to hypotension o n occasion. • Milrinone, a phosphodiesterase 3 inhibitor, is a potent positive inotrope with moderate vasodilation activity. It is used alone or i n combination with p-agonists to achieve an inotropic effect, especially when myocardial P-receptor down-regulation is suspected (i.e., chronic myocardial failure). • Epinephrine, a P-agonist and a-agonist, is used when both inotropic and vasopressor effects are needed to support cardiac output and correct severe hypotension. Its princi pal indication is during and immediately after cardiac surgery. • Dopamine is a dopaminergic P-agonist and a-agonist, w i t h effects that depend o n the dosage. A t lower dosages, dopa mine supports myocardial function through its beta effect and improves b l o o d flow to the kidneys, heart, brain, and mesenteric organs through dopaminergic receptors. At higher dosages, dopamine adds an a-mediated vasopressor effect. • Phenylephrine, an a-agonist, can be administered alone or in combination w i t h other drugs when a pure vasopressor effect is necessary. A l l o f the above drugs carry a significant risk o f promoting tachycardia and arrhythmias. Animals should be monitored for these adverse effects. Benefits and hazards o f inotropic sup port should be weighed carefully i n each patient. 2
ARRHYTHMIA MANAGEMENT Arrhythmias are c o m m o n after cardiac surgery, especially i n an animal with preexisting myocardial dysfunction. Arrhyth mias can cause considerable m o r b i d i t y after cardiac surgery and increase the risk for sudden cardiac arrest. Arrhythmias encountered after cardiac surgery include both tachyarrhyth mias and bradyarrhythmias. Tachyarrhythmias include sinus tachycardia, ventricular ectopy including ventricular tachy cardia, atrial fibrillation or flutter, and the supraventricular tachycardias. Bradyarrhythmias include sinus bradycardia, atrial standstill, and atrioventricular block. Sinus tachycardia is often present after cardiac surgery. Management should be directed toward relieving its under lying causes including pain, apprehension, cardiovascular instability, or drug therapy (e.g., inotropic drugs).
Ventricular ectopy i n the form of ventricular premature contractions, ventricular couplets and triplets, or paroxys mal or sustained ventricular tachycardia are encountered frequently after cardiac surgery. N o t all ventricular ectopy requires treatment. Ventricular premature contractions are not generally dangerous or associated w i t h hemodynamic alterations, and they do not generally require therapy. Sus tained ventricular tachycardia, paroxysmal ventricular tachy cardia that is unstable (i.e., close or irregular Q R S coupling), or multifocal ventricular ectopy should be suppressed. Lidocaine (2 m g / k g I V boluses, then 50 to 80 ug/kg/min CRI) is usually the initial therapy of choice for ventricular ectopy. Fast sustained ventricular tachycardia that causes hemodynamic instability and is not responsive to I V lidocaine should be terminated w i t h synchronous direct cur rent cardioversion. Slower sustained ventricular rhythms ( 155 m E q / L ) , then a low-sodium crystalloid fluid (e.g., 0.45% saline) should be administered. Judicious administration of furosemide (0.1 to 0.2 mg/kg I V q2-4h) may also be necessary to counter inappropriate sodium retention. It may take several days for hypernatremia to resolve once it develops. Lastly, hypomagnesemia commonly occurs after C P B . Prophylactic treatment of this deficiency with intravenous magnesium supplementation (0.75 mEq/kg/day) decreases the likelihood of post-CPB atrial and ventricular arrhythmias.
COAGULOPATHY AND HEMORRHAGE C P B must be conducted under a state of complete anticoagu lation. D u r i n g C P B , activated clotting time ( A C T ) is main tained at over 480 seconds with administration of sodium heparin (300 U / k g IV). After termination of C P B , the effects of heparin are reversed with protamine sulfate (0.5 to 1 mg/kg IV) to return the A C T to preoperative levels. After protamine administration, a unit of fresh whole blood is given to replace cells lost during C P B , including platelets. Antifibrinolytic ther apy during C P B is undertaken by administration of 8-aminocaproic acid (Amicar) by C R I (15mg/kg/hr) to decrease intravascular fibrinolysis. Despite these efforts to reduce the effects of C P B , coagu lopathy is invariably present during the first 12 to 24 hours after C P B . Coagulopathy results from any of several causes, including dilution and consumption of coagulation factors, consumptive thrombocytopenia, platelet dysfunction, intra vascular fibrinolysis, and incomplete reversal of heparin. Coagulation status should be assessed periodically after C P B and should include A C T , prothrombin time, activated partial thromboplastin time, and platelet counts. Comparison of A C T with and without heparinase provides information about residual u n b o u n d heparin that could be contributing to coagulopathy. 14
Hemorrhage into the pleural space is a frequent compli cation after C P B i n dogs. Hemorrhage after C P B can be sur gical (i.e., inadequate closure of cardiotomy sites) or biologic (i.e., coagulopathy). Distinguishing between surgical and biologic bleeding can be very difficult after CBP. If surgical
hemorrhage is suspected, then returning to the operating room is the most appropriate option. If hemorrhage is the result o f biologic derangement, then supportive care and time is the best option. The volume o f bleeding alone does not distinguish between surgical and biologic bleeding, because both can result i n considerable hemorrhage. The best assurance that bleeding is biologic rather than surgical comes from confidence o f the surgical team that cardiotomy incisions were closed well. If i n doubt, biologic bleeding should be assumed and a conservative approach o f time and supportive care adopted. Time and supportive care are often the best treatment for coagulopathy after CBP. Supportive care consists o f treating the underlying causes of coagulopathy, replacement therapy for lost RBCs. Administration o f fresh frozen plasma to replace lost coagulation factors is helpful. Supportive care during hemorrhage consists o f administration o f type stored RBCs and autotransfusion o f shed blood. Shed b l o o d should be washed in a cell washer before it is readministered to the patient. Most dogs will require autotransfusion o f washed shed blood after C P B . In general, biologic bleeding will diminish by 12 to 18 hours after surgery.
CARDIAC SUPPORTIVE CARE Patients undergoing open heart surgery and C P B by their very nature have compromised cardiac function going into the procedure. Superimposed o n that dysfunction are the insults imposed by cardiac surgery, cardioplegic cardiac arrest, and C P B . The combined effect of these insults is myo cardial injury that, i n turn, compromises systolic function and predisposes to atrial and ventricular arrhythmias. Most, i f not all, dogs undergoing C P B will require some degree o f inotro pic support and arrhythmia management after surgery (see Chapter 149, Post-Cardiac Surgery Management). 1 5
PULMONARY SUPPORTIVE CARE The lung is a target organ for the adverse effects associated with S I R A B . Pulmonary vascular injury and leak ("pump lung") should be anticipated i n all dogs undergoing C P B . Pulmonary dysfunction may not be apparent during the first hours after surgery but will become apparent by 4 to 6 hours after surgery. Preexisting pulmonary conditions such as chronic bronchitis and chronic left-sided C H F w i l l add to the degree of pulmonary dysfunction after C P B , and these factors should be considered i n case selection for cardiac surgery. 16
Arterial b l o o d gases should be monitored every 2 to 4 hours during the first 24 hours after C P B . P u l m o n a r y dys function manifests as varying degrees o f hypoxemia caused by impaired gas exchange and hypoventilation. Impaired gas exchange results from a combination o f ventilationperfusion inequality and pulmonary shunt and, depending on the relative distribution of these mechanisms, responds to supplemental oxygen to varying degrees. Hypoventilation results from the combined effects o f sedation associated w i t h analgesia and residual anesthetic drugs and decreased pulmonary compliance. Most dogs will require ventilator support for at least a few hours after C P B . The amount o f time depends on the pro cedure, the size o f the dog, the duration o f C P B , and
preexisting pulmonary disease. Dogs undergoing mitral sur gery, small dogs, and dogs w i t h chronic bronchitis are likely to require longer artificial ventilation. M o s t dogs can be weaned from a ventilator by 12 hours after C P B . Thereafter supplemental oxygen w i l l generally be required for an additional 24 to 48 hours (see Chapters 213 and 214, Basic Mechanical Ventilation and Advanced Mechanical Ventila tion, respectively).
RENAL SUPPORTIVE CARE Renal function can be altered i n patients that have under gone C P B , secondary to both predisposing patient factors and physiologic alterations that occur during the periopera tive period. The mortality rate i n h u m a n patients who develop renal failure after cardiac surgery is over 50%, despite appropriate and intensive therapy. Fortunately, renal failure is a relatively rare occurrence after cardiac surgery, although m i l d renal impairment occurs more fre quently. Dogs have been found to develop hematuria and renal tubule swelling post experimental C P B . Even m i l d renal dysfunction results i n increased m o r b i d i t y and length of hospitalization for these patients. 17
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The two most important risk factors for renal failure i n patients after C P B are renal ischemia secondary to decreased cardiac output and preexisting diminished renal functional reserve. Perioperative cardiac dysfunction, lengthy proce dures, and a need for postoperative vasopressor drug sup port increase the risk o f renal ischemia. Renal functional reserve tends to be decreased i n older patients w i t h more advanced disease. Renal protective strategies for patients undergoing C P B should focus o n avoiding renal hypoperfu sion by m a x i m i z i n g cardiac output and m i n i m i z i n g surgery time. 19
Renal function is evaluated by m o n i t o r i n g urine produc tion, urine concentrating ability, electrolytes, and degree o f azotemia. These parameters should be evaluated at least every 4 hours after C P B . The presence o f azotemia or oliguria sug gests insufficient cardiac output. Oliguria after C B P should be treated w i t h intravenous furosemide and drugs to improve cardiac output and renal b l o o d flow. Polyuria with an inability to concentrate urine can indicate medullary washout second ary to preoperative high-dose diuretic therapy, preexisting renal insufficiency, or CPB-related injury. C R I o f dopamine to improve cardiac output and renal b l o o d flow is an appro priate treatment for renal insufficiency i n dogs after C P B . Appropriate fluid support is important, but most p o s t - C P B patients w i l l not tolerate high-volume administration o f crystalloid fluids to support renal function.
GASTROINTESTINAL SUPPORTIVE CARE H i g h mortality rates are associated w i t h gastrointestinal (GI) complications after C P B . As w i t h renal dysfunction, G I , hepatic, and pancreatic complications are associated with multiple factors including prolonged duration o f C P B , advanced age and concomitant disease, l o w cardiac output, and vasopressor therapy. Gastric mucosal p H is often decreased during C P B i n both h u m a n and animal studies, suggesting decreased splanchnic perfusion. GI permeability increases significantly, and endotoxemia due to translocation from the gut has been documented after C P B . ' 2 0
2 1
Unfortunately, current clinical indexes are unable reliably detect splanchnic perfusion abnormalities, GI function, or gastrointestinal injury i n the perioperative setting. Clinical signs o f G I dysfunction are subtle, which contributes to delays i n diagnosis and treatment. Clinical signs o f impaired G I function include anorexia, v o m i t i n g , hematochezia, hematemesis, melena, decreased or absent borborygmus, and failure to produce stool. Bleeding, usually duodenal or gastric, is the most c o m m o n G I complication noted i n patients after C P B . Gastroprotective strategies including m a x i m i z i n g cardiac output, precipitous discontinuation o f drug therapy, administration o f gastroprotective medica tions, and nutritional support should be instituted i f altered GI function is suspected. High-risk patients should be trea ted prophylactically during the perioperative period.
NUTRITIONAL SUPPORT M a n y patients with advanced cardiac disease have clinical signs o f cardiac cachexia. C P B and the postoperative medical therapy associated with it i m p a i r G I function i n many patients. Decreased nutrient intake depresses the i m m u n e system and impairs w o u n d healing, while early nutritional support can prevent such undesirable complications. Early enteral nutrition increases cardiac index and splanchnic blood flow i n p o s t - C P B patients.
Nutritional support can be provided to post-CPB patients by both the enteral and parenteral routes. Enteral nutrition by voluntary oral consumption should begin as soon as the patient is ready, generally on the second or third day after surgery. A d d i t i o n a l support can be provided with judicious use of parenteral nutrition, the absorption of which is not affected by G I dysfunction. Parenteral nutrition may be required i n dogs w i t h preexisting cardiac cachexia or i n dogs with G I dysfunction that delays oral feeding by more than 3 days after C P B . SUGGESTED FURTHER R E A D I N G * Klement P, del Nido PJ, Mickleborough L, et al: Technique and postopera tive management for successful cardiopulmonary bypass and open-heart surgery in dogs, / Am Vet Med Assoc 190:869, 1987. Description of method for CPB and mitral valve replacement in normal dogs. Orton E C , Hackett TA, Mama K, Boon JA: Technique and outcome of mitral valve replacement in dogs, J Am Vet Med Assoc 226:1508, 2005. Surgical technique and outcome of dogs undergoing mitral valve replacement. Orton E C , Herndon G D , Boon JA, et al: Intermediate-term outcome in dogs with subvalvular aortic stenosis: Influence of open surgical correction, / Am Vet Med Assoc 216:364, 2000. Intermediate-term outcome of dogs after open resection for subvalvular aortic stenosis. Orton E C , Mama K, Hellyer P, Hackett TB: Open surgical repair of tetralogy of Fallot in two dogs, ] Am Vet Med Assoc 219:1089, 2001. Surgical technique and outcome of dogs undergoing correction of tetralogy of Fallot.
22
"See the C D - R O M for a complete list of references.
Chapter 151 KIDNEY TRANSPLANTATION Lillian R. Aronson, V M D , DACVS
KEY POINTS • Kidney transplantation is a viable option for cats in both acute and chronic renal failure. • Careful case selection of a potential recipient is critical to prevent both short-term and long-term complications. • Cats with a history of recurrent urinary tract infections or those with significant cardiac disease are not typically good candidates for the procedure. • Lifelong immunosuppression is necessary and consists of a combination of the calcineurin inhibitor, cyclosporine (CsA), and a glucocorticoid, such as prednisolone. • Postoperative hypertension is managed with hydralazine (2.5 mg SC for a 4-kg cat) to prevent central nervous system complications (i.e., seizures). • If acute rejection is suspected, treatment should be initiated immediately to prevent graft loss. • Treatment of complications secondary to long-term immunosuppressive therapy including mycobacterial infections, toxoplasmosis, and neoplasia have been largely unsuccessful.
Box 151-1 Preoperative Screening for a Potential Feline Renal Transplant Recipient •
Complete blood count
•
Serum chemistry profile
•
B l o o d type and crossmatch
•
Thyroid hormone
•
Urinalysis, urine culture, urine protein-to-creatinine ratio
•
A b d o m i n a l radiography
•
A b d o m i n a l ultrasonography
•
Thoracic radiography
•
Electrocardiography, echocardiography, blood pressure
•
Feline leukemia virus, feline immunodeficiency virus
"
Toxoplasmosis titer, IgG and I g M
IgG, Immunoglobulin G ; IgM, immunoglobulin M .
with either a percutaneous endoscopic gastrostomy or esophagostomy feeding tube ( K G Mathews, personal c o m m u nication, 1998). Both physical and biochemical parameters need to be eval uated carefully to determine i f a cat is a suitable candidate. Cats should be free of other disease conditions including sig nificant heart disease, recurrent urinary tract infections, uncontrolled hyperthyroidism, a n d underlying neoplasia. Cats with a fractious temperament are also often declined as candidates. N o t enough information exists to determine i f cats with diabetes or inflammatory bowel disease should be declined as potential candidates. Preoperative exami nation involves various laboratory tests including a complete blood count, biochemical evaluation, blood type, thyroid function studies, evaluation o f the urinary tract (urinalysis, urine culture, urine protein-to-creatinine ratio, abdominal radiographs, abdominal ultrasonography), evaluation for car diovascular disease (thoracic radiography, electrocardiogra phy, echocardiography, blood pressure), a n d screening for infectious disease including feline leukemia virus (FeDV), feline immunodeficiency virus (FIV), Toxoplasma titer, and i m m u n o g l o b u l i n (Ig) G and I g M ' (Box 151-1). There is no age restriction for a potential transplant recipient. The feline recipient must also have compatible blood (via crossmatch) to a prospective kidney donor and to two or three b l o o d donor cats. 2
INTRODUCTION Kidney transplantation is an accepted treatment option for cats i n both acute and chronic renal failure. Since its intro duction to the veterinary c o m m u n i t y i n 1987 by Drs. Clare Gregory and Ira Gorley from the University o f California, Davis, School o f Veterinary Medicine, it is estimated that over 400 cases of feline renal transplantation have been per formed at various centers around the country. Information from different centers suggests that survival times are continuing to improve; however these cases remain a chal lenge for the veterinary clinician. This chapter w i l l discuss the most up-to-date information with regard to case selec tion, preoperative and postoperative care, anesthetic a n d surgical management, and handling o f the most c o m m o n long-term complications.
CASE SELECTION
3
Thorough screening for a potential feline renal transplant recipient is critical to decrease the incidence o f m o r b i d i t y and mortality that can occur following the procedure. Although the best time to intervene with surgery is still sub jective, clinicians with experience treating these patients sug gest that the best candidate for renal transplantation is one in early decompensated renal failure. ' Indications o f decompensation include worsening of azotemia and anemia, as well as continued weight loss while receiving medical ther apy. Some clinicians have been successful i n altering the physical deterioration of individual patients for up to 2 years 1
2
4
Evaluation of the Urinary Tract Evaluation o f the urinary tract is essential, particularly to rule out any underlying infection or neoplastic disease. If abdominal ultrasonography o f the kidneys leads to a suspicion o f feline infectious peritonitis (FIP) or neoplasia,
a fine-needle aspirate or biopsy is. recommended. If a patient has recently been treated for a urinary tract infection or has had recurrent urinary tract infections, but at the time of arrival has negative urine culture results, then a cyclosporine (CsA) (Neoral, Novartis) challenge is recommended before trans plantation to determine i f the cat will "break" with an infec tion. To perform this challenge, C s A is administered for approximately 2 weeks at the recommended dosage for trans plantation immunosuppression. The urine is evaluated for infection after therapeutic CsA blood levels have been achieved and at the end of the 2-week period. It is important to note that a negative urine culture result following a challenge will not guarantee that a patient will remain infection free follow ing surgery and during long-term immunosuppression. Finally, i f unilateral or bilateral hydronephrosis is identi fied in any patient during the screening process, a pyelocentesis and culture are recommended before transplantation. The author has identified five cats with obstructive calcium oxalate urolithiasis that have had a negative culture result from urine collected via cystocentesis and a positive culture result from urine collected by pyelocentesis ( L R A r o n s o n , unpublished data, 2005). Immunosuppression i n a patient harboring an infection can not only potentiate the rejection process, but also lead to increased m o r b i d i t y and mortality.
Cardiovascular Disease At the time of presentation for transplantation, a systolic m u r m u r may be auscultated o n physical examination. These are often physiologic murmurs associated with the anemia o f chronic renal failure and may not represent significant heart disease. In a recent study from the University of California, Davis, evaluating cardiac abnormalities in 84 potential trans plant recipients, 78% o f patients had abnormalities including both papillary muscle and septal muscle hypertrophy. The authors suggested that these changes may be related to hypertension, chronic uremia, age, or early changes of hypertrophic cardiomyopathy. Cats with diffuse hypertro phic cardiomyopathy or those with congestive heart failure are declined as candidates for renal transplantation at our facility. A decision is made on a case-by-case basis i n those cats with less severe disease. 1
5
Infectious Disease If a cat's test results are positive for FeDV or the animal has an active F I V infection, it is declined as a candidate for transplantation. Additionally, all potential donors and reci pients undergo serologic testing (IgG and I g M ) for toxoplas mosis. Toxoplasma gondii can cause significant m o r b i d i t y and mortality in both h u m a n and veterinary i m m u n o c o m promised patients. As a matter of policy at our facility, sero positive donors are not used and seropositive recipients are placed on lifelong prophylactic clindamycin (25 mg P O q l 2 h ) , which is started when immunosuppression is initiated. If the cat does not tolerate the clindamycin, other anti biotics such as trimethoprim-sulfamethoxazole (Tribrissen) have been used.
DONOR SELECTION Kidney donors are typically between 1 and 3 years o f age and in excellent health. Standard evaluation includes a complete
blood count, serum chemistry profile, urinalysis and culture, FeLV and F I V testing, and a toxoplasmosis titer (IgG and IgM). The feline kidney donor must also have a compatible blood crossmatch to the recipient and be of a similar size. Additionally, we perform computed tomographic angiogra phy on all of the donors to evaluate the renal vasculature and the renal parenchyma for any abnormalities that may preclude successful transplantation. 6
PREOPERATIVE MANAGEMENT O n admission to the transplant facility, intravenous fluid ther apy is begun with a balanced electrolyte solution at 1.5 to 2 times the daily maintenance requirements. This rate may vary i n cases of severe dehydration or i n cats with underlying cardiac disease. At some centers, hemodialysis is performed before transplantation for cats that are anuric or those with severe azotemia (blood urea nitrogen > 100 mg/dl, creatinine >8 mg/dl). Additionally, i f the cat is hypertensive, the cal cium channel blocker amlodipine (Norvasc, 0.625 mg/cat P O q24h) may be indicated before surgery. Anemia is typi cally corrected at the time of surgery with crossmatchcompatible whole blood or packed red blood cell transfu sions. The first unit that is administered is one that has been previously collected from the kidney donor. If the patient has evidence of decreased oxygen delivery from the anemia, blood products can be given at the time of admission to the transplant facility. If a delay i n the transplant procedure is expected, erythropoietin (Epogen) can be administered and may greatly reduce the need for blood products at the time of surgery. Dosage is 100 IU/kg 3 times per week for the first 1 to 2 weeks and then tapered accordingly. Phosphate binders and gastrointestinal protectants are given i f deemed necessary (see Chapter 181, Gastrointestinal Protectants). If the cat is anorectic, a nasogastric, esophagostomy, or percu taneous endoscopic gastrostomy tube may be placed for nutritional support before surgery (see Chapter 13, Enteral Nutrition). 7
Immunosuppression for the Feline Renal Transplant Recipient The immunosuppressive protocol used at our facility con sists of a combination of the calcineurin inhibitor, CsA, and the glucocorticoid, prednisolone. Because of the small dosage of C s A that cats often require for immunosuppres sion, the liquid microemulsified formulation, Neoral ( l O O m g / m l ) , is recommended so that the dosage can be titrated for the individual cat. CsA administration is begun 72 to 96 hours before trans plantation at a dosage of 1 to 4 mg/kg P O q l 2 h depending on the cat's appetite. In the author's experience, cats that are anorexic or are eating a m i n i m a l amount have a much lower drug requirement to obtain appropriate drug levels before surgery. Additional agents that inhibit P-450 may alter drug concentrations and should be used with caution i n these patients. A 12-hour whole blood trough concentra tion is obtained the day before surgery so that the dosage can be adjusted preoperatively i f necessary. The drug level is measured using high-pressure liquid chromatography. The goal is to obtain a trough concentration of 300 to 500 n g / m l . This level is maintained for approximately 1 to 3 months 4
following surgery and is then tapered to approximately 200 to 250 ng/ml for maintenance therapy. Prednisolone is ad ministered beginning the morning of surgery. A t our facility, prednisolone is started at a dosage range of 0.5 to 1 mg/kg PO q l 2 h for the first 3 months and then tapered to q24h. It is important to note that protocols for both C s A and prednis olone vary among transplantation facilities. A second protocol used by some clinicians for feline immunosuppression combines the antifungal medication ketoconazole (10 mg/kg P O q24h) with C s A and predniso lone. ' Ketoconazole can affect C s A metabolism by inhibit ing both hepatic and intestinal cytochrome P-450 oxidase activity, resulting i n increased b l o o d C s A concentrations. Once ketoconazole is added to the immunosuppressive pro tocol, C s A and prednisolone are administered once a day, and C s A dosage is adjusted into the therapeutic range by measuring whole blood trough levels daily. This protocol may reduce the cost of C s A and be more appealing for owners whose work schedule does not permit twice daily medication administration. 8 9
9
ANESTHESIA MANAGEMENT At the time of anesthesia induction, both the donor cat and the recipient are given cephalexin (22 mg/kg I V q2h). A n epidural is given to both cats (bupivacaine 0.1 mg/kg and morphine 0.15 mg/kg) for analgesia. In addition to a periph eral catheter, a double-lumen indwelling jugular catheter is placed, preferably using the recipient right jugular vein. The left side of the neck is preserved i n cases that need an esophagostomy tube. Using this catheter, b l o o d products can be given as needed, blood sampled regularly for evalua tion of blood gases, electrolytes, packed cell volume, and total protein, and central venous pressure monitored if needed. Because the procedure can last up to 6 hours, hypothermia is of serious concern. A Bair Hugger or heating pads, or both, are used throughout the procedure and esophageal temperatures are monitored continuously. Systemic arterial blood pressure is monitored regularly throughout the procedure i n both cats using a Doppler technique. Intraoperative hypertension is treated w i t h hydralazine (2.5 mg SC for a 4-kg cat) and intraoperative hypotension corrected by decreasing the concentration of inhalant anesthetic or by administering fluid boluses, b l o o d products, or dopamine (starting at 5 pg/kg/min).
SURGERY Each transplant procedure involves a team of three surgeons. The donor cat is brought into the surgical suite approxi mately 30 to 45 minutes before the recipient. D u r i n g this time, the donor kidney will be prepared for the nephrec tomy. W h e n the abdominal incision is made, the donor is given a dose of mannitol (0.25 g/kg I V over 15 minutes) to help prevent renal arterial spasms, improve renal blood flow, and protect against injury that can occur during the warm ischemia period. The renal artery and vein are cleared of as much fat and adventitia as possible, and the ureter is dis sected free to the point where it joins the bladder. The left kidney is preferred because it has a longer vein. It is essential, however, to harvest a donor kidney w i t h a single renal artery at the point where the artery joins the aorta. A m i n i m a l
length o f 0.5 c m of single renal artery is necessary for the arterial anastomosis. The nephrectomy w i l l be performed when the recipient is prepared to receive the kidney. Fifteen minutes before nephrectomy, an additional dose of m a n n i t o l (1 g/kg I V ) is given to the donor cat. M o s t of the recipient surgery is performed using a m i c r o scope. The renal artery is anastomosed end-to-side to the caudal aorta (proximal to the caudal mesenteric artery), and the renal vein is anastomosed end-to-side to the caudal vena c a v a . Partial occlusion clamps are used to obstruct blood flow i n both the aorta and the caudal vena cava, and holes are created i n both to match the size of the renal artery and vein. Both aorta and vena cava, as well as the allograft, are flushed w i t h a heparinized saline solution. The renal artery is anastomosed to the aorta using 8-0 nylon i n a sim ple continuous pattern, and the renal vein is anastomosed to the vena cava using 7-0 silk i n a simple continuous pattern. 1
10
Once the vascular anastomosis is complete, a ureteroneocystostomy is performed using an intravesicular mucosal apposition technique. A ventral midline cystotomy is per formed and the end of the ureter brought directly into the bladder lumen through a hole created at the bladder apex. The bladder is everted, the distal end of the ureter is excised, periureteral fat is removed, and the end of the ureter is spatulated. The ureteral mucosa is sutured to the bladder mucosa using either 8-0 nylon or 8-0 V i c r y l i n a simple inter rupted pattern. Following completion of the anastomosis, the bladder is inverted and closed routinely. Before closure, a biopsy of one of the native kidneys is performed and the allograft pexied to the abdominal wall using six inter rupted sutures of 4-0 polypropylene. The recipient's native kidneys are usually left i n place to act as a reserve i n case graft function is delayed ( C o l o r Plate 151-1). Patients with polycystic kidney disease are an exception, because at least one of the native kidneys often needs to be removed to make r o o m i n the abdomen for the allograft.
POSTOPERATIVE MANAGEMENT AND PERIOPERATIVE COMPLICATIONS Following surgery, the recipient is maintained on I V fluid therapy that should be adjusted to the cat's renal function, hydration status, and oral water intake. B l o o d transfusions are given only i f necessary. M i n i m a l stress and handling and hypothermia prevention are critical during the early postoperative period. W h i l e a catheter is i n place, the cat is maintained on I V antibiotic therapy (cefazolin, 22 mg/kg I V q8h). Once all catheters are removed, the cat is then m a i n tained o n oral antibiotic therapy (ampicillin-clavulanate [Clavamox] 62.5 mg P O q l 2 h ) for another 3 to 4 weeks or until the feeding tube is removed and C s A levels regulated. If Toxoplasma titers are positive, clindamycin (25 mg P O q l 2 h ) is administered i n conjunction w i t h the i m m u n o s u p pression and continued for the lifetime of the cat. Postopera tive pain has been controlled successfully at our facility using buprenorphine (0.005 to 0.02 mg/kg I V q4-6h), hydromorphone (0.05 to 0.2 mg/kg or S C q4-6 h), or a constant rate infusion of butorphanol (0.1 to 0.5 mg/kg/hr). Initially blood work is performed twice daily to evaluate acid-base sta tus, packed cell volume, total protein, electrolyte, and blood glucose levels and then tapered accordingly depending on the stability of the cat. A renal panel is checked every 24 to 48 hours, and a b l o o d C s A level is checked every 3 to 4 days
and the dosage adjusted accordingly. V o i d e d urine is weighed and recorded w h e n possible. A b d o m i n a l palpation is not allowed d u r i n g the postoperative period. W i t h improvement i n azotemia and appropriate p a i n control, most cats w i l l start eating w i t h i n 24 to 48 hours following the surgical procedure. If the cat remains anorexic, a feeding tube may be necessary. Because o f the association between postoperative hyper tension and postoperative central nervous system disorders including seizure activity, indirect blood pressure is m o n i tored every 1 to 2 hours during the first 24 to 48 hours to assess for hypertension. If the systolic b l o o d pressure is equal to or greater that 180 m m H g , hydralazine (2.5 m g SC for a 4-kg cat) is administered. The hydralazine dose can be repeated i f the systolic pressure has not decreased w i t h i n 15 to 30 minutes. If the cat is refractory to hydral azine, acepromazine (0.005 to 0.01 mg/kg I V ) has been used. It is important to note that the incidence o f hypertension and central nervous system ( C N S ) disorders is not seen w i t h equal frequency among transplant centers, and thus the cause of C N S disorders i n cats following renal transplanta tion still remains a challenge for some clinicians. 11
8
Complications can also arise i f postoperative hypotension occurs. At our facility, systolic b l o o d pressure is maintained at 100 m m H g or greater. Sustained hypotension can lead to poor graft perfusion and needs to be managed aggres sively to prevent acute tubular necrosis and delayed graft function. If surgery is technically successful, azotemia typically resolves w i t h i n the first 24 to 72 hours following surgery. If improvement does not occur during this time or i f improvement i n renal function is initially identified but then worsens, an ultrasonographic examination o f the allograft is recommended. The allograft should be evaluated for adequate b l o o d flow, as well as any signs o f a ureteral obstruction including hydronephrosis or hydroureter. If subsequent ultrasonographic evaluations reveal worsening hydronephrosis, then a ureteral obstruction should be sus pected. The cat is taken back to surgery so that the allograft can be evaluated. In some cases, the ureter may need to be reimplanted into the urinary bladder. If graft perfusion is adequate and no signs o f obstruction are present, then delayed graft function should be considered. Cats without complications are discharged from the hos pital when graft function appears adequate and the animal is clinically stable. Cats w i t h delayed graft function can also be discharged i f otherwise clinically stable. Improvement i n graft function often occurs w i t h i n the first few weeks following surgery. M e d i c a l management o f the renal failure can be continued i n this subset o f patients until graft function returns to normal. If the transplanted kidney fails to function, a biopsy should be performed on it before retransplantation.
LONG-TERM MANAGEMENT AND COMPLICATIONS
cell volume, total protein level, C s A level, and a urinalysis if a free-catch urine sample is available. A complete blood count and serum chemistry panel should be performed every 3 to 4 months and i f the cat has been diagnosed with under lying cardiac disease, an echocardiogram should be per formed every 6 to 12 months. If a feeding tube has been placed, it should be removed once oral intake of food and water is deemed appropriate. Renal complications following transplantation include renal rejection, calcium oxalate nephrosis, hemolytic uremic syndrome, and retroperitoneal fibrosis. Acute rejection can occur at any time but is most c o m m o n within the first 1 to 2 months following surgery. Cats that are experiencing a rejection episode may or may not have overt clinical signs that include polyuria and polydipsia, lethargy, depression, and anorexia. For this reason, weekly b l o o d sampling is essential during the early postoperative period. Histopatho logic as well as sonographic and scintigraphic examination o f allograft rejection i n cats has been described. ' 12
13
Sonographic examination often reveals a significant increase i n cross-sectional area of the allograft, a subjective increase i n echogenicity, and a decrease i n corticomedullary demarcation. A l t h o u g h normal allograft enlargement is expected during the first week postoperatively, a gradual decline should then occur. Rejection should be suspected if the renal enlargement persists or progresses beyond this period. If possible, before starting the rejection protocol, urine sediment should be evaluated to rule out an underlying infec tion. Suspected acute rejection episodes are managed with intravenous administration o f C s A (6.6 mg/kg q24h given over 4 to 6 hours) and prednisolone sodium succinate (Solu Delta Cortef, 10 mg/kg I V q l 2 h ) . Each milliliter of the CsA is diluted with 20 to 100 m l of either 0.9% sodium chloride or 5% dextrose. The infusion o f C s A can be repeated. 13
14
Another cause for the azotemia should be considered if the creatinine concentration does not improve within 24 to 48 hours. C h r o n i c rejection is characterized by gradual loss of organ function over months to years, often without evi dence o f a rejection episode. The cause of chronic rejection is unknown. Hemolytic uremic syndrome is a rare, but fatal, side effect of C s A therapy. Patients develop hemolytic ane mia, thrombocytopenia with rapid deterioration o f renal function secondary to glomerular and renal arteriolar plate let and fibrin t h r o m b i . In the author's experience, the mortality rate has been 100%. 15
Results o f a study suggest that renal transplantation is a treatment option for cats whose underlying cause o f renal failure is associated w i t h calcium oxalate urolithiasis. N o dif ference i n long-term outcome was found between a group of stone formers and a control group o f cats whose underlying cause o f renal failure was not related to urolithiasis. A d d i tionally, o f 19 stone formers, 5 cats formed calculi within the allograft between 4 and 22 months postoperatively. A l t h o u g h formation o f calculi i n the allograft d i d not signif icantly reduce survival, cautious interpretation of the data is necessary until more patients are evaluated. 16
Another cause o f recurrence o f azotemia within the first few months following surgery is retroperitoneal fibrosis. A b d o m i n a l ultrasonography i n these patients reveals hydro nephrosis with or without hydroureter, and occasionally a capsule can be identified surrounding the allograft. Surgery has been successful i n relieving the obstruction and restoring normal renal function. The exact cause is unclear. 17
Patients should be evaluated by their veterinarians once a week for the first 4 to 6 weeks initially, and then visits can be extended to monthly intervals depending o n the cat's sta bility. D u r i n g each examination, the cat should be weighed and b l o o d work performed including a renal panel, packed
Finally, complications may occur secondary to long-term immunosuppressive therapy. These have included chronic urinary tract infections and pyelonephritis, fungal infections, mycobacterial infections, toxoplasmosis, diabetes, and neo plasia. Bacterial urinary tract infections i n the transplant patient cause direct m o r b i d i t y and mortality due to the infection itself, and may also activate the rejection process. Treatment often includes long-term antibiotic therapy based on cultures and sensitivity. Two cats developed fatal myco bacterial infections following long-term immunosuppressive therapy; one cat had systemic involvement and the other a septic arthritis ( L R A r o n s o n , personal communication, 2005). Five cats died following a reactivation o f a latent toxoplasmosis infection post transplantation. Attempts to treat systemic mycobacterial and toxoplasma infections i n feline renal transplant recipients have resulted i n poor out comes. The prevalence o f malignant neoplasia i n cats fol lowing renal transplantation has been reported from 9.5% to 14%, with l y m p h o m a being the most c o m m o n type reported. Treatment with chemotherapy has also resulted in poor outcomes. Patients that have developed diabetes fol lowing long-term C s A and steroid therapy have responded successfully to decreasing the dosage o f the steroids or the CsA, or both. Some patients require insulin therapy. 19
CONCLUSION Renal transplantation offers a unique method of manage ment of renal failure i n cats. Approximately 90% to 9 5 % of cats recover sufficiently and w i l l go home following renal
transplantation, and approximately 70% o f the cases are alive and continuing to do well 1 year after transplant. O w n ers need to understand the risks involved with the procedure and that it demands a commitment for the life o f the animal.
SUGGESTED FURTHER R E A D I N G * Adin C A , Gregory CR, Kyles A E , et al: Diagnostic predictors and survival after renal transplantation in cats, Vet Surg 30:515, 2001. An article that provides information regarding preoperative diagnostic results that predict postoperative complications and survival in the feline renal transplant recipient. Aronson LR, Kyles A E , Preston A , et al: Renal transplantation in cats diag nosed with calcium oxalate urolithiasis: 19 cases (1997-2004), J Am Vet Med Assoc 228:743, 2006. A paper that describes the outcome of 19 cats that had a renal transplant per formed because of renal failure secondary to calcium oxalate urolithiasis. Gregory CR, Bernsteen L: Organ transplantation in clinical veterinary prac tice. In Slatter D H , editor: Textbook of small animal surgery, Philadelphia, 2000, Saunders. A chapter that provides an excellent overview to renal transplantation in the dog and cat. Katayama M , McAnulty JF: Renal transplantation in cats: techniques, com plications, and immunosuppression, Compendium 24:874, 2002. An article that contains information regarding surgical technique including hypothermic storage, short-term and long-term complications, and techni ques for immunosuppression used at the University of Wisconsin, Madison. Mathews K G : Renal transplantation in the management of chronic renal fail ure. Consultation in feline internal medicine, ed 4, Philadelphia, 2001, Saunders. An excellent overview of renal transplantation
in the cat.
*See the C D - R O M for a complete list of references.
Part XV TRAUMA Chapter 152 TRAUMATIC BRAIN INJURY Chapter 153 THORACIC TRAUMA Chapter 154 ABDOMINAL TRAUMA Chapter 155 ABDOMINOCENTESIS Chapter 156 DIAGNOSTIC PERITONEAL LAVAGE Chapter 157 WOUND MANAGEMENT Chapter 158 THERMAL BURN INJURY Chapter 159 ELECTRICAL AND LIGHTNING INJURIES Chapter 160 MASSIVE TRANSFUSION
Chapter 152 TRAUMATIC BRAIN INJURY Daniel J. Fletcher,
D V M , PhD, DACVECC •
Rebecca S. Syring,
KEY POINTS • Identification and management of extracranial disorders, such as systemic hypotension, hypoxemia, and hypoventilation, should be the first priority when treating a patient with acute traumatic brain injury (TBI). • Mannitol is effective in treating intracranial hypertension, but it can compromise cerebral perfusion if its osmotic diuretic effects are not ameliorated rapidly with intravascular volume replacement. • Hypertonic saline (7% to 8%) is effective in treating intracranial hypertension and is less likely to lead to hypovolemia and decreased cerebral perfusion. • Corticosteriods are not recommended for the treatment of TBI. • Prognosis varies, but even patients with severe neurologic deficits can recover with aggressive supportive care.
INTRODUCTION Incidence and Prevalence of Head Injury Traumatic injuries (TBIs) are c o m m o n i n dogs and cats, w i t h m o t o r vehicle accidents, animal interactions, and u n k n o w n etiologies being the most c o m m o n causes seen i n a multicenter study o f 1099 dogs and 191 cats. In that study, 26% o f dogs and 4 2 % o f cats had evidence o f head injury. Other c o m m o n causes o f head injury i n dogs and cats include falls from heights, blunt trauma, gunshot wounds, and other malicious h u m a n activity. The overall prevalence and incidence o f head injury i n veterinary medicine has not been well studied, but a retrospective study from a large, urban veterinary hospital reported an average of 145 cases of confirmed T B I per year from 1997 to 1999.
DVM, DACVECC
Box 152-1 Most Common Factors Leading to Secondary Brain Injury • • • • • • • •
Excitotoxicity Ischemia Inflammation ATP depletion Production of reactive oxygen species Accumulation of intracellular sodium and calcium Nitric oxide accumulation Cerebral lactic acidosis
ATP, Adenosine triphosphate.
injury. P r i m a r y injury occurs as an immediate result of the traumatic event. Secondary injury occurs during the hours to days after trauma and is caused by a complex series of bio chemical events, including release of inflammatory mediators and excitatory neurotransmitters, and changes i n cellular membrane permeability.
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General Approach to the Patient With a Head Injury
Primary Injury The least severe p r i m a r y brain injury is concussion, character ized by a brief loss o f consciousness. Concussion is not asso ciated w i t h any underlying histopathologic lesion. Brain contusion consists o f parenchymal hemorrhage and edema. C l i n i c a l signs can range from m i l d to severe. Contusions can occur i n the brain directly under the site of impact ("coup" lesions), or i n the opposite hemisphere ("contrecoup" lesions), or both, as a result o f displacement of the brain w i t h i n the skull. A l t h o u g h m i l d contusion can be difficult to differentiate from concussion, unconsciousness for more than several minutes is most consistent with contusion. 4
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W h e n treating a patient w i t h an acute head injury, both extra cranial and intracranial priorities must be acknowledged and evaluated. Identification o f life-threatening extracranial inju ries such as hemorrhage, penetrating thoracic or abdominal wounds, airway obstruction, and compromise o f oxygenation, ventilation, or volume status is o f paramount importance. Once life-threatening extracranial factors have been identified, intracranial priorities should include maintenance o f adequate cerebral perfusion pressure ( C P P ) , ensuring adequate oxygen delivery to the brain, and treatment of acute intracranial hyper tension, as well as continued monitoring o f neurologic status.
Laceration is the most severe o f p r i m a r y brain injury and is characterized by physical disruption of the brain paren chyma. A x i a l hematomas w i t h i n the brain parenchyma and extraaxial hematomas i n the subarachnoid, subdural, and epidural spaces can occur, causing compression o f the brain and leading to severe localizing signs or diffuse neurologic dysfunction. The literature suggests that extraaxial hemor rhage is rare i n dogs and cats after head injury; however, there is m o u n t i n g evidence that this type of hemorrhage occurs in up to 10% o f animals w i t h m i l d head injury and more than 80% o f dogs and cats w i t h severe head injury. '
PATHOPHYSIOLOGY
Secondary Injury
The underlying injuries that result from head trauma can be separated into two categories: p r i m a r y injury and secondary
T B I triggers a series o f biochemical events that ultimately result i n neuronal cell death. Box 152-1 is a list of the most c o m m o n types o f secondary injury. These secondary injuries
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are caused by a combination o f intracranial and systemic insults that occurs i n both independent and interrelated ways. Systemic insults that contribute to secondary brain injury include hypotension, hypoxia, systemic inflammation, hyper glycemia, hypoglycemia, hypercapnia, hypocapnia, hyper thermia, electrolyte imbalances, and acid-base disturbances. Intracranial insults include increased intracranial pressure (ICP), compromise o f the blood-brain barrier, mass lesions, cerebral edema, infection, vasospasm, and seizures. A l l o f these factors ultimately lead to neuronal cell death. 7
Immediately after injury, there is massive release o f excit atory neurotransmitters that causes influx o f s o d i u m and calcium into neurons, resulting i n depolarization and further release of excitatory neurotransmitters. Increased influx o f calcium overwhelms mechanisms for removal, causing severe intracellular damage and ultimately neuronal cell death. Excessive metabolic activity also results i n depletion o f aden osine triphosphate (ATP) stores.
Table 152-1 Interpretation of Pupil Size and Pupillary Light Response in Head Trauma Pupil Size
Response to Light
Level of Lesion
Prognosis
Midposition
Normal
—
Good
Bilateral miosis
Poor to none
Cannot localize
Variable
Unilateral mydriasis
Poor to none
Cranial nerve III
Guarded to poor
Unilateral mydriasis and ventrolateral strabismus
Poor to none
Midbrain
Guarded to poor
Midposition
None
Pons, medulla
Poor to grave
Bilateral mydriasis
Poor to none
—
Poor to grave
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Several factors favor the production o f reactive oxygen spe cies after TBI, including hypoperfusion and local tissue acidosis. Hemorrhage provides a source o f iron, which favors the pro duction of hydroxyl radicals. Catecholamines may also contrib ute to the production o f free radicals by direct and indirect mechanisms. These reactive oxygen species then oxidize lipids, proteins, and deoxyribonucleic acid ( D N A ) , resulting i n further destruction o f neurons. Because the brain provides a lipid-rich environment, it is particularly susceptible to oxidative injury. Nitric oxide has been associated w i t h perpetuation o f sec ondary brain injury after trauma, most likely due to its vasodilatory effects and its participation i n free radical reactions, but the exact mechanism is not well understood. TBI is associated w i t h production o f inflammatory me diators. These mediators perpetuate secondary brain injury via a number of mechanisms, including inducing nitric oxide production, triggering influx o f inflammatory cells, activating the arachidonic acid and coagulation cascade, and disrupting the blood-brain barrier. Because studies have shown both neuroprotective and neurotoxic effects o f inflammation, research is focusing o n the development o f targeted antiinflammatory agents that preferentially affect the more acute, destructive inflammatory processes. 8
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rise i n M A P and reflex decrease i n heart rate (see Chapter 100, Intracranial Hypertension). The central nervous system ( C N S ) ischemic response i n a patient w i t h head trauma is a sign o f a potentially life-threatening increase i n I C P and should be treated promptly.
NEUROLOGIC ASSESSMENT Initial neurologic examination should focus o n the level o f consciousness, posture, and p u p i l size and response to light (Table 152-1). A more detailed neurologic examination can be performed once stabilizing therapy has been instituted. Based o n findings from this examination, a score can be assigned to grade the severity o f injury (see Chapter 97, C o m a Scales). The initial neurologic examination should be interpreted i n light o f the cardiovascular and respiratory system because shock can have a significant effect on neuro logic status, reducing the patient's level o f consciousness and pupillary responses.
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Primary and secondary intracranial injuries, i n combination with systemic effects of the trauma, ultimately result i n worsen ing of cerebral injury as a result o f a compromised C P P , the force driving blood into the calvarium and providing the brain with essential oxygen and nutrients. C P P is defined as the dif ference between mean arterial b l o o d pressure ( M A P ) and ICP. Blood flow to the brain per unit time, or cerebral b l o o d flow (CBF), is a function of C P P and cerebrovascular resis tance. The n o r m a l brain is capable o f maintaining a constant C B F over a wide range o f M A P (50 to 150 m m H g ) via autoregulatory mechanisms. However, the traumatized brain often loses m u c h of this autoregulatory capacity, making it suscepti ble to ischemic injury w i t h even small decreases i n M A P . The following equation summarizes the " M o n r o - K e l l i e Doctrine," developed i n the early nineteenth century to describe intracranial dynamics: ^intracranial
=
Vbrain
+ VcSF + Vblood + Vmass lesion where V = volume. Sudden increases i n any o f these volumes as a result o f primary and secondary brain injuries can lead to dramatic increases i n ICP. Initially, increases i n I C P w i l l trigger the Cushing reflex, or central nervous system ischemic response, a characteristic
DIAGNOSTIC TESTS AND MONITORING Because o f the likelihood o f multisystemic injury associated w i t h head trauma, initial diagnostic tests and patient m o n i toring should focus u p o n a global assessment o f patient sta bility. Emergency b l o o d screening should consist o f a packed cell volume and total solids determination to assess for hem orrhage, b l o o d glucose to assess the severity o f injury, and a b l o o d gas (venous or arterial) to assess ventilation, perfusion, and acid-base status. W h e n available, electrolyte, lactate, and renal values, and markers o f hepatic damage should also be obtained before therapy is instituted. Serial m o n i t o r ing o f these values is essential because dramatic changes can occur w i t h therapy. Jugular venipuncture should be avoided because occlusion o f the jugular vein can result i n marked increases i n I C P as a result o f decreased venous outflow from the brain. 3
Diligent m o n i t o r i n g o f the cardiovascular and respiratory systems is imperative to m i n i m i z e the risk o f secondary brain injury. For each episode o f hypoxemia or hypotension, the prognosis for neurologic recovery dramatically decreases i n h u m a n patients w i t h T B I . Basic m o n i t o r i n g o f the 1 0
cardiovascular system focuses o n maintenance of adequate tis sue perfusion (pink mucous membranes, capillary refill time of 1 to 2 seconds, good peripheral pulse quality, and a n o r m a l heart rate). In addition, systemic b l o o d pressure should be monitored routinely. M A P should be maintained at or above 80 m m H g i n order to maintain C P P . B l o o d pressure as measured w i t h the Doppler technique should be maintained above 100 m m H g because this value is thought to represent the systolic b l o o d pressure i n small animals. Heart rate should be assessed when hypertension ( M A P > 100 m m H g or systolic >120 m m H g ) is present. If evidence o f the central nervous system ischemic response is present, therapy directed toward lowering I C P should be instituted. Alternatively, hypertension associated with tachycardia suggests pain or anxiety, w h i c h should be treated. M o n i t o r i n g o f the respiratory system focuses on mainte nance o f oxygenation and ventilation. Oxygenation can be assessed via pulse oximetry, w i t h a goal o f maintaining satu ration above 94%. W h e n arterial sampling is possible, oxy gen tension should be maintained above 80 m m H g . If oxygenation cannot be monitored, oxygen should be supple mented. Failure to maintain oxygenation above these levels may warrant intubation and positive-pressure ventilation. Ventilation can be assessed by b l o o d gas analysis or end-tidal capnometry. A l t h o u g h arterial blood gas sampling is the gold standard for assessing carbon dioxide tension, a venous blood gas can be substituted i f tissue perfusion is normal. Venous car bon dioxide concentrations will exceed arterial by 2 to 5 m m H g ; however, this difference is exacerbated w i t h poor tissue perfu sion. E n d - t i d a l capnometry tends to underestimate arterial carbon dioxide tension by 5 m m H g , and changes i n cardiac output can significantly alter the values obtained. Radiographs o f the skull i n patients that have sustained head trauma are an insensitive diagnostic tool and rarely pro vide valuable information. C o m p u t e d tomography ( C T ) is the preferred imaging method. C T scans are superior to magnetic resonance imaging ( M R I ) for assessing bone and areas o f acute hemorrhage or edema. A s the time from injury increases, or when subtle neurologic deficits are present, M R I becomes a more useful t o o l . Advanced imaging provides information about mass lesions (epidural, subdural, or intraparenchymal hemorrhage) or depressed skull fractures that may require sur gical intervention. Such studies should be considered i n patients w i t h moderate to severe signs o n presentation, lateralizing signs, or failure to improve significantly w i t h i n the first few days or those w i t h an acute deterioration i n neurologic status. 11
TREATMENT W h e n formulating a treatment plan for a patient with TBI, both intracranial and extracranial concerns must be addressed. Extracranial priorities include ventilation, oxygenation, and maintenance of normal blood pressure, and intracranial priori ties include treatment o f intracranial hypertension and control of cerebral metabolic rate.
Extracranial Therapy The first priority i n treating a patient w i t h head trauma is extracranial stabilization. As w i t h any severely injured patient, the basics o f airway, breathing, and circulation should be eval uated and addressed i f necessary. Patency o f the airway should
be assessed as soon as possible and treated with endotracheal intubation or emergency tracheostomy, i f indicated. The pharynx and larynx should be inspected visually and suc tioned as needed to maintain airway patency. Hypoxia is also c o m m o n , and supplemental oxygen is indicated i n the initial treatment of all patients w i t h significant head injury. Increases i n the b l o o d C 0 concentration can lead to cerebral vasodila tion and increased intracranial b l o o d volume, worsening ICP (see Secondary Injury section). Conversely, hypocapnia due to hyperventilation can lead to cerebral vasoconstriction, decreasing cerebral b l o o d flow and leading to cerebral ische mia. Therefore C 0 should be maintained at the low end of the normal range i n patients with head trauma (e.g., venous C O 40 to 45 m m H g , arterial C 0 35 to 40 m m H g ) . In some patients, this w i l l require mechanical ventilation (see Chapter 213, Basic Mechanical Ventilation). 2
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z
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Patients with head trauma commonly present i n hypovole mic shock, and volume resuscitation goals should be aggressive ( M A P o f 80 to 100 m m H g , see Chapter 65, Shock Fluids and Fluid Challenge). For patients without electrolyte distur bances, normal saline (0.9%) is the best inital choice for fluid resuscitation because it contains the smallest amount of free water (sodium concentration 154 mEq/L) o f the isotonic fluids and is therefore least likely to contribute to cerebral edema. C o l l o i d resuscitation may also prove beneficial. For hydrated patients with evidence o f hypovolemia and increased ICP, a combination colloid and hyperosmotic (hypertonic saline) solution is recommended (see Intracranial Therapy later i n this chapter and Table 152-2). Patients that do not respond to volume resuscitation require vasopressor support (see Chapter 176, Vasoactive Catecholamines).
Intracranial Therapy Hyperosmotic Agents M a n n i t o l has been shown to decrease ICP, increase C P P and CBF, and have a beneficial effect on neurologic outcome i n patients with head i n j u r y . M a n n i t o l may also possess free radical scavenging properties. Its positive effects can be seen clinically w i t h i n minutes o f administration, most likely a result o f its rheologic its effects (decreased b l o o d viscosity) causing an increase i n C B F and cerebral oxygen delivery. W i t h i n 15 to 30 minutes, its osmotic effects predominate, drawing water out o f the brain parenchyma (primarily n o r m a l tissue) and into the intravascular space. These effects can last from 1.5 to 6 hours. In humans, mannitol may induce acute renal failure i f serum osmolarity exceeds 320 m O s m / L , suggesting that serial measurement o f serum osmolality may be useful i n patients receiving repeated doses. M a n n i t o l may cause increased permeability of the blood-brain barrier, allowing it to leak into the brain paren chyma where it can exacerbate edema. Because this effect is most pronounced when mannitol remains i n the circulation for long periods, the drug should be administered as repeated boluses rather than as a constant rate i n f u s i o n . M a n n i t o l boluses o f 0.5 to 1.5 g/kg have been recommended for the treatment o f I C P i n dogs and cats. High-dose man nitol therapy (1.4 g/kg) resulted i n significiant neurologic improvement compared to low-dose therapy (0.7 g/kg) in 44 people with head i n j u r y . Treatment must be followed w i t h isotonic crystalloid solutions or colloids, or both, to maintain intravascular volume. 13
14
13
15
16
Hypertonic saline is an alternative hyperosmotic solution that may have advantages over mannitol i n some patients
Table 152-2
Drugs, Fluids, and Dosages for the Treatment of Patients With Head Trauma
Indication
Drug or Fluid
Dosage
Notes
Any patient with evidence of head trauma and hypotension
Isotonic crystalloid solution (0.9% saline preferred)
Administer boluses of one fourth to one third of the shock dose (shock dose = 90 ml/kg for the dog, 60 ml/kg for the cat)
May repeat as needed Consider colloid boluses if no response after 2 to 3 crystalloid boluses
Increased ICP in normotensive or hypertensive patients
Mannitol 25%
0.5 to1.5 g/kg IV over 15 minutes May repeat
Use filter during administration; can lead to severe dehydration; follow with isotonic crystalloids to prevent dehydration and hypovolemia Closely monitor intake and output
Increased ICP in hypovolemic or hypotensive patients
HTS (7%)* plus dextran-70 or hydroxyethyl starch
3 to 5 ml/kg IV over 15 minutes May repeat
Do not use in hyponatremic patients Monitor serum sodium levels
Increased ICP, normotensive, hypertensive, or hypotensive patients
HTS (7% to 7.8%)+
3 to 5 ml/kg IV over 15 minutes May repeat
Do not use in hyponatremic patients Monitor serum sodium levels
HTS, Hypertonic saline; ICP, intracranial pressure; IV, intravenous. *lf using 23.4% HTS, dilute 1 part HTS with 2 parts sterile water or normal saline. tlf using 23.4% HTS, dilute 1 part HTS with 2 parts dextran-70 or hydroxyethyl starch. If using 7% to 7.5% HTS, administer separate doses of HTS and colloid (3 to 5 ml/kg HTS, 2 to 3 ml/kg artificial colloid). with head injury. Because s o d i u m does not freely cross the blood-brain barrier, hypertonic saline has similar rheologic and osmotic effects to mannitol. In addition, it improves hemodynamic status and has beneficial vasoregulatory and i m m u n o m o d u l a t o r y effects. Because s o d i u m is reabsorbed in the kidneys, hypotension is a less likely sequela than with mannitol, making it a better choice for patients with increased I C P and systemic hypotension. Hypertonic saline can be administered w i t h a colloid i n such cases to allow for a more prolonged volume expansion effect (see Table 152-2). 17
Corticosteroid Corticosteroids are potent antiinflammatory agents and have historically been used extensively i n h u m a n and veterinary medicine to treat patients that have sustained head trauma. A clinical trial evaluating over 10,000 h u m a n adults w i t h head injury showed that corticosteroid treatment was asso ciated with worse outcomes at 2 weeks and 6 months after i n j u r y . ' The Brain Trauma Foundation recommends that corticosteriods not be administered to patients w i t h T B I . 18
19
1 3
Furosemide Furosemide has been used i n patients w i t h head trauma either as a sole agent to reduce cerebral edema or i n c o m b i nation w i t h mannitol to decrease the initial increase i n intra vascular volume and hydrostatic pressure associated w i t h the drug. However, the use o f this drug as a sole agent i n patients w i t h head trauma has been called into question because of the potential for intravascular volume depletion and systemic hypotension, leading to decreased C P P . The Brain Trauma Foundation guidelines do not recommend that furosemide be used i n combination w i t h m a n n i t o l . Therefore it should be reserved for those patients i n w h o m it is indicated for reasons other than cerebral edema, such as those with pulmonary edema or oligoanuric renal failure.
degrees reduces C B V by increasing venous drainage, decreas ing ICP, and increasing C P P without deleterious changes i n cerebral oxygenation. A slant board should be used instead of pillows or towels to prevent occlusion o f the jugular veins by bending o f the neck. Higher elevations o f the head may cause a detrimental decrease i n C P P . 21
Prevention o f hypoventilation, as described above, can reduce cerebral vasodilation and decrease C B V . The goal should be nor mocapnia (arterial carbon dioxide of 35 to 40 m m H g ) . In cases of acute intracranial hypertension, short-term hyperventilation to an arterial carbon dioxide o f 25 to 35 m m H g may be used to reduce C B V and ICP, but long-term hyperventilation is not recommended because o f evidence that the decrease i n C B F leads to cerebral ischemia and worsens o u t c o m e . 13
Decreasing Cerebral Metabolic Rate Increased cerebral metabolic rate after head injury due to excitotoxicity and inflammation can lead to cerebral ische m i a and cellular swelling, increasing ICP. Interventions that decrease cerebral metabolic rate may lessen secondary brain injury. A l t h o u g h rarely used i n veterinary medicine, induc tion o f a barbiturate coma and therapeutic hypothermia have been used i n experimental studies and clinical trials i n humans and can be effective i n decreasing I C P and i m p r o v ing outcome i n patients w i t h refractory intracranial hyper t e n s i o n . The Brain Trauma Foundation states that there is insufficient evidence to publish treatment standards o n the use o f barbiturates, but this therapy may be considered i n patients w i t h elevated I C P that is refractory to medical and surgical therapy. 22
13
2 0
13
Decreasing Cerebral Blood Volume Techniques to decrease C B V have been proposed as methods for lowering increased ICP. Elevation o f the head by 15 to 30
PROGNOSIS The prognosis is difficult to predict following T B I . Although the initial neurologic status may be helpful i n predicting outcome, reassessment after stabilizing therapy is recommended because the level o f consciousness may improve once tissue perfusion has been corrected. Pupillary dilation, loss o f pupillary light responses, and deterioration i n the level o f consciousness
during therapy are poor prognostic indicators (see Table 152-1). It is likely that younger animals, particularly kittens, can make remarkable recoveries despite severe dysfunction immediately following trauma, although definitive research is lacking. O w n ers should be aware that animals who survive severe T B I may be left w i t h persistent neurologic deficits, which may take months to resolve or may never resolve. These animals can also develop delayed seizure disorders. The Small A n i m a l C o m a Scale was developed to quantita tively assess functional impact of brain injury (see Chapter 97, C o m a Scales). This scale assesses three major categories: motor activity, level of consciousness, and brain stem reflexes. Although this scale has not been validated prospectively i n ani mals, it has been shown retrospectively to correlate w i t h 48hour outcome i n dogs w i t h head t r a u m a . This may be most useful when evaluated serially i n patients to determine i f there has been improvement or deterioration following treatment. 23
In h u m a n medicine, hyperglycemia at admission and per sistence o f hyperglycemia have been associated w i t h worsened
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mortality and o u t c o m e . Hyperglycemia has been associated w i t h more severe injury i n head-injured veterinary patients but has not been validated as an independent predictor of outcome. 3
SUGGESTED FURTHER R E A D I N G *
Dewey C, Budsberg S, Oliver J, et al: Principles of head trauma management in dogs and cats. Part II, Comp Cant Educ Pract Vet 15:177, 1993. A useful overview of treatment strategies for dogs and cats with head tra Piatt SR, Radaelli ST, McDonnell JJ, et al: The prognostic value of the mod ified Glasgow Coma Scale in head trauma in dogs, ] Vet Intern Med 15:581, 2001. A retrospective study showing that modified Glasgow Coma Scale scor dicted 48-hour survival in dogs with TBI. Zink BJ: Traumatic brain injury, Emerg Med Clin North Am 14:115, 1996. A thorough description of the pathophysiology of TBI, with emphasis on chemical pathways. Also provides management guidelines. *See the CD-ROM for a complete list of references.
Chapter 153 THORACIC TRAUMA Kimberly Slensky, D V M , DACVECC
1
KEY POINTS • Thoracic injuries are common in any animal suffering from significant trauma. • Multiple thoracic injuries often coexist in an individual patient. • The diagnosis of thoracic trauma is typically made from the history, physical examination, and imaging techniques (e.g., thoracic radiographs). • Pulmonary contusions are the most common thoracic injury. Other injuries include pneumothorax, diaphragmatic hernia, and rib fractures. • Because of the structure and resilience of the chest wall, animals are able to sustain high forces to the thorax without demonstrating signs related to thoracic trauma. • Life-threatening injuries are uncommon; however, aggressive medical and surgical management may be necessary. • Mechanical ventilation may be warranted in cases of severe respiratory compromise, pain, or respiratory failure.
INTRODUCTION Injury to the respiratory system is c o m m o n i n any animal suffering from significant trauma. It has been estimated that 39% o f dogs that incur skeletal injuries due to m o t o r vehic ular accidents also sustain thoracic injury. O f those injuries, p u l m o n a r y contusions predominate. ' Over half o f the ani mals suffering from thoracic trauma have more than one 1
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thoracic injury. Therefore it is imperative that the myriad of potential thoracic injuries be identified rapidly and trea ted appropriately. Thoracic injuries may vary i n severity from those less likely to result i n significant morbidity and mortality to those that are life threatening and warrant immediate intervention. This chapter focuses o n the more c o m m o n thoracic injuries, including the pathophysiology and treatment o f these injuries.
PNEUMOTHORAX The pleural space is a potential space that is created by the opposing surfaces o f the parietal pleura and the visceral pleura (see Chapter 30, Pleural Space Disease). The normal pleural space is occupied by only a small amount of serous fluid that helps lubricate the surfaces of the pleurae. This space also maintains a resting negative intrathoracic pressure relative to the atmosphere. W h e n this negative intrapleural pressure is not maintained, there is disruption o f the normal expansive and relaxation properties o f the lung. A pneumo thorax is created when air accumulates w i t h i n the pleural space. A i r can be introduced into the pleural space via two mechanisms: alveolar rupture secondary to increased force applied to the chest w i t h a closed glottis or secondary to lac eration o f the p u l m o n a r y parenchyma. Progression of the pneumothorax w i l l depend o n several factors: the respiratory 3
pattern o f the patient, the size o f the defect, and whether the defect is unidirectional, prohibiting the escape o f air from the pleural space. A i r i n the pleural space can lead to partial or complete lung atelectasis and disturbances i n pulmonary and car diac hemodynamics. Ventilation-to-perfusion mismatch is a result of instantaneous lung collapse and results i n a decreased arterial partial pressure o f oxygen. M i n u t e ventila tion is maintained by an increased respiratory rate that c o m pensates for decreased tidal v o l u m e . However, i f there is severe atelectasis from increased air i n the pleural space, hypoxemia develops rapidly and overwhelms compensatory mechanisms. For example, a tension pneumothorax develops when the intrathoracic pressure exceeds the atmospheric pressure. This causes a decrease i n venous return and can cause complete respiratory and hemodynamic collapse. If pleural pressure exceeds central venous and p u l m o n a r y artery pressures, there is decreased venous return to the heart. Tachycardia results i n an effort to maintain cardiac output. Systemic hypotension results when the myocardial oxygen demand is higher than delivery, thus further decreas ing cardiac output. These patients often present with c l i n i cal signs o f shock, similar to that witnessed w i t h cardiac tamponade, because atrial diastolic filling is compromised by decreased venous return to the heart from the increased intrapleural pressure.
placed to create a closed pneumothorax. The dressing should be secured only o n three sides to allow for air escape from the pleural space without risk o f developing a tension pneumo thorax. Alternatively, a full occlusive dressing can be placed and secured on all four sides i f a thoracostomy tube is inserted. O p e n chest wounds w i l l require surgical exploration once the patient has been stabilized. Treatment decisions should be based o n the respiratory and cardiovascular status o f the patient. In an otherwise stable patient, repeated monitoring (physical parameters, pulse oximetry, and arterial b l o o d gases) can take the place o f immediate evacuation o f the pleural space.
A pneumothorax may be open or closed. A n open pneu mothorax occurs when the pleural space communicates directly with the atmosphere. In this situation, the unaf fected lung is not ventilated normally and there is a paradox ical decrease i n pulmonary volume w i t h inspiration and an increase on exhalation. A sucking chest wound is present i f air is heard moving i n and out o f the pleural space with respirations. W i t h a closed pneumothorax, air is contained within the pleural space. This may be accompanied by other signs o f thoracic trauma (e.g., rib fractures) and may be a result of damage to the larger nonconducting airways (tra chea and bronchi), other mediastinal structures (esophagus), or the pulmonary parenchyma itself (most c o m m o n ) . '
P u l m o n a r y contusions are the most c o m m o n type o f injury following blunt thoracic trauma (see Chapter 25, P u l m o n a r y Contusions and Hemorrhage). The most frequent cause i n h u m a n medicine is motor vehicle accidents; other possible causes include falls and penetrating chest trauma. In veteri nary medicine, 17% o f animals have evidence o f pulmonary contusions after a motor vehicle accident. P u l m o n a r y con tusions rarely exist as an isolated injury and are often found i n association with other thoracic injuries (e.g., rib fractures, pneumothorax, hemothorax, diaphragmatic hernia) (see Chapter 25, P u l m o n a r y Contusions and Hemorrhage).
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3
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According to one study, the prognosis for patients with pneumothorax may depend o n the need for thoracocentesis and the length of the intensive care unit stay. Animals that required repeated thoracocenteses or had shorter hospitaliza tions were more likely to be euthanized i n one study. Animals that present dyspneic also tended to have a poorer prognosis. Overall, the prognosis for animals with a traumatic pneumo thorax is good, with an 87% survival rate reported. However, animals may succumb to other serious concurrent injuries. 6
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PULMONARY CONTUSIONS
3
3
3
3
7
3
8
7
4
Diagnosis is made most commonly with thoracic radio graphs, although a high clinical suspicion should exist based on physical examination alone. D u l l dorsal breath sounds and hyperresonance on percussion o f the affected lung dorsally are hallmarks o f a pneumothorax. The best radiographic view is a ventrodorsal view. Radiography often reveals that a can cause retraction of the lungs from the body wall, elevation of the heart off the sternum, and atelectasis i n patients with a pneumotho rax. A diagnosis of tension pneumothorax is often suspected in patients that are air hungry, tachycardic, tachypneic, and cyanotic. In this case, immediate therapy is vital, and waiting for a thoracic radiograph may prove fatal. 5
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The goal o f treatment for pneumothorax is reexpansion o f the collapsed lung. This may be accomplished by thoraco centesis or tube thoracostomy i f the volume o f air is such that negative pressure cannot be established w i t h i n the pleural space or i f repeated thoracocenteses are required (see Chap ters 31 and 32, Thoracentesis and Thoracostomy Tube Place ment and Drainage, respectively). Intermittent or continuous pleural drainage w i l l be necessary following thoracostomy tube placement, depending o n the rate o f air accumulation. If an animal with a rapidly progressive pneumothorax pre sents, an immediate thoracotomy and intubation with posi tive-pressure ventilation may prove lifesaving. If an open pneumothorax is present, an occlusive dressing should be
RIB FRACTURES R i b fractures may occur secondary to any thoracic trauma and are the most c o m m o n type o f thoracic injury i n h u m a n patients. R i b fractures rarely occur i n isolation and often occur i n conjunction with p u l m o n a r y contusions or pleural space disease. They may be evident o n initial physical exam ination i f a flail segment or open fracture is present. H o w ever, a majority o f rib fractures are most readily diagnosed w i t h thoracic radiographs. It seems that the ribs can sustain forces greater than other long bones before a fracture occurs. H u m a n cadaver studies indicate that the thorax can tolerate a 20% volume reduction before rib fractures occur. H o w ever, underlying lung tissue can sustain significant injury as a result o f the concussive forces o f the traumatic event. 3
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Rib fractures may cause hypoxemia indirectly by leading to lung injury; therefore oxygen supplementation is warranted. Rib fractures may also lead to hypoventilation as a result o f pain. Pain management is o f utmost importance and may con sist of local or systemic use of analgesics. Local anesthetic agents (i.e., lidocaine and/or bupivacaine) are useful because they do not inhibit ventilation. Local blocks should be administered to the caudal surface o f the fractured rib(s), both dorsally and ventrally to enhance efficacy. Systemic analgesia should be used cautiously to prevent respiratory depression. 5
FLAIL CHEST Flail chest is a relatively u n c o m m o n condition i n veterinary patients, but occurs most c o m m o n l y secondary to dog-bite trauma and motor vehicle trauma. Flail chest occurs sec ondary to the fracture o f two or more adjacent rib segments, both dorsally and ventrally. This segmental chest wall injury can lead to thoracic instability and paradoxical chest wall m o t i o n . ' Intrathoracic injuries affect respiratory function more than the rib fractures themselves. 9
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P u l m o n a r y contusions have the greatest effect o n oxyge nation and ventilation, but hemothorax or pneumothorax and pain w i l l also affect p u l m o n a r y mechanics. Patients usually present tachypneic or dyspneic, w i t h paradoxical m o t i o n o f the chest wall flail segment (see following para graph). In most patients, the diagnosis is confirmed with thoracic radiography. Radiographs often reveal the flail seg ment and also highlight any concurrent injuries (pulmonary contusions or pleural space disease). 3
The flail component moves paradoxically i n relation to the rest o f the thorax. The flail segment moves inward w i t h inspiration as a result of the negative intrathoracic pressure and outward w i t h exhalation. The flail segment has been shown to cause a small reduction i n the arterial partial pressure o f oxygen, although this does not appear to be sig nificant i n experimental studies. In humans, the incidence of concomitant injuries, such as p u l m o n a r y contusions and a pneumothorax, are 50% and 77%, respectively. In ani mals, the likelihood o f p u l m o n a r y contusions secondary to flail chest is estimated to be between 7 5 % to 1 0 0 % . These injuries, i n combination w i t h pain, contribute the most to the hypoxemia and hypoventilation that occur i n patients with flail segments. 10
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Treatment o f the underlying intrathoracic injuries depends on the severity o f the injuries. H y p o x e m i a secondary to p u l monary contusions may require oxygen supplementation, and mechanical ventilation may be necessary for patients i n respiratory failure (see Chapters 19 and 213, Oxygen Therapy and Basic Mechanical Ventilation, respectively). Pneumotho rax may warrant thoracocentesis, placement o f a chest tube, or an emergency thoracotomy. Hemothorax is usually selflimiting and related to the initial t r a u m a , but may require surgical exploration i f continued hemorrhage is suspected. A l t h o u g h rare, cases o f cardiac rupture or aortic or great ves sel laceration have been reported. Stabilization o f the flail segment is often not necessary, but it should be considered if there is evidence of an open pneumothorax, continued hemothorax, or other evidence o f continued trauma to the underlying tissues, and/or an exploratory thoracotomy is otherwise warranted. Additionally, patients that require mechanical ventilation as a result o f severe intrathoracic inju ries and respiratory failure may benefit from stabilization o f the flail segment. 10
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ventilation centrally. The fractured ribs should be injected both dorsal and ventral to the fracture on the caudal surface of the rib. O n e rib caudal and cranial to the segment should also be included i n the nerve block. Bupivacaine or lidocaine, or both, can be administered every 6 hours as needed. Epidural analgesia has shown improved benefit over patientcontrolled analgesia i n human medicine and may be under utilized i n veterinary patients. Because o f the potential for hypotension, cardiovascular stability is a prerequisite to epidural analgesia. Systemic analgesia with opioids is also effec tive, but they should be employed cautiously to minimize respi ratory depression. Placing the animal i n lateral recumbency with the flail segment down or a light external chest wrap may prevent excessive outward movement of the segment. 3
HEMOTHORAX Hemothorax occurs when blood collects i n the pleural space. Hemothorax may result from injury to the lung paren chyma, chest wall and associated vessels, or great vessels. Gener ally, animals with severe injuries to the great vessels causing massive hemothorax do not survive long enough for a diagnosis to be made. The clinical picture may be similar to that of patients with a pneumothorax and includes rapid, shallow respirations. However, the pleural space can accommodate large volumes o f blood (50 to 60 ml/kg) without causing outward signs of respiratory compromise. These patients may have dull heart and lung sounds ventrally and may be i n shock sec ondary to hemorrhage. 5
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The diagnosis o f hemothorax is made by thoracocentesis. Nonclotting b l o o d within the pleural space confirms the diagnosis. Radiographs and thoracic ultrasound may be helpful i n determining relative quantities of pleural effusion and for m o n i t o r i n g purposes. However, clinical signs should determine treatment. B l o o d does not have to be removed from the pleural space unless it is causing respiratory com promise. Medical treatment for hypovolemic shock should consist o f a combination o f crystalloids, colloids, and/or b l o o d products as indicated, including autotransfusion if necessary (see Chapters 65 and 66, Shock Fluids and Fluid Challenge and Transfusion Medicine, respectively). Signifi cant hemorrhage may dictate volume replacement with packed red b l o o d cells or whole blood, and ongoing hemor rhage indicates the need for exploratory thoracotomy.
PENETRATING CHEST WOUNDS
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Treatment is most dependent o n assessment o f p u l m o n a r y function. Pain management should be considered early, because pain impairs n o r m a l chest wall movement and ventilation (see Chapters 161 and 164, Pain and Sedation Assessment and Analgesia and Constant Rate Infusions, respectively). Pain contributes not only to hypoventilation, but also to atelectasis and a decreased cough reflex, allowing the accumulation o f p u l m o n a r y secretions. The latter increases the likelihood for pneumonia. As with single rib fractures, local anesthetics provide analgesia without affecting 9
Chest wounds occur most commonly secondary to bite wounds, accounting for approximately 30% of all chest injuries i n small animals. Bite wounds to the upper airway, trachea, or chest wall can cause severe respiratory distress. Patients with upper airway compromise may require endotracheal intubation with positive-pressure ventilation i f the trauma precludes ade quate respiratory function. If the larynx cannot be visualized or the degree o f upper airway trauma is such that endotracheal intubation is not possible, a tracheostomy may be necessary (see Chapter 18, Tracheostomy). 12
Penetrating thoracic bite wounds may cause a pneumo thorax or hemothorax or may damage the lung parenchyma, resulting i n p u l m o n a r y contusions. Thoracic radiographs are helpful i n determining i f a bite w o u n d has penetrated the
thorax but should be reserved for stable patients. Dyspneic patients will require supplemental oxygen and/or evacuation of the pleural space via thoracocentesis, placement o f a thor acostomy tube, or thoracotomy, i f necessary. Wounds may be sealed temporarily with a water-soluble gel and then cov ered with a sterile bandage until surgical exploration and repair is possible. Because o f the high likelihood for bacterial contamina tion o f these wounds, all animals should be placed o n broad-spectrum antibiotics and a culture and sensitivity per formed. According to a recent study, the most likely con taminants are Staphylococcus spp, Escherichia coli, and other coliform bacteria. The prognosis for bite wounds depends on the associated injuries. It has been estimated that 6% to 25% o f patients with thoracic bite wounds die or are euthanized. ' 13
These patients may present i n respiratory distress several days post trauma as a result o f a p n e u m o t h o r a x . Clinical signs, when present, most often consist o f tachypnea, dys pnea, and coughing. If subcutaneous emphysema is present, tracheal trauma should be suspected. Thoracic radiographs may show a pneumomediastinum, pneumothorax, or evi dence o f tracheal discontinuity (bulging o f the peritracheal or mediastinal tissues surrounding the site o f rupture). Bronchoscopy is still considered the gold standard for the diagnosis and is often necessary before surgical correction is possible. 517
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HIGH-RISE SYNDROME The injuries o f high-rise syndrome are a result o f decelera tion t r a u m a . The extent o f injury is thought to increase up to seven stories, a point just beyond terminal velocity i n cats. A t the time terminal velocity is reached, the vestib ular system is no longer stimulated and the cat's body takes on a more horizontal position. This enables it to distribute the impact over a wider surface area and helps to m i n i m i z e 18
GUNSHOT WOUNDS
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In veterinary medicine, the most c o m m o n projectile injury is related to gunshot w o u n d s . In a retrospective study, 26% of the wounds associated with gunshots involved the tho rax. Injuries occur secondary to laceration or crushing o f tissues and can result i n extensive trauma to adjacent tissues, as well as those i n the direct path o f the bullet. However, the lung tends to be somewhat resilient because o f its elasticity, limiting the amount of tissue destruction. Penetration o f the thorax can cause damage to the great vessels and result in severe and massive hemorrhage. Animals may present with a hemothorax or pneumothorax. 15
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These patients w i l l be tachypneic or dyspneic and may require evacuation of the pleural space via thoracocentesis, tube thoracostomy, or thoracotomy (tension pneumotho rax). Blood products may be the initial fluid o f choice for volume resuscitation i f significant b l o o d loss has occurred (see Chapter 66, Transfusion Medicine). Bleeding tends to occur from the pulmonary arterial system, a low-pressure system, and often responds to management w i t h tube thora costomy. Although surgical exploration o f the thorax is not recommended routinely, it may be necessary i n animals w i t h continued hemorrhage or air leaks or i f the esophagus or other vital structures are d a m a g e d . ' 16
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TRACHEOBRONCHIAL INJURY Although u n c o m m o n , injury to the trachea or other n o n conducting airways can be lethal. It has been shown i n human studies that most patients suffering from tracheo bronchial injury die before arriving at a hospital. Also con sidered u n c o m m o n i n veterinary medicine, most o f the literature focuses o n tracheal rupture i n cats secondary to endotracheal intubation. Traumatic injury may be the result of traction at the carina during thoracic compression, caus ing stretching and tearing o f the trachea immediately cranial to the carina, increased intrabronchial pressure, especially against a closed glottis, and shearing forces o n a fixed carina during deceleration. ' 3
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injury. ' A triad o f injuries to the head and face, extremities, and thorax is c o m m o n to high-rise syndrome i n dogs and cats. ' Thoracic injury is the most c o m m o n l y sustained injury related to high-rise syndrome i n cats. According to W h i t n e y and others, thoracic trauma accounts for 90% o f feline injuries. The most c o m m o n thoracic injuries were pneumothorax (68%) and p u l m o n a r y contusions (63%). A l t h o u g h dogs can suffer from similar injuries, the extent and distribution o f their injuries is different from cats and is dependent o n the height o f the fall and the landing sur face. Dogs are also prone to more extremity and spinal cord injuries. Clinical signs o f high-rise syndrome are often attributable to the degree o f thoracic trauma. M o s t animals w i l l present w i t h some degree o f tachypnea or dyspnea that may be related to thoracic trauma or pain and shock. Thoracic radiographs should be done for assessment purposes i n all patients w i t h high-rise injuries. In a recent study, thoracic trauma was noted i n only 33.6% o f cats; however, thoracic radiography was used only i n those patients with abnormal respirations and may have underestimated the degree o f thoracic involve ment. If pneumothorax is suspected, thoracocentesis or tube thoracostomy may be necessary. Assessment for other inju ries, including those to the extremities, head and face, or spine, should be performed after the patients are treated for shock and respiratory compromise. Cats have a reported 90% survival r a t e and i n the study by G o r d o n and others, all but 1 o f 81 dogs survived. However, other reports state that most dogs who suffer from injuries related to high-rise syn drome are euthanized. 18
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Tracheobronchial trauma is generally secondary to a fall or motor vehicle accident. Patients have varying degrees o f respiratory distress and may even be asymptomatic initially. In cats, the mediastinum may allow continuity o f the i n trathoracic airway and limit immediate signs o f dyspnea.
DIAPHRAGMATIC HERNIA Trauma is the most c o m m o n cause o f diaphragmatic injury, accounting for 85% o f the hernias noted i n the largest study of dogs and cats. M o s t o f the injuries sustained concurrent w i t h a diaphragmatic hernia were found caudal to the tho rax. Bony lesions, including pelvic, pelvic limb, and rib frac tures, were most c o m m o n . Other injuries included hernias at other locations, myocardial contusions, hip luxations, and 23
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damage to the liver and urinary bladder. The liver is the most likely organ to herniate through a ruptured diaphragm, followed by the small intestine, stomach, spleen, and omen tum. M o s t insults occur o n the right side o f the dia phragm, possibly because the gas-filled stomach sits o n the left and cushions some o f the f o r c e . The pathogenesis may be related to a sudden rise i n intraabdominal pressure. W i t h an open glottis, this rise i n intraabdominal pressure increases the pleuroperitoneal pressure gradient and causes a tear i n the d i a p h r a g m . ' The extent and location o f the tear w i l l determine which, i f any, abdominal organs move into the thorax. 2 3
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Clinical signs are often attributable to the herniated organs, pleural effusion associated w i t h the herniated contents, and concurrent injuries. Hypoxemia may be the result o f pleural effusion, decreased lung volume secondary to pulmonary compression by organs, and overinflation o f adjacent alveoli. Hypoxemia may be exacerbated by concurrent thoracic inju ries (pulmonary contusions, pneumothorax, or chest wall dis ease). ' Patients may present w i t h varying degrees o f respiratory signs. D u l l ventral heart sounds may be the result of pleural effusion or the presence o f solid organs w i t h i n the thoracic cavity. W h e n the intrahepatic pressure increases more than 5 to 10 m m H g , pleural effusion results from transuda tion o f fluid from the hepatic c a p s u l e . ' Intestinal borborygmi may be auscultated over the thorax i f air is contained w i t h i n the herniated intestines. Gastric dilation w i t h i n the hernia can result i n severe respiratory and cardiovascular col lapse and gastric necrosis. The stomach may compress the cau dal vena cava, leading to decreased venous return and subsequent decreased cardiac output. 5
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The diagnosis o f diaphragmatic hernia is made most c o m m o n l y with thoracic radiography. There appears to be a high correlation w i t h radiographic signs and observations during surgery, indicating the value o f thoracic radiography i n the diagnosis o f diaphragmatic h e r n i a . There may be loss o f the n o r m a l diaphragmatic outline, air-filled intestines or stomach w i t h i n the thoracic cavity, or displacement o f the heart, lungs, or trachea by other soft tissue structures or effu s i o n . ' Because some hernias are not readily apparent with plain radiography, ultrasonography and positive contrast gastrography or peritoneography may be helpful i n making a diagnosis. 23
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Definitive treatment requires surgical repair o f the hernia. There is some debate over the ideal t i m i n g o f surgery. Some reports predict a poorer outcome i n patients taken to surgery w i t h i n 24 hours o f i n j u r y , although other studies do not support those findings. ' Emergency surgery is necessary when the patient cannot be stabilized because lung expansion is severely compromised, or when there is strangulated viscera or evidence o f gastric dilation w i t h i n the t h o r a x . 25
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A l l attempts should be made to stabilize the patient before surgical correction o f the hernia. This should include fluid therapy to maximize cardiac output and oxygen deliv ery to the tissues, oxygen therapy to treat hypoxemia related to ventilation-to-perfusion abnormalities, and evacuation o f the pleural space via thoracocentesis or tube thoracostomy for pleural effusion and pneumothorax. Care must be taken during thoracentesis or tube thoracostomy to prevent punc ture or rupture o f the herniated contents. Hemorrhage asso ciated w i t h splenic or hepatic damage may require b l o o d transfusions. 23
W i l s o n and others report a 30% mortality rate i n dogs and cats w i t h i n 24 hours to 7 days after the trauma, and
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Schmiedt and others report an almost 18% mortality rate i n cats during hospitalization. Some studies predict that the mortality is greatest for dogs and cats within 24 hours of surgery. Concurrent thoracic trauma also decreases sur v i v a l . Death may be the result o f hemothorax or pneumo thorax, reexpansion pulmonary edema, cardiac arrhythmias, and multiple organ f a i l u r e . ' ' 26
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MYOCARDIAL CONTUSIONS Myocardial contusions are caused by a deceleration force acting o n the chest wall. This force causes both direct com pression o f the myocardium and shearing stresses secondary to increased intrathoracic pressure. Myocyte necrosis secondary to epicardial hemorrhage occurs with severe contusions. The diagnosis o f myocardial contusion is often based o n abnormalities associated with an electrocardio gram ( E C G ) and evidence o f hemodynamic compromise. In h u m a n medicine, echocardiography, cardiac enzymes, and radionuclear imaging often aid i n the diagnosis. ' A true diagnosis is one that depends on histopathology or gross examination o f the heart. 28
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Clinical signs are more typically related to the trauma, rather than any direct damage to the myocardium. Patients may be i n respiratory distress from a concurrent pulmonary parenchymal or pleural space disease. Additionally, most patients have evidence of hypovolemic or hypoxemic shock. M o s t animals with significant thoracic trauma have altera tions i n their heart rate and rhythm, and repeated or contin uous monitoring o f the E C G is therefore recommended. Evidence o f arrhythmias may not be present for 12 to 48 hours after injury, although most arrhythmias occur with i n 24 h o u r s . ' Sinus tachycardia is commonly present after trauma and may be the result o f stress, pain, anemia, and/or h y p o v o l e m i a . This arrhythmia often responds to intravenous fluid therapy and correction o f associated hypoxemia, anemia, electrolyte abnormalities, and ventricu lar arrhythmias, particularly V P C s , are the most common arrhythmia post trauma, but they rarely require treatment. Evidence o f ventricular arrhythmias usually abate within 72 hours o f the trauma. 28
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Treatment o f the arrhythmia should be aimed at correc t i o n o f associated shock and maintenance of euvolemia before considering antiarrhythmic therapy. Appropriate pain management is also necessary. If the E C G (rate and rhythm), b l o o d pressure, and clinical status o f the patient are compro mised, antiarrhythmic therapy should be considered. Supra ventricular arrhythmias may be treated with calcium channel blockers or P-blockers. Ventricular tachyarrhythmias can be treated w i t h lidocaine or procainamide (see Chapter 190, Antiarrhythmic Agents).
SUGGESTED FURTHER R E A D I N G * Bjorling DA, Sicard GK: Diaphragmatic hernia. In King LG, editor: Textbook of respiratory diseases in dogs and cats, St Louis, 2004, Saunders. Chapter that provides a great overview of diaphragmatic hernias, including anatomy of the diaphragm and the pathophysiology and management of hernias. Brockman DJ, Puerto DA: Pneumomediastinum and pneumothorax. In King LG, editor: Textbook of respiratory diseases in dogs and cats, St Louis, 2004, Saunders. Chapter that provides a great in-depth look at the pathophysiology and man agement of the disease processes in veterinary patients.
Holt DE, Griffin G: Bite wounds in dogs and cats, Vet Clin North Am Small Vnuk D, Pirkic B, Maticic D, et al: Feline high rise syndrome: 119 cases (1998-2001), J Feline Med Surg 6:305, 2004. Anim Tract 30:669, 2000. Article that focuses on high-rise syndrome in an urban area; describes the Chapter that reviews the mechanism of injury for bite wounds and provides various injuries incurred and evaluates the association between the height recommendations for initial stabilization and then definitive managements. Smith MM: Flail chest. In King LG, editor: Textbook of respiratory diseases in of the fall and the injuries sustained. dogs and cats, St Louis, 2004, Saunders. the CD-ROM for a complete list of references. Chapter that provides an excellent overview of the pathophysiology and*See man agement of flail chest.
Chapter 154 ABDOMINAL TRAUMA William T. N. Culp,
VMD •
Deborah C. Silverstein, D V M , DACVECC
KEY POINTS • The extent of abdominal trauma is often not known at the initial evaluation, and extensive diagnostic tests are typically necessary to fully assess the status of a particular patient. • In a patient with suspected abdominal trauma, more immediately life-threatening injuries (such as thoracic or brain-associated neurologic trauma) should be addressed first. • Important sequelae to abdominal trauma may include hemoperitoneum/hemoretroperitoneum, uroperitoneum/ uroretroperitoneum, bile peritonitis, septic peritonitis, and diaphragmatic or body wall ruptures. • Although some animals experiencing abdominal trauma can be managed conservatively, surgery is often necessary to correct associated abnormalities.
INTRODUCTION Rapid assessment and triage o f a dog or cat following abdominal trauma is essential. A history and physical examination w i l l assist i n targeting appropriate diagnostic testing and prevent delays i n stabilization. The traumatic event is often not witnessed a n d the full extent o f injury to the animal may not be readily apparent. Injury may be confined to the skin and superficial tissues or may be life threatening and involve avulsion or rupture o f a b d o m i n a l organs. Conservative management and observation are indicated i n some cases; however, others require immediate surgery and prolonged hospitalization. This chapter w i l l discuss specific causes o f a b d o m i n a l trauma, the secondary effects o f such trauma, and the diagnostic and treatment options.
occur w i t h these events i n dogs and cats. W h e n blunt trauma to the abdomen does occur, the severity o f the abdominal injury is often not recognized immediately, while other life-threatening injuries are being addressed. A retrospective study o f 600 dogs that were struck w i t h a m o t o r vehicle noted that 5% experienced a b d o m i n a l t r a u m a (as diagnosed by surgery or necropsy). The liver was the a b d o m i n a l organ most often damaged ( 3 1 % o f the a b d o m i n a l organ injuries), w i t h injuries ranging from fissures o f the capsule/parenchyma to fragmentation o f a hepatic lobe. Other organs that were injured frequently i n c l u d e d the u r i n a r y bladder, d i a p h r a g m , a n d kidney. O f the 33 dogs that died from their injuries, 8 (24%) had a b d o m i n a l i n j u r y alone a n d 13 (39%) h a d b o t h a b d o m i n a l and thoracic injury. It is i m p o r t a n t to remember that some dogs a n d cats m a y not experience internal a b d o m i n a l trauma, but may still require aggressive surgical proce dures for damage that occurs to the skin or a b d o m i n a l muscles, especially when a vehicle drives over or drags the a n i m a l . 1
High-rise falls i n dogs and cats result i n a b d o m i n a l i n juries i n 15% and 7% o f cases, respectively. ' Dogs falling from a height o f greater than three stories are more likely to experience abdominal injury than those falling less than or equal to three stories. Also, dogs that fall accidentally more often experience a b d o m i n a l and h i n d l i m b injury than dogs that purposefully j u m p from a height. In most studies of dogs and cats, thoracic trauma is diagnosed more c o m m o n l y than abdominal trauma, perhaps due to the readily apparent respiratory compromise i n those patients. 2 3
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Unfortunately, h u m a n abuse o f c o m p a n i o n animals is another cause o f blunt a b d o m i n a l trauma. In a study inves tigating nonaccidental i n j u r y to animals, internal injury to the abdomen was documented less frequently than super ficial injuries or fractures. However, 13 o f 217 (6%) dogs i n this study experienced rupture o f an organ, including spleen, liver, bladder, and kidney. Cats tended to experience abdom inal muscle rupture. K i c k i n g o f the animal was the cause of the abdominal injury i n most cases. 4
BLUNT TRAUMA Although motor vehicle accidents, high-rise falls, and inten tional physical injuries are often encountered i n a veterinary emergency setting, abdominal trauma does not c o m m o n l y
PENETRATING TRAUMA Penetrating trauma to the abdomen often results i n both superficial and internal injuries. Skin wounds may not reveal the full extent of the injury i n deeper tissues. The reported incidence of internal organ injury after penetrating trauma has been reported to be as high as 7 0 % . Bite wounds can result i n both blunt and penetrating trauma. Exploration o f superficial wounds is often necessary to fully recognize the extent o f any organ damage that has occurred. Wounds that do not penetrate the abdomen still require close surgical exploration, because bacteria from the biting animal's m o u t h or environment w i l l likely con taminate the w o u n d and result i n abscess formation. W h e n large animals attack smaller animals, the victims may be lifted and shaken. This can result i n severe crushing and tearing injury as well as avulsion o f internal organs or body wall/ diaphragmatic herniation. The organs most c o m monly injured from bite wounds included the liver, kidney, diaphragm, and stomach i n one study. Gunshot wounds to the abdomen have been reviewed in several papers. O f 84 animals reported i n one retrospective study, 14 abdominal injuries were encountered. Animals with abdominal injury also tended to have more cardiovascular com promise o n presentation than those without abdominal injury. Other types o f penetrating abdominal wounds include stab wounds and impalement injuries (from sticks or other devices) or following a high-rise f a l l . Some o f these injuries are self-induced, and others are the result of mis treatment. Either way, early intervention is likely required to maximize the success of treatment. 5
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a specific cause. The presence o f intraabdominal gas suggests that abdominal wall penetration or organ perforation has occurred and requires immediate attention. The general loss o f serosal detail i n the abdomen is suggestive of fluid in the peritoneal space, retroperitoneal space, or both. Animals with traumatic pancreatitis or very young or thin animals may also have poor serosal detail on radiographs. Fluid i n the peritoneal space may originate from a bleed ing organ or ruptured vessel, urine from a distal ureteral, bladder, or proximal urethral rupture, bile from a rupture in the biliary system, or a septic exudate due to septic peri tonitis. Fluid i n the retroperitoneal space is most commonly urine from damage to the kidney or proximal ureter or blood from a great vessel. Subcutaneous emphysema can be seen when gas accumulates i n the subcutaneous spaces, with or without abdominal injury. Diaphragmatic and body wall ruptures are commonly diagnosed w i t h radiographs. Both thoracic and abdom inal radiographs should be taken i n cases o f suspected diaphragmatic rupture. Characteristic changes seen on radio graphs i n animals with diaphragmatic rupture include loss of continuity o f the diaphragm, loss o f intrathoracic detail (spe cifically cardiac silhouette), and the presence of gas-filled bowel loops or a mass effect i n the thorax. These changes are not always present, and further imaging may be necessary to confirm the diagnosis. 9,10
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Ultrasonography Ultrasonography is useful i n some cases o f abdominal trauma. As with radiographs, ultrasonography can diagnose the pres ence o f air or gas i n the abdomen. One study found that abdominal ultrasound correctly revealed a diaphragmatic her nia i n 9 3 % o f cases. A suspected body wall rupture can be definitively diagnosed with an ultrasound examination, and the organs displaced through the rupture may be assessed. A n ultrasonographic modality that is gaining popularity in veterinary medicine is the focused assessment with sonog raphy for trauma, or FAST, technique. This approach involves quickly looking at the abdomen with two ultrasono graphic views (transverse and longitudinal) i n four specific areas, "just caudal to the x i p h o i d process, just cranial to the pelvis, and over the right and left flanks caudal to the ribs at the most gravity-dependent location of the abdo men." This technique was found useful for detecting abdominal fluid, even when used by veterinarians with min imal ultrasonographic experience. 11
DIAGNOSTIC TESTS Blood work B l o o d work may support a diagnosis o f intraabdominal trauma; however, it rarely localizes the injury to a specific organ(s). A complete b l o o d count may demonstrate the pres ence of anemia i n a dog or cat that is experiencing a bleed from either a superficial w o u n d or a deep injury (such as organ rup ture), although this change is not typically present i n the acute setting. The white b l o o d cell count can increase secondary to stress, inflammation, or an infection that may be localized (in abscess form) or systemic (as w i t h sepsis). The platelet count may be decreased from acute b l o o d loss and subsequent consumption during clot formation. In severe cases of abdom inal trauma, disseminated intravascular coagulation ( D I C ) may occur, leading to thrombocytopenia and prolongation of the p r o t h r o m b i n and activated partial thromboplastin times (see Chapter 117, Hypercoagulable States). Liver enzyme elevations are often noted on the chemistry screen i f hepatic trauma has occurred. If the biliary system is ruptured, progressive increases i n total b i l i r u b i n w i l l be observed. Azotemia and electrolyte disturbances (e.g., hyper kalemia) w i l l occur secondary to urinary tract rupture. A n i mals w i t h sterile or septic peritonitis or a persistently draining w o u n d may develop hypoproteinemia.
Radiography A b d o m i n a l radiographs are useful i n the diagnosis o f abdominal pathology, but it is not always possible to identify
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Additional Imaging Other imaging modalities employed i n cases of abdominal trauma include fluoroscopy and computed tomography (CT) scans. Both are useful i n the diagnosis o f urinary tract injuries and body wall or diaphragmatic ruptures, and C T scans are used c o m m o n l y for surgical planning i n human patients that have experienced abdominal t r a u m a . 13
Abdominal Fluid Analysis W h e n an abdominal effusion is suspected from results of the physical examination, radiographs or ultrasonog raphy, it is important to obtain a sample of the fluid for evaluation (see Chapter 155, Abdominocentesis). Several analyses should be performed on the fluid sample, including
hematocrit, total solids, bilirubin, creatinine, potassium, and glucose. Other tests may include carbon dioxide, lactate, amylase, and lipase. In addition, a slide o f the sample should be made for cytologic examination. The presence of red b l o o d cells i n an abdominal effusion does not necessarily confirm a hemoperitoneum. W i t h a true hemoperitoneum, red b l o o d cells are usually observed w i t h i n macrophages, signifying erythrophagocytosis (although this may not be present during the acute stages). Hemosiderin from the broken d o w n red b l o o d cells usually fills the cyto plasm o f the involved phagocyte. Alternatively, i f the packed cell volume ( P C V ) o f the fluid is increasing or nears that found i n the peripheral blood, ongoing hemorrhage should be suspected. Cardiovascular changes are typically present i n these animals (i.e., tachycardia, hypotension). 14
Comparison of the concentrations o f creatinine and potassium i n an abdominal effusion to the serum levels is a useful indicator of uroperitoneum i n both dogs and cats. In cats, mean serum-to-abdominal fluid creatinine ratio and mean serum-to-abdominal fluid potassium ratio have been found to be 1:2 and 1:1.9, respectively, i n cases o f uroperito n e u m . Therefore a cat with a creatinine or potassium concen tration i n the abdominal effusion that is 2 times (or more) greater than the peripheral blood likely has a uroperitoneum. In dogs, the sensitivity and specificity are both 100% when using a ratio greater than 1.4:1 i n comparing abdominal fluid potassium concentration with peripheral b l o o d potassium con centration for the diagnosis o f uroperitoneum. Similarly, using abdominal fluid creatinine concentration (as compared with peripheral blood creatinine concentration) was beneficial, i n that a ratio o f greater than 2:1 was 86% sensitive and 100% specific for the diagnosis o f uroperitoneum. 15
16
A bilirubin concentration i n an abdominal effusion greater than twice that o f the peripheral b l o o d is diagnostic for bile leakage. Bile crystals are occasionally evident o n cytologic examination. Biliary effusions are often septic, and cytologic evaluation may reveal the presence o f bacteria. The importance of abdominal fluid analysis i n the diagnosis of septic peritonitis has been well documented. Cytologic exam ination is especially important i n the diagnosis of septic perito nitis, and the presence o f intracellular bacteria confirms the diagnosis (assuming that gastrointestinal contents have not been aspirated). The glucose and lactate concentrations o f the peritoneal fluid should also be compared with the respective concentrations i n the blood (see Chapter 133, Peritonitis). 17
TREATMENT Initial Assessment Although abdominal trauma may be life threatening, many animals will have other injuries that warrant more i m m e d i ate attention. The respiratory and cardiovascular systems should be assessed and stabilized (see Chapters 2 and 65, Patient Triage and Shock Fluids and F l u i d Challenge, respec tively). Thoracic injuries may require immediate intervention (see Chapter 153, Thoracic Trauma). Obvious bleeding should be controlled as soon as possible. In addition, neuro logic dysfunction resulting i n seizure activity or signs o f intra cranial swelling should be a treatment priority (see Chapter 152, Traumatic Brain Injury). Subsequently, an assessment of abdominal, superficial, and orthopedic injuries should be performed.
Hemoperitoneum/Hemoretroperitoneum The diagnosis o f a hemoperitoneum may prove challenging on physical examination. However, many o f these animals w i l l present i n shock with obvious signs o f b l o o d loss and cardiovascular compromise, such as mental depression, pale mucous membranes, prolonged capillary refill time, poor pulse quality, and tachycardia (see Chapter 10, Shock). In the initial treatment o f these patients, it is essential to treat hemorrhagic shock and improve perfusion by administering isotonic crystalloids (up to 50 m l / k g i n the cat and 90 ml/kg in the dog) and/or synthetic colloids (10 to 20 ml/kg), or both (see Chapter 65, Shock Fluids and F l u i d Challenge). "Hypotensive resuscitation" to a mean arterial pressure of 60 m m H g or systolic b l o o d pressure o f 80 m m H g may pre vent excessive bleeding or disruption o f clot formation and function. Some animals may also require b l o o d transfusions during the resuscitation period (i.e., whole b l o o d , packed red b l o o d cells, and plasma; see Chapter 66, Transfusion Medicine). A n i m a l s that are unresponsive to crystalloid and synthetic colloid fluid resuscitation and have evidence of severe hemorrhage should be given fresh whole b l o o d or packed red b l o o d cells and fresh frozen plasma i n an attempt to stabilize the clinical signs o f shock, maintain the hemato crit above 25%, and sustain the clotting times w i t h i n the normal range. Packed red b l o o d cells and fresh frozen plasma are administered at a dosage o f 10 to 15 m l / k g and fresh whole b l o o d at a dosage o f 20 to 25 m l / k g (a b l o o d type and crossmatch should be performed, i f possible). 18
Following initial stabilization, the decision to manage these cases conservatively (medically) or surgically must be made. External counterpressure with an abdominal bandage has been advocated as a means o f stabilizing mean arterial pressure and i m p r o v i n g s u r v i v a l . Other immediate m a n agement options include internal counterpressure and autotransfusion. The decision to perform surgery is case dependent, but i f a patient is not responding to fluid resus citation efforts, has a rising abdominal P C V , or is obviously continuing to effuse based o n ultrasonographic evaluation or physical examination, surgery should be performed. 19
20
21
In a veterinary retrospective s t u d y evaluating cases o f traumatic hemoperitoneum, the spleen, liver, and kidney were bleeding i n 58%, 50%, and 23% o f cases, respectively (determined during surgery or necropsy). O f the 28 small animals evaluated i n that study, 9 underwent exploratory laparotomy; 4 cases survived to discharge, 2 died, and 3 were euthanized. Discounting the euthanized small animals, the mortality rate for the cases managed surgically was 33%, and the mortality rate for the cases managed medically was 25%. The reasons for choosing surgical versus medical m a n agement o f these cases were not discussed.
Uroperitoneum/Uroretroperitoneum A uroperitoneum can occur secondary to injury to the kidneys, ureters, urinary bladder, or urethra. Often, ani mals experiencing urinary tract trauma w i l l present w i t h hematuria before signs o f a uroperitoneum are apparent. In cats, blunt abdominal trauma has been reported to cause 59.1% o f the cases o f u r o p e r i t o n e u m , and i n 84.6% o f those cases the source o f urine leakage was a ruptured bladder. 22
15
Initial stabilization o f the patient with a uroperitoneum revolves around the correction o f electrolyte abnormalities,
especially hyperkalemia. Characteristic electrocardiographic abnormalities noted in cases with hyperkalemia may include tall, tented T waves, absence o f P waves, and bradycardia. If not addressed immediately, this can become life threatening. Medical treatment may include the administration o f drugs such as calcium gluconate, insulin and/or glucose, bicarbonate, or (3-agonist therapy (see Chapters 55 and 133, Potassium Dis orders and Peritonitis, respectively). Definitive surgical treatment for cases of uroperitoneum sec ondary to renal or ureteral injury is generally necessary for a successful outcome and often results in a ureteronephrectomy. Bladder ruptures often require surgical correction, although small leaks may heal with continuous decompression provided by a urinary catheter and collection system. Surgical correction typically is accomplished by placing sutures over the rupture site. Bladder resection may be necessary i f the tissue appears severely damaged. Urethral trauma is treated conservatively in some cases by inserting a urethral catheter or a cystostomy tube, or both. If conservative treatment is unsuccessful, surgical clo sure o f the urethral defect is necessary. Postoperative supportive care and intensive m o n i t o r i n g are necessary in these animals to ensure a positive outcome. Urine output must be monitored strictly, and resolution o f azotemia should be expected if the injury has been managed properly.
Bile Peritonitis Leakage o f bile from the gallbladder or biliary ducts can occur secondary to blunt or penetrating abdominal t r a u m a . It is reportedly more c o m m o n for blunt trauma to result in ductal rupture than gallbladder rupture, and the site o f rupture is typically just distal to the last hepatic d u c t . ' 23
of the fluid should be performed regularly to monitor for recurrence o f a septic effusion or a secondary infection.
Diaphragmatic Rupture Trauma is the most c o m m o n cause of diaphragmatic ruptures in small animals. '' Therefore it should be sus pected in any dog or cat with respiratory distress following a traumatic event. Furthermore, other obvious clinical lesions may not be present in 48% of cases o f traumatic diaphragmatic ruptures. 2
26
These animals may have clinical signs o f shock at presen tation, and early stabilization and oxygen therapy should be initiated. Following stabilization, surgery is indicated to repair the rupture (Color Plate 154-1). If the stomach is displaced into the thoracic cavity or respiratory stability is unachievable, surgery is indicated on an emergency basis (see Chapter 30, Pleural Space Disease).
Body Wall Rupture A b d o m i n a l body wall rupture in dogs occurs secondary to bite wounds or vehicular trauma in 86% to 88% of cases. These patients should be evaluated carefully for bony trauma as well, because fractures may be the source of the rupture. Body wall ruptures are generally surgical emergencies, espe cially i f caused by bite wounds. Organs can be trapped in the defect, resulting in strangulation and rapid demise of the patient. Intestines are reportedly displaced through the rupture in as many as 54% of cases, ' and many require a resection and anastomosis to remove devitalized tissue (Figure 154-1). Other 9,27
2
2
Bile leakage should be addressed surgically as soon as possible. Bile i n the peritoneal cavity can cause severe peritonitis, because bile acids are toxic to living tissues. In addition, many biliary effusions are septic and may prove life threatening (see Chapter 133, Peritonitis). Appropriate antibiotic therapy and supportive care are vital.
Septic Peritonitis Gunshot wounds, bite wounds, and vehicular trauma to the abdomen can result i n septic peritonitis either from direct contamination with bacteria or leakage from an abdominal organ. In a retrospective canine study evaluating gunshot and bite wounds to the abdomen, peritonitis was noted in 40% o f the dogs with gunshot wounds and 14% o f the dogs with bite wounds. Another study in cats found that 8 o f 51 cases of septic peritonitis occurred secondary to trauma (gunshot wounds, bite wounds, and motor vehicle t r a u m a ) . 5
24
Animals with septic peritonitis often present i n shock and have a palpable abdominal effusion. As with cases o f hemoperitoneum, treatment o f the cardiovascular and respiratory systems should be instituted first. Fluid resuscitation and antibiotic therapy with broad-spectrum antibiotics are essential (see Chapters 65 and 133, Shock Fluids and Fluid Challenge and Peritonitis, respectively). W h e n the patient has been stabilized, surgical exploration should be performed, and the inciting cause must be found and eliminated. Septic peritonitis can be managed postoper atively with either open abdominal drainage or primary clo sure with placement o f closed suction d r a i n s . If drains are placed, the amount o f effusion produced should be m o n i tored and recorded every 2 to 6 hours. Cytologic examination 25
Figure 154-1 Ventrodorsal radiograph of a dog recently bitten by another dog. Note the presence of abdominal viscera (including intes tines) in the subcutaneous space that have passed through a rupture in the right lateral body wall.
organs commonly displaced include omentum, the liver, and the urinary bladder. ' In one study, 73% o f dogs and 80% o f cats survived until discharge from the hospital after surgical repair of a body wall rupture. 9
SUGGESTED FURTHER R E A D I N G *
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9
POSTOPERATIVE CARE Many cases o f abdominal trauma require surgery. The postop erative care often entails antibiotic therapy with broad-spec trum coverage until a sensitivity can better target an antibiotic choice i n small animals suffering from septic peritonitis, bile peritonitis, and bite wounds. M a n y patients will be either unable to eat or reluctant to eat for several days after a traumatic event, and an alternative method o f nutrition such as a feeding tube or total parenteral nutrition may be indicated. F l u i d and blood product supplementation often continue into the post operative period, as well. Multiple surgeries are often required in animals with concurrent orthopedic injuries.
Holt DE, Griffin G: Bite wounds in dogs and cats, Vet Clin North Am Small Anim Pract 30:669, 2000. A good summary of the effects of bite wounds and their treatment. McLoughlin MA: Surgical emergencies of the urinary tract, Vet Clin North Am Small Anim Pract 30:581-601, 2000. A review article that discusses the causes of urinary tract trauma and the associated treatment modalities, including some useful diagrams and radiographic examples. Shaw SP, Rozanski EA, Rush JE: Traumatic body wall herniation in 36 dogs and cats, / Am Assoc Hosp Assoc 39:35, 2003. A study that evaluates only those patients that received surgical correction of body wall hernias and follows their clinical course from presentation to outcome. Whitney WO, Mehlhaff CJ: High-rise syndrome in cats, J Am Vet Med Assoc 191:1399, 1987. A large retrospective study of this syndrome in cats that adequately describes injuries sustained and minimally discusses treatments. Worth AJ, Machon RG: Traumatic diaphragmatic herniation: pathophysiol ogy and management, Comp Cont Educ Pract Vet 27:178, 2005. Paper that provides an excellent overview of the pathogenesis, treatment, and prognosis of this condition in companion animals. "See the CD-ROM for a complete list of references.
Chapter 155 ABDOMINOCENTESIS Karl E. Jandrey,
D V M , DACVECC
KEY POINTS • Cytology of peritoneal fluid obtained by abdominocentesis may yield a diagnosis and lead to further directed therapy or emergency surgery. • The focused assessment with sonography for trauma, or FAST, protocol is a rapid and simple technique to detect free abdominal fluid. A needle paracentesis may be successful if directed toward the identified areas. • A blind-needle paracentesis may yield peritoneal fluid when 5.2 to 6.6 ml/kg of abdominal fluid is present. • A peritoneal dialysis catheter used for abdominocentesis may detect the presence of 1 to 4.4 ml/kg of abdominal fluid. • Complications of abdominocentesis include the introduction or spread of infection, laceration of a viscus, and hemorrhage from a punctured vessel or organ.
INTRODUCTION Frequent physical examinations are the most informative por tion of the diagnostic evaluation o f an emergency or intensive care patient w i t h abdominal disease. Assessment o f the abdo men should be as complete as time and the patient's c o n d i t i o n permit. Increasing abdominal size and progressive pain can be important clues for intraabdominal injury. Consequently, measurements o f the abdominal girth at the umbilical level
should be made soon after admission. This baseline measure ment can be used to assess subsequent significant changes. A b d o m i n a l rigidity and tenderness are important clinical signs o f peritoneal irritation by b l o o d or intestinal contents. A l t h o u g h physical examination findings can help i n the dis covery o f abdominal disease, they do not further a diagnosis. Samples o f peritoneal fluid obtained by abdominocentesis, however, may yield the diagnosis of an a b d o m i n a l disease process and lead to directed and specific therapy.
INDICATIONS Indications for abdominocentesis are (1) radiographic loss o f serosal detail, (2) abdominal injury without obvious perito neal entry wounds, (3) shock, multiple injuries, or signs o f abdominal injury after blunt trauma, (4) head or spinal injury precluding reliable a b d o m i n a l examination, (5) per sistent abdominal p a i n or fluid distention o f u n k n o w n cause, and (6) postoperative complications possibly caused by leak age from an enterotomy or anastomotic site. Periumbilical ecchymosis (Cullen sign) may indicate hemorrhage i n the peritoneum or retroperitoneum. Contraindications to abdominocentesis include coagulopathy, organomegaly, or distention o f an abdominal viscus. Intestinal or uterine 1
penetration is rare unless the viscus is dilated and adherent to the abdominal w a l l . Complications include the introduc tion or spread o f infection, laceration o f a viscus, and h e m orrhage from a punctured vessel. Following the techniques described below w i l l reduce the risk o f complications. 2
TECHNIQUE Abdominocentesis is completed using a single paracentesis or four-quadrant approach. Single paracenteses are done w i t h an open-needle or a closed-needle technique. Ultrason ographic guidance can highlight a smaller accumulation offluid and allow for a more directed approach for abdominocentesis.
Focused Assessment With Sonography for Trauma The focused assessment w i t h sonography for trauma, or FAST, protocol was studied i n dogs to prove that it is a rapid and simple technique to detect free abdominal fluid i n the emergency r o o m by veterinary clinicians w i t h m i n i m a l pre vious ultrasonography experience. This technique scanned four regions i n longitudinal and transverse planes o f the abdomen w i t h dogs i n lateral recumbency. These regions are areas where fluid accumulation c o m m o n l y occurs: caudal to the x i p h o i d process, midline over the urinary bladder, and each flank. O f 100 dogs studied w i t h i n 24 hours o f a m o t o r vehicle accident, 45 had free abdominal fluid. A diag nosis was made i n all 40 o f the dogs that received an abdom inocentesis (29 w i t h ultrasonographic guidance); 38 had hemoabdomen, 2 had uroabdomen. Diagnostic peritoneal lavage was not performed o n any o f the dogs. 3
Patient Preparation Patient positioning i n left lateral recumbency may be most effective to avoid puncture o f the spleen. Restraint may be completed manually or with sedatives and analgesics. Before the abdomen is penetrated, a wide surgical clip and prepara tion o f the site using aseptic technique must be completed along the ventral midline centered at the umbilicus (Color Plate 155-1). If abdominal ultrasonography has revealed a focal area of peritoneal fluid accumulation, a standard aseptic clip and preparation o f that location is prudent.
Closed-Needle Abdominocentesis A closed-needle diagnostic abdominocentesis can be c o m pleted using a 20- or 22-gauge needle placed o n an extension set that is attached to a 6- or 12-cc syringe. Local anesthetic infusion of 2 % lidocaine may be used at the a b d o m inocentesis site. Penetration o f the abdominal cavity can be completed i n the right cranial quadrant caudal to the edges of the liver, because peritoneal fluid is gravity dependent and the falciform fat may extend along midline to the umbilicus. Gently insert the needle completely at this site and avoid fur ther movement o f the needle tip to prevent laceration o f inter nal structures. W i t h d r a w the peritoneal fluid and observe for clots i f the fluid is hemorrhagic. F l u i d w i t h i n the abdominal cavity should not clot; hemorrhagic fluid obtained from puncture o f the spleen, liver, or any vessel w i l l clot readily. If the abdominal fluid clots, remove the needle and
attempt abdominocentesis i n another location. Cytologic and biochemical analysis and culture o f the abdominal fluid should be completed immediately after removal. A closed-needle abdominocentesis may also be used for therapeutic removal o f peritoneal fluid. Therapeutic removal of large volumes o f fluid may be indicated i f the abdominal distention impairs diaphragmatic motion, increases abdom inal pressure impeding b l o o d flow to the visceral organs, or causes pain. To maintain a closed system, a three-way stopcock can be placed between the syringe and extension set. Another extension set placed o n the stopcock can be directed into a bowl or graduated cylinder. Free gas should not be evident o n radiographs after a closed-needle abdominocentesis.
Open-Needle Abdominocentesis A n open-needle abdominocentesis is completed i n a similar fashion except that the needle, alone, is inserted into the peritoneal cavity. Fluid from the peritoneum is allowed to flow freely through the needle into a container or a sample submission tube. Rotation o f the hub o f the needle may facilitate flow. This technique helps prevent occlusion with or aspiration o f omentum or intestinal viscera. False negative results are more likely to occur i f suction is applied. Free gas on radiographs is possible after this procedure. 4
Four-Quadrant Abdominocentesis A modification o f the open-needle technique is the fourquadrant abdominocentesis. Instead o f one open needle, four open needles are placed simultaneously, one i n each quadrant surrounding the umbilicus (see C o l o r Plate 155-1). Gravity dependency or changes i n transabdominal pressure between the needles may increase the likelihood of obtaining fluid. One study i n dogs showed that fluid was obtained i n 78 of 100 needle paracenteses when 5.2 to 6.6 ml/kg (ml of abdom inal fluid per k g o f body weight) was present. 5
Alternatives to Needles for Abdominocentesis A peritoneal dialysis catheter used for abdominocentesis can detect 1 to 4.4 m l / k g . A larger diameter and multiple side holes make this apparatus more reliable for detecting smaller volumes o f peritoneal fluid compared with a standard needle or catheter (see Chapter 156, Diagnostic Peritoneal Lavage). A 14- or 16-gauge over-the-needle catheter with manually created fenestrations placed using a N o . 10 scalpel blade can increase the surface area for drainage (Color Plate 155-2, A). Complete occlusion by the omentum or bowel is less likely and may increase the yield of peritoneal fluid. It is important to make small, smooth fenestrations. D o not place them opposite each other o n the catheter or place too many; this w i l l weaken the integrity o f the catheter (Color Plate 155-2, B). If the catheter is weakened or the fenestrations are not smooth, a p o r t i o n o f the catheter may break and remain i n the subcutaneous tissue or intraabdominal space when removed from the abdomen. Once the stylet is removed, do not replace it i n the catheter. Despite these caveats, the use o f a fenestrated catheter increases the likelihood of fluid collection compared with needle abdominocentesis alone. 6
7
ABDOMINAL FLUID ANALYSIS Packed cell volume ( P C V ) and creatinine, glucose, and b l o o d urea nitrogen ( B U N ) levels should be measured from the peritoneal fluid sample. Potassium and lactate are other b i o chemical markers that can be tested to add diagnostic value to the fluid sample. If the P C V o f the peritoneal fluid exceeds the peripheral P C V , it is suggestive o f parenchymal organ laceration or large vascular disruption. H e m o d i l u t i o n w i t h urine may cause a decreased P C V o f abdominal fluid i n patients with both abdominal hemorrhage and urologic injury. Uroabdomen can be diagnosed from simultaneous measurement o f creatinine a n d potassium i n both the abdominal fluid and peripheral b l o o d . Elevation o f potas sium i n the abdominal fluid compared w i t h that o f periph eral blood (greater than 1.4:1) suggests urologic injury. Rapid assessment and comparison o f the B U N i n abdominal fluid and peripheral blood can be completed using reagent strip technology. However, B U N can readily equilibrate across the peritoneal lining and is less reliable for the diag nosis of uroabdomen. Because o f its high molecular weight, a creatinine concentration i n the abdominal fluid higher than twice that o f peripheral b l o o d is highly suggestive o f free urine i n the abdominal cavity.
greater than 20 m g / d l was 100% sensitive and 100% specific for the diagnosis o f septic peritoneal effusion i n dogs. W i t h gallbladder or c o m m o n bile duct injury, icterus may be delayed. A dark green to black or dark amber color o f peritoneal fluid suggests the presence o f bile pigments. Peri toneal fluid can be analyzed for total bilirubin. If the abdom inal fluid b i l i r u b i n is significantly greater than peripheral b i l i r u b i n , then bile peritonitis is present. A b d o m i n a l disease and the associated abdominal fluid can change rapidly. A s a result these patients require fre quent reassessments o f their physical status and diligent crit ical care m o n i t o r i n g . Repeated abdominocentesis may play a role i n clinical decision making.
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Cytologic analysis and culture o f abdominal fluid w i t h sensitivity testing should be carried out. Emergency cyto logic analysis often assists the clinician i n initiating appro priate therapy. In many cases, the decision for medical versus surgical therapy can be readily apparent before receiv ing the official clinical pathologic review. T h e emergency clinician or intensivist should examine the gross appearance of the fluid. A n abdominal fluid sample that is completely clear and colorless makes the diagnosis o f peritonitis, severe intraabdominal injury or perforation, and leakage from the gastrointestinal tract less likely. F l u i d that appears opaque, cloudy, or flocculent should be examined immediately. 4
A direct smear that has been dried and stained appropri ately can be examined at low power for large particulate material such as plant material or crystals. High-power mag nification is used to identify bacteria, fungi, and b l o o d cells. Intracellular bacteria (with or without extracellular bacteria) and degenerate neutrophils characterize a septic effusion. One s t u d y showed these parameters were 100% accurate for the diagnosis o f septic peritonitis. Surgical intervention should be considered and undertaken immediately i f this is found, often before confirmation by a reference laboratory. Surgery is not necessarily indicated when only extracellular bacteria are found i n the fluid sample. Glucose and lactate measurements o n peritoneal fluid can also a i d i n the diag nosis o f septic peritonitis. In one prospective analysis o f 18 dogs with septic effusion, peritoneal fluid glucose con centration was always lower than the b l o o d glucose concen tration. A blood-to-peritoneal fluid glucose difference 10
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CONCLUSION Physical examination findings a n d diagnostic studies are required to decide when acute abdominal disease should be explored surgically versus managed medically. Blunt abdom inal trauma cases are a challenge to diagnose, because the clinical manifestations may be delayed for hours or days. Abdominocentesis is a valuable tool to obtain a sample for laboratory and cytologic analysis i n the emergency r o o m or intensive care unit. SUGGESTED FURTHER R E A D I N G * Boysen SR, Rozanski EA, Tidwell AS, et al: Evaluation of afocusedassess ment with sonography for trauma protocol to detect free abdominal fluid in dogs involved in motor vehicle accidents, J Am Vet Med Assoc 225:1198, 2004. An interesting, prospective study that reports the focused assessment with sonography for trauma protocol as adapted from human medicine for rapid identification of free peritoneal fluid within 24 hours after blunt trauma in dogs. Giacobine J, Siler VE: Evaluation of diagnostic abdominal paracentesis with experimental and clinical studies, Surg Gynecol Obstet 110:676, 1960. A seminal article that reports the use of needle abdominal paracentesis in dogs, including false-positive rates and peritoneal fluid volumes detected with this technique. Kolata RJ: Diagnostic abdominal paracentesis and lavage: experimental and clinical evaluations in the dog, f Am Vet Med Assoc 168:697, 1976. A prospective, descriptive article evaluating the experimental and clinical use of a peritoneal dialysis catheter for abdominocentesis and diagnostic peritoneal lavage in dogs. Schmiedt C, Tobias KM, Otto CM: Evaluation of abdominal fluid:peripheral blood creatinine and potassium ratios for diagnosis of uroperitoneum in dogs, / Vet Emerg Crit Care 11:275, 2001. An interesting article that prospectively establishes the abdominal fluid—toperipheral blood creatinine ratios used for diagnosis of uroperitoneum in dogs. *See the CD-ROM for a complete list of references.
Chapter 156 DIAGNOSTIC PERITONEAL LAVAGE Karl E. Jandrey,
D V M , DACVECC
complication rate is quite low. D P L does not reliably exclude significant injuries to retroperitoneal structures. Diagnostic peritoneal lavage is performed when alterna tive diagnostic methods such as sonography are unavailable or when the patient's condition does not allow other diag nostic tests or imaging to be performed. The focused assess ment w i t h sonography for trauma (FAST) protocol was studied i n dogs to prove that it is a rapid and simple tech nique to detect free abdominal fluid i n the emergency room by veterinary clinicians w i t h m i n i m a l ultrasonography expe rience. Using this technique, the operators scanned four regions i n longitudinal and transverse planes o f the abdo m e n w i t h dogs i n lateral recumbency. These regions are caudal to the x i p h o i d process, midline over the urinary blad der, and each flank. FAST was completed within a median time o f 6 minutes. A n accurate cytologic diagnosis was made i n all dogs that received needle abdominocentesis. D P L was not performed o n any o f the dogs.
KEY POINTS • Diagnostic peritoneal lavage (DPL) is performed when intraabdominal injury is suspected and when alternative diagnostic methods such as sonography are unavailable or the patient's condition does not allow other diagnostic techniques or imaging to be performed. • DPL is complementary to abdominocentesis. • DPL does not reliably exclude significant injuries to retroperitoneal structures. • Significant hemorrhage is present if the packed cell volume (PCV) of the peritoneal fluid exceeds 5%. • Creatinine in the abdominal fluid more than twice that of peripheral blood is highly suggestive of free urine in the abdominal cavity.
4
INTRODUCTION A b d o m i n a l disease can have life-threatening consequences, and i n some cases surgical intervention is essential. Deter m i n i n g when surgery is indicated can be challenging, because a b d o m i n a l clinical signs are c o m m o n l y vague and nonspecific. Blunt trauma to the abdomen is a major c o m ponent o f traumatic injury and can be deadly. It can occur as a consequence o f falls, m o t o r vehicle accidents, or severe blows to the abdomen. M a n y other causes for an acute c o n d i t i o n o f the abdomen may warrant further diagnosis w i t h the aid o f abdominal fluid cytology. W h e n there is 5.2 to 6.6 m l o f abdominal fluid per kg o f body weight, abdominocentesis is a valuable diagnostic procedure. W h e n there is insufficient fluid for a b d o m i n o centesis, diagnostic peritoneal lavage D P L can provide a fluid sample for analysis. The cytologic and biochemical information obtained from a D P L helps determine whether an intraabdominal injury exists and whether surgery is required. 1
INDICATIONS
TECHNIQUE 5
C r o w e and Crane described an open technique for D P L . A 1-cm i n c i s i o n is made carefully i n the abdomen for direct visualization o f catheter insertion into the peritoneal cav ity. Careful hemostasis must be maintained to prevent false-positive results o n fluid analysis. A closed tech nique has also been described using a catheter w i t h an inner stylet that is rotated gently to penetrate the fascia a n d p e r i t o n e u m . A m o d i f i c a t i o n o f the closed technique is presented. ' 1
6
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Supplies D P L is performed w i t h a large-diameter catheter with multi ple holes. C o m m e r c i a l peritoneal dialysis catheters work well, but over-the-needle catheters can be fenestrated and used w i t h good results. Use o f a peritoneal dialysis catheter for abdominocentesis alone, without lavage, has been shown to detect 1 to 4.4 m l / k g o f free abdominal f l u i d . The larger diameter and multiple side holes o f a peritoneal dialysis catheter make occlusion w i t h o m e n t u m or bowel less likely. A 14-gauge or 16-gauge over-the-needle catheter with fenes trations placed manually using a N o . 10 scalpel blade can increase the surface area for drainage (see Chapter 155, Abdominocentesis, and C o l o r Plate 155-2, A). Fenestrations should be small and smooth. Fenestrations should not be too numerous or placed opposite each other o n the catheter; this w i l l weaken the integrity o f the catheter (see Chapter 155, Abdominocentesis, and C o l o r Plate 155-2, B). If the catheter is weakened or the fenestrations are not smooth, a p o r t i o n o f the catheter may break and remain i n the 8
D P L should be considered when a diagnostic sample was not obtained by abdominocentesis. Specific indications for a diag nostic peritoneal lavage are (1) an acute condition o f the abdo men, (2) penetrating or blunt abdominal trauma, (3) shock despite m a x i m a l fluid resuscitation, (4) central nervous system disease precluding reliable abdominal examination, (5) persis tent abdominal pain o f u n k n o w n cause, and (6) to assess post operative dehiscence o f an enterotomy or anastomotic site. ' Contraindications include coagulopathy, organomegaly, and distention o f an abdominal viscus. Complications include the introduction or spread o f infection, laceration o f a viscus, and hemorrhage from a punctured vessel, although the 2
3
Box 156-1 Supplies Needed for Diagnostic Peritoneal Lavage • Clippers • Surgical antiseptic scrub • Peritoneal dialysis catheter or 14- or 16-gauge over-the-needle catheter • No. 10 scalpel blade • 2% Lidocaine • No. 11 scalpel blade • Fluid administration set • Warm 0.9% saline, 22 ml/kg
cloudy (i.e., highly cellular) but may appear less so with dilu tion from a peritoneal lavage. A n abdominal fluid sample that appears grossly clear and colorless should still be submitted to a reference laboratory for cytologic analysis. A fluid sample should be kept for culture and sensitivity testing. Cytologic characteristics o f the white b l o o d cells are more meaningful than absolute cell counts because of the d i l u tional consequences o f a peritoneal lavage. ' In a study c o m paring preoperative and postoperative D P L samples, recent surgery increased the white b l o o d cell counts from normal (1000 cells/mm ) to usually less than 10,000 c e l l s / m m . Elevations i n the peritoneal white b l o o d cell count i n response to sepsis occur over variable periods that overlap these n o r m a l ranges. Intracellular bacteria (with or without extracellular bacteria) along with an increased number of degenerate neutrophils characterize a septic effusion. Surgi cal intervention should be undertaken immediately i f this is found, often before confirmation by a reference laboratory. It is important to note that the presence o f extracellular bac teria i n the absence o f intracellular bacteria is not diagnostic of septic peritonitis and hence not an indication for surgery. 6 9
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1
subcutaneous tissue or intraabdominal space when removed from the abdomen. Other supplies needed for a diagnostic peritoneal lavage include local anesthetic, a N o . 11 scalpel blade, a fluid a d m i n istration set, and sterile w a r m 0.9% sodium chloride for infu sion (Box 156-1).
Patient Preparation Left lateral recumbency may be the best position for preven tion of splenic puncture. Restraint may be completed m a n u ally or with sedatives and analgesics. Before penetration o f the abdomen, a wide surgical clip and preparation o f the site using aseptic technique must be completed along the ventral midline, centered about the umbilicus. Local infiltration o f 2% lidocaine should be performed at the puncture site either at the umbilicus or 2 to 3 c m lateral to it to avoid the falciform fat.
Catheter Placement A small stab incision is made i n the skin with the N o . 11 scalpel blade at the site of local anesthetic infiltration. The commercial dialysis catheter is introduced through the incision completely into the abdomen. Slow, gentle rotation o f the closed-end dial ysis catheter is needed to overcome considerable resistance from fascia and the linea alba. If using a fenestrated over-the-needle catheter, advance the catheter completely off the stylet once the tip has penetrated the peritoneal cavity. A syringe may be attached to the catheter at this point. If no peritoneal fluid is obtained, saline is infused into the abdomen through the catheter. Infuse 22 m l / k g warm, sterile 0.9% sodium chloride by gravity through the drip set attached to the catheter. Gently massage the abdomen or roll the patient without dislodging the catheter to distribute the saline throughout the abdomen. Either attach a syringe and gently aspirate fluid from the catheter or allow gravity to fill the drip set and fluid bag. Large volumes o f fluid are gener ally not obtained because of the wide dispersion throughout the abdomen. A n y amount retrieved should be submitted for biochemical and cytologic evaluation, including culture and sensitivity testing.
FLUID ANALYSIS Peritoneal lavage fluid should be examined for color, packed cell volume ( P C V ) , and white blood cell count. Fluid that appears opaque, cloudy, or flocculent should be examined immediately. Fluid from a patient with peritonitis is often
Because o f dilution, the P C V o f the D P L fluid cannot be compared directly w i t h the peripheral b l o o d P C V . It has been reported that a P C V o f the D P L fluid o f greater than 5% indicates significant hemorrhage. Serial assessments o f the abdominal fluid with increasing P C V s may more clearly define continuing hemorrhage. Creatinine and potassium elevations i n the lavage fluid are more difficult to interpret because o f the dilutional effects o f the infusate. Excretory urography, retrograde con trast cystourethrography, or surgical intervention may be indicated. W i t h gallbladder or c o m m o n bile duct injury, icterus may be delayed. Some o f the peritoneal fluid should be submitted for analysis o f total bilirubin. A dark green to black color suggests bile pigments w i t h i n the fluid. If the abdominal fluid b i l i r u b i n is disproportionately greater than peripheral bilirubin, an exploratory laparotomy is indicated. 6
CONCLUSION Injury to abdominal viscera must be excluded i n all victims of abdominal trauma. Patients requiring intensive care may also develop progressive abdominal disease. Physical exami nation remains the initial step i n diagnosis but has limited utility under some circumstances. The specific tests selected are based on the clinical stability o f the patient, the ability to conduct a reliable physical examination, and the clini cian's access to diagnostic modalities. Diagnostic peritoneal lavage is indicated i n a patient that has significant abdominal injury but no diagnostic sample was identified by FAST or routine abdominal ultrasonography or obtained by abdominocentesis. D P L does not reliably exclude significant injuries to retro peritoneal structures. Kane and others performed c o m puted tomography following D P L i n 44 hemodynamically stable h u m a n patients that had sustained blunt trauma. In 16 patients, computed tomography revealed significant intraabdominal or retroperitoneal injuries not diagnosed by D P L . Moreover, the findings o f computed tomography resulted i n a modification to the original management plan i n 58% o f the patients. There are no similar studies i n veterinary medicine. 11
Giacobine J, Siler VE: Evaluation of diagnostic abdominal paracentesis with experimental and clinical studies, Surg Gynecol Obstet 110:676, 1960. Bjorling DE, Latimer KS, Rawlings CA, et al: Diagnostic peritoneal lavage A seminal article that reports the use of needle abdominal paracentesis in d before and after abdominal surgery in dogs, Am J Vet Res 44:816, 1983. including false-positive rates and peritonealfluidvolumes detected with A study that measured complete blood counts and peritoneal lavagefluid2technique. days before and 2 days after abdominal surgery. Dialysis catheter insertion in a Kolata RJ: Diagnostic abdominal paracentesis and lavage: experimental and right paramedian location resulted in more contamination with blood than clinical evaluations in the dog, J Am Vet Med Assoc 168:697, 1976. when the catheter was inserted on the abdominal midline. A prospective, descriptive article that evaluates the experimental and clin use of a peritoneal dialysis catheter for abdominocentesis and diagno Boysen SR, Rozanski EA, Tidwell AS, et al: Evaluation of a focused assess peritoneal lavage in dogs. ment with sonography for trauma protocol to detect free abdominal fluid in dogs involved in motor vehicle accidents, J Am Vet Med Assoc 225:1198, 2004. *See the CD-ROM for a complete list of references. An interesting, prospective study reporting the FAST protocol as adapted from human medicine for rapid identification of free peritonealfluidwithin 24 hours after blunt trauma in dogs. SUGGESTED FURTHER R E A D I N G *
Chapter 157 WOUND MANAGEMENT Caroline K. Garzotto,
V M D , DACVS
KEY POINTS • The patient should always be stabilized and assessed for internal trauma (radiographs of chest and abdomen) before treating external wounds. • In the first aid care of wounds, it is important to keep the wound moist, clean, and covered until definitive treatment can be done. • Open wounds containing penetrating foreign bodies or projecting bone should not be manipulated until the patient has been stabilized. • Once the patient is stable, all wounds should be cleaned and debrided, even if the animal will eventually be transferred to a surgical specialist. Surgical exploration is indicated for all penetrating wounds. • Most wounds can be managed successfully with appropriate technique, close follow-up, cooperative owners, and minimal materials. • The diagnosis and prognosis for full return to function should be discussed with the owner as soon as possible. Discuss the patient's treatment regimen (e.g., daily bandage changes) and give an estimate for the cost of treatment in the short and long term.
INTRODUCTION M o s t traumatic wounds seen i n the small animal veterinary patient include bite wounds, abrasions or shearing injuries resulting from m o t o r vehicle trauma, degloving, lacerations, and punctures. W o u n d s can also result from decubitus ulcers i n the recumbent animal secondary to p o o r nursing care, or wounds can appear i n postoperative surgical incisions that dehisce or become infected.
WOUND HEALING PRINCIPLES Wound Classification W o u n d s are classified based o n degree o f contamination as follows " : 1
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•
Clean: Atraumatic, surgically created under aseptic conditions (e.g., incisions) • Clean contaminated: M i n o r break i n aseptic surgical technique (e.g., controlled entry into the gastrointesti nal ( G I ) , urogenital, or respiratory tracts) i n which the contamination is m i n i m a l and easily removed •
Contaminated: Recent w o u n d related to trauma with bacterial contamination from street, soil, or oral cavity (e.g., abrasion or shearing wound); can also be a surgi cal w o u n d w i t h major breaks i n asepsis (e.g., spillage from the G I or urogenital tracts)
• Dirty or infected: O l d traumatic w o u n d with exudate or obvious infection (e.g., abscess i n a bite wound, puncture w o u n d , or traumatic w o u n d with retained devitalized tissue); contains more than 10 organisms per gram o f tissue 5
If a w o u n d is associated with a broken bone, this is called an open fracture, a n d these can be classified as follows : 4
•
Grade I: Small break i n the skin caused by the bone penetrating through • Grade II: Soft tissue trauma contiguous with the frac ture, often caused by external trauma (e.g., bite wound, low-velocity gunshot injuries)
•
Grade III: Extensive soft-tissue injury, c o m m o n l y i n addition to a high degree o f c o m m i n u t i o n o f the bone (e.g., distal extremity shearing wounds, high-velocity gunshot injuries) Although definitive repair o f an open fracture should be done as soon as possible for patient comfort, initial care o f the soft tissues should not be delayed i f a surgeon is not immediately available or i f the patient is not stable enough to undergo general anesthesia for several hours. A n y exposed bone should be covered with sterile lubricating jelly and a sterile bandage but should not be pushed back below the skin surface because this can cause deeper contamination of the w o u n d or further injury to the tissues. Similar guide lines exist for wounds with penetrating foreign bodies such as arrows, large wooden splinters, or knives. The foreign body may be tamponading a large vessel, and removal may lead to severe hemorrhage. These objects should be removed only under controlled surgical conditions. Other w o u n d classifications describe the length o f time that the w o u n d has been open because this relates to h o w quickly bacteria can multiply i n a w o u n d . A l t h o u g h this is important to know, it is not as vital as assessing the patient and the w o u n d directly. It is more important to understand the local and systemic defenses o f the patient and the types and virulence of bacteria that may be present i n the w o u n d so that appropriate treatment can be initiated. 1
Phases of Healing A basic understanding of the phases o f w o u n d healing gives the clinician an idea o f h o w long it w i l l take for a w o u n d to improve i n appearance and for making w o u n d management decisions. W o u n d healing can be described i n four phases: (1) inflammation, (2) debridement, (3) repair/proliferation, and (4) maturation. The phases overlap and the transitions are not visible to the naked eye. The inflammatory phase occurs during the first 5 days after injury. Immediately after trauma there is hemorrhage caused by disruption of blood vessels, and then vasoconstriction and platelet aggregation limits the bleeding. Vasodilation follows within 5 to 10 minutes, allowing fibrinogen and clotting ele ments to leak from the plasma into the w o u n d to form a clot and eventually a scab. The clot serves as scaffolding for invading cells such as neutrophils, monocytes, fibroblasts, and endothe lial cells. Also contained i n the plasma are inflammatory mediators (cytokines) such as histamine, prostaglandins, leukotrienes, complement, and growth factors. 1
The debridement phase occurs almost simultaneously with the inflammatory phase. It is marked by the entry of white blood cells into the wound. Neutrophils are the first to appear i n the w o u n d approximately 6 hours after injury. They remove extracellular debris via enzyme release and phagocytosis. Monocytes appear approximately 12 hours after trauma, and they become macrophages w i t h i n 24 to 48 hours. The monocytes stimulate fibroblastic activity, col lagen synthesis, and angiogenesis. Macrophages remove necrotic tissue, bacteria, and foreign material. 5 6
The repair phase, also called the proliferative phase, ' begins 3 to 5 days after injury and lasts about 2 to 4 weeks. This is the most dramatic healing phase and is characterized by angiogenesis, granulation tissue formation, and epithelialization. Fibroblasts proliferate and start synthesizing collagen, and then capillary beds grow i n to form granulation tissue. Granulation tissue provides a surface for epithelialization
and is a source o f myofibroblasts that play a role i n w o u n d contraction. N e w epithelium is visible 4 to 5 days after injury and occurs faster i n a moist environment. W o u n d contrac tion is first noticeable by 5 to 9 days after injury and continues into the maturation phase. Finally, the maturation phase occurs once adequate colla gen deposition is present and is marked by w o u n d contraction and remodeling o f the collagen fiber bundles. It starts at about 17 to 20 days after injury and may continue for several years. Healed wounds are never as strong as the normal tissue; a scar is only about 80% as strong as the original tissue. 1
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INITIAL PATIENT ASSESSMENT Before handling the patient, the clinician and patient should be protected by the use o f examination gloves. Initial stabiliza tion of the patient should address oxygenation and circulatory requirements (see Chapter 2, Patient Triage). Intravenous catheter placement, fluid therapy, and supplemental oxygen may be required for the severely traumatized patients or patients i n shock (see Chapters 19 and 65, Oxyen Therapy and Shock Fluids and F l u i d Challenge, respectively). A c o m plete b l o o d count, biochemical analysis, urinalysis, and venous or arterial b l o o d gas analysis should be performed on admission. Direct pressure should be applied to any bleeding wounds. If bleeding cannot be controlled by direct pressure, surgical inter vention is required. Bleeding o f appendages can be controlled with tourniquets by using a pneumatic blood pressure cuff inflated to 200 m m H g for not more than 1 hour. It is impor tant to remember that bite wounds c o m m o n l y result from the penetration o f both the upper and lower teeth. If bite marks are seen only o n one side o f the limb or trunk, then the other side should be shaved to search for the corresponding wounds. Wounds should be kept clean and moist and protected immedi ately from the hospital environment. A sterile, water-soluble lubricant and saline soaked sponges can be applied initially to the wounds and then covered with a sterile towel and soft padded bandage i f the patient must be moved. It is important that the damaged tissue remain moist because desiccation impairs w o u n d healing. 7
If the animal has wounds associated with trauma, radio graphs are indicated to assess for other more immediate, life-threatening injuries. These radiographs might include views o f the spine, chest, abdomen, and pelvic region, i n addition to appendages, i f there is suspicion o f a fracture. Blunt trauma, such as motor vehicle trauma or falling from heights, warrants chest and abdominal radiographs to assess for p u l m o n a r y contusions, pneumothorax or hemothorax, diaphragmatic hernia, and peritoneal effusion secondary to b l o o d or urinary tract trauma. Cursory abdominal ultraso nography may also assist i n detecting free fluid w i t h i n the thoracic or abdominal cavity. A thorough neurologic assess ment is also important, to rule out spinal or neurologic injury. Assessment o f perfusion and sensation to the digits is important when severe trauma to peripheral b l o o d supply and nerves might prohibit a successful outcome.
DEBRIDEMENT AND LAVAGE Once the patient has been thoroughly examined, stabilized, and all diagnostic tests performed, and i f sedation or
anesthesia can be administered safely, initial assessment and debridement o f the w o u n d should be done. The primary goal i n the management o f all wounds is to create a healthy w o u n d bed w i t h a good b l o o d supply that is free o f necrotic tissue and infection to promote healing. M o s t wounds w i l l require daily debridement and bandage changes, and the cli nician should not be discouraged i f the w o u n d cannot be closed initially. The following summarizes the steps for daily w o u n d evaluation: 5
1. Assess need for or response to antibiotic therapy. 2. Debride, removing necrotic tissue, and then lavage the wound. 3. Determine i f the w o u n d can be closed. 4. Protect the w o u n d w i t h a bandage, Elizabethan collar, or both. Initial debridement w i l l require general anesthesia, local anesthesia, or neuroleptanalgesia. For future w o u n d evalua tions, the patient may require only sedation or analgesia and restraint, i f surgical debridement is m i n i m a l . Local anes thetics are ideal for the patient that is not stable enough for general anesthesia and has injuries to the limbs. In these cases, wounds i n the h i n d l i m b area can be debrided using epidural analgesia (see Chapter 164, Analgesia and Constant Rate Infusions) and forelimb wounds can be debrided using a brachial plexus b l o c k .
spectrum o f antimicrobial activity. Povidone-iodine is more irritating to tissues, toxic to cells needed for wound healing, and inactivated by organic debris, so it may not be the ideal lavage solution. Lactated Ringer's or normal saline are the most commonly used lavage solutions. A n i n vitro study demon strated that normal saline and tap water cause m i l d and severe cytotoxic effects o n fibroblasts, respectively, whereas lactated Ringer's solution d i d not cause significant fibroblast injury. 1
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Lavage is performed by flushing with a bulb syringe or a 60-ml syringe with an 18-gauge needle. For efficiency, the syringe and needle setup can be connected to a three-way stopcock and an intravenous fluid bag to facilitate refilling. Sugar has a bactericidal effect. Its osmotic action draws macrophages to the w o u n d and accelerates sloughing of devi talized tissue. It is especially advantageous because it is effec tive and economical for large wounds. Indications include degloving and shearing injuries, infected wounds (Streptococ cus, Escherichia coli, and Pseudomonas spp), burns, and other wounds that require further debridement. The w o u n d is first debrided and lavaged. The area is then patted dry with a sterile towel before applying a coating (up to 1 c m thick) of granu lated sugar. A wet-to-dry dressing is applied and changed daily, or more frequently if strike-through occurs. Sugar appli cation is stopped when epithelialization begins. 10
8
Sterile lubricating jelly should be applied to the exposed w o u n d to protect it from further contamination, and a wide area of fur clipped from the skin around the wound. Gross dirt from the skin around the w o u n d should be cleaned by applying surgical scrub solution (chlorhexidine or povidone-iodine) to unbroken skin, but not to the surface o f the w o u n d because these solutions are damaging to exposed tissues. Debridement should be done using aseptic technique: use sterile gloves, sterile gown, cap and mask, and the w o u n d should be draped w i t h sterile towels or water-impermeable drapes. A t the time o f initial assessment and subsequent ban dage changes, necrotic tissue should be excised. A l l bite wounds should be explored, even i f they look minor, because teeth exert a macerating or crushing force that can damage tissues deep below the skin surface (Color Plate 157-1). The hole around the bite w o u n d should be t r i m m e d and then tented up to evaluate the subcutaneous tissues. A probe, such as a mosquito or Kelly forceps, can be used to assess for dead space or pockets under the skin that could form hematomas, seromas, and abscesses. Obviously necrotic tissue (black, green, or gray) is removed first. In areas that have ample skin for closure, i n i tial t r i m m i n g o f skin can be done more aggressively. In areas such as the distal limbs, t r i m m i n g o f skin should be done conservatively, and time can be given to let questionable tis sues "declare" themselves (Color Plate 157-2). Bone, ten dons, nerves, and vessels are preserved as m u c h as possible unless segments o f these vital structures are completely sepa rated from the tissue and obviously nonviable. The w o u n d can be lavaged with a variety o f solutions. In wounds heavily contaminated with road dirt or soil, lukewarm tap water with a spray nozzle may be the most efficient way to remove debris. Maggots should be removed from severely necrotic wounds manually or with aggressive flushing. Chlor hexidine and povidone-iodine can be used i n dilute form (chlorhexidine 0.05% solution: 1 part chlorhexidine 2% + 40 parts sterile water; povidone-iodine 1% solution: 1 part povi done-iodine 10% + 9 parts sterile saline) as initial lavage i n contaminated and infected wounds because o f their wide 1
WOUND CLOSURE The decision o n when and how to close a w o u n d depends on the cleanliness and extent of the wound. Clean, fresh wounds, small, contaminated wounds, or even infected wounds that can be excised completely can be closed primarily. Monofilament absorbable suture should be used i n subcutaneous tissue and muscle, and nonabsorb able suture should be used on the skin. A v o i d tight sutures and tension o n the suture line. Closure should be delayed for contaminated wounds or large wounds with questionable viability. Closure can be performed when a healthy granulation bed is present, which occurs during the repair phase o f healing. Healthy granulation tissue should be pink, smooth, or slightly bumpy, cover the entire wound, and should bleed on the cut surface or when an adhered dress ing is removed. If i n doubt, the w o u n d should be treated as an open infected w o u n d until the granulation bed improves. Delayed primary closure of a w o u n d is performed 2 to 5 days after the injury. Secondary closure o f a wound is defined as clo sure o f a w o u n d 5 or more days after wounding and is usually selected for wounds that were initially classified as dirty (Color Plate 157-3). If the w o u n d is at least 5 days old, granulation tis sue and epithelialized skin edges may need to be excised to allow closure. If the w o u n d is too large to be closed, the clinician should consider a skin graft or flap or closure by second-inten tion healing. Second-intention healing occurs over a healthy granulation bed by the processes of w o u n d contraction and epi thelialization, which continue until the two epithelialized edges of the w o u n d meet. Second-intention healing, even of very large wounds, can often be successful and does not require anything more than diligent bandaging. 2
Exposed Bone Exposed bone is prone to slow healing and must be covered w i t h a granulation bed before skin graft or flap application. Injuries with exposed bone are seen most often with carpal
or tarsal shearing injuries caused by motor vehicle trauma. Exposed bone i n most cases is eventually covered by advanc ing granulation tissue from surrounding healthy soft tissues. Bone perforation can enhance w o u n d healing by encourag ing growth o f granulation tissue over the exposed b o n e . ' ' Once the w o u n d has entered the repair phase, a Jacob's chuck and 0.045- to 0.062-inch K-wires may be used to perforate the surface o f exposed bone through to the medullary cavity. Blood should not be wiped away. A nonadherent dressing with antibiotic ointment should be applied as the primary layer of the bandage. Bandage changes are done at 3- to 5day intervals. Once a complete layer of granulation tissue is present (approximately 7 to 10 days), a free skin graft is applied or ongoing w o u n d management continued u n t i l second-intention healing is complete. 1
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Drains D r a i n placement is indicated d u r i n g w o u n d closure i n areas w i t h excessive dead space, areas w i t h potential for fluid accumulation, or infected or contaminated areas (e.g., abscess, bite w o u n d ) . The drain should exit from the dependent p o r t i o n o f the w o u n d via a separate stab incision, not through the suture line. Ideally the drain should be covered w i t h a bandage to prevent removal by the patient, to further compress dead space, and to keep the area clean. Drains are removed when drainage is clear or m i n i m a l (2 to 7 days). There are two types o f drains, passive and active. A Pen rose drain is the best means o f passive gravitational drainage. This type o f drain can be secured at the proximal extent o f the w o u n d pocket with a simple interrupted suture through the skin that catches the flimsy rubber tubing while it is held in position with a hemostat. A separate opening to secure a Penrose drain proximally should never be made because this allows bacteria to migrate into the w o u n d . There are many types o f active or closed-suction drains, which consist o f a vacuum-generating reservoir connected to fenestrated tubing. These can be used only i n areas that can be closed completely because a vacuum must be created within the wound. There are numerous commercially avail able closed-suction drains such as the J - V A C (Johnson & Johnson, Arlington, T X ) and the S i l - M e d V a c u u m drain (Sil-Med Corp., Taunton, M A ) , which has a grenade-type reservoir. There are also several ways to make closed suction d e v i c e s . A butterfly catheter and red-top b l o o d collection tube can be used for small spaces. Intravenous tubing connected to a 60-ml syringe w i t h the plunger held open with a p i n can be used to drain larger spaces. 112
BANDAGING
Box 157-1
Materials for Dressing Changes
• Sterile lubricating jelly, sterile gauze, umbilical tape, sterile impermeable drape material, cast padding, 18-gauge needles, 35- to 60-ml syringe, Vet Wrap or Elastikon • Triple antibiotic ointment, silver sulfadiazine • Isotonic crystalloids such as lactated Ringer's solution or 0.9% saline • 4-0 to 0 monofilament, absorbable and nonabsorbable suture material • A variety of splints for forelimb and hind limb stabilization
A n adherent dressing is used when the w o u n d is i n the debridement phase, providing mechanical debridement. The most c o m m o n of these is the wet-to-dry dressing, i n w h i c h sterile gauze sponges soaked w i t h sterile saline are wrung out and applied directly to the surface o f the w o u n d , then covered w i t h dry sterile gauze sponges. The dry sponges soak up moisture from the wet ones, and this wicking action causes necrotic tissue and debris to adhere to the sponges when they are removed. It is often necessary to wet the dress ing slightly with sterile saline to allow easier removal and to make it less uncomfortable for the patient. D u r i n g the debridement phase, it is necessary to change the dressing and bandage at least once daily. Sometimes it w i l l be necessary to change it up to 3 times a day initially, depending on h o w dirty the w o u n d is or i f moisture quickly "strikes through" to the outer layer o f the bandage. Nonadherent dressings are used when a healthy, p i n k granulation bed has covered the surface o f the w o u n d and it is no longer infected. Nonadherent dressings help retain moisture, promote epithelialization, and prevent w o u n d dehydration. The most c o m m o n l y used nonadherent dres sings are semiocclusive, meaning that they are permeable to air and maintain a moist environment while allowing exudates to be absorbed from the w o u n d surface. Examples include cotton pads such as Telfa pads (Kendall) or widemesh gauze impregnated with petrolatum, such as Adaptic (Johnson & Johnson). 1
Once the primary layer is applied, the next layer can be either a soft padded bandage or a tie-over bandage. Soft pad ded bandages are used to protect soft tissue wounds on the limbs, and a splint can be incorporated between the second and t h i r d layers to stabilize distal fractures or ligamentous injuries. W i t h these bandages, the secondary layer is rolled cot t o n that is held i n place w i t h rolled gauze. The splint is placed over the cotton and under the gauze. The tertiary layer is often Vet Wrap or Elastikon (placed over the secondary layer but without compression o f the bandage or w o u n d ) . The tie-over bandage is used for wounds o n areas o f the body that are not amenable to soft padded bandages, such as the flank, perineum, or hip areas. Materials include 2-0 to 0 nylon, umbilical tape, gauze, and water-impermeable drape material. Loose suture loops are applied circumferentially around the w o u n d (see C o l o r Plate 157-2). The second ary layer consists o f several layers o f dry gauze squares or laparotomy sponges that are applied for padding and moisture absorption. The tertiary layer is a water-impermeable drape cut to fit the w o u n d , and then all three layers are held i n place by the umbilical tape that is looped through the sutures i n a shoelace fashion. 5
G o o d bandaging practice is essential to maintaining and protecting the wound. Ideally a bandage should cover all open wounds. A bandage consists o f three layers: (1) p r i mary, (2) secondary, and (3) tertiary layers. The necessary supplies are listed i n Box 157-1. The primary layer is the dressing applied directly to the wound. This layer determines the purpose o f the bandage by whether it is an adherent or nonadherent dressing. The secondary layer is composed o f padded material that aids in absorption of exudates. The tertiary layer is the outermost protective layer that holds the others i n place.
The bandage should be protected from the patient by judicious use o f an Elizabethan collar. If the bandage is on
Table 157-1 Antibiotic Use Recommendations in Wound Management 1,15
Antibiotic Use
Situation
Indicated
Obvious local or systemic signs of infection Wounds older than 6 hours Deep tissue injury involving muscle, fascia, bone, tendon Wounds likely to become infected such as bite wounds, penetrating wounds, and wounds involving body orifices Wounds requiring staged debridement, wetto-dry bandaging Prophylactic use to prevent contamination of surrounding normal tissues To keep bacterial numbers low when planning a flap or graft Chronic nonhealing wounds Immunocompromised patient or one that has other condition that might jeopardize healing (e.g., diabetes or Cushing's disease) Clean wounds Superficial wounds less than 6 hours old A contaminated wound that can be converted easily to a clean wound with primary closure Wounds with a mature, healthy granulation bed
May not be indicated
a l i m b , the foot should be covered w i t h a strong plastic bag taped to the bandage when the patient is taken outside to keep it from getting wet or dirty. The bandage should be changed immediately when it gets wet, dirty, or slips, or when there is strike-through from the w o u n d .
If a w o u n d appears infected o n presentation, a G r a m stain can be done to determine the predominant bacterial popula t i o n a n d help i n determining, the initial antibiotic selection. Culture a n d sensitivity testing o f the w o u n d should be done after initial debridement a n d lavage. For superficial wounds i n systemically stable animals, it is best to start w i t h a bactericidal antibiotic that is effective against gram-positive bacteria, such as cefazolin or cephalexin pending culture a n d sensitivity results (see Chapter 108, Gram-Positive Infections). Infected, deeper wounds m a y require a broader-spectrum antibiotic such as a m o x i c i l l i n w i t h a P-lactamase i n h i b i t o r (Unasyn or Clavamox). W i t h bite wounds, the most c o m m o n l y cultured bacteria {Staphylococcus, E. coli, Enterococcus spp) were 100% sensitive to C l a v a m o x . A recent p a p e r suggests that i n i t i a l antibiotic coverage for severe bite wounds should include intravenous a m p i c i l l i n a n d either a fluoroquinolone or aminoglycoside. If the w o u n d becomes infected, another culture o f the w o u n d is recommended because initial results taken d u r i n g the first surgical debridement are o f little value i n predicting the organism involved. These antibio tic recommendations can also apply to most other types o f severe wounds or trauma resulting i n extensive deep tissue d i s r u p t i o n . 14
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W h e n systemic antibiotics are used, they should be started as soon as possible after the injury, used for a m i n i m u m o f 5 to 7 days, and changed i f necessary based o n cul ture and sensitivity results. Wounds can be sampled for repeat culture after 3 to 4 days to determine the effectiveness of antibiotic therapy. If w o u n d healing does not appear to be progressing after the first 2 to 3 days or the animal's condi tion is worsening, a change i n antibiotic therapy may be indicated. Once mature granulation tissue has become estab lished, antibiotic usage is usually unnecessary because this tissue is resistant to infection. 1
1
Topical antibiotics are often used to decrease bacterial populations o n the w o u n d , but they should always be used i n conjunction w i t h debridement and lavage. The following medications are best used by spreading a thin layer on a nonadherent p a d that is the primary layer o f the bandage. Triple antibiotic ointment is more effective for preventing infection than treating it, and it has poor activity against Pseudomonas. Silver sulfadiazine cream is fairly broadspectrum and enhances epithelialization. It is the agent o f choice for b u r n wounds. Nitrofurazone is a broad-spectrum antimicrobial agent w i t h hydrophilic properties; it dilutes exudate. Gentamicin sulfate is good for wounds infected w i t h Pseudomonas and is often used o n open wounds before skin grafting is done. 1
ANTIMICROBIAL THERAPY The most c o m m o n bacterial w o u n d pathogens include gram-positive Staphylococcus spp a n d Streptococcus spp and gram-negative organisms such as Escherichia coli, Enterococcus, Proteus spp, and Pseudomonas spp. ' ' W h e n humans are bitten by dogs a n d cats, Pasteurella multocida is a c o m m o n oral p a t h o g e n , a n d the most c o m m o n anaerobic isolates i n bite wounds include Bacillus spp, Clostridium spp, a n d Corynebacterium spp. Often Pseudomonas w i l l be an acquired infection o n the surface o f the granulation bed, noticeable by the wound's slimy feel a n d obvious pungent odor. Rarely does this cause systemic infection a n d thus does not necessitate systemic antibiotic use. 3
4
1 3 , 1 4
13
14
Antibiotics are not an excuse for inappropriate w o u n d care. Debridement, lavage, and bandaging are the most important parts o f w o u n d management, p r o m o t i n g healing of the tissues a n d creating an environment that negatively affects the ability o f bacteria to proliferate. Systemic antibiot ics are indicated for contaminated and infected wounds to help eliminate bacteria a n d promote h e a l i n g . Some clean, recent wounds, such as sharp lacerations, do not require microbial evaluation, a n d superficial wounds that are easily debrided and closed may require only perioperative antibi otic use (Table 157-1). 15
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1
PATIENT CARE Patients w i t h extensive wounds that require daily debride ment and bandage care may need intensive care initially (see Chapters 64 and 65, Daily Intravenous Fluid Therapy and Shock Fluids a n d F l u i d Challenge, respectively). They also require pain management (see Chapter 164, Analgesia and Constant Rate Infusions) and nutritional therapy (see Chap ters 13 and 14, Enteral N u t r i t i o n and Parenteral Nutrition, respectively) while recovering from trauma. Table 157-2 lists some of the c o m m o n l y used pain medications and antibiotics w i t h their dosages.
Table 157-2
Drugs Commonly Used During Wound Management
Key Drug
Drug Class
Dosage Range
Frequency
Route
Indications
Amoxicillin or ampicillin
Extendedspectrum penicillin antibiotic
15 to 22 mg/kg
q6-8h
PO (amoxicillin) or IV or IM (ampicillin)
Infection, dirty wounds
Amoxicillinclavulanic acid
Extendedspectrum penicillin antibiotic with P-lactamase inhibitor
13.75 to 20 mg/ kg
q8-12h
PO
Superficial wounds
Amoxicillinsulbactam
Extendedspectrum penicillin antibiotic with P-lactamase inhibitor
13.75 to 20 mg/ kg
q8-12h
IV, IM
Superficial wounds
Cefazolin
Cephalosporin antibiotic
22 mg/kg
q6-8h; for perioperative use give 20 min before surgery and then q2h until surgery is complete
IV, SC
Infection, dirty wounds
Enrofloxacin
Fluoroquinolone antibiotic
q24h (or divided q12h) 5 to 20 mg/kg (do not exceed 5 mg/kg q24h in cats)
IV
Infection, dirty wounds
Metronidazole
Antimicrobial
7 to 10 mg/kg
q8-12h
PO, IV
Anaerobic infection, dirty wounds
Hydromorphone or oxymorphone
Opioid
0.05 to 0.1 mg/ kg
q4-6h
IV, IM
Pain management
Acepromazine
Phenothiazine anxiolytic
0.005 to 0.02 mg/ As needed kg
IV, IM
Used with oxymorphone for restraint with bandage changes
Fentanyl patch (Duragesic)
Opioid
30kg: 100ng
Dermal
Pain management
Epidural morphine (Duramorph)
Opioid
0.1 mg/kg diluted in 0.1 ml/kg 0.9% saline, not to exceed 6 ml
Produces pain relief in 30 Epidural to 60 min that lasts 10 to 24 hr
Pain management; local analgesia if combined with bupivacaine (use 0.1 ml/kg of 0.5% bupivicaine instead of saline)
Bupivicaine 0.5%
Local anesthetic
1.5 mg/kg maximum dose
Duration of effect 4 to 6hr
Local block
Pain management, early assessment, aid in restraint during debridement
Vitamin A
Vitamin
10,000 lU/dog
Once a day
PO
Antagonizes the effect of corticosteroids on wound healing
IM, Intramuscular; IV, intravenous; PO, per os; SQ subcutaneous.
COMPLICATIONS The biggest concern for the clinician managing severe wounds is poor w o u n d healing. A n e m i a , severe trauma, or hypovolemia can delay w o u n d healing due to poor oxygen delivery to the w o u n d . Poor perfusion and nutritional status can also have detrimental effects o n healing. Serum protein levels less than 2 g/dl impedes w o u n d repair by decreasing fibrous tissue deposition. Infection and foreign bodies cause 6
intense inflammatory reactions that interfere w i t h healing. Patients w i t h cancer that are receiving chemotherapy or those who have had radiation therapy to the area of the w o u n d w i l l also be prone to delayed w o u n d healing. Patients w i t h diabetes, uremia, liver disease, or hyperadrenocorticism are susceptible to infection or delayed healing as well. C o r t i costeroids decrease the inflammatory phase o f healing and the rate o f protein synthesis; however, v i t a m i n A can antag onizes these detrimental effects o f corticosteroids. 6
M o s t wounded patients are dogs; however, cats often pres ent the more challenging cases. A x i l l a r y wounds i n cats can be particularly difficult to manage. A n experimental study found that cats have significant differences i n w o u n d healing c o m pared w i t h d o g s . Sutured wounds i n cats were only half as strong as those i n dogs by day 7, and cats demonstrated signif icantly less granulation tissue p r o d u c t i o n than dogs d i d i n wounds that were evaluated for second-intention healing.
u n c o m m o n i f injuries require daily bandage changes and w o u n d debridement, and expenses can go up to $6000 or more i f fracture repair is needed. In some cases, patients can be treated o n an outpatient basis with bandage changes every other day. Complicated w o u n d healing can take several months and require multiple surgical procedures.
Lack o f bleeding or negative sensation i n a l i m b indicates a poor prognosis and may necessitate amputation. These changes may not be predictable at the time o f the initial evaluation. As with any surgery other complications can include infection, dehiscence, and scarring. Contracture i n l i m b wounds that are allowed to close by second intention can result i n decreased mobility and may require referral to a surgeon for skin reconstruction.
SUGGESTED FURTHER R E A D I N G *
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PROGNOSIS The owner should be advised as early as possible o f the prog nosis, extent o f care involved, and cost. Prognosis depends on the extent o f injury and the location. Some wounds may be irreparable, leading to the loss o f a limb. Cost depends o n the extent o f the injury and increases w i t h multiple inju ries and i f fracture repair or abdominal exploration is required. Length o f hospitalization depends o n the extent o f debilitation, whether intravenous fluids or a feeding tube is required, and whether daily bandage changes and w o u n d debridement are needed. Costs o f $3000 or more are not
Crowe DT: Emergency care of wounds, DVM Best Pract Februaryll, 2002. Article with excellent step-by-step instructions on managing the trauma patient with wounds. Companion articles in this periodical, a supplement to DVM Magazine, useful as well. Davidson DB: Managing bite wounds in dogs and cats. Part II, Comp Cont Educ Pract Vet 20:974, 1998. The second part of a two-part article that goes in depth on surgical debride ment, drains, and bandaging; includes useful tables and intraoperative photos. Fossum TW, Hedlund CS, Hulse DA, et al: Surgery of the integumentary system. In Fossum TW, editor: Small animal surgery, ed 2, St Louis, 2002, Mosby. Best surgery textbook for those who want to invest in just one. Chapter on the skin good for getting started and goes into some depth on more advanced reconstructive techniques. Mathews KA, Binnington AG: Wound management using sugar, Comp Cont Educ Pract Vet 24:41-50, 2002. An article that reviews the use of sugar as an inexpensive dressing to clean and debride wounds. Swaim SF, Henderson RA: Small animal wound management, ed 2, Balti more, 1997, Williams & Wilkins. An excellent text on wound management, especially for the student, intern, and resident; includes useful tables and illustrations and the best review of topical agents for wounds *See the CD-ROM for a complete list of references.
Chapter 158 THERMAL BURN INJURY Caroline K. Garzotto,
V M D , DACVS
A l t h o u g h these are n o w considered older terms, many physicians still like to refer to b u r n wounds as first-degree, second-degree, and third-degree injuries (Table 158-1). ' First-degree b u r n wounds are superficial and are confined to the outermost layer o f the epidermis. The skin w i l l be reddened, dry, and painful to touch.
KEY POINTS • Electric heating pads, motor vehicles with hot mufflers, and fire exposures are the most common sources of burn injuries seen in the veterinary patient. • If the injury is from a fire exposure, the patient should be assessed for smoke inhalation (see Chapter 28, Smoke Inhalation). • If more than 20% of the total body surface area is involved, cardiovascular shock, major metabolic derangements, and sepsis can occur. These patients will need both medical and surgical treatment. • Burn wounds may take several days to "declare" themselves, because heat dissipates slowly from burned skin. • The eschar should be removed early to help establish a healthy granulation bed and prevent infection. • Silver sulfadiazine is the mainstay of topical treatment for burn wounds. • Cost of treatment and prognosis, especially in animals with severe metabolic derangements needing critical care, should be thoroughly discussed with owners.
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Second-degree burn wounds are partial-thickness injuries that involve the epidermis and a variable amount of the dermis. If only the superficial part of the dermis is affected, there will be thrombosis of blood vessels and leakage of plasma. The hair fol licles are spared. In deeper partial-thickness burns, hair follicles are usually destroyed, the skin appears yellow-white or brown, and there is decreased sensation except to deep pressure. 1
Third-degree b u r n wounds are full-thickness injuries that have destroyed the epidermis and dermis and can affect deeper tissues such as muscle, tendon, and bone. The skin is leathery and charred and lacks sensation. W h e n burned, skin retains heat, so an accurate assessment o f the degree o f the w o u n d may not be apparent initially. It can take up to 3 days for the b u r n to "declare" itself, and during that time thermal injury and circulatory compromise from thrombosed vessels can continue. 1
INTRODUCTION Thermal b u r n wounds are relatively u n c o m m o n i n veterinary medicine. The most c o m m o n sources o f burns i n small ani mals include electric heating pads, fire exposures, scalding water, stove tops, radiators, heat lamps, automobile mufflers, improperly grounded electrocautery units, and radiation ther apy. M o s t b u r n wounds can be managed the same as trau matic wounds (see Chapter 157, W o u n d Management). Like traumatic wounds, b u r n wounds can be labor intensive and expensive for the owner. In addition, numerous metabolic derangements can adversely affect the patient, prolong hospi talization, and complicate the recovery. 1
DEFINITIONS Burn wounds are assessed using two major parameters: the degree o f the injury and the percentage o f body surface area involved. First, a review o f skin anatomy is helpful. The most superficial layer of skin is the epidermis and the deeper layer o f skin is the dermis. The dermis is comprised of a superficial plexus and a middle plexus, where hair and glandular struc tures arise. Below the dermis lies the hypodermis, w h i c h con tains the deep or subdermal plexus and the panniculus muscle. The subdermal plexus brings the b l o o d supply to overlying skin through the superficial and middle plexus. Capillary loops i n the superficial plexus supply the epidermis; however, they are poorly developed i n the dog and cat compared to humans, which is why these animals do not develop blisters. 1
1
Patients w i t h burns involing more than 20% o f their total body surface area ( T B S A ) can have serious metabolic derange ments. Patients w i t h more than 50% o f their T B S A involved have a poor prognosis, and euthanasia should be discussed w i t h the owners as a humane alternative. T B S A can be estimated i n animals using percentages allotted to body area using the rule o f nines as described i n Table 1 5 8 - 2 . 1-3
W h e n skin is severely burned, it forms an eschar w i t h i n 7 to 10 days. Eschar is a deep cutaneous slough o f tissue composed o f full-thickness degenerated s k i n . It appears as a black, firm, thick movable crust that separates from the surrounding skin, and purulent exudates often lie beneath it ( C o l o r Plate 158-1). 4
PATIENT ASSESSMENT AND MEDICAL MANAGEMENT The patient should be assessed immediately for airway, breath ing, and circulatory compromise as for all trauma patients (see Chapter 2, Patient Triage). Following a full physical examina tion, including inspection o f the patient from head to foot pads, an assessment o f the degree and T B S A o f the b u r n wounds should be performed to help determine prognosis and the extent o f treatment necessary. B l o o d should be col lected for evaluation o f packed cell volume, total solid and electrolyte levels, and b l o o d gas parameters, minimally.
Table 158«1 Bum Wound Assessment and Healing Degree
Depth
Appearance
Healing
First
Superficial
Erythematous Painful to touch
Healing rapid, reepithelializes in 1 week with topical wound management No systemic affects
Second
Superficial partial thickness
Epidermis will be charred and sloughs; plasma leakage occurs Hair follicles spared Painful to touch
Healing by epithelialization from the wound margin with minimal scar in 10 to 21 days May have systemic effects
Second
Deep partial thickness
Skin appears black or yellow-white Hair follicles destroyed Decreased pain sensation
Healing by contraction and epithelialization but scarring significant without surgical intervention Significant systemic effects expected
Third
Full thickness
Skin is black, leathery; muscle, bone, tendons can be affected Eschar insensitive to touch
Healing often requires extensive surgical intervention, possible skin grafts and flaps May have life-threatening systemic effects stabilized, a constant rate infusion (CRI) of synthetic colloids (e.g.,hydroxyethyl starch, dextran-70) may be beneficial at a rate o f 20 to 40 ml/kg/day. Plasma is given at 0.5 ml/kg body weight x % T B S A burned i n humans, although this has not been investigated i n dogs and cats. By 48 hours after injury, plasma volume is mostly restored, and thus patients are at high risk for generalized edema and fluid overload from the high initial demands for fluid replacement. Ideally, fluid therapy should be adjusted for the individual patient based o n cardio vascular stability, central venous pressure (0 to 10 c m H 0 ) , and urine output (>1 ml/kg/hr).
Table 158-2 Estimating Total Body Surface Area Bumed Area Head and neck
Percentage (%)
Total %
9
9
Each forelimb
9
18
Each rear limb
18
36
Thorax
18
18
Abdomen
18
18
TOTAL
72
99
3
2
Nutrition Metabolic Derangements If more than 20% o f a patient's T B S A is burned or i f the wounds are classified as second or t h i r d degree, hypovolemic shock should be anticipated. As a result o f capillary t h r o m b o sis and plasma leakage, massive amounts o f fluid are retained i n the w o u n d leading to b u r n w o u n d edema. This results i n the loss o f fluid and electrolytes, w i t h the most dramatic losses occurring during the first 12 hours. Systemic abnormalities should be anticipated, i n c l u d i n g anemia, hypernatremia or hyponatremia, hyperkalemia or hypokalemia, acidosis (meta bolic and respiratory), oliguria, and prerenal azotemia. The course o f the systemic abnormalities changes w i t h t i m e . 3
2
Hemoconcentration w i l l be noted initially because o f the dramatic loss o f plasma; however, red b l o o d cell hemolysis also occurs simultaneously from both direct damage and destruction through the damaged microcirculation. The patient should be m o n i t o r e d for disseminated intravascular coagulation ( D I C ) , upper airway edema and oliguria. Between days 2 and 6, the patient should be assessed for anemia, D I C , i m m u n e dysfunction, systemic inflammatory response syndrome, and early b u r n w o u n d infection. F r o m day 7 and on, the clinician should watch closely for hyper thermia, hyperventilation, pneumonia, sepsis, and w o u n d demarcation. F l u i d losses can result i n hypovolemic shock (see Chapter 65, Shock Fluids and F l u i d Challenge). After initial shock resuscitation w i t h isotonic crystalloids up to 90 m l / k g I V i n dogs (50 m l / k g i n cats) and synthetic colloids or b l o o d products, i f needed, total fluid delivery rate during the first 24 hours should be 1 to 4 m l / k g body weight x % T B S A b u r n e d . After 12 to 24 hours, when vascular permeability is 2
The importance o f adequate nutrition cannot be overempha sized i n assisting w i t h healing o f b u r n wounds, because of the fragile metabolic state of the patient. Nutritional requirements should be based o n the patient's needs; an initial estimate is made by calculating the resting energy requirement. The diet should be high calorie, high protein and the quantity of food can be increased as tolerated by the patient. It is best i f the patient can eat voluntarily, but i f the animal is not consuming adequate nutrition, an esophagostomy tube should be placed or total parenteral nutrition commenced (see Chapters 13 and 14, Enteral N u t r i t i o n and Parenteral N u t r i tion, respectively). Gastrointestinal (GI) protectants (famoti dine at 0.5 to 1 mg/kg P O or I V ql2-24h) are recommended to compensate for GI hypoperfusion and ulceration secondary to hypovolemic shock (see Chapter 181, Gastrointestinal Protectants).
Patient Comfort A l t h o u g h severely damaged skin is often numb, deeper viable tissues and surrounding areas are often hypersensitive and thermal damage may be ongoing; thus one should assume that b u r n patients experience extreme pain. G o o d systemic analgesics include oxymorphone and hydromorphone (0.05 to 0.1 mg/kg I V q4-6h) and fentanyl as a C R I (2 to 5 ug/kg/hr I V ) . A fentanyl patch may not be appropri ate i n animals w i t h more than 20% T B S A burned or who are still being treated for hypovolemic shock. G o o d nursing care is important, and animals should be turned every 4 hours if recumbent to prevent decubitus ulcers. Passive range-ofm o t i o n l i m b exercises can help prevent edema and maintain mobility. 2
Antibiotics Sepsis is one of the greatest threats to burn patients with extensive T B S A involvement, because bacteria can colonize and proliferate i n wounds that have lost the protective skin bar rier. The best way to prevent local and systemic infection is to protect the wound from contamination i n the hospital environ ment, and to remove all necrotic tissue and purulent exudates from the w o u n d surface as aggressively as possible through serial debridement. Systemic antibiotics are not indicated unless the patient is immunocompromised, has pneumonia or pulmonary injury, or sepsis is suspected. Topical antibiotics are the antimicrobial treatment o f choice (see Burn W o u n d Management i n the following section). Because most invasive burn wound infections are caused by Pseudomonas or other gram-negative organisms, antibiotics against these bacteria are administered empirically until culture and sensitivity results are available (see Chapter 109, Gram-Negative Infections). 3
BURN WOUND MANAGEMENT Although early w o u n d closure is the primary goal to decrease further electrolyte, protein, and fluid losses, this is not expected to take place for at least 3 to 7 days while the wound is "declaring" itself. Daily w o u n d care, however, is critical. Once systemically stable, the patient is sedated w i t h neuroleptanalgesia or placed under general anesthesia and the fur is liberally clipped to assess the damage. If fur pulls easily out o f the skin, the w o u n d is likely a deep partialthickness or full-thickness b u r n (see Table 158-1). If the patient presents w i t h i n 2 hours o f the b u r n injury (which is usually not the case), cold water lavage for 30 m i n utes w i l l often help to release heat from the skin and limit the depth o f injury. The temperature o f the water should not be below 3° C , and i f large body surface areas require treatment, it is important to prevent iatrogenic hypothermia. The affected area can be submerged i n a cold water bath i f it is on a limb, and cool towels or cool water from a spray noz zle can be applied to other areas.
Conservative debridement is characterized by the daily serial piecemeal removal o f necrotic tissue (black a n d hard, burned skin) using aseptic technique, w i t h either sterile gauze or sterile scissors and thumb forceps. Because necrotic tissue is w i t h o u t sensation, this may not require daily anes thesia; however, m a n i p u l a t i o n o f deeper viable tissues and s u r r o u n d i n g hyperemic areas w i l l likely be painful d u r i n g lavage. This f o r m o f debridement is acceptable initially when there is no clear definition o f nonviable tissue or when it is necessary to be conservative i n areas overlying tendons, liga ments, and bone. 1
Enzymatic debridement is the use o f topical agents to soften, loosen, and digest necrotic tissue, making removal possible with gentle lavage. The advantage is that it does not require general anesthesia and involves sparing of healthy tissue. Because some o f the commercially available agents are expensive, it is most cost effective to use them on small l i m b wounds. The most c o m m o n o f these enzy matic topical agents is trypsin-balsam o f Peru castor o i l (Granulex, Pfizer A n i m a l Health, West Chester, P A ) . It is recommended that this be applied only i n the early stages of w o u n d therapy and that its use discontinued once a healthy bed o f granulation tissue has been established. 4
Aggressive surgical excision o f an entire b u r n w o u n d requires general anesthesia and is indicated i n deep partialthickness and full-thickness burn wounds that may otherwise take days or weeks to be debrided conservatively. This is done most easily on large areas o f the trunk or small areas o f the limbs, which can then be closed primarily (Color Plates 158-2 and 158-3). If the area cannot be closed primarily, it will take about 5 to 7 days for a healthy granulation bed to form and then a flap or skin graft surgery can be performed. 1
1
Treatment of the w o u n d then depends o n its depth. In superficial burns or superficial partial-thickness burns, it may be appropriate to use daily lavage and topical agents alone until the depth of the w o u n d is determined i f the w o u n d goes deeper. Deep partial-thickness and full-thickness burns require debridement. Debridement can be done i n three ways: conservatively, enzymatically, or aggressively with surgery. Conservative debridement is often used for the first 3 to 7 days, until more aggressive surgical debridement can be per formed based on the status of the w o u n d and o f the patient. 1
1
Daily treatment of b u r n wounds with conservative debride ment involves hydrotherapy, removal o f necrotic tissue, t o p i cal therapy, and bandaging. This may need to be done more than once a day initially for wounds that are particularly necrotic or exudative. Hydrotherapy consists o f gentle lavage of the w o u n d with r o o m temperature sterile saline or lactated Ringer's solution. This helps to loosen and separate any n o n v i able or necrotic tissue from the surface of the burn. The i r r i gants should be delivered using a 35-ml syringe and a 19gauge needle to create a pressure o f 8 psi. Higher pressures may induce tissue trauma and cause deeper seeding of bacteria into the burn. A wet-to-wet dressing under a bandage can also be placed on burns for several hours at a time to slowly loosen the necrotic tissue and facilitate debridement. ' 1
4
Topical Agents Following hydrotherapy and debridement, topical agents and bandages are applied. Aloe vera cream has antithromboxane effects that prevent vasoconstriction and thromboembolic seeding o f the microcirculation. Early use can help prevent progression o f superficial partial-thickness burns. Aloe vera is applied liberally to the surface of the w o u n d with a sterile gloved finger within the first several days o f injury while the patient is sedated, because these wounds are painful when touched. The w o u n d can be covered with a nonadherent dressing and a ban dage. The bandage is changed at least once a day. 4
Silver sulfadiazine is the most well-known b u r n cream used in humans and animals. It has a wide spectrum o f bactericidal activity against gram-positive and gram-negative bacteria and Candida. The cream is placed directly o n the w o u n d under the contact layer o f a bandage using sterile gloves. For very large areas that are not amenable to bandaging, patients can be trea ted "open" without a bandage, by slathering silver sulfadiazine over the w o u n d and keeping the patient confined i n a lowfomite environment (empty clean cage w i t h no blankets or stuffed toys). ' The cream can be rinsed off gently before reapplication up to 2 to 3 times a day, i f needed. Silvadene can be used during both the early debridement stage under wet-towet dressings and through the repair stages of healing using nonadherent bandages. 1
4
Unpasteurized honey has been shown to demonstrate many favorable properties i n the management o f wounds, including b u r n wounds (see Chapter 157, W o u n d Manage ment). It has been shown to outperform more expensive
5
commercial products. Healing properties of honey are varied; honey decreases inflammatory edema, accelerates sloughing o f necrotic tissue, and provides a rich cellular energy source, pro moting a healthy granulation bed. In addition, honey has anti bacterial properties due to its high osmolarity, acidity, and hydrogen peroxide content. The hydrogen peroxide is present in levels that are harmless to healthy tissue. H o n e y can be used during the debridement phase and also over infected granula t i o n tissue. H o n e y is applied to the w o u n d after hydrotherapy and debridement o f necrotic tissue. Gauze sponges soaked i n honey are applied directly to the w o u n d as the p r i m a r y layer and then covered w i t h an absorbent second layer to prevent it from leaking out o f the bandage.
Closure Options and Healing Superficial and partial-thickness b u r n wounds have a favor able outcome w i t h no surgical intervention. These wounds reepithelialize quickly and can heal w i t h i n 1 to 3 weeks w i t h open w o u n d management. If only the superficial layer o f the dermis is involved i n partial-thickness burns, healing can be rapid. The overlying burned epidermis w i l l slough, and healthy epithelium w i l l be apparent below. Deeper burns involving the hair follicles, especially i f they are large, can heal more slowly (up to 3 weeks). Deep dermal partialthickness and full-thickness burns heal by contraction and epithelialization once a healthy granulation bed has been created by diligent debridement. These wounds can eventu ally closed primarily. Full-thickness burns covering large areas o f the body or o n the limbs may require skin grafts or skin flaps for complete closure. Hyperbaric oxygen therapy has not been well studied i n dogs and cats but may promote angiogenesis (which is fos tered by the increased oxygen gradient), collagen deposition, reepithelialization, cellular respiration, and oxidative killing of bacteria. In addition, decreased edema following hyperbaric therapy allows better diffusion o f oxygen and nutrients through the affected tissues, while relieving pressure o n
surrounding vessels and structures. There is limited access to hyperbaric oxygen chambers for dogs and cats, but this may prove to be a beneficial treatment strategy i n the future. Vacuum-assisted closure strategies have been used with success i n humans with b u r n injuries, especially following graft placement, to promote the removal of interstitial edema, increase local b l o o d flow, and stimulate granulation tissue formation. Tissue bacterial counts are also decreased w i t h this technique; however, veterinary research is lacking. 6
7
Complications Scarring and w o u n d contracture are the biggest complica tions i n patients w i t h b u r n wounds left to heal by second intention. This is particularly a concern for b u r n wounds i n the axillary or inguinal areas or around joints, which can lead to decreased mobility and range of m o t i o n of the limbs. Wounds i n these areas should be managed by some one experienced i n reconstructive surgery, because these cases most likely w i l l require skin grafts or flaps.
SUGGESTED FURTHER R E A D I N G *
Dhupa N, Pavletic MM: Burns. In Morgan R, editor: Handbook of small ani mal practice, ed 4, 2003, Saunders. An easy-to-follow veterinary text in outline format. Mathews KA, Binnington AG: Wound management using honey, Comp Cont Educ Pract Vet 24:53, 2002. An interesting article with historical perspective and review of research on the use of honey in medicine. Includes nice photos showing examples of treat ment burn wounds with honey. Pope ER: Burns: Thermal, electrical, and chemical burns and cold injuries. In Slatter D, editor: Textbook of small animal surgery, ed 3, Philadelphia, 2003, Saunders. A chapter from the well-known veterinary surgery textbook with a very thor ough review of burn pathophysiology. Swaim SF, Henderson RA: Small animal wound management, ed 2, Balti more, 1997, Williams & Wilkins. An excellent text especially for the student, intern, and resident. Has nice table and illustrations. *See the CD-ROM for a complete list of references.
Chapter 159 ELECTRICAL AND LIGHTNING INJURIES F. A. Mann,
DVM, MS, DACVS, DACVECC
Ultimately, the result is necrosis o f the superheated tissues and those tissues that become ischemic from the vascular consequences. Direct thermal injury may also occur from arcing o f a current that leaves the electrical source, crosses an air gap, and strikes tissue.
KEY POINTS • Electrical injury results from the direct effects of the electrical current and from the transformation of electrical energy to heat. • The severity of electrical injury depends on the resistance of the stricken body part, the nature of the current, and the intensity of the current. • The most common electrical injury in small animals occurs when young dogs and cats chew on household electrical cords. • Clinical manifestations of electrical injury include surface burns, cardiac arrhythmias, respiratory distress, and neurologic abnormalities, and treatment is tailored to the clinical effects that are evident. • Dogs and cats are less likely to be struck by lightning than are large animal species but, when struck, dogs might be more susceptible to the effects of lightning than are humans.
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The severity o f electrical injury varies depending o n the electrical resistance o f the part o f the body that is struck, the nature o f the current (alternating versus direct), and the intensity o f the current (amperage). Less energy w i l l be transferred to areas o f the body that have high resistance to electrical flow. D r y skin has h i g h resistance; therefore less energy w i l l be transferred i n dry skin than i n wet skin. Wet skin and moist mucous membranes have l o w electrical resistance; therefore one can expect high flow o f electricity i n these tissues and propensity for m a x i m a l tissue damage. 1,4
INTRODUCTION Electrocution may occur by contact w i t h high-voltage or lowvoltage electrical sources or by a lightning strike. It is generally accepted that chewing through household electrical cords is the most c o m m o n cause o f electrocution i n dogs and cats. From 1968 to 2003, a database from several institutions* recorded that 280 dogs and 92 cats sustained electrical injuries. O f these, 54 dogs and 26 cats had chewed electrical cords, and 4 dogs and no cats were identified as having been struck by lightning. It is likely that many o f the unspecified electrocu tions were low-voltage injuries from chewing household electrical cords.
Alternating currents tend to cause more severe injury than direct currents at the same amperage. Higher exposure may occur w i t h alternating current electricity than w i t h direct current because the former elicits muscular contraction that prevents the v i c t i m from releasing the power source. A s such, the exposure time is typically longer w i t h alternating current than w i t h direct current. Direct current electricity does not usually cause muscular tetany. Given the same resistance, high-voltage electricity can be expected to cause more damage than low-voltage electricity. One might expect more injury from 240-volt outlets used for large household appliances than w i t h 120-volt standard wall outlets. However, current (amperage) is a function o f voltage divided by the resistance; therefore the magnitude o f the cur rent w i l l depend o n the affected tissue as discussed previously. ' 1
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MECHANISM OF ELECTRICAL INJURY The mechanisms o f electrical injury are related to the direct effects o f the electrical current and the transformation of electrical energy to heat. The electrical current may disrupt elec trophysiologic activity, leading to muscle spasms, cardiac arrhythmias, loss o f consciousness, and respiratory arrest. Direct cellular injury may occur through the process o f electroporation. Electroporation is the development o f momentary holes i n cellular membranes induced by electrical shock. The holes allow passage of macromolecules across membranes, causing osmotic damage to cells. 1
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As electrical current is transformed to heat, intracellular and extracellular fluids may become superheated, resulting i n coagulation of tissue proteins, thrombosis o f small ves sels, and degenerative changes i n small arterial w a l l s . ' ' 1
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T h e Veterinary Medical Data Base (VMDB), Purdue University, West Lafayette, IN (http://www.vmdb.org). The VMDB does not make any implicit or implied opinion on the subject of this chapter.
PREDISPOSITION TO ELECTRICAL INJURY Young dogs and cats are the most c o m m o n victims of electrical injury because they are more likely to chew o n electrical cords than are older animals. The average age of dogs w i t h electrical injury has been reported to be 3.5 months (range, 5 weeks to 1.5 years; n = 29); the range o f age for seven cats was reported to be 2 months to 2 years. F r o m 1968 to 2003, a database collected i n several institutions* revealed that the most c o m m o n age range for electrical injuries was 2 to 12 months; 186 o f 280 (66%) dogs and 44 o f 92 (48%) cats w i t h electrical injuries and 38 o f 54 (70%) dogs and 12 o f 26 (46%) cats that sustained electrical injury from chewing electric cords were 2 to 12 months old. Seasonal predisposition is generally accepted, but there is some difference i n o p i n i o n as to what time o f year most injuries are seen. H o l i d a y seasons characterized by use o f decorative lights (Halloween, Christ mas) certainly pose electrical risks, but one study reported 1
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Figure 159-1 Lateral (A) and ventrodorsal (B) thoracic radiographs of a puppy that was electrocuted by chewing an electrical cord. Note the prom inent infiltration of the caudodorsal lung fields. (Courtesy Dr. Everett Aronson.)
that 79% o f canine cases occurred d u r i n g the 6 months from M a r c h through August. 1
CLINICAL FINDINGS
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Surface burns may be noted at the point o f contact with the electrical source. The thermal injury may be superficial, characterized by m i l d hyperemia, or may manifest as a severe full-thickness b u r n . Burns from chewing electrical cords have been noted o n the lips, gums, tongue ( C o l o r Plate 159-1), and palate. " Some oral cavity electrocutions pro duce enough trauma to cause dental fractures and oronasal fistulas. 1
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Cardiac arrhythmias may be present, the severity o f which depends on the intensity o f the electrical current. Sudden death from electrical shock is likely due to ventricular fibril lation caused by low-voltage current, as with most house hold exposures. ' ' High-voltage exposure may cause asystole. Animals that survive the initial shock may experi ence ventricular arrhythmias. Ventricular or sinus tachycardia may be noted o n presentation. 4
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Respiratory distress is less severe with electrical cordinduced pulmonary edema than with other causes o f noncar diogenic pulmonary edema. Likewise, there is less radiographic involvement than with other causes o f noncardiogenic pulmonary edema, and there is often radiographic evidence o f resolving pulmonary infiltrates within 18 to 24 hours (Figures 159-1 and 159-2).'
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Respiratory distress is a c o m m o n clinical feature noted i n the form o f tachypnea, cyanosis, orthopnea, coughing, or apnea. Respiratory arrest from tetanic contractions o f respi ratory muscles occurs d u r i n g contact w i t h the electrical source, but breathing typically resumes when the v i c t i m is separated from the source o f electricity. 8
Causes o f respiratory distress include facial or nasopha ryngeal edema, diaphragmatic tetany, and neurogenic p u l monary edema. Neurogenic pulmonary edema is a form o f noncardiogenic pulmonary edema i n w h i c h central nervous system ( C N S ) insult results in massive sympathetic outflow that causes pronounced vasoconstriction and systemic hypertension. As a consequence, there is marked elevation of left ventricular afterload and decreased left ventricular stroke volume, which causes blood to accumulate in the pulmonary circulation, resulting i n increased pulmonary capillary pressure and subsequent edema. The typical radio graphic pattern is alveolar infiltration o f the caudodorsal quadrant (Figure 159-1). 9
Neurologic injury as a result o f direct C N S stimulation may be noted immediately upon electrical contact. Stiffening of the animal has been noted by people who have witnessed a dog or cat biting an electrical c o r d . The victim usually loses consciousness. There may be focal muscle tremors or seizures, sometimes accompanied by defecation or vomit ing. Extensor rigidity and death may occur rather rapidly. Tetanic l i m b contraction has been noted after surviving high-voltage electrical s h o c k . The neurologic manifesta tions are thought to be due to electrically induced neural activity rather than electroporation and resultant tissue hyp oxia, although hypoxia from excess energy consumption could play a r o l e . " 3
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Gastrointestinal (GI) abnormalities may result from elec trical interference with motility. A b d o m i n a l radiographs or ultrasonography may show G I gas patterns characteristic of ileus. Ocular manifestations o f electrical injury (cataracts) are usually later findings noted several months after the episode. Cataracts are c o m m o n l y seen in humans, following nearly fatal electrical injury and lightning strike and have been reported in a dog that was electrocuted by chewing an elec trical c o r d . 4
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SECONDARY EFFECTS OF ELECTRICAL INJURY A l t h o u g h complete blood count and serum chemistry results are usually within normal limits, tissue hypoxia from electri cally induced ischemia and pulmonary edema may lead to necrosis o f the affected tissues and subsequent hematologic changes and additional organ damage. Tissue necrosis may lead to hyperkalemia, myoglobinemia and myoglobinuria,
Figure 159-2 Lateral (A) and ventrodorsal (B) thoracic radiographs of the puppy in Figure 159-1 taken approximately 24 hours after the radio graphs in Figure 159-1. Note the significant progress in resolution of the pulmonary infiltration. (Courtesy Dr. Everett Aronson.)
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and hemoglobinemia and hemoglobinuria. Hyperkalemia may also result from excessive muscular activity d u r i n g electrical shock; this muscular activity also contributes to acidemia and hyperlactatemia. ' Hypoproteinemia may ensue in patients with severe burns. 1 1
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TREATMENT OF ELECTRICAL INJURY Initial treatment at the scene o f the exposure includes precautions to prevent inadvertent injury to rescuers. The source of electricity should be turned off before touching the victim. Preferably, the electricity should be turned off at the electrical panel but, alternatively, the offending electrical cord may be unplugged carefully from the outlet. Once the victim is removed from the electrical source, immediate medical attention should be sought regardless o f the victim's apparent condition. Victims in cardiopulmonary arrest require cardiopulmonary-cerebral resuscitation. Better results might be expected in a hospital environment, but lifesaving techniques on the scene may be required i f there is any hope of success. Treatment for animals that survive the initial electrical insult is tailored to the clinical effects. Animals i n shock are treated with intravenous fluids to expand intravascular volume because the mechanism of shock is likely a relative hypovolemia. H o w ever, because a cardiogenic component to the shock from arrhythmia and subsequently decreased stroke volume is possi ble, and because neurogenic pulmonary edema may develop quickly, the volume of fluids administered should be strictly controlled. Fluids that typically are given i n low volumes (i.e., hypertonic saline, synthetic colloids) are recommended. Respiratory distress requires prompt attention. A i r w a y obstruction from edematous oropharyngeal tissues may require temporary tracheostomy tube placement. Partial obstructions may be managed conservatively with sedation and, if not contraindicated, antiinflammatory drugs and diuretics. Supplemental oxygen is recommended, but if the respiratory distress is due entirely to obstruction, relief o f the obstruction should return oxygenation to normal.
Oxygen supplementation should continue until it is ascertained that neurogenic pulmonary edema has not devel oped or has resolved. Treatment o f pulmonary edema is facilitated by furosemide, particularly i f the animal received shock doses o f fluids; however, caution should be exercised to prevent creating a state o f hypovolemia from excessive diuresis. Bronchodilators may also be useful (see Chapter 21, Pulmonary Edema). Positive-pressure ventilation may be required i f the patient is hypoxic and does not respond to supplemental oxygen (see Chapter 213, Basic Mechanical Ventilation). Burned tissues are treated conservatively using standard w o u n d treatment principles. Reconstructive surgery, i f indicated, is performed after recovery from the electrical shock when it is determined that the tissues are healthy enough that one can expect good surgical results. Ventric ular arrhythmias are managed w i t h antiarrhythmic agents and by reversing the underlying pathophysiologic derange ments (see Chapters 47 and 190, Ventricular Tachyarrhyth mias and A n t i a r r h y t h m i c Agents). Seizures are controlled w i t h anticonvulsant therapy (see Chapters 98 and 186, Sei zures and Status Epilepticus and Anticonvulsants). G I is best managed w i t h early nutritional support, via an appro priate feeding tube i f necessary (see Chapter 13, Enteral Nutrition). Pain management is necessary because burn wounds are painful and because there is likely muscle soreness from exces sive activity d u r i n g the electrical stimulation. Initially opioids are preferred, but nonsteroidal antiinflammatory drugs may be used when GI integrity is presumed to be normal.
PROGNOSIS The prognosis for victims that survive the initial shock epi sode is generally good, as long as the clinical effects are reversible. Respiratory abnormalities are the clinical effects most likely to alter prognosis. M o s t cases o f electrically induced noncardiogenic pulmonary edema resolve quickly, but one study reported a fatality rate o f 38.5%.' Some
animals w i l l require follow-up surgery to treat residual effects o f burns. Recovering victims should be monitored for potential long-term effects. Owners should be instructed to observe for cataract development that could occur several months after recovery.
(4) step voltages produced by current flowing through the soil beneath, and (5) an upward streamer that does not connect or complete a full lightning strike. W i t h the latter mechanism, injury is caused by the upward streamer o f charge that is induced from an object o n the ground, as a lightning leader of flash approaches the ground from a t h u n d e r c l o u d . ' In addition to direct electrical and thermal injury, mechanical energy can be imparted to the lightning victim. A blast effect from rapid air movement caused when super heated air is then cooled may result i n physical injury. Humans are often thrown to the ground and report muscle pain. Lumbosacral fracture w i t h resultant spinal cord injury was the only lesion identified i n three pigs i n an outdoor pen that was struck by l i g h t n i n g . A l t h o u g h not reported in dogs and cats, similar effects o f mechanical energy should not be surprising. 17
LIGHTNING INJURY Lightning injury is more likely to occur i n large animal spe c i e s " than dogs and cats because o f greater outdoor expo sure. However, companion animals, especially dogs, share outdoor activities with humans and, therefore, may occasion ally be exposed. A carefully studied lightning strike at a scene where 2 adults and 26 girls were camping included 7 dogs. Fatal injuries occurred i n 4 o f the girls and 4 o f the dogs. 14
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O f the surviving dogs, the smallest one, a Maltese-Poodle, escaped injury. O n e surviving dog sustained burns and the other suffered damage to an eye that subsequently became opaque. Because the deceased dogs were farther from the stricken tent pole than surviving humans, it was speculated that dogs might be more susceptible to the effects of lightning injury than are h u m a n s . It is possible that small dogs, as i n the camping scene incident, are less susceptible to lightning injury than larger d o g s . In cattle, adults are more likely to be struck by lightning than are calves. 17
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The pathophysiology o f lightning injury is similar to that o f other electrical injuries, except for the mechanism by w h i c h the electricity reaches the v i c t i m and the potential for injury from mechanical energy. There are five possible mechanisms by which lightning can deliver electrical injury to a v i c t i m : (1) direct lightning strike, (2) direct strike o f an object that the victim is touching, (3) side flash from a stricken object,
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SUGGESTED FURTHER R E A D I N G *
Marks SL: Electrocution, Proc North Am Vet Conf 18:176, 2004. Proceedings notes that provide a concise summary of electrical cord and light ning injury in dogs and cats. Morgan RV: Environmental injuries. In Hoskins I, editor: Veterinary pediat rics: dogs and cats from birth to six months of age, ed 3, Philadelphia, 2001, Saunders. First section of chapter discusses electrical shock in dogs and cats; a good ove view of the causes, pathophysiology, clinical findings, treatment, and owner education. Presley RH, Macintire DK: Electrocution and electrical cord injury, Stand Care Emerg Crit Care Med 7:7, 2005. An excellent overview of electrical cord injury in dogs and cats, with a good summary of pathophysiology followed by clinical features and treatment in a quick, easy-to-read outline format. *See the CD-ROM for a complete list of references.
Chapter 160 MASSIVE TRANSFUSION L. Ari Jutkowitz,
V M D , DACVECC
ELECTROLYTE DISTURBANCES
KEY POINTS • Massive transfusion is traditionally defined as the transfusion of 1 or more blood volumes within a 24-hour period. • Electrolyte abnormalities such as hypocalcemia, hypomagnesemia, and hyperkalemia are common following massive transfusion. • Hemostatic defects frequently develop as a result of dilution and consumption of platelets and clotting factors. • Hypothermia and acidosis may exacerbate hemostatic defects and are associated with a poor outcome.
INTRODUCTION
Stored b l o o d undergoes changes i n b o t h the concentration and availability o f various electrolytes. Recipients o f massive transfusions may therefore develop electrolyte disturbances, w i t h hypocalcemia, hypomagnesemia, and hyperkalemia most c o m m o n l y reported. ' Hypocalcemia and hypomagne semia result from the citrate that is added to b l o o d products as an anticoagulant. Once i n the body, citrate binds rapidly to both calcium and magnesium w i t h equal affinity, resulting i n decreases i n ionized calcium and magnesium levels. In one veterinary study, ionized hypocalcemia was documented i n 100% o f cases following massive transfusion, w i t h severe hypocalcemia (10 ) o f an organism, thus including those C F U s or isolates that have undergone the first-step mutation. The M I C obtained from culture and susceptibility testing most likely reflects the majority of C F U s causing infection i n the patient. However, the M I C is less likely to reflect those C F U s that already have undergone the first-step mutation (i.e., are characterized by higher M I C ) . Should drug therapy target the M I C , compet ing isolates will be inhibited or killed, allowing the mutants to emerge. In healthy patients, this population can probably be controlled by host defenses. However, i n less capable patients, the new emergent population will be characterized by a higher M I C that is potentially unattainable with a safe dosing regimen. 5
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Unfortunately, determining the M P C of an isolate cultured from a patient requires culture based on 10 or more organisms; current techniques cannot achieve this large an inoculum. Experimentally, the ratio of M P C to M I C for various fluoroquinolones given for infection by human pathogens ranges from a low of 6 to 10 for E. coli but 23 to 50 (and as high as 125) for selected drugs given for infection by Staphylococcus aureus. Rational combination antimicrobial therapy can be a powerful tool for enhancing efficacy while reducing resis tance i n the C C P . C o m b i n a t i o n therapy should be consid ered routinely for organisms often associated with M D R (e.g., P. aeruginosa, Enterococcus spp, and M R S A ) . Resistance to a combination of antimicrobial drugs should be antici pated when the population reaches 1 0 or more C F U s . Drugs chosen for combination therapy should be selected rationally, based o n target organisms. Mechanisms o f action should complement, rather than antagonize, one another. 7
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In general, "bacteriostatic" drugs that inhibit ribosomes and thus microbial growth (e.g., chloramphenicol, tetracy clines, and erythromycin) should not be combined with drugs whose mechanism of action depends o n protein syn thesis, such as growth of the organism (e.g., P-lactams) or formation o f a target protein. The bactericidal activity o f P-lactams and fluoroquinolones depend o n continued syn thesis of bacterial proteins. Antagonistic effects have been well documented between P-lactam antimicrobials and i n hibitors of ribosomal activity. Chemical antagonism is also possible among two or more antimicrobials; the prototypical example is chemical inactivation of aminoglycosides and quinolones by P-lactams. However, chemical antagonism is unlikely to occur at concen trations achieved systemically i n the clinical patient. In con trast to antagonism, drugs that have the same mechanism of action may act i n an additive or synergistic fashion. The pro totypical example of synergism is the combination of p-lac tams and aminoglycosides; aminoglycoside penetration is facilitated by penicillin-induced cell wall failure. Indeed, ami noglycoside activity against Enterococcus spp is adequate only when the agent is used synergistically with a cell wall-active antibiotic, such as a P-lactam or vancomycin. Synergism has also been demonstrated against some strains of Enterobacteriaceae, P. aeruginosa, staphylococci (including M R S A ) , and other microorganisms. Enhanced movement into the bacteria 21
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may occur with other drugs (e.g., potentiated sulfonamides, fluoroquinolones) when combined with a P-lactam. C o m b i n a t i o n antimicrobial therapy may be selected for a polymicrobial infection. Aminoglycosides or fluoroquino lones are often combined with P-lactams, metronidazole, or clindamycin to target both aerobic gram-positive and gram-negative infections, or aerobic infections caused by both aerobes and anaerobes. The combined use of selected antibiotics may result i n effective therapy against a given microbe, even when either drug alone w o u l d be ineffective.
ANTIMICROBIAL SELECTION The following approach is recommended whenever antimi crobial therapy is being considered i n the C C P . Critique the Need for Antimicrobial Therapy Perhaps more so than i n other patients, the need for prophy lactic or treatment is a necessary consideration i n the C C P . The sense of urgency, the need to cover all bases in the face of unclear diagnostics, and standards o f care that include "routine" use of drugs all lend themselves to empiric antimi crobial therapy. Few studies have demonstrated appropriate timing of antimicrobial therapy. In humans, up to 53% of hospitalized patients receive antibiotics, with between 14% and 43% deemed unnecessary. Statistics are not available for veterinary patients but are probably similar. 6
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The advent o f a fever should not always be assumed to reflect infection; guidelines have been offered by the Infec tious Diseases Society of A m e r i c a . A n exception might exist for neutropenic patients for w h o m fever cannot other wise be explained. Culture results do not necessarily con firm infection, because they may not discriminate between normal, commensal flora and opportunistic, pathogenic iso lates. Vibrant and pure growth supports, but does not con firm, a cultured organism as the infecting isolate. G r a m staining o f cytologic samples w i t h evidence o f phagocytized organisms is an often forgotten, but potentially pivotal, guide for initial selection o f antimicrobial therapy. Empiric selection is more directed at nosocomial infections, although confirmation should be based on culture results. 23
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The number o f isolates considered necessary for diagnosing definitive infection varies with the tissue, but for the urinary tract generally is considered to be 10 C F U or more versus 10 C F U or more for the respiratory tract. The conundrum facing the critical care specialist is that little information exists to help confirm evidence of infection, yet empiric use is likely to contribute to resistance. This situation is likely to persist until molecular diagnostic techniques catch up with diagnostic needs. To prevent adding injury to insult, once the decision is made to treat with antimicrobials, all subsequent decisions should be oriented toward both ensuring therapeutic efficacy and reducing the risk of resistance. 5
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Identify t h e T a r g e t a n d Its S u s c e p t i b i l i t y Initial empiric therapy should be accompanied by properly collected culture samples with the drug and dosing regimen based o n susceptibility testing. The complex nature of nos ocomial organisms mandates that they also be c u l t u r e d . The use of broad-spectrum drugs increases the risk of resistance. A l t h o u g h by its nature empiric drug selection is 3
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broad, an attempt should be made to narrow the spectrum of the chosen drug. E m p i r i c selection should be based o n appropriate evidence provided i n the literature, hospital sus ceptibility data, and the relevant medical history of the patient, including site and cause o f assumed infection, and previous antimicrobial therapy. Historical data reported i n the literature may be useful i n identifying the most likely infecting organisms i n sample populations of animals, but they have often failed to dis criminate commensal versus pathogenic (causing harm to the patient) isolates. Incorrect choices have been docu mented i n close to 50% o f patients i n shock. For critically ill patients, organisms generally represent the normal flora of the alimentary canal or nosocomial organisms. The source of infection may help narrow the spectrum of empiric ther apy i f selected organisms are more likely to infect some body systems more than others. For example, genitourinary tracts often are infected with gram-negative aerobes, whereas abdominal infections generally are caused by gram-negative aerobes initially, followed by anaerobes. Anaerobic coverage should also be considered for selected infections (e.g., osteomyelitis) or those involving deep, isolated areas or hollow organs or those associated w i t h a foul smell and marked inflammation, i n c l u d i n g abscess formation. Granulocytopenic or otherwise i m m u noincompetent patients are more likely to be infected by aerobic gram-negative organisms. Previous antimicrobial use (the author recommends w i t h i n the past 3 months) should be assumed to have selected for resistant organisms i n the patient and thus, should influence drug selection. Use o f p-lactams is likely to have resulted i n resistance toward other P-lactams, whereas previous use o f fluorinated quinolones is more likely to be associated w i t h M D R bacteria (unpublished data, author). Identification o f the target microbe is not enough. The tar get must also be assessed for relative susceptibility to the drug of interest. Tube dilution rather than agar gel diffusion meth ods are preferred for the quantitative information that they provide. If an isolate is not yet identified, sample population data should be considered. Organism susceptibility statistics, should be generated o n an annual basis for each hospital, and such data should help govern the selection of empiric therapy. Comparison o f sample population M I C of organ isms cultured from previous patients i n the hospital or from the literature ' to the breakpoint M I C or peak plasma drug concentration ( C ) o f the drug obtained with the recom mended dosage can provide insight into relative susceptibility, as well as the design of a regimen (see later discussion). 3
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Identify t h e Site o f I n f e c t i o n Three levels o f drug penetration exist i n n o r m a l tissues. Sinusoidal capillaries, found primarily i n the adrenal cortex, pituitary gland, liver, and spleen, present essentially no bar rier to b o u n d or u n b o u n d drug movement. Fenestrated capillaries such as those located i n kidneys and endocrine glands contain pores that do not present a barrier to u n b o u n d drug, and movement is thus facilitated between the plasma and i n t e r s t i t i u m . However, culture and suscep tibility testing is based o n a M I C determined i n vitro i n the absence o f protein. Therefore the M I C overestimates active concentrations o f drugs b o u n d i n vivo to proteins (e.g., doxycycline, cefazolin). Continuous capillaries, such as those found i n the brain, cerebrospinal fluid, testes, prostate, 25
muscle, and adipose tissue, present a barrier of endothelial cells with tight junctions that precludes drug movement. For infections i n tissues with nonfenestrated capillaries, the dosing regimen o f water-soluble drugs (e.g., P-lactams and aminoglycosides, selected sulfonamides and selected tetracy clines) should be adjusted for potentially poor drug distribu tion to the site of infection. Indeed, dosages for P-lactams are often adjusted up to 10-fold i n treating human central nervous system infections. The volume o f distribution of a drug indicates the likeli hood o f tissue penetration, although it cannot indicate to which tissues the drug w i l l be distributed. Distribution of water-soluble drugs tends to be limited to the extracellular fluid compartment, resulting i n a volume of distribution approximating extracellular fluid (i.e., 0.2 to 0.3 L / k g ) . In contrast, a lipid-soluble drug that can penetrate cell mem branes w i l l be distributed to a volume approximating that of total body water (i.e., >0.6 L/kg). Accumulation of a drug i n selected tissues can facilitate successful therapy and reduce the development of resistance. Phagocyte accumulation of selected drugs (e.g., fluoroquino lones, macrolides, selected lincosamides) up to several hun dred-fold higher than i n plasma may facilitate treatment of intracellular infections (e.g., Brucella spp, cell wall-deficient organisms, intracellular parasites, and facultative intracellular organisms such as Staphylococcus). ' Furthermore, accumu lated drug released by dying phagocytes at the site of infection will increase concentrations to which the infecting microbe is exposed. Although renally excreted drug will accumulate in urine and biliary excreted drug i n the bile, these high concen trations may occur only i n the fluid and not i n surrounding tissues; therefore caution must be used when dosing regimens are designed. However, culture and susceptibility testing will underestimate efficacy of drugs that can be applied topically at the site o f infection. In such situations, several thousand fold o f the M I C may be reached. O n the other hand, topical application of antimicrobial drugs i n the C C P is not com m o n . A n example might include aerosolization, but limited aerosol penetrability and potential side effects of aerosolized particles preclude aerosolization as the sole method of drug administration for respiratory tract infections. 26
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M i n i m i z e t h e Impact o f M i c r o b i a l Factors In addition to the development of resistance, microbes can negatively affect antimicrobial therapy. One mechanism is the adverse impact that the microbe imparts to the host's response to infection. Materials released from microbes facil itate invasion, impair cellular phagocytosis, and damage host tissues. The " i n o c u l u m effect" of ESBLs results i n cephalo sporin resistance with a larger (10 ) compared to smaller (10 ) i n o c u l u m . Infection in epithelial tissues (i.e., uroepithelium and respiratory epithelium) is facilitated by bacterial adherence. Materials secreted by organisms often contribute to the marked inflammatory host response and clinical signs of infection. Soluble mediators released by organisms (hemoly sin, epidermolytic toxin, leukocidin) may damage host tis sues or alter host response. Staphylococci produce slime, Nocardia spp produce calcium-containing "sulfur granules," and Pseudomonas and other gram-negative organisms pro duce glycocalyx, or biofilm. 7
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Biofilm consists of microcolonies of pathogenic and host microbes embedded i n a polysaccharide that is produced by
the bacteria. Translocation o f the n o r m a l microflora i n the biofilm to otherwise sterile tissues (which can be facilitated by foreign bodies) may lead to acute infections (again, asso ciated with biofilm) and the accompanying inflammatory response. Persistent, chronic bacterial infections may reflect biofiim-producing bacteria; persistent inflammation asso ciated with immune complexes contributes to the clinical signs. Unfortunately, bacteria growing i n biofilms resist anti microbial killing and i m m u n e defenses o f the host more eas ily. Biofilm can facilitate organism growth i n foreign bodies in the host, including catheters. The nidus o f bacteria may ultimately cause infection, as was demonstrated i n dogs undergoing experimental catheterization o f the portal v e i n . However, organism growth i n catheters does not necessarily lead to infection, and isolates cultured from urinary catheter tips are not necessarily those causing urinary tract infection. 30
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D e l i n e a t e H o s t Factors T h a t W i l l C o m p l i c a t e Therapy Careful consideration must be given to host factors that can reduce concentrations o f active drug at the site o f infection. Changes
in Drug
Disposition
Pathophysiologic changes associated with the critical nature o f patient illness have an impact o n each drug's disposition, including absorption, distribution, metabolism, and excre tion. Either the dose or dosing interval must be adjusted accordingly. D r u g concentrations are most likely to be affected by changes i n absorption and distribution, whereas changes i n distribution, metabolism, and excretion can alter the elimina tion half-life and thus the dosing interval. Fortunately, changes i n absorption no longer require consideration with intravenous administration i n critically i l l patients. However, for subcutaneous or intramuscular drug administration, changes i n blood flow i n the C C P may slow the rate o f absorp tion. Distribution will similarly be affected by changes i n perfusion, particularly i n the patient i n cardiovascular shock; volume replacement may correct some o f these changes. Changes in drug concentration are influenced by the changes in the volume to which the drug is distributed. A n increase i n the volume o f distribution decreases plasma drug concentration and vice versa. However, the clinical impact differs with the lipophilicity o f the drug. For water-soluble drugs (aminoglycosides, P-lactams and glycopeptides), the v o l ume o f distribution can be increased by the accumulation o f fluids i n peripheral tissues, including the pleural space and peri toneal cavity. Septic shock and trauma are the two most c o m mon causes o f volume o f distribution expansion i n the C C P . Aggressive fluid therapy may also decrease drug concentrations.
not b o u n d significantly, probably due to peripheral fluid retention. In general, dosage increases o f 1.5-fold to 2-fold are indicated. F o r lipid-soluble drugs, the impact o f disease-induced changes i n distribution volume should be negligible i f the dosage is calculated o n a mg/kg basis. However, this assumes that dosing is based on an accurate weight, w h i c h may change as intravascular and interstitial volumes are replaced. Changes i n drug elimination, expressed as changes i n elimination half-life, accompany changes i n both clearance (inversely proportional) and volume o f distribution (directly proportional). In general, critical illness decreases drug clear ance, although an exception is patients i n the hyperdynamic state o f septic shock (frequently associated w i t h increased clearance). The impact o n clearance, as w i t h volume of distribution, also varies w i t h lipophilicity. Water-soluble drugs are generally excreted renally. Changes i n glomerular filtration will be associated w i t h pro portional changes i n renal clearance o f drugs. Lipophilic drugs are typically metabolized by the liver before renal and, less commonly, biliary excretion occurs. Excretion o f these drugs may be decreased i n animals w i t h hepatic dis ease, although the degree o f hepatic dysfunction generally must be profound (i.e., altered a l b u m i n concentration) before drug metabolism is affected. In general, decreased clearance causes a proportional decrease i n e l i m i n a t i o n half-life and thus a prolongation of dosing interval, or a decreased rate o f constant infusion for potentially toxic drugs. F o r increased clearance, dosing intervals may need to be shortened for time-dependent drugs (see "Designing the Dose Regimen" later i n this chapter). It is important to remember that clearance and volume o f distribution have opposite and equal effects o n the e l i m i n a t i o n half-life. Further, predicting the proper dosing regimen is complicated by the complex pathophysi ology o f critical diseases. For example, increased clearance associated w i t h the hyperdynamic state o f septic shock may be balanced by decreased renal function. In patients that are dehydrated, decreased clearance may be balanced by a decreased v o l u m e o f distribution such that e l i m i n a t i o n half-life may not change despite marked changes i n both parameters. However, once the v o l u m e is replaced, the elimination half-life may be prolonged. 1
Host Immune
Response
Each o f the foregoing examples w i l l decrease tissue anti microbial exposure. Several studies have associated thera peutic failure o f aminoglycosides w i t h decreased plasma drug concentrations i n septic patients. Dosages should be increased proportionately i n these situations. M o n i t o r i n g o f peak concentrations (1.5 to 2 hours after administration) might be considered for patients receiving aminoglycosides to ensure that therapeutic concentrations are being achieved at the chosen dosage. Although volume contraction associated with dehydration may cause the opposite effect (higher plasma drug concentrations), volume repletion rather than dosage modification should be implemented.
O n the one hand, immunocompromise increases the risk o f infection, mandating the need for achievement o f bactericidal concentrations o f drug at the site o f infection. O n the other hand, too m u c h o f a good thing (inflammatory response) can also lead to therapeutic failure. Bactericidal concentrations are paramount to therapeutic success i n immunocompromised hosts (e.g., viral infections, granulopoietic patients, those receiving immunoinhibiting drugs) or immunocompromised sites (septicemia, meningitis, valvular endocarditis, and osteo myelitis). However, classification o f bactericidal versus bacteri ostatic actions is based o n i n vitro methods, and the m i n i m u m bactericidal concentration o f bactericidal drugs may not be achievable at the site o f infection i n the patient. Dosing regi mens should be designed to ensure bactericidal concentrations are reached when possible. OccasionaUy, bactericidal concen trations o f a bacteriostatic drug can be achieved i n some tissues (e.g., i f the drug accumulates at the site o f infection).
Interestingly, hypoalbuminemia also contributes to decreased antimicrobial exposure, even for drugs that traditionally are
Host inflammatory response can profoundly alter drug efficacy. A l t h o u g h acute inflammation may initially increase
1
1
1
drug delivery to and drug concentration at the site o f infec tion, a marked inflammatory response or chronic inflamma tion may result i n the opposite effect. Purulent exudates present an acidic, hyperosmolar, and hypoxic environment that impairs the efficacy of many antimicrobial agents. H e m o g l o b i n and degradative products o f inflammation can b i n d them. Selected drugs, including aminoglycosides (and probably highly protein-bound drugs), are b o u n d to, and thus inactivated by, proteinaceous debris that accumulates secondary to inflammation. Aminoglycosides (which require active transport into the microbe) may be ineffective i n an anaerobic environment. Some antimicrobial drugs can inhibit neutrophil function. Accumulation of cellular debris associated w i t h the inflam matory process can present a barrier to passive antibiotic distribution. Deposition o f fibrous tissue at the infected site further impairs drug penetrance and distribution. Host
Toxicity
Host (patient) cells are eukaryotic; but bacterial targets are prokaryotic and, as such, targets o f antibacterial therapy are sufficiently different from mammalian cells that, as a class, many antibacterial agents are safe. Exceptions do occur if the microbial target occurs i n mammalian cells and is structurally similar to them. Accordingly, drugs that target cell membranes, such as colistin and polymyxin, predictably cause sufficient nephrotoxicity that antimicrobial use is gen erally limited to the topical route of administration. Other toxicities associated w i t h antimicrobial drugs tend to reflect actions unique from their antibacterial effects. A m i noglycosides remain the most effective drugs for treatment o f gram-negative infections, but they are predictably nephro toxic. Toxicity is related to the duration o f exposure. Accord ingly, kidneys must be allowed sufficient time to eliminate accumulated drug such that trough plasma drug concentra tions (PDCs) drop below a threshold, generally less than 1 to 2 u g / m l . Toxicity is further m i n i m i z e d by ensuring hydration w i t h sodium-containing fluids, once-daily therapy, a high dosage such that duration o f therapy is m i n i m i z e d , administration i n the m o r n i n g (diurnal animals), and the avoidance of nephroactive drugs (e.g., nonsteroidal antiin flammatory drugs, angiotensin enzyme inhibitors, diuretics). Fluoroquinolone-induced retinal degeneration i n cats limits their general use to 5 mg/kg q 2 4 h , w h i c h is probably a dos age conducive to resistance. ' Geriatric cats and cats w i t h renal disease may be predisposed to retinal toxicity. A n ana phylactoid reaction to enrofloxacin caused by direct mast cell degranulation may be m i n i m i z e d by rapid administration. Staphylococcus pyogenes i n humans and Streptococcus canis in animals have been associated with streptococcal toxic shock syndrome and necrotizing fasciitis associated w i t h fluoroquinolone u s e . ' 32
33
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Release of endotoxin by dying microbes can lead to thera peutic failure despite successful eradication o f infection. The amount released varies among, and within, the antimicrobial classes, perhaps reflecting the drug's mechanism of action. Aminoglycosides have been associated w i t h the least and P-lactams the most endotoxin release. A notable exception to P-lactams occurs w i t h the carbapenems (e.g., imipenem or meropenem), w h i c h are associated w i t h the least endotoxin release. The varying amounts o f endotoxin released from bacteria i n response to p-lactams may reflect different affi nities o f the drugs for different penicillin-binding proteins. Selected third-generation cephalosporins also appear to be 37
associated w i t h less endotoxin release. The reported release o f endotoxin associated w i t h quinolones is variable, depend ing o n the study; quinolones, as with low (nonantimicrobial) dosages of polymyxins, may reduce endotoxin sequelae by binding the toxin. Designing the Dosing Regimen Clearly, the closer the M I C o f the infecting isolate is to the breakpoint M I C o f the drug, or the m a x i m u m drug concentration achieved at recommended dosages, the more important it is that appropriate modifications be made to the recommended dosing regimen. The relationship between M I C and the magnitude and time course of P D C allows drugs to be categorized as either time-dependent or concentration-dependent (sometimes referred to as dosage-dependent). Time-dependent drugs are exemplified by P-lactams, whose presence is necessary as long as the isolate is building new cell walls. Thus efficacy is best predicted by the per centage of time (T) that the P D C is above the M I C (or T > M I C ) , which ideally is at least 50% o f the dosing inter v a l . ' Increasing the frequency of dosing is likely to be more cost effective than increasing the dosage. For example, a dosage of 20 mg/kg of amoxicillin achieves approximately 13 p g / m l i n the plasma and the drug elimination half-life is approximately 1.2 hours. If the M I C of the infecting microbe is 4 p g / m l , the P D C w i l l decline such that the M I C is reached in less than 3 half-lives, or approximately 4 hours. This w o u l d allow an 8-hour dosing interval. Doubling the dosage of the drug adds 2.4 hours (twice the half-life i f 50% of the dosing interval is to be covered), but it will have to be qua drupled to allow a 12-hour dosing interval. This assumes that drug concentrations achieved i n the plasma are also achieved i n tissues and targets the m i n i m u m 50% period. 3
3 8
3 9
40
Constant rate infusions ( C R I s ) might be ideal for timedependent drugs as was demonstrated i n an i n vitro model of ceftazidime C R I for treatment o f P. aeruginosa infection. Slow-release products whose drug release is sufficiendy fast to allow C to surpass the M I C also might be more effective than intermittent administration Drugs with a long half-life, such as cefpodoxime, also are appealing because they allow for a convenient dosing interval as long as the organism M I C is sufficiendy distant from peak plasma drug concentrations. Finally, efficacy should also be enhanced for timedependent drugs that accumulate i n the active (unbound) f o r m i n tissues (i.e., macrolides ) or drugs that accumu late i n phagocytes. Some drugs (e.g., macrolides) are char acterized by time dependency for some organisms but concentration dependency for others. Concentration-dependent drugs, best represented by the fluoroquinolones and aminoglycosides (both of which irre versibly b i n d to their targets), are characterized by efficacy that is predicted by the C compared w i t h the M I C of the infecting o r g a n i s m . For such drugs, the magnitude of the C / M I C generally should be a m i n i m u m of 10 to 12 and greater for more difficult infections (e.g., P. aeruginosa or infections caused by multiple o r g a n i s m s ) . ' M o r e recently, efficacy of concentration-dependent drugs is best predicted by the area under the curve ( A U I C ) , the ratio of A U C (area under the curve for 24 hours, which is influenced by both dose and interval) to M I C . A n A U I C of over 125 is generally associated with bacterial killing and decreased resistance. Thus for treatment o f some infections, the dosing regimen 41
m a x
4 2
43
m a x
3,39
m a x
44
45
might be designed to maximize both the C / M I C and the A U C / M I C (i.e., a higher dosage, targeting a higher C / M I C , and a shorter dosing interval, targeting a higher A U C / M I C ) . Concentration-dependent drugs i n particular exhibit a postantibiotic effect, which describes the phenomenon o f prolonged antimicrobial effects after brief exposure to the drug. Design o f the dosing regimen also includes consideration of the duration o f therapy. In humans, discontinuing unnec essary antimicrobial therapy has been associated w i t h a decrease i n hospital stay, cost, antimicrobial resistance, and suprainfection. Short courses (i.e., 3 to 5 days) o f intensive therapy are increasingly accepted i n lieu o f the traditional 7 to 10 days o f therapy. m a x
m a x
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6
SUGGESTED FURTHER READING* Boothe D M : Principles of antimicrobial therapy, Vet Clin North Am Small Anim Pract 36:1003, 2006. An article that addresses more in-depth approaches through which antimicro bial therapy may be rationally applied to the individual patient such that resistance might be minimized without compromising patient response. Hsu DI, Okamoto MP, Murther R: Fluoroquinolone-resistant Pseudomonas aeruginosa: risk factors for acquisition and impact on outcomes, JAntimicrob Chemother 55:535, 2005. Risk factors for the development of fluoroquinolone resistance in humans included fluoroquinolone exposure, nosocomial infections, and diabetes mellitus. Fluoroquinolone-resistant cases experienced delays before receiving effective therapy and also had poorer outcomes. Hughes WT, Armstrong D, Bodey GP, et al: 1997 Guidelines for the use of antimicrobial agents in neutropenic patients with unexplained fever, Clin Infect Dis 25:551, 1997; http://www.idsociety.org. Accessed June 4, 2007. General guidelines for the empiric treatment of neutropenic human patients. Website has updated information. Johnson JA: Nosocomial infections, Vet Clin North Am Small Anim Pract 32:1101, 2002. A review and discussion of nosocomial infections and their importance in small animal medicine.
Lee N , Yuen KY, Kumana CR: Clinical role of fl-lactam/p-lactamase inhibi tor combinations, Drugs 63:1511, 2003. A review of the use of p-lactam plus lactamase inhibitor combination therapy for the treatment of a wide variety of infections and MDR bacteria. Li R C , Z h u ZY: The integration of four major determinants of antibiotic action: bactericidal activity, postantibiotic effect, susceptibility, and phar macokinetics, / Chemother 14:579, 2002. A review of the advantages of using the mentioned four factors to prescribe antibiotics in a fashion that would effectively treat the cultured organism(s) while minimizing the development of bacterial resistance. Schwaber M , Cosgrove SE, Gold H , et al: Fluoroquinolones protective against cephalosporin resistance in gram-negative nosocomial pathogens, Emerg Infect Dis 10:94,2004; http://www.cdc.gov/eid. Accessed June 4,2007. Study that examined 282 cases with a resistant gram-negative pathogen and found that risk factors for resistant nosocomial organisms included surgery, intensive care unit stay, and receipt of a /S-lactam/fl-lactamase inhibitor, a ureidopenicillin, or a third-generation cephalosporin. Slavik RS, Jewesson PJ: Selecting antibacterials for outpatient parenteral antimicrobial therapy: pharmacokinetic-pharmacodynamic considera tions, Clin Pharmacokinet 42:793, 2003. Reviews the pertinent pharmacokinetic-pharmacodynamic considerations that should be taken into account when prescribing antimicrobial therapy for outpatients. Smarick SD, Haskins SC, Aldrich J, et al: Incidence of catheter-associated urinary tract infection among dogs in a small animal intensive care unit, / Am Vet Med Assoc 224:1936, 2004. Article that discusses risk factors of catheter-associated urinary tract infection in dogs and specifically addresses bacterial culture of urine samples versus that of catheter tips. Sturenburg E , Mack D: Extended spectrum P-lactamases: implications for the clinical microbiology laboratory, therapy and infection control, / Infect 47:273, 2003. Paper that aims to increase awareness and understanding of the growing resis tance patterns of bacteria, specifically the ESBL organisms. Toutain P L , del Castillo JR, Bousquet-Melou A : The pharmacokineticpharmacodynamic approach to a rational dosage regimen for antibiotics, Res Vet Sci 73:105, 2002. Pharmacokinetic-pharmacodynamic surrogate indices (AUIC, AUC/MIC, C /MlC, T greater than MIC) for measuring antibiotic efficacy are reviewed and discussed, with specific relevance to various types of antibiotics. max
*See the C D - R O M for a complete list of references.
Chapter 195 PENICILLINS AND CEPHALOSPORINS Scott P. Shaw, DVM, DACVECC
K E Y POINTS •
Penicillins a n d c e p h a l o s p o r i n s v a r y w i d e l y in t h e i r s p e c t r u m o f activity.
•
R e s i s t a n c e t o p e n i c i l l i n s a n d c e p h a l o s p o r i n s is a g r o w i n g c o n c e r n .
•
M e t h i c i l l i n - r e s i s t a n t Staphylococcus p-lactam antibiotics.
aureus
is resistant t o all
and do not enter living cells well. After oral administration, bioavailability will vary greatly among drugs depending u p o n their acid stability and protein binding. Ampicillin, in particular, has poor bioavailability when administered orally. Despite their wide volume of distribution, most of the P-lactams do a poor job o f crossing biologic membranes, and their concentration i n the eye and prostate may be only one tenth that of the serum concentration. However, peni cillins and cephalosporins are indicated for certain infections w i t h i n the central nervous system ( C N S ) because bacteri cidal levels o f drugs can be found within the C N S , benefit ting those with active inflammation of the meninges. Most absorbed P-lactams are excreted actively by the kidney into the urine. As a result, urine levels of P-lactams may be several-fold higher than those seen i n serum. 2
3
INTRODUCTION Fleming's observation i n 1929 that colonies of staphylococci lysed o n a petri dish contaminated with the Penicillium m o l d ushered i n the era of modern antimicrobial therapy. H i s initial efforts to extract the bactericidal substance failed, and it was 11 years before C h a i n and Florey succeeded i n purifying large quantities of the first penicillins from Penicillium notatum. B y the end o f the decade penicillin G was i n widespread clinical use. Limitations to penicillin G's efficacy were noticed almost immediately. These included poor oral bioavailability, rapid development of resistance due to the presence of P-lactamase, and poor activity against gram-negative organisms. Develop ment o f the cephalosporins overcame many of these limitations. The penicillins, cephalosporins, and carbapenems are referred to as /J-lactam antibiotics. A l l members of this class share a basic structure, the presence of a p-lactam ring. The P-lactam ring is essential for the biologic activity of these drugs. Substitutions can be made o n the p-lactam ring for specific purposes such as increasing P-lactamase resistance, enhanced efficacy against specific pathogens, and altering pharmacokinetic properties.
2
Classically cephalosporins have been divided into three, and more recently four, generations. As a general rule cepha losporins became more gram-negative specific with increas ing generations. However, the advent of newer drugs such as ceftiofur and cefpodoxime, with a spectrum of action most similar to that of first-generation cephalosporins, has made this scheme confusing. A s a result, a new classification scheme consisting o f seven groups has been proposed. Using this scheme, drugs are divided by both their spectrum of action and whether they require parenteral or enteral administration. 2
RESISTANCE Production of p-Lactamase
MECHANISM OF ACTION A l l P-lactam antibiotics w o r k by interfering with bacterial cell wall synthesis. They do this by binding to and inhibiting transpeptidases and peptidoglycan-active enzymes that are collectively referred to as penicillin binding proteins (PBPs) that catalyze the cross-linking of the glycopeptides that form the bacterial cell wall. P-Lactams are bactericidal, but they do require actively growing cells to be efficacious. The difference i n susceptibility o f gram-positive and gram-negative organisms depends u p o n the number and type of drug receptors, the amount of peptidoglycan present (gram-positive organisms have a m u c h thicker cell wall), and the amount o f l i p i d i n the cell w a l l . 1
Some bacteria, such as staphylococci and most gram-negative rods, produce a P-lactamase that inactivates P-lactams by breaking their P-lactam ring. More than 60 enzymes have been described. M a n y of these enzymes are found on plasmids, which allows for transmission of resistance both within and between bacterial species. C h a n g e s in Cell W a l l P e r m e a b i l i t y Some bacteria do not produce P-lactamase but avoid the effects of P-lactams by changing their cell wall to limit the permeability of the drug, thus preventing the drug from reaching the PBP.
PHARMACOLOGY
C h a n g e s in P e n i c i l l i n - b i n d i n g P r o t e i n s
W h e n administered intravenously, P-lactams are distributed widely i n body fluids and tissues. They are l i p i d insoluble
Some bacteria can become resistant to P-lactam antibiotics by altering their PBP. The P B P can still cross-link glycopep tides, while preventing binding of the P-lactam antibiotic.
The most important instance of this type of mutation i n the acquisition by S. aureus o f a plasmid that codes for PBP-2a. As a result of this alteration i n its PBPs, S. aureus is resistant to all P-lactam antibiotics.
moderate activity against gram-negative organisms, and m i n i mal activity against anaerobes. Cephalothin demonstrates less gram-negative activity than cefazolin. Members o f this group are used commonly as initial empiric and perioperative therapy because of their spectrum of action and safety profile.
S E L E C T E D PENICILLINS A N D CEPHALOSPORINS
Second-Generation Cephalosporins
Penicillin G In general penicillin G has a good spectrum of action against gram-positive and anaerobic infections, with the exception of some Staphylococcus spp. Penicillin G is synergistic with aminoglycosides, and this combination may be effective against staphylococci. Penicillin G is the drug o f choice for the treatment of streptococcal infection (e.g., necrotizing fas ciitis), clostridial infection, and actinomycosis. E x t e n d e d - S p e c t r u m Penicillins Both amoxicillin and ampicillin have similar spectrums o f action; however, the oral bioavailability o f amoxicillin is much greater, and as a general rule ampicillin should be given only parenterally. The extended-spectrum penicillins are less active against gram-positive and anaerobic infections than penicillin G , but they have a m u c h greater efficacy against gram-negative species. Unfortunately, growing resis tance is a problem and therapeutic failures are becoming more c o m m o n . Both ampicillin and amoxicillin are available i n a poten tiated form combined with sulbactam and clavulanic acid, respectively. The addition o f a P-lactamase inhibitor results in a much greater efficacy against gram-negative organisms as well as some p-lactamase-producing gram-positive organisms. A n t i p s e u d o m o n a l Penicillins The antipseudomonal penicillins (ticarcillin, piperacillin) exhibit a greater activity against Pseudomonas and Proteus than is seen with the other penicillins. It should be noted that the antipseudomonal penicillins exhibit poor activity against Escherichia coli and many other gram-negative organisms. The combination o f ticarcillin with clavulanic acid does provide for greater gram-negative coverage. First-Generation Cephalosporins First-generation cephalosporins (cefazolin, cephalothin, cepha lexin) have increased activity against some P-lactamaseproducing organisms such as Staphylococcus. I n general, they display a high level of activity against gram-positive organisms,
Because of their stability against P-lactamase, second-gener ation cephalosporins (cefaclor, cefoxitin, cefotetan, cefuroxime) have a broad spectrum o f activity. In general, they are moderately efficacious against gram-positive organisms and have a greater spectrum against gram-negative organisms than the first-generation cephalosporins. Third-Generation Cephalosporins Third-generation cephalosporins (cefotaxime, ceftriaxone, ceffiofur, cefixime, ceftazidime, cefpodoxime) vary greatly i n their spectrum o f action, and the efficacy o f one drug i n this class against an organism does not guarantee efficacy i f other class members are employed. The classic third-genera tion cephalosporins cefotaxime, ceftriaxone, cefixime, and ceftazidime have a high degree o f specificity and efficacy for gram-negative organisms. These drugs are considered the treatment o f choice for empiric therapy o f infections located w i t h i n the C N S . Carbapenems The carbapenems (imipenem, meropenem) are the only class o f antibiotics w h i c h are considered to be truly broad spectrum when employed alone. It should be noted that, as w i t h a l l p-lactam antibiotics, methicillin-resistant S. aureus w i l l be resistant to the carbapenems. Imipenem is combined w i t h cilastin, w h i c h decreases the rate o f renal excretion, resulting i n higher plasma levels. It should also be noted that neurologic side effects, i n c l u d i n g seizures, have been noted i n veterinary patients treated w i t h i m i p e nem. M e r o p e n e m has a lower incidence o f neurologic side effects i n humans. I n general, carbapenems should be reserved for treating severe life-threatening infections when other options are not available.
SUGGESTED FURTHER READING* Boothe D: Small animal clinical pharmacology and therapeutics, Philadelphia, 2001, Saunders. An excellent reference for everyday use that covers basic pharmacology and pro vides practical guidance for choosing appropriate antimicrobials for clinical patients. "See the C D - R O M for a complete list of references.
Chapter 196 AMINOGLYCOSIDES Reid P. Groman, DVM, DACVIM
KEY •
S P E C T R U M OF ACTIVITY
POINTS
D e s p i t e c o n s i d e r a b l e a d v a n c e s in t h e d e v e l o p m e n t o f n e w e r antimicrobial drugs, aminoglycosides remain important agents for t r e a t i n g serious i n f e c t i o n s w i t h a e r o b i c g r a m - n e g a t i v e a n d select gram-positive microorganisms.
• A m i n o g l y c o s i d e s a r e k n o w n t o e x h i b i t synergistic b a c t e r i c i d a l e f f e c t s w h e n a d m i n i s t e r e d in c o m b i n a t i o n w i t h p - l a c t a m a n t i b i o t i c s . • A m i n o g l y c o s i d e s , like t h e f l u o r o q u i n o l o n e s , e x h i b i t c o n c e n t r a t i o n d e p e n d e n t k i l l i n g ; t h a t is, b a c t e r i a l k i l l i n g is m o r e r a p i d a n d e f f e c t i v e w h e n t h e y a r e p r e s e n t at h i g h e r c o n c e n t r a t i o n s at t h e site o f i n f e c t i o n . This d i s t i n g u i s h e s t h e a m i n o g l y c o s i d e s f r o m p - l a c t a m s a n d o t h e r c o m m o n l y u s e d a n t i m i c r o b i a l s t h a t kill b a c t e r i a in a time-dependent fashion. •
N e p h r o t o x i c i t y is t h e m o s t s e r i o u s side e f f e c t o f a m i n o g l y c o s i d e s .
•
S i n g l e daily d o s i n g ( S D D ) o f t h e a m i n o g l y c o s i d e s is p o s s i b l e because of their rapid c o n c e n t r a t i o n - d e p e n d e n t killing a n d p o s t a n t i b i o t i c e f f e c t . S D D a p p e a r s t o b e s a f e a n d e f f i c a c i o u s in most small animal populations.
• T h e role o f t h e r a p e u t i c d r u g m o n i t o r i n g u s i n g S D D is n o t w e l l d e f i n e d in s m a l l a n i m a l m e d i c i n e .
INTRODUCTION Aminoglycoside antimicrobial drugs, notably gentamicin and amikacin, constitute some of the best choices for treat ment o f severe gram-negative infections. " Despite the large number of antibacterial agents that have appeared over the last few years as alternatives to aminoglycosides, the latter still play an important role i n clinical practice. The amino glycosides, i n comparison w i t h other antimicrobial agents that rapidly select for resistant mutants (e.g., P-lactams and fluoroquinolones), are predictably effective for many aerobic gram-negative pathogens. " One of the primary reasons for limiting clinical use o f the aminoglycosides is the nephrotoxicity observed w i t h conven tional multiple daily d o s i n g . ' Over the past several years, m u c h has been learned about the efficacy and toxicities of the aminoglycosides, and a new dosing strategy has emerged using single daily dosing ( S D D ) . ' ' Practitioners are encour aged to reevaluate the utility o f the aminoglycosides as an important component of the modern antimicrobial arsenal. 1
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Aminoglycosides are effective against most communityacquired gram-negative aerobes and select gram-positive pathogens. Organisms commonly susceptible to these drugs include Klebsiella, Citrobacter, Enterobacter, Serratia, and most Acinetobacter spp. ' They are frequently, although not uniformly, effective against Pseudomonas aeruginosa and Escherichia coli. ' Aminoglycosides are not active against anaerobes because their uptake across bacterial cell membranes depends on energy derived from aerobic metabolism. This dependence on aerobic metabolism is the cause of markedly reduced activity o f these agents i n areas of low p H and oxygen ten sion, such as abscesses and other infected hypoxic tissues. ' A m o n g gram-positive organisms, the aminoglycosides, particularly gentamicin, are active against many Staphylococ cus spp. Other gram-positive organisms, such as Streptococcus spp and many enterococci, are relatively resistant. Studies of bacteria i n cell culture have shown that combin ing an aminoglycoside with a P-lactam agent results i n bac terial killing superior to the simple added activity of each of these antimicrobials, a phenomenon termed synergism. ' The efficacy of the aminoglycosides appears to be enhanced by increased cell permeability induced by the P-lactam antibi otic, favoring the uptake of the aminoglycoside into certain bacteria. Classically, synergy is observed between penicillins and gentamicin toward susceptible strains of Enterococcus faecium and Enterococcus faecalis, although synergy has also been described for gram-negative pathogens, including Pseudo monas aeruginosa. ' Synergism is particularly important in cases o f partial resistance to gentamicin, and when low tissue p H and low oxygen tension (e.g., abscesses or tissue hypoxia) decrease aminoglycoside transport into bacteria. 1
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The aminoglycosides are active against some mycobac teria, as well as less c o m m o n pathogens such as Yersinia pestis, Brucella spp, and Francisella tularensis. ' Amikacin and gentamicin are used i n similar circumstances, often inter changeably. A m i k a c i n , however, is not degraded by the c o m m o n enzymes that degrade gentamicin and therefore has a broader spectrum of activity. It is the preferred agent for serious nosocomial infections caused by Klebsiella spp and Pseudomonas aeruginosa. ' 1 3
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1 3
MECHANISM OF ACTION 1 6
The aminoglycosides are bactericidal agents. ' They penetrate the bacterial cell wall and membrane, and impair protein synthesis by binding to components o f the prokaryotic 30s ribosomal subunit. ' This binding leads to bacterial misread ing of messenger ribonucleic acid ( m R N A ) , w i t h subsequent production of nonfunctional proteins, detachment o f ribosomes from m R N A , and cell death. 5
6
5
INDICATIONS The aminoglycosides are used for short-term (30 days). Also of note is that the normal renal response to respi ratory acidosis and alkalosis (namely H C O j retention and excretion, respectively) will take several hours to days to correct after correction of the primary respiratory acid-base disorder. The patient may require treatment of the electrolyte changes (chloride in particular) that accom pany the renal response to respiratory acid-base disorders before full correction to baseline H C O j values can be achieved. '
3
2
3
2
2
6 9
2
Number 3: What's Happening With the Metabolic Indexes?
2
Metabolic acid-base disturbances are among the most com mon acid-base disorders described in veterinary medicine. A prominent feature of metabolic disturbances is a change in the H C O j level, but this should not be the sole indicator p H changes produced by one component may be opposed by of a metabolic disturbance because H C O j also changes with opposite changes in the other component. For instance, to alterations in P C 0 . Consequently, the concept of buffer compensate for a respiratory acidosis the organism will base is used to define metabolic disorders. attempt to increase the concentration of H C O j in the blood. The compensation may be strong, but rarely is it complete, Base excess (BE) is derived from the whole blood and overcompensation does not normally occur. buffer curve developed by Siggaard-Anderson and is defined as the amount of acid or base necessary to titrate a 1 Number 2: What's Happening With Ventilation? liter of blood to a p H of 7.4 if P C 0 is held constant at 40 mm H g . Because P C 0 is held constant, the BE is Control of ventilation arises from respiratory centers within reflective of the nonrespiratory component of the organism's the brainstem that are sensitive to C0 -induced changes in buffer system. Tables 208-2, 208-3, and Box 208-2 show the cerebral p H . Arterial C 0 levels are held steady by balanc most common causes of metabolic acidosis and alkalosis, ing minute ventilation with metabolic production of C 0 ; as well as relevant acid-base responses.* The question however, normal ventilatory response to changes in P C 0 remains as to whether cats typically have the expected venti are so sensitive that a 1-mm Hg change in P C 0 can qua latory response to metabolic acidoses. There is experimental druple minute ventilation. Although ventilation may exceed evidence to suggest that they do not. the production of C 0 , it is unlikely that C 0 production exceeds ventilatory capacity in normal animals. Number 4: Is There One Problem or Many? Respiratory acidosis therefore is almost always caused by some aspect of ventilatory failure. Tables 208-2, 208-3, and One of the hardest parts of acid-base analysis can be deciding Box 208-1 show the most common causes of respiratory acidosis what the primary disorder is. A good rule of thumb is that the and alkalosis in dogs and cats and the expected acid-base changes p H of the sample will reflect the primary disorder. This sounds that subsequently occur. " It is important to note that simple, but it becomes more and more complicated as although dogs and cats respond similarly to acute respiratory aci compensation and multiple disturbances occur. Various dosis, there is some question as to whether cats adjust as well to acid-base disturbances may occur simultaneously, except for chronic respiratory acidosis as dogs. This may be because cats lack the adaptive process of urinary ammoniagenesis that allows * References 5, 7, 19, 20, 23, 24. H C O j , Bicarbonate; PC0 , partial pressure of carbon dioxide. 2
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2 1 , 2 2
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1 6
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7
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Box 208-2 Causes of Metabolically Induced Acid-Base Disorders
up to 100 mm Hg when the F i 0 is 100%. It is possible for normal dogs living at high altitudes to have a P a 0 of 60 mmHg ( P A 0 and P a 0 are decreased with low baromet ric pressure). Similarly, a P a 0 reading of 100 mmHg is not acceptable if a dog is anesthetized and breathing 100% oxygen (the P a 0 should be 500 mmHg). The alveolar-arterial (A-a) gradient is calculated as a way to quantify the efficiency of gas exchange. At 0 concentra tions of 21%, the A-a gradient is expected to be less than 10 mmHg, however, at 0 concentrations of 100% the A-a gradient can normally be up to 100 m m H g . " Consequently, the patient's F i 0 must always be considered when evaluating the A-a gradient. The a:A ratio and P a 0 - t o - F i 0 ratio are two other indexes of hypoxemia. O f the two, the P a 0 - t o - F i 0 is the easiest to calculate and shows the most reasonable stability across variable inspired oxygen concentrations. Normal values for the P a 0 - t o - F i 0 ratio should be greater than 400 mm Hg. Values below 300 m m H g indicate severe defects of gas exchange. Values less than 200 m m H g may indicate acute respiratory distress syndrome. ' The P a 0 - t o - F i 0 ratio demonstrates some dependency on P a C 0 , but this diminishes at an F i 0 higher than 50%, which is usually the point at which this ratio is likely to be employed. The oxygen content ml/dl (Ca0 ) value is a calculated value that is included with many blood gas analyses. It is an assessment of the total amount of oxygen carried in the blood. It includes the oxygen dissolved in the plasma and bound to hemoglobin and is an important measure of the oxygen carrying capacity of the blood as follows: 2
2
2
Causes of Metabolic Acidosis Normochloremic Causes
2
2
Lactic acidosis Ketoacidosis Toxins Renal failure
2
2
Hyperchloremic Causes
2
26
Gastrointestinal losses Renal
28
2
Other Causes of Metabolic Alkalosis Chloride-Responsive Causes
2
2
2
Vomiting Diuretic therapy Correction of respiratory acidosis
2
Chloride-Resistant Causes Primary hyperaldosteronism
2
2
26 28
Hyperadrenocorticism Overadministration o f alkaline fluids
2
Other
2
2
2
2
a respiratory alkalosis and acidosis, which are mutually exclu sive. Multiple primary disorders that change the p H in the same direction are readily apparent (see Table 208-2). Multiple primary disorders that change the p H in different directions can be distinguished from a single primary disorder with compensation by determining the expected compensation in P C 0 , H C O J , or p H and comparing it with the observed compensation (see Table 208-3). If the two are not equal, there are most likely multiple primary disorders. ' "
C a 0 = (PaQ x 0.003) + (1.34 x Hb x Sa0 ) 2
2
2
2
3 7
9
Number S: What's Happening With Oxygenation?
where 0.003 = the solubility of oxygen in plasma, 1.34 = the amount of oxygen in milliliters that each gram of hemoglobin (Hb) can hold if it is 100% saturated with 0 , and SaO = oxygen saturation. Normal C a 0 is 20 ml of 0 per dl of blood. Oxygen saturation (Sa0 ) is a measure of the percentage of the heme groups in an arterial blood sample that are occupied by oxygen molecules as measured using a co-oximeter. The relationship between S a 0 and P a 0 is sigmoidal, with maximum saturation seen above a P a 0 of 100 mmHg. Most blood gas analyzers do not measure S a 0 and instead calculate it using a nomogram derived from the oxygen dissociation curve. Under normal circumstances this has few drawbacks; however, if dysfunctional hemoglobin species (such as carboxyhemoglobin, methemoglobin, sulfhemoglobin, and carboxy sulfhemoglobin) or fetal hemoglobin are in circula tion, it is important to measure oxygen saturation with a cooximeter. These devices use four wavelengths of light passed through a blood sample to distinguish between oxygenated hemoglobin and the other types of hemoglobin not carrying oxygen or unable to contribute to gas exchange. 2
2
Oxygen is necessary for aerobic metabolism. Hypoxia occurs whenever oxygen levels in the blood are low enough to cause abnormal organ function. Hypoxemia occurs when oxygen levels in the blood are too low to meet metabolic demands. Pa02 is the partial pressure of oxygen dissolved in the arterial blood (plasma). It is the most common blood gas parameter used to monitor the progress of patients with respiratory disor ders. Normal P a 0 values for a dogs and cats breathing room air (21% 0 ) are shown (see Table 208-1). A P a 0 less than 80 mm Hg is considered hypoxemia. Although P a 0 is very useful and reliable, it is dependent on the alveolar partial pres sure of oxygen (PA0 ) according to the alveolar gas equation: 16
2
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16
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PA0
2
= (P - PH 0)Fi0 B
2
2
-
z
2
2
2
2
2
2
3
where P = the barometric pressure, P H 0 = the partial pressure of water vapor in the air at a given barometric pres sure, F i 0 = the fractional inspired concentration of oxygen, and R = the respiratory quotient that is the ratio of oxygen consumption to C 0 production (0.78 to 0.92 in dogs). In normal healthy lungs, oxygen diffuses readily from the lungs to the arterial circulation. The P a 0 should be within 10 mmHg of the P A 0 in animals breathing room air and B
Pulse Oximetry
2
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25
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Pulse oximeters are bedside monitors that measure the S p 0 rather than the S a 0 and take advantage of the simple principle used by co-oximeters: blood that is oxygenated is a different color than blood that is not well oxygenated. When light is passed through a tissue bed it is possible to determine the oxygen saturation within that tissue. Deoxygenated hemoglobin absorbs more red light, and 2
2
oxygenated blood absorbs more infrared light. By using two wavelengths (940 and 660 nm), a high light transmittance speed, fast sample rate, and a microprocessor that filters any nonpulsatile data as nonarterial blood flow, it is possible to build a monitor capable of providing a non invasive measure of oxygenation. Pulse oximetry is useful for several reasons. It provides an inexpensive, noninvasive means of monitoring oxygenation that is well tolerated and reliable in dogs and cats, when more invasive monitoring is either unwarranted, undesirable, impossible to obtain, or some combination thereof. " The machines are small, quiet, portable, can be used for extended periods, and can be used as an indirect measure of perfusion. As with most screening equipment, there are drawbacks. Pulse oximetry probes typically perform well on the tongue, but this location is difficult or impossible to use in a conscious patient. The probes may be placed on the shaved skin of the lip, pinna, toe web, flank, or tail, but many conscious patients will not readily tolerate it. Additionally, pulse oximetry readings can be affected by bright overhead lights, vasoconstriction, dark skin pigment, hypothermia, and hypoperfusion. Abnormal hemoglobin will also cause the machine to read inaccurately. Unlike co-oximeters, pulse oximeters cannot distinguish dys functional hemoglobins (i.e., carboxyhemoglobin, methemoglobin, sulfhemoglobin, and carboxy sulfhemoglobin) from normal hemoglobin. Carboxyhemoglobin will absorb infrared light similarly to oxygenated hemoglobin and will provide falsely high S p 0 readings. Methemoglobin on the other hand absorbs both wavelengths of light equally well. In the presence of this hemoglobin species the pulse oximeter will default to a reading of 85%, reading high or low depending on the patient's actual saturation. Most importantly, pulse oximetry gives little information about the efficiency of gas exchange. A n S p 0 of 100% in a patient breathing an F i 0 of 100% does not evaluate whether the patient's P a 0 is 500 mm Hg or 100 mm Hg. It is more appropriate to perform arterial blood gas analysis anytime that precise information is needed regarding the patient's oxygenation status.
the use of electrolyte shifts to qualify metabolic acid-base disturbances, to Stewart's concept of strong ion differences (acid-base disturbances explained as a series of polynomial equations) are now being used to further refine acid-base analysis when the numbers do not fit the clinical picture. 8,35
29
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34
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Number 6: Looking at the Whole Picture The final step in blood gas analysis is to fit the analysis to the patient. Make sure the conclusions fit the clinical picture. Multiple ancillary techniques from the anion ion gap, or 5,7
Venous Blood Gases Venous blood gases are often more simple to obtain than arterial gases. The P C 0 of venous blood is usually 4 to 6 mm Hg higher and the p H is usually 0.02 to 0.05 units lower than those of arterial blood. In stable hemodynamic states venous blood gases may be used for clinical assessment of acid-base disorders. Peripheral venous P 0 values are not representative of arterial oxygen values; however, the blood from veins in the tongue or the claw may be "arterialized" under certain conditions and used for this purpose. " A venous P 0 of less than 30 mm Hg may suggest poor tissue oxygenation and should be investigated further. 2
15,36
2
15,37
39
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SUGGESTED FURTHER READING* deMorais H A , DiBartola SP: Ventilatory and metabolic compensation in dogs with acid-base disturbances, J Vet Emerg Crit Care 1:39, 1991. Provides useful information about compensatory mechanisms with acid-base disturbances. DiBartola SP: Introduction to acid-base disorders. In DiBartola SP, editor: Fluid, electrolyte, and acid-base disorders in small animal practice, ed 3, St Louis, 2006, Saunders. Excellent introduction to acid-base disorders. Haskins SC: Interpretation of blood gas measurements. In King LG, editor: Textbook of respiratory disease in dogs and cats, ed 1, St Louis, 2004, Saunders. Very good reference chapter. More physiologically oriented than practically oriented. Hendricks JC, King LG: Practicality, usefulness, and limits of pulse oximetry in critical small animal patients, / Vet Emerg Crit Care 3(1):512, 1993. Very complete and useful reference on the use and drawbacks of pulse oximetry in critically ill small animals. Wagner AE, Muir WW, Bednarski R M : A comparison of arterial and lingual and venous blood gases in anesthetized dogs, / Vet Emerg Crit Care 1(1):14, 1991. Good study with very practical information. *See the C D - R O M for a complete list of references.
Chapter 209 INTRACRANIAL PRESSURE MONITORING Beverly K. Sturges, DVM, DACVIM (Neurology)
Benefits of Intracranial Pressure Monitoring
KEY POINTS
Box 209-1
• Maintaining adequate cerebral perfusion pressure (CPP) is considered the cornerstone of successful treatment of acquired brain injury. • By monitoring intracranial pressure (ICP) and mean arterial blood pressure (MAP), the clinician can quantitatively assess CPP as expressed by the formula: CPP = MAP - ICP. • Normal ICP varies between 5 and 10 mm Hg above atmospheric pressure in dogs and cats. • Catheter tip ICP transducers (fiberoptic or miniature strain gauge) have been used with ease and accuracy in dogs and cats when placed subdurally or intraparenchymally in the brain. • Monitoring ICP is most important in patients with intracranial hypertension from severe brain disease or head injury and in animals that are anesthetized or comatose.
1. Allows assessment of actual I C P as well as fluctuations and overall trends i n I C P 2. Allows optimization of cerebral perfusion pressure-guided therapy 3. Allows for early intervention 4. Reduces indiscriminate treatment of I C H 5. Allows assessment of the effects of treatment of I C H 6. Allows assessment when clinical monitoring is not possible (anesthetized or comatose animals) 7. Provides assessment of brain death (cerebral perfusion ceases once I C P exceeds diastolic blood pressure) ICH, Intracranial hypertension; ICP, intracranial pressure.
INTRODUCTION Acquired brain injury is a common neurologic emergency typically caused by head trauma, brain disease (tumors, meningoencephalitis, hypoxic injury), metabolic derange ments, prolonged seizures, or surgical trauma. Increased intracranial pressure (ICP) often is associated with these processes and may affect outcome seriously. Because the intracranial contents (blood, cerebrospinal fluid [CSF], and brain parenchyma) are encased in a rigid container, there is limited space available for expansion of the contents. As vol ume increases in the cranial vault from any cause (edema, hemorrhage, mass), there must be a reciprocal decrease in the other volumes for ICP not to increase beyond limits compatible with life. When compensatory mechanisms in the brain are exhausted, ICP increases and cerebral blood flow is compromised, resulting in secondary injury. Secondary injury is a complex sequence of events that leads to further elevations in ICP, reduced cerebral blood flow, tissue hypoxia, and ischemia. This ultimately perpetuates neuronal death and may result in brain herniation. ' Thus, secondary injury is a major con tributor to the mortality of animals with acquired brain injury. The primary goal in the treatment of these animals is to minimize the impact of the secondary injury by appro priate and timely treatment to maintain adequate cerebral blood flow. In the clinical setting, cerebral blood flow is reflected most accurately by cerebral perfusion pressure (CPP). CPP is dependent on the mean arterial pressure (MAP) and the ICP, and this relationship is expressed by the formula: CPP = M A P - I C R ' By measuring the ICP, the clinician is able to assess whether CPP is maintained ade quately in a patient with severe brain disease or injury. ' 1,2
1 2
1
2
3 4
Although a growing number of studies in humans have suggested decreased mortality rates and improved long-term
outcome with ICP-guided therapy, a randomized clinical trial showing that ICP monitoring improves outcome has not been done. The "Guidelines for the Management of Severe Traumatic Brain Injury" (published in 1995 and revised in 2007) outline the evidence-based recommenda tions for using ICP monitoring to improve the treatment and outcome from severe brain injury. Similar guidelines and recommendations were published in 2004 for the man agement of severe brain injury in infants and children. As yet, no specific guidelines have been established in veteri nary medicine for treating severe brain injury. The standard of care has been primarily that of repeated and careful assessments of an animal's neurologic status in an attempt to detect increases in ICP. Unfortunately, most clinical signs indicating life-threatening intracranial hypertension (ICH) occur as a result of damage to brain tissue, and therapies administered at this point often are ineffective. There are potential benefits gained by monitoring ICP, especially when one expects prolonged and/or life-threatening I C H (Box 209-1). ' 4
4 5
DETERMINATION OF INTRACRANIAL PRESSURE Intracranial Pressure ICP refers to the pressure exerted by the tissues and fluids against an inelastic cranial vault. The total pressure recorded when monitoring ICP is actually composed of several components ' : 1. Atmospheric pressure results from the weight of the atmo sphere on the brain; for example, a higher altitude results 1 2
Box 209-2 Considerations for Choosing an Intracranial Pressure Transducer
!
External Pressure Transducer Pros
Figure 209-1
Intracranial pressure monitoring locations.
in a higher absolute ICR Because ICP is always reported rel ative to the atmospheric pressure, this component is usually not taken into consideration. 2. Hydrostatic pressure is influenced by the orientation of the neuraxis relative to gravity (e.g., consider a giraffe versus a rat). 3. Filling pressure refers to the volume of fluid within the cranial vault and affects the compliance or "give" of the brain tissues.
Locations for Monitoring intracranial Pressure in the Brain ICP monitoring commonly is done through a burr hole in the skull or a craniectomy site. It can be measured directly or reflected through measurement of CSF pressure or brain tissue pressure. CSF pressure measurements can be taken from the lateral ventricles or the cerebral subarachnoid space; brain tissue pressure measurements are taken intraparenchymally from within a cerebral hemisphere. Measurement of ICP from the brain's surface may be taken epidurally or subdurally over a cerebral convexity (Figure 209-1). Although there are very few data in veterinary medicine with respect to the role of ICP monitoring in patients with brain disease, several studies in animals have shown that ICP can be monitored accurately. Historically, CSF pressure was measured using a manometer and needle puncture of the cisterna magna. This method requires that the patient undergo general anesthesia and does not allow for ongoing ICP mea surements needed to guide the clinician in treatment decisions. In addition, CSF pressures measured at the cisterna magna may not accurately reflect more compartmentalized elevations in ICR In animals with global ICH, there is the added risk of brain herniation through the foramen magnum with this method. 2,3
1,2,4
Types of Intracranial Pressure Monitoring Devices Pressure transducers convert ICP into a graded electrical sig nal that is recorded and displayed. They can be situated either intracranially or extracranially depending on the sys tem used. Extracranial strain gauge type transducers com municate with the intracranial compartment via fluid-filled tubing and require that ICP measurements be taken at fixed reference points. Pressure transducers situated intracranially are incorporated into the tip of a catheter and implanted into one of several compartments of the brain. Some of the important considerations in choosing a transducer are listed in Box 209-2. " 2
4
Accurate May be recalibrated after insertion Minimal zero drift Less expensive Cons Fluid couple may obstruct and give false readings Measurements must be taken at fixed reference points Allows little movement in awake animals Leakage may occur in the system Internal Pressure Transducer Pros Allows freedom of movement Accurate Technically easy to place Cons Cannot be rezeroed after insertion Some zero drift over time More expensive
Intracranial Pressure Monitoring Systems Ventriculostomy Catheter With External Transducer The ventriculostomy catheter is a fluid-filled hollow tube that is inserted into the lateral ventricle, usually through a burr hole craniotomy. The catheter is connected to an external strain gauge transducer via fluid-filled pressure-resistant tub ing. The transducer is leveled or zeroed at an external reference point that represents the level of the foramen of Monro in the brain. Strain gauge transducers convert mechanical pressure (or "strain") into a graded electrical signal. " Thus changes in ICP cause changes in the pressure exerted on the diaphragm and hence strain on the sensor element. The electrical resis tance that is generated is recorded and displayed. Ventriculostomy catheters provide the most accurate reflection of ICP and have become the "gold standard" or reference standard for monitoring ICP. In addition to ICP measurements taken from the ventricle, CSF can be with drawn as needed for treatment of elevated ICP. Because of this advantage, it is commonly used in humans. The external landmarks defining the trajectory for accurate placement of a ventriculostomy catheter are easily identified in humans, and the location of the lateral ventricle is reliably predicted most of the time. However, in dogs and cats, several ana tomic considerations impede the feasibility of using this sys tem clinically. These include the marked variation in skull size and shape among breeds of dogs, variation in the size, shape, and location of the lateral ventricles in the brain, and the presence of substantial musculature overlying the cranial vault and obscuring identifying bony landmarks. In addition, when there is distortion of the lateral ventri cles caused by intracranial pathology, ventricular catheter placement ecomes even more difficult. 2
4
Transducer-Tipped Catheters Transducer-tipped catheters are a newer class of ICP moni-, toring devices. The primary pressure transducer is mounted
on the distal tip of the implanted catheter. Because the trans ducer is intracranial, these devices do not require leveling. Both fiberoptic and electrical sensors (miniature strain gauge type) are used in these monitoring systems. Fiberoptic pressure sensing methods include intensity modulation and interferometry. A mechanical diaphragm moves with changes in pressure in both methods and a mon itor displays the corresponding ICP value. In the case of intensity modulation, the position of the diaphragm alters the intensity of the light reflected from its rear surface; with the interferometer, the position of the diaphragm is sensed by measuring the ratio of returned light intensities in two spectral bandwidths. This ratio is a function of spectral interference that varies with the position of the diaphragm. Fiberoptic transducers can record pressures from the in traventricular, intraparenchymal, subarachnoid and/or sub dural compartments of the brain. Fiberoptic ICP monitoring systems, developed for use in humans, have been effective for dogs and cats. ICP can be measured from the CSF or brain parenchyma and is effective in monitoring changes in ICP under anesthesia and during intracranial surgery. Catheter tip strain gauge pressure sensing devices use a miniaturized silicon transducer enclosed in a titanium case and implanted in the tip of a flexible nylon catheter. Changes in the position of the diaphragm cause changes in the electrical resistance that is recorded and displayed by interface with a control unit for continuous monitoring of ICP. The control unit may then be interfaced with a wide variety of standard patient monitoring systems for ICP values, waveform display, or for consolidation of data with other physiologic parameters being monitored. Catheter tip ICP sensors are versatile and may be placed in a ventricle, in brain parenchyma, or the subarachnoid, subdural and/or epidural spaces. This system has been used experimentally in awake and anesthetized normal dogs. It has also been used successfully in anesthetized dogs during craniotomy procedures with continued monitoring in awake dogs for 2 to 5 days postoperatively. Placement of the sensor is tech nically easy and the system allows complete freedom of movement in awake animals. 4
2,3
Figure 209-2 Intracranial pressure tracings of the pulse pressure waves are shown on the right. Alterations in the amplitude and shape of the waveforms occur with changes in intracranial pressure and compliance of the neural tissues are shown on the left. This may be used to estimate where a patient's condition is located on the pressure-volume curve.
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Subarachnoid Bolt The subarachnoid bolt is a metal tube or screw secured to the calvarium through a burr hole placed over a cerebral convexity. The tube, which opens into the subarachnoid space, allows for measurement of ICP via fluid coupling to an external pressure transducer or from a sensor placed intracranially into the subarachnoid space. 2,3
Fluid-Filled Catheter Epidural or subdural placement of a sensor or a simple fluidfilled catheter connected to an arterial pressure monitoring system is cost effective and serves the purpose of monitoring adequately. Although the accuracy of this system may be questionable, fluctuations and trends in ICP are generally reliable. Dewey et al reported the use of such a system in normal cats and found that it was a reliable alternative to the fiberoptic intraparenchymal monitoring system. Transcranial Doppler ultrasonography is a noninvasive method of assessing the state of the intracranial circulation and can indirectly predict ICP. It may be useful occasionally in young puppies or hydrocephalic dogs with fontanelles for measuring changes in cerebral vascular resistance. 7
EVALUATION OF INTRACRANIAL PRESSURE Normal Intracranial Pressure Normal ICP values reported in the dog and cat vary from 5 to 12 mm Hg above atmospheric pressure. ICP is not a static state, but one that is influenced by several factors. When recording ICP, two types of phasic changes can nor mally be seen in the pressure tracing. These fluctuations in ICP are the result of cyclic changes in cerebral blood vol ume caused by the cardiac and respiratory cycles. • The CSF fluid pulse pressure wave is caused by contrac tion of the left ventricle of the heart with resulting disten tion of the arterioles. The ICP tracing is similar to that of the peripheral arterial blood pressure tracing, with a sys tolic rise followed by a diastolic fall and a dicrotic notch. • The pulse pressure waves exhibit characteristic waveforms at faster graphing speed. Changes in the amplitude and shape of this waveform often provide an early indication of changes in ICP and brain compliance (see Figure 209-2). • The ICP respiratory waves are slower pressure oscillations that fall with inspiration and rise with expiration. They are produced by both fluctuations in arterial blood pressure and cerebral venous outflow that cause an overall fluctua tion in cerebral blood volume and, consequently, ICP (Figure 209-2). Various physiologic phenomena such as coughing, sneez ing, straining, or a low head position can raise pressure dra matically in the brain secondary to increased central venous pressure and the resulting retrograde transmission to the CSF. In a normal animal, the intracranial tissues are com pliant, and such intermittent elevations in ICP are transient and go unnoticed clinically. In animals with intracranial pathology and preexisting I C H , ICP may increase precipi tously and may stay that way. Similarly, ICP can be affected by maneuvers such as compression of the jugular veins, suc tioning the back of the throat, and regurgitation. An absolute level wherein ICP is considered pathologi cally elevated has not been established in humans or animals. Treatment of ICH generally is recommended in humans for ICP measurements greater than 15 to 20 mm Hg. Because adequate CPP is more important than ICP per se, giving 5,6
1,2
1,2
2,6
an exact value whereby treatment is initiated in an animal is not possible until studies, using similar monitoring systems, are done on larger numbers of animals with similar disease processes. General trends in ICP, as well as significant, sus tained changes in CPP, may be as useful to guiding therapy and prognosis as the specific ICP measurement that is recorded. In patients that have not been anesthetized, ICP monitoring is used in combination with meticulous and ongoing visual assessment of the patient to guide treat ment decisions for animals with ICH. ICPs of 25 to 40 mm Hg, with adequately maintained CPPs, are seen routinely in severely brain-injured animals that subsequently fully recover. ' In anesthetized or comatose patients, treatment of I C H should be considered when ICP values are 15 to 20 mm Hg and slowly increasing, when ICP values are lower than 15 mm Hg but rapidly increasing, or when CPP is not being maintained adequately. 5 6
Accuracy of Intracranial Pressure Monitoring Systems In human medicine, with defined limits of treatment of ICH (i.e., 15 to 20 mm Hg), there is considerable discussion on the accuracy of ICP monitoring technology; clinicians worry that ICP may be underestimated or overestimated and there fore they may either incorrectly treat or not treat patients. Although treatment standards have not been so well defined in veterinary medicine, the user must have an understanding of the limitations of the device being used. In addition, compartmentalization within the cranium, zero drift (with catheter tip transducers), and leveling to obtain accurate measurements (with external transducers) must be taken into account. In particular, fluid-filled systems may have inac curacies from leakage in stopcocks, improper positioning in the CSF space, and occlusion with debris. ' Although ventricular pressure measurement is still con sidered the gold standard for accuracy in monitoring ICP, catheter tip pressure transducers have a similar accuracy. Many studies have been done looking at the phenomenon of compartmentalization in the brain. ICPs can vary within and between the intracranial compartments: brain and CSF, supratentorial versus infratentorial location, and within and between hemispheres. In addition, because the contents are not homologous due to variation in tissue and capil lary density, pressures may vary throughout the brain even without pathology. In human studies, ICP is assessed most accurately by monitoring the cerebral hemisphere ipsilateral to the lesion. Surface ICP monitors, such as epidural and subdural cathe ters and bolts, generally are considered less accurate than ventricular catheters or intraparenchymal devices, because they are not necessarily reflective of events occurring deep within the brain. In a study monitoring ICP in seven nor mal dogs using catheter tip strain gauge transducers, no sig nificant difference in ICP was recorded within or between 4
3 7
3
3
cerebral hemispheres when multiple recordings were taken simultaneously in anesthetized and awake dogs. 6
Complications of Intracranial Pressure Monitoring Complications are rare overall and should not be used as a deterrent in deciding to use an ICP monitor if it is indi cated. The most common complications reported in humans include infection, hemorrhage, malfunction, obs truction, and malposition. " Infection and hemorrhage are associated more commonly with intraventricular catheter placement, and malfunction (obstruction, breakage) may be more common with catheter-tipped devices. 4
2
4
Indications for Intracranial Pressure Monitoring in Dogs and Cats The correlation between elevated ICP and a poorer outcome in patients with severe brain injury has been shown in many human studies. Lowering elevated ICP ensures adequate CPP, reduces the risk of herniation, and optimizes recovery. Because placing an ICP monitor is associated with a small risk of complications as well as added cost, it is reasonable to limit its use to patients that are at most risk of herniation from ICH. ICP monitoring of brain-injured animals is likely to be most useful in the following situations: 1. Animals that are anesthetized or comatose, including ani mals undergoing and/or recovering from intracranial surgery 2. Animals with severe, progressive neurologic deterioration that may respond to a specific therapy with time, such as intracranial infection or inflammatory brain disease 3. Severely and traumatically head-injured patients 4. Research animals
SUGGESTED FURTHER READING* Bagley RS: Options for diagnostic testing in animals with neurologic disease. In Bagley RS, editor: Fundamentals of veterinary clinical neurology, ed 1, Oxford, 2005, Blackwell Publishing. Chapter that provides a synopsis of most of what has been published on ICP monitoring in dogs and cats and also summarizes most of the work that has been done using the Camino ICP monitor in dogs and cats. Marmarou A M , Beaumont A : Physiology of the cerebrospinal fluid and intracranial pressure. In Winn HR, Youmans JR, editor: Youmans neuro logical surgery, ed 5, Oxford, 2004, Saunders. The human neurosurgeon's "bible" on general intracranial physiology. Sturges BK, LeCouteur RA, Tripp L D : Intracranial pressure monitoring in clinically normal dogs using the Codman ICP Express and Codman Microsensor ICP transducer, 18th A C V I M Annual Veterinary Medical Forum, Seattle, WA, 2000. Summarizes the use of the miniature strain gauge transducer (Codman ICP monitoring system) in normal dogs.
2
""See the C D - R O M for a complete list of references.
Chapter 210 SEDATION MONITORING Laurie Sorrell-Raschi,
DVM, DACVA
KEY POINTS • Sedation is the practice of delivering sedative and/or analgesic drugs to patients for procedures in which general anesthesia is considered unwarranted or undesirable. • Because respiratory and cardiovascular depression may result following sedative or analgesic drug administration, the clinician should always be prepared to give the patient ventilatory and cardiovascular support. • All sedated patients should receive supplemental oxygen. • The minimum standard of sedation monitoring is vigilance. • Continuous electrocardiographic and blood pressure monitoring, as well as capnography of the sedated patient, is valuable. • Pulse oximetry is one of the most useful monitoring tools for the sedated patient. • Level of consciousness must be monitored closely in all sedated patients. • If the animal needs to be unconscious during the procedure, general anesthesia should be considered.
progressively deeper levels of sedation are required, careful monitoring is essential. The level of monitoring necessary to ensure patient safety will depend on the patients status and the drugs and dosages employed to produce the required level of sedation.
BEFORE GETTING STARTED Before any means of chemical restraint or sedation is employed, it is important to keep in mind that although many of the drugs used in sedation protocols cause minimal change in mentation or depression of the cardiovascular and/or respiratory system by themselves, few of these drugs are used alone. There are two rules of thumb: (1) the drugs that work best alone are those most likely to have adverse affects on their own (e.g., a -agonists, propofol) and (2) drugs may cause more adverse respiratory and cardiovascular effects when given together than any of them demonstrates when given alone. Respiratory depression is one of the more common adverse sequelae of sedation. It is therefore advisable to have supplemental oxygen available whenever sedative drugs are administered. Oxygen via a face mask is benign and well tolerated by most sedated dogs and cats. It is also recommended that emergency airway supplies are nearby (e.g., endotracheal tubes, laryngoscope and blade, Ambu bag) should intubation become necessary (see Chapter 17, Endotracheal Intubation). 2
INTRODUCTION Sedation can be defined as a chemically induced state of ease, or extreme calm and well-being. In such a state a patient is capable of responding to his surroundings but is unafraid and calm. Ideally, sedation should be achieved with minimal change in the patient's level of consciousness, pro duce few adverse cardiovascular and respiratory effects, and require minimal monitoring. In clinical practice, however, sedative drugs rarely are given merely for their calming effects. In modern veterinary medicine, sedation is evolving as a method of performing procedures that are too long, stressful, and/or painful for the patient to undergo without the benefit of some form of hypnotic, anxiolytic, and/or analgesic agent. Because no single drug is generally capable of providing all of those things, sedation strategies often rely on combinations of drugs to provide appropriate levels of relaxation. This increases the likelihood of undesirable side effects such as cardiovascular and respiratory depression. In human medicine, the term conscious sedation was derived to describe the practice of delivering sedative and/ or analgesic drugs to patients for procedures in which gen eral anesthesia is considered unwarranted or undesirable. This method relies heavily on the human ability communi cate. The principle is a simple one: the greatest danger with sedation is that as sedative levels deepen, the patient becomes more likely to lose consciousness, lose control of the gag reflex, and suffer from cardiovascular and respiratory depression. In humans, loss of verbal responsiveness is an early indicator that sedation has become too deep and the transition from sedation to anesthesia has occurred. Because most veterinary species are nonverbal, it is important to watch for less overt signs of patient stability. When
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DRUGS See Chapter 162, Sedation of the Critically 111 Patient, for more information.
Tranquilizers Phenothiazines Acepromazine is the most commonly used drug in this class. It is a 2-acetyl derivative of promazine with a long duration of action (4 to 6 hours, however there have been some reports of effects as long as 12 hours). Many routes of administration can be employed (intramuscular [IM], intravenous [IV], subcutaneous [SC], or per os [PO]), but it has a slow onset of action (20 or more minutes) with all routes except IV (approximately 10 minutes). " As with all phenothiazine tranquilizers, acepromazine acts within the central nervous system (CNS) to inhibit dopa mine and 5-hydroxytryptamine receptors within the basal ganglia, limbic system, reticular activating system (RAS), hypothalamus, and brainstem. Acepromazine also exhibits 2
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antiemetic effects at the chemoreceptor trigger zone and vomiting center and has centrally mediated antihistamine-1 effects. It produces little respiratory or direct myocardial depression. There is experimental evidence that acepromazine may be protective against epinephrine-induced cardiac arrhyth mias and may increase vagal tone. ' ' It may cause periph eral a receptor blockade in the vasculature, leading to peripheral vasodilation. Although this drug is generally well tolerated in stable, hydrated animals, it may lead to cardiovascular instability in more compromised patients. 3 6 7
r
Benzodiazepines Benzodiazepines are multipurpose drugs used to provide not only tranquilization, but muscle relaxation, antiseizure activ ity, and anxiolysis (see Chapter 185, Benzodiazepines and Flumazenil). Benzodiazepines exert sedative and behavioral effects through actions on the limbic system and muscle relaxing effects through inhibition of internuncial neurons of the spinal cord. Benzodiazepines potentiate the actions of y-aminobutyric acid (GABA), one of the two main inhib itory amino acid transmitters in the brain (glycine being the other). Diazepam and midazolam are the two most com monly used drugs in this category in veterinary medicine in the United States. Benzodiazepines produce minimal respiratory depression and very little cardiovascular depres sion. Midazolam may cause a greater decrease in blood pres sure secondary to a decrease in systemic vascular resistance (SVR) compared with diazepam. Although benzodiazepines by themselves produce little sedation in healthy dogs and cats, their utility lies in combination with other drugs. These drugs also have the added feature of reversibility (flumazenil). 8
Sedatives a -Agonists
Opioid Analgesics Opioid drugs, like a -agonists, exert their effects through receptors (u, K, 8) that are located throughout the spinal cord and brain (see Chapter 184, Narcotic Agonists and Antagonists). Of these, the u, and K receptors modulate analgesia and sedation. Depending on the specific opiate chosen, dose and route of administration, opioids may produce a range of sedative effects from minimal to profound sedation. Paradoxically, like the benzodiazepines, opioids may also produce excite ment rather than sedation in healthy alert animals, particu larly cats. Opioid drugs are advantageous because they may be given by many routes (TV, I M , SC, PO), have a short or long duration of action, are cardiovascular sparing (although may increase vagal tone), provide analgesia, and are reversible (with naloxone). The primary drawback to opioid drugs is that they may cause respiratory depression. This effect may be minimized by using butorphanol, a mixed u-agonist-antagonist, or buprenorphine, a partial (i-agonist, both of which should have less respiratory depression effect than more selective u-agonists. Alternatively, respiratory depression may be reversed with an antagonist such as naloxone. Although sedated patients undergoing procedures will ide ally remain conscious with an intact gag reflex, it is important to keep in mind that opioid analgesics may also lead to decreased gastrointestinal motility and increased chance of vomiting. Whenever possible, patients should fast for an appro priate period before receiving opioid sedation, and general anesthesia with intubation should be considered in patients at high risk for vomiting or regurgitation and aspiration. 2
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The oc -agonists have potent sedative effects when adminis tered by themselves. ' oc -Receptors are located throughout the spinal cord and brain and play a role in pain modula tion as well as sympathetic outflow. When stimulated, oc receptors in the brain and spinal cord produce sedation and analgesia. oc -Agonists may be given by many routes, including sublingual (SL). They are fast-acting drugs and their effects may be of short or long duration depending on individual drug pharmacokinetics (xylazine versus medetomidine). These drugs are also reversible with yohimbine or atipamezole, among others. Unlike the tranquilizers previously mentioned, the car diovascular effects of ot -agonists can be profoundly negative. <x -Receptors exist on the peripheral vasculature, as well as in the CNS. After the administration of an a -agonist these receptors are activated and cause an increase in peripheral vasoconstriction that can be severe, more so when the drug is given IV than I M or SC. This usually is followed by a reflex bradycardia that may be profound, particularly if the blood pressure is high. This may persist as the centrally mediated effects of the drug (namely decreased sympathetic outflow) occur, and hypotension may result. Typically patients ventilate and oxygenate adequately, but respiratory side effects may occur. The mucous membranes appear pale, but this color change is often the result of vaso constriction rather than poor ventilation or oxygenation; however, hypoventilation has been reported subsequent to a -agonist administration.
Dissociative Anesthetics
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Ketamine is the most commonly used dissociative anesthetic in veterinary medicine. " Ketamine and other dissociative drugs disrupt the connection between the thalamoneocortical and limbic systems and depress the thalamoneocortical system. Patients usually breathe well, and although they may experience apneustic (short gasping breaths) respira tions, they retain good laryngeal reflexes and continue to respond to their surroundings (may even have hypersensitive responses). Ketamine stimulates release of norepinephrine from adrenergic nerve terminals, thus indirectly augmenting sympathetic outflow. Generally ketamine helps maintain blood pressure; however, it has a direct negative inotropic effect on myocardial performance and may cause a decrease in blood pressure in critically ill patients. Ketamine may also cause muscle rigidity and seizures or hyperresponsive states when used alone in animals for chemical restraint. 11
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Tiletamine is packaged in a fixed ratio with zolazepam as the drug Telazol. Because it is combined with a benzodiazepine, it has all of the advantages and disadvantages of both a dissociative drug and a benzodiazepine. Tiletamine, however, lasts much lon ger than ketamine (1 to 2 hours versus 15 to 20 minutes) and is more of a respiratory and cardiovascular depressant.
Propofol Propofol is a sedative-hypnotic emulsion that induces CNS depression by enhancing the effects of GABA in the brain
and decreasing the brain's metabolic activity. Propofol is administered IV and absorbed rapidly, providing quick loss of consciousness with a short duration, after a single bolus, in both dogs and cats. Propofol can be administered in combination with other drugs but also works well on its own. Propofol has a large volume of distribution and most likely some extrahepatic source of clearance, which allows for rapid recovery after a single injection. Sedation can be as short as 5 minutes following a single dose or as long as desired if repeated boluses or a continuous infusion is given. Infusions of longer than 1 hour may prolong the recovery time from propofol. Propofol may cause hypoventilation and hypotension secondary to peripheral vasodilation and myocardial depres sion when administered rapidly in dogs and cats. ' In cats, propofol can also cause oxidative injury to red blood cells, producing Heinz bodies if it is given repeatedly over a period of hours to days. 14
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application of the leads unless they are heavily sedated. Stick-on electrode pads may be more tolerable than alligator clips, especially in lightly sedated patients.
Noninvasive Blood Pressure Monitors Multiple brands of monitors are available to measure blood pressure noninvasively in humans and animals. Most machines, employ one of three main methods: oscillometric, plethysmographic, or Doppler methods. All three techniques have their advantages and disadvantages depending on the species (cat or dog) and the circumstances in which they are used. " Regardless of the method, all of these techniques provide a more precise determination of blood pressure when used properly than does pulse palpation alone. Particularly in animals with deepening levels of sedation, it is advantageous to use some type of noninvasive blood pressure monitoring to assess the patient's cardiovascular status. 17
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Capnometry A capnometer monitors end-tidal carbon dioxide (ETC0 ) which, under normal circumstances (normal lung paren chyma, normal lung perfusion), is a reflection of arterial carbon dioxide (see Chapter 207, Capnography). It is, there fore, an indirect measure of effective ventilation. Although capnography is most effective when used on intubated patients, other techniques have been described for use in patients that are breathing spontaneously. Sidestream capnographs have been used in oxygen masks or in cannulae placed in the nares of more sedate patients, providing read ings that correlate well with blood gas results in spontane ously breathing, nonpanting dogs. The advantage of capnometry is that it may allow real-time monitoring of ventilatory status as well as perfusion. Abrupt decreases in E T C 0 can indicate a profound decrease in cardiac output, ventilation, or both. At the very least, such a decrease should warrant further investigation. 2
MONITORING Basic There are three main goals of monitoring patients during conscious sedation: 1. Monitor patient comfort and ensure that the animal tol erates the procedure. 2. Monitor the cardiopulmonary status. Ensure that the patient is ventilating and oxygenating well and is main taining adequate perfusion. 3. Monitor the level of consciousness and ensure that the patient has not become anesthetized. Whenever sedative procedures are performed, the mini mum standard in monitoring is vigilance. Trained personnel should be on hand to observe the patient for signs of distress. If instrumentation is unavailable, ventilatory status may be evaluated by monitoring respiratory rate and effort. Mucous membrane color may give an indication as to the patient's oxy genation status (i.e., cyanosis may indicate hypoxia). Pulse rate, rhythm, and quality, mucous membrane color, and capil lary refill time should be monitored to assess cardiovascular status. With deepening levels of sedation the palpebral reflex, patellar reflex, withdrawal to toe pinch, and reflex response to sound may be used to determine the patient's level of con sciousness. Loss or severe blunting of one or more of these reflexes may indicate that the patient has made the transition from sedation to general anesthesia and may be in need of cardiovascular and/or ventilatory support.
Advanced Although instrumentation should never be used as a substi tute for trained personnel, it can be invaluable when moni toring a sedated patient, particularly those undergoing procedures that require deeper levels of sedation.
Electrocardiography The electrocardiogram (ECG) is a means of continuously monitoring the electrical activity of the heart. Changes in rate, rhythm, or electrical configuration of the QRS com plexes (ST segment depression and/or elevation) may give an early indication that the patient is in distress. One drawback to this monitoring device is that dogs and cats may object to
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Pulse Oximetry The pulse oximeter is used to noninvasively monitor arterial oxygen saturation (see Chapter 208, Blood Gas and Oximetry Monitoring). In humans undergoing anesthesia, the pulse oximeter is considered one of the most valuable monitoring tools. According to the American Society of Anesthesiologists (ASA) Committee on Professional Liability analysis of closed anesthesia claims, adverse respiratory events occurred more frequently than any other outcome claimed and probably could have been detected if a pulse oximeter had been employed. ' As a result of this study and others, pulse oxim etry is now considered part of the ASA standard of monitored sedation care. Although dogs and cats have a high tolerance for the respi ratory depressant effects of opioids, sedation of animals always carries the risk of respiratory depression. Pulse oximetry is a useful tool because it is noninvasive, easy to apply, and gener ally well tolerated. It also has the advantage of providing infor mation about cardiovascular status. Because the pulse oximeter must detect a pulse signal to function, changes in the quality of the pulse signal may alert the clinician to changes in perfusion when more cumbersome monitoring equipment is not available or not tolerated by the patient. 1 22
Temperature With deeper levels of sedation the patient's body temperature should be monitored every 15 minutes, as tolerated by the
patient. Many drugs used for sedation (e.g., phenothiazines, a -agonists) may disrupt thermoregulation. Smaller patients such as cats and small dogs will be more likely to cool with deeper levels of sedation than larger ones because of their low body mass-to-surface ratios. Shivering will increase oxy gen consumption and may predispose the patient to hypoxia if supplemental oxygen is not employed. Every attempt should be made to keep the patient within 2° to 3° F of normal body temperature while sedated. 2
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Monitoring the Level of Consciousness Conscious sedation was developed in humans as a means of accomplishing two tasks: 1. Providing comfort and analgesia for people during proce dures that were too painful to be done without chemical support, but did not warrant general anesthesia 2. To provide an alternative method of performing proce dures on patients who were considered too high risk for general anesthesia In veterinary medicine, sedation has evolved similarly. However, veterinary medicine differs from human medi cine inasmuch as most veterinary patients are nonverbal. One of the main difficulties inherent in sedating animals is that there are no clear guidelines as to what constitutes sedation. Even in human literature there is little agreement as to what distinguishes light from mild, moderate, or deep sedation. What is agreed upon, however, is that as the patient's level of sedation gets deeper, laryngeal, ventilatory, and cardiovascular function are more likely to be compromised. It is of paramount importance that the patient's level of consciousness be monitored. In human medicine, the level of consciousness is monitored continuously by assessing a patient's response to verbal and tactile stimuli. As this is not possible in veterinary patients, it is generally assumed that the patient is comfortable if there is no voluntary movement, and this lack of movement is often used as the end-point of drug administration. However, even at the deepest level of sedation, the patient should maintain a palpebral reflex and respond to verbal or tactile stimuli such as a toe pinch withdrawal or involuntary reflexes such as the patellar reflex (if the patient is sedated appropriately and the clinician is careful, one or more of these reflexes can be assessed without unduly disturbing the patient during the procedure). If the patient will not remain still enough to allow the proce dure to be performed at this level of consciousness, then it is likely more prudent to perform the procedure under general anesthesia. 1
CONCLUSION Conscious sedation is a useful procedure to allow various diagnostic, medical, and surgical procedures to be per formed when general anesthesia is unavailable, too danger ous, or unwarranted. It is a valuable tool to the practicing veterinarian; however, it must be used appropriately to be performed safely. All sedated patients should be monitored for ventilatory and cardiovascular stability and their level of consciousness should be observed. Sedation should never be performed without careful consideration of the patient's needs during the procedure. The veterinarian should not think of sedation as the quicker, safer alternative to general anesthesia. Too often clinicians choose to perform sedation rather than general anesthesia, thinking that sedation will be quicker, use less medication, cause less cardiovascular compromise, obviate the need for intubation, and provide for a quicker recovery. However, procedures may last for an extended period (requiring multiple bolus doses of sedative drugs), during which time the patients are actually unconscious with unprotected airways. Under these circumstances, none of the actual benefits of sedation exist, and general anesthesia would be a better and safer choice.
SUGGESTED FURTHER READING* Binns SH, Sisson DD, Buoscio DA, Schaeffer DJ: Doppler ultrasonographic, oscillometric sphygmomanometric, and photoplethysmographic tech niques for noninvasive blood pressure measurement in anesthetized cats, J Vet Med 9:^5, 1995. A good comparative study that found the oscillometric technique to be the least accurate and least efficient of the tested methods; underestimated blood pres sure in cats by increasing amounts as the blood pressure increased. Grosenbaugh DA, Muir WW: Blood pressure monitoring, symposium, Vet Med 93:48, 1998. An excellent review of basic blood pressure monitoring techniques in small animals. Hendricks JC, King LG: Practicality, usefulness and limits of end-tidal carbon dioxide monitoring in critical small animal patients, J Vet Emerg Crit Care 4:29, 1994. One of the only studies that uses an ETC0 monitoring technique in awake ani mals. A well-executed study whose authors discuss its limitations and provide valuable insight into the use of ETC0 monitoring in small animal medicine. Simon C H : Monitored anesthesia care. In Barash P G , Cullen BF„ Stoelting RK, editor: Clinical anesthesia, ed 4, Philadelphia, 2001, Lippincott Williams 8t Wilkins. One of the primary anesthesia texts used in human medicine. A well-referenced textbook chapter. Thurmon JC, Tranquilli WJ, Benson GJ: Preanesthetics and anesthetic adjuncts. In Thurmon JC, Tranquilli WJ, Benson GJ, editor: Lumb and Jones' veterinary anesthesia, ed 3, Baltimore, 1996, Williams & Wilkins. A commonly referenced anesthesia text for veterinarians at all levels. 2
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"See the C D - R O M for a complete list of references.
Chapter 211 ELECTROCARDIOGRAM EVALUATION Matthew S. Mellema, DVM, PhD
KEY POINTS • The electrocardiogram (ECG) is an extremely useful and costeffective monitoring tool. • ECG monitoring is indicated for nearly all critically ill patients. • Rather than a limited study of multiple leads, continuous monitoring of a single lead is the basis of most ECG monitoring in the critically ill patient. • ECG interpretation should be systematic and thorough to gain the most benefit from its use. • Trends in ECG alterations may alert the clinician to changes in the patient's condition even when the absolute values of those parameters still fall within the normal ranges. • Electrolyte abnormalities, hypoxemia, effusions, and pain may cause acute detectable ECG changes without necessarily altering the underlying rhythm.
Some might argue that all critically ill animals warrant continuous ECG monitoring, and such statements may be true. However, some patients may have conditions that pre clude continuous ECG monitoring and may instead mandate that intermittent evaluations be performed instead. One example of such a patient is a dog with central nervous system disease that is exhibiting circling. In this patient's case, ECG lead wires may represent a significant tangling or tripping hazard to the patient. Also, patients with diffuse dermatologic disease may not tolerate typical lead placement. With such exceptions in mind, one can state that most critically ill patients may benefit from continuous E C G monitoring. In particular, any patient with an irregular rhythm, increased heart rate, or decreased heart rate detected on physical exami nation should have ECG monitoring.
INTRODUCTION
ELECTROCARDIOGRAPHIC PRINCIPLES
Disorders of cardiac rhythm and conduction are encountered frequently in critically ill veterinary patients. Arrhythmias may be encountered in patients with primary cardiac disease or may be one manifestation of systemic illness. The severity of rhythm and conduction disturbances can range from inconsequential to acutely life threatening and can progress rapidly from one extreme to the other in some patients. The electrocardiogram (ECG) is the diagnostic and mon itoring tool used to confirm, detect, and define cardiac con duction and rhythm disturbances. In addition, the ECG provides the clinician with continuous real-time data regard ing the patient's heart rate and rhythm, which can be infor mative even in the absence of gross abnormalities. This chapter will focus on the use of the E C G as a monitoring tool. For details of the recognition and treatment of specific cardiac rhythm disorders the reader is referred to other sec tions of this book (see Chapters 45 to 47, Bradyarrhythmias and Conduction Abnormalities, Supraventricular Tachycar dia, and Ventricular Tachyarrhythmias, respectively).
During depolarization and repolarization of the myocar dium, the heart generates an electrical field that can be detected at the surface of the body by ECG leads. The system used in clinical practice consists of a series of positive and negative leads that when placed around the heart (roughly in the frontal plane either on the trunk or the limbs) will record complexes associated with the various phases of the cardiac electrical cycle. The E C G detects the sum of all the electrical impulses generated by the individual myocytes during each cycle. When a positive deflection is seen on the ECG tracing it signifies that the sum of the heart's electrical impulses was moving toward the positive electrode of that lead. A negative deflection signifies that the sum of the impulse was moving away from the positive electrode at that time. Impulses traveling perpendicular to an electrode do not cause a deflection in the tracing. When these deflections are plotted over time, a series of waveforms (P, QRS, and T) are detected.
INDICATIONS The ECG is an extraordinarily cost-effective and useful mon itoring tool. In veterinary intensive care the ECG may be sec ond only to serial, well-performed physical examinations in terms of its usefulness in overall patient monitoring. Although a brief multiple lead evaluation of a patient's ECG is an important part of any diagnostic workup of suspected intrathoracic disease, in the intensive care setting continuous monitoring of cardiac rate and rhythm (typically one or a few leads at a time) is of greatest utility.
The standard leads used in veterinary practice include the three bipolar leads (I, II, and III) and the augmented leads (aVR, aVL, and aVF). Each lead can produce a tracing of the heart's electrical activity from a different angle. In combina tion, the information obtained from multiple leads can aid in the diagnosis of rhythm and conduction disturbances. When measurements of the P-QRS-T waveforms are performed, these should be done using a lead II tracing.
TECHNIQUE Many lead attachment systems are available. When selecting a system it is important to bear in mind that high-quality
ECG recordings require good contact between the leads and the patient's skin. If commercially available self-adhesive lead pads are to be used, then it is advised that the hair be clipped and the skin cleaned and dried before application. Generally, lead pads placed over the lateral thorax on each side and a third pad in the left inguinal region is sufficient to obtain good quality tracings. Alligator clips are not advised for con tinuous monitoring, because their prolonged use can dam age the patient's skin and cause discomfort. Once the lead pads are placed and lead wires attached, it is often helpful to place a mesh stockinette shirt around the patient's trunk so that all leads can be collected into a single "stalk" exiting the mesh shirt dorsally. This can enhance patient comfort, prevent lead detachment, and reduce obstacles to patient repositioning. When selecting a lead to display during continuous ECG monitoring one should select the one that the caregiver believes provides the most easily recognizable waveforms. Lead II is used for rhythm evaluation in cardiac examina tions, because in most patients this lead lies well within the mean electrical axis of the heart and will produce easily rec ognizable waveforms. However, in the critically ill patient the caregiver may need to evaluate several leads to find the one which gives the most robust signal. If one is relying on the monitor to calculate heart rates automatically, one will often get more accurate readings if a lead is picked in which the QRS amplitude is markedly dif ferent from that of the P and T waves (otherwise double or triple counting may occur, giving erroneously high heart rate readings). It should always be noted in the patient's record which lead is being monitored. It is essential that the clini cian and nursing staff bear in mind that the normal values for canine and feline ECGs are obtained from still animals in right lateral recumbency. During continuous monitoring the patients are seldom, if ever, in the ideal position and changes in waveform amplitude are to be expected relative to normal values. The utility of the continuous ECG is pre dominantly in monitoring heart rate and rhythm; however, it can also alert the clinician as to whether a standardized recording of all six leads and a rhythm strip should be performed.
ELECTROCARDIOGRAM
WAVEFORMS
Figure 211-1 shows a normal canine lead II P-QRS-T com plex with the waveforms, intervals, and ST segment identi fied. The P wave is a reflection of the depolarization of the atria. Its duration and amplitude should be noted. The PR interval is measured from the beginning of the P wave to the start of the QRS complex and is a measure of the time it took for the electrical impulse to travel from the sinoatrial node to the ventricular myocardium (including the normal delay that occurs as the impulse travels through the atrioven tricular node). The QRS complex is a reflection of ventricu lar depolarization. As with the P wave, the duration and amplitude of the QRS complex should be evaluated. The ST segment is measured from the end of the QRS complex to the beginning of the T wave. Disease states can cause the ST segment to be shifted upward or downward from the base line, and any such shifts should be noted. The T wave is the result of ventricular repolarization. Although the shape and amplitude of the T wave can be extremely variable in normal dogs, progressive or acute changes in the conformation of
Figure 211-1 Component waveforms, segments, and intervals of the normal electrocardiogram.
the T wave of an individual patient can be a marker of important disease states such as hypoxemia. The QT inter val is an indicator of the time required for ventricular con traction to occur. This interval is measured from the start of the QRS complex to the end of the T wave. The dura tion of the QT interval can be an important indicator of electrolyte abnormalities.
ELECTROCARDIOGRAM INTERPRETATION The most important principle in ECG interpretation is that each E C G should be evaluated in the same systematic way. Any thorough evaluation should include the following: 1. Calculation of heart rate 2. Determination of the rhythm 3. Identification of the waveforms (P-QRS-T) with particu lar attention paid to changes relative to previous evalua tions of this same patient 4. Evaluation of the PR and QT intervals 5. Inspection of the ST segment for elevation or depression Each of the above should be compared with normal values (Table 211-1) and to previous measurements made from this same patient. Serial evaluation can provide impor tant early indications of changes in the patient's condition, even when values fall within the normal range. For example, progressive elongation of the QT interval or QRS duration may signal worsening hyperkalemia in a patient long before the absolute values of these measurements leave the accepted normal range. Care must be taken when evaluating the amplitude or orientation of the waveforms relative to nor mal values if they were not obtained from a still animal in right lateral recumbency (as the normal values were). Changes in the durations of the intervals and waveforms sel dom are affected by patient position, whereas the orientation and amplitude of the waveforms can vary markedly.
Table 211-1 Normal Canine and Feline Lead II Electrocardiogram Values Canine
Feline
Heart rate
Puppy: 70 to 220 beats/ min Toy breeds: 70 to 180 beats/min Standard: 70 to 160 beats/ min Giant breeds: 60 to 140 beats/min
120 to 240 beats/ min
Rhythm
Sinus rhythm Sinus arrhythmia Wandering pacemaker
Sinus rhythm
Amplitude
Maximum: 0.4 mV
Maximum: 0.02 mV
Duration
Maximum: 0.04 sec (giant breeds 0.05 sec)
Maximum: 0.04 sec
0.06 to 0.13 sec
0.05 to 0.09 sec
Amplitude
Small breeds: 2.5 mV Large breeds: 3 mV
Maximum: 0.9 mV
Duration
Small breeds: 0.05 sec maximum Large breeds: 0.06 sec maximum
Maximum: 0.04 sec
Depression
No more than 0.2 mV
None
Elevation
No more than 0.15 mV
None
QT Interval
0.15 to 0.25 sec at normal heart rate
0.12 to 0.18 sec at normal heart rate
T Wave
May be positive, negative, or biphasic Not more than one fourth of R wave amplitude
Usually positive
P Wave
PR Interval QRS
concentrations can cause alterations in cardiac electrical and mechanical functions.
Hyperkalemia Although most critically ill patients are faced with large ongoing potassium losses, a subset of animals may arrive with or develop elevated extracellular potassium levels. Such hyperkalemia may occur either as a result of the underlying disease process (e.g., Addison's disease), as a result of treatment (e.g., lysis of a saddle thrombus with subsequent reperfusion), or because of inadver tent administration of excess parenteral potassium ion (e.g., poorly mixed fluids supplemented with potassium chloride). Regardless of the etiology, the ECG can serve as an invaluable tool in the detection of hyperkalemia. As serum potassium levels rise above 5.5 mEq/L, the ECG may begin to show tall peaked T waves. As potassium levels rise to 8 to 9 mEq/L, QRS duration may become prolonged and P wave amplitude may diminish. With further increases in potassium, the QRS waves may take on a sinusoidal appearance, P waves may no longer be apparent, and ST segment elevation or depression may be noted.
Hypokalemia
ST Segment
Modified from Tilley LP, Goodwin J, editors: Manual of canine and feline cardiology, ed 3, Philadelphia, 2001, WB Saunders.
Low serum potassium levels are a common finding in the critically ill patient and frequently need to be addressed when a fluid plan is formulated. When hypokalemia devel ops it may result in nonspecific ECG changes such as pro longation of the QT interval, reduced T wave amplitude, and ST segment depression. Severe hypokalemia may lead to both atrial and ventricular tachyarrhythmias.
Hypercalcemia Similar to how they handle potassium, most sick and injured animals struggle to maintain a normal serum ionized cal cium level. However, hypercalcemia may occur, resulting from either a primary disease state or administration of intravenous calcium preparations, or both; the elevation of this ion may be reflected by changes in the ECG. The most notable of these changes is QT interval shortening, and this finding can be an important signal to the clinician to mea sure both total and ionized calcium levels.
Hypocalcemia EFFECTS OF DISEASE STATES ON THE ELECTROCARDIOGRAM Specific arrhythmias and their management are discussed elsewhere in this book (see Chapters 45 to 47, Bradyarrhythmias and Conduction Abnormalities, Supraventricular Tachy cardia, and Ventricular Abnormalities respectively). However, many disease states can produce detectable changes in the ECG before they become so severe that they alter the rhythm or shift the heart rate outside the normal range.
Electrolyte Abnormalities The normal action potentials generated by both contractile and noncontractile cardiac cells are dependent on the sequential opening of a multitude of ion channels and the flow of ionized sodium, potassium, and calcium through these channels across the cell membranes. Further, other electrolytes such as magne sium serve as important cofactors in cellular actions relying on adenosine triphosphate, such as the function of cellular pumps that reestablish resting membrane potential after a depolariza tion. Thus it is not surprising that alterations in electrolyte
As one might expect, the effects of hypocalcemia on the ECG are in direct contrast to those caused by hypercalcemia. Pro longation of the QT interval may be an indication of reduced serum calcium concentrations. Nonspecific changes in the shape of the T wave may be noted as well.
Magnesium In humans, hypermagnesemia may cause prolonged PR intervals and QRS durations. Little is known about elevated magnesium levels in critically ill dogs and cats, although hypomagnesemia is a recognized condition occurring in a significant number of critically ill veterinary patients. Low magnesium levels cause ECG changes quite similar to those noted for hypokalemia.
Hypoxemia Low partial pressure of arterial oxygen has a profound effect on cardiac function, sympathetic nervous system activation and, not surprisingly, the ECG. Severe or prolonged hypox emia can produce both tachyarrhythmias and bradyarrhythmias and may lead to cardiac arrhythmias. However, in many patients the ECG can also provide early warning signs
of worsening tissue oxygenation. Myocardial hypoxia may be reflected by elevation or depression of the ST segment. The sudden appearance of large T waves can herald hypoxemia, although any abrupt change in T wave appearance warrants an evaluation of the patient's blood gases.
Intrathoracic Effusions The accumulation of effusions (or tissues as may be seen with diaphragmatic hernias) within the pericardial or pleural spaces can result in dampening of the E C G waveforms. Diminished or variable amplitude of the QRS complex should prompt the clinician to pursue further diagnostic measures to rule out intracavitary effusions.
Pain Patient discomfort can lead to nonspecific alterations in the ECG. A progressively increasing heart rate with or without changes in T wave conformation can be a sign of increasing sympathetic nervous system output. When these changes are seen in a patient exhibiting other signs of discomfort, allevia tion of pain may lead to normalization of the ECG parameters.
SUGGESTED FURTHER READING* Braunwald E, Zipes DP, Libby P, Bonow R editors: Braunwald's heart disease: A textbook of cardiovascular medicine, Philadelphia, 2004, Saunders. One of the most widely used textbooks in human cardiology. Very detailed. An excellent reference book. Darke P, Bonagura JD, Kelly DF: Color atlas of veterinary cardiology, MosbyWolfe, 1996, London. A high-quality atlas containing full-color reproductions of ECGs, echocardio grams, radiographs, and pathology specimens. Tilley LP: Essentials of canine and feline electrocardiography, ed 3, Philadel phia, 1992, Lea & Febiger. An excellent resource that covers the interpretation of ECGs as well as the man agement of arrhythmias in dogs and cats. Also contains discussions of the pathophysiologic basis of common arrhythmias. An updated edition due out in late 2006. Tilley LP, et al: Canine and feline cardiology, ed 4, St. Louis, 2008, Saunders. A very-easy-to-use and straightforward text. Updated extensively from the second edition. Tilley LP, Miller M S , Smith FW, Jr: Canine and feline arrhythmias: Selfassessment, Philadelphia, 1993, Lea 8c Febiger. A high-quality collection of ECGs presented in a case-based format that allows for self-paced learning and practice. Highly recommended. "See the C D - R O M for a complete list of references.
Chapter 212 CARDIAC OUTPUT MONITORING Matthew S. Mellema, DVM, PhD
KEY POINTS • Cardiac output is the volume of blood transferred by the heart to the systemic circulation over time. • It is a key determinant of oxygen delivery and an early indicator of hemodynamic instability. • Cardiac output should be measured in any patient wherein appropriate clinical decisions cannot be made without this information. • Both invasive and minimally invasive methods of cardiac output measurement are available for clinical use in dogs and cats. • Disease states can have a profound and complex impact on cardiac output. • Complications of pulmonary artery catheters are rare, but placement should be done either by, or under the supervision of, experienced personnel.
INTRODUCTION
work in concert in a complex yet deeply integrated fashion. Each system relies on a pumping mechanism to accomplish the transport of blood or respiratory gases to the sites where the exchange of substrates and waste occurs. In the case of the cardiovascular system, the heart pro vides the pumping force and the blood vessels serve to con duct and distribute the pumped blood to the tissues. The elastic properties of the vascular tree allow the force gener ated by the heart to be stored and applied to the column of flowing blood throughout the cardiac cycle. The volume of blood transferred to the systemic circulation over time is termed cardiac output. Cardiac output in humans is typically measured in liters per minute (L/min). Veterinary patients often come in a much broader range of shapes and sizes and, as such, cardiac output is often referenced in terms of milliliters of blood per kilogram body weight per minute (ml/kg/min). Normal values for dogs and cats typically range from 120 to 200 ml/kg/min. ' A related measure is termed cardiac index and relates the volume of blood pumped over time to the animal's body surface area rather than body mass, because the former is thought to correlate with meta bolic rate (the principal determinant of cardiac output). 1 2
Delivery of oxygen to the body and the removal of cellular metabolic waste are the fundamental roles of the cardiovas cular and pulmonary systems. To accomplish these vital functions the pulmonary and cardiovascular systems must
Cardiac index is expressed in liters per minute per square meters (L/min/m ). Cardiac output is an important measure of cardiovascular function. It provides insights into the adequacy of blood delivery to the body as a whole. When taken together with measurements of the oxygen content of blood, it allows for the determination of whole body oxygen delivery. If one knows the patient's heart rate, then knowledge of cardiac output allows the clinician to determine stroke volume. Car diac output measurements also make it possible for the care giver to determine important physiologic indicators such as intrapulmonary shunt, systemic and pulmonary vascular resistance, and oxygen consumption. This vast array of addi tional parameters that can be derived once cardiac output is known allow the clinician to make better informed decisions about the need for, or adequacy of, therapeutic interventions and to provide a detailed account of the patient's cardiovascular status. 2
2
1,2
INDICATIONS FOR CARDIAC OUTPUT MEASUREMENT When performed by an experienced clinician, physical exam ination of the patient will reveal a great deal about the ade quacy of oxygen delivery and cardiac output. Many of the findings of the physical examination relate directly to regional or organ-specific blood flow (e.g., capillary refill time, pulse pressure, mentation, urine production). Although these physical parameters are invaluable in the repeated assessment of patients and require little more equipment than a wristwatch, some are subjective measures and corre late poorly with an individual patient's actual cardiovascular status. However, it must be noted that although an individ ual value for capillary refill time, for example, may correlate poorly with more direct measures of cardiac output, the trends in serial physical examination findings in an individ ual patient provide the best and most reliable measure of alterations in that patient's cardiovascular status. Unfortu nately, the converse is not true: a patient whose physical examination findings are not changing may be experiencing a decline in cardiac performance that will not be detectable until compensatory mechanisms are exhausted or overcome. 3
The findings of a thorough physical examination, partic ularly when complemented with hemodynamic monitoring (see Chapter 203, Hemodynamic Monitoring), will be suffi cient to guide the clinician in directing the care of most patients. However, there exists a subset of critically ill veteri nary patients in whom more direct assessment of cardiac output (and its derived parameters) is essential to proper case management. Patients with sepsis, septic shock, sys temic inflammatory response syndrome, and multiple organ dysfunction syndrome make up the bulk of veterinary patients that are likely to require more invasive measures of cardiac output. Patients with severe compromise of the pulmonary or cardiovascular system may also require car diac output monitoring to optimize their care. It is in the care of these patients that clinicians may find themselves unable to make appropriate decisions regarding manage ment without the additional information provided via cardiac output monitoring. In patients with complex disease states such as those mentioned above, the individual's cardiovascular and pul monary systems may be compromised to such an extent
that the typical measures of cardiovascular status and per formance may give contradictory information and suggest therapies that have opposing mechanisms of action (e.g., expanding or depleting extracellular fluid volume). A n alltoo-common example is a septic patient that has devel oped capillary leak syndrome (enhanced permeability of systemic capillaries and venules, promoting tissue edema). This patient typically has a low central venous or mean arterial pressure, or both (suggesting additional intrave nous fluid therapy would be of benefit), while at the same time exhibiting marked peripheral edema (which might lead the clinician to want to be less aggressive with fluid administration). The treatment of such a patient would be enhanced by the knowledge of the cardiac output and oxygen delivery, which are always of primary importance and can mandate a course of action in the face of conflicting findings. Cardiac output can also be a much earlier indicator of deteriorating cardiovascular status, because compensatory mechanisms such as reflex vaso constriction can maintain other indicators such as mean arterial pressure near normal levels in the face of worsen ing cardiac performance.
MEASUREMENT OF CARDIAC OUTPUT Invasive Methods of Determining Cardiac Output All invasive techniques to measure cardiac output rely on one of two methods: the Fick oxygen consumption method or the indicator-dilution method. The commonly used thermodilution method is, in principle, a modification of the indicator-dilution method using thermal energy as the indi cator. Both methods will be discussed. 4
Fick Oxygen Consumption Method This technique is considered the gold standard and is the oldest method for measuring cardiac output. The method relies on the Fick principle that states that the total uptake of (or release of) a substance by the peripheral tissues is equal to the product of the blood flow to the peripheral tis sues and the arterial-venous concentration difference (gradi ent) of the substance. For a substance that is taken up by the tissues (such as oxygen), the Fick principle says "what went in minus what came out must equal what was left behind." The Fick principle when applied to cardiac output and oxygen uptake can be expressed as the following:
When one uses the Fick method to determine cardiac output, oxygen consumption is determined by measuring the oxygen concentration difference in the inhaled air and the exhaled air collected from the patient over time (typically 3 minutes). The arteriovenous oxygen content difference is determined by mea suring the oxygen content of both an arterial and a mixed venous blood sample. Although oxygen content analyzers are available, it is more typical for the clinician to measure the oxy gen partial pressure (P0 ), hemoglobin saturation (S0 ), and hemoglobin concentration ([Hb]) with a blood gas analyzer and manually calculate oxygen content using the formula: 2
2
Oxygen content = ([Hb] x 1.36 x S 0 ) + (0.003 x P 0 ) 2
2
The principal drawbacks to this method in veterinary medicine are that it is not a continuous real-time measure of cardiac output and that reliable collection of respiratory gases requires that the patient be intubated. In addition, the Fick method relies on the patient maintaining a stable hemodynamic and metabolic state throughout the period of gas collection; thus the less stable the patient the less reli able this method becomes. Lastly, results obtained by the Fick method are invalid in the presence of significant intracardiac or intrapulmonary shunting of blood.
Indicator-Dilution Method (Including Thermodilution) In actuality, the indicator-dilution method is simply an adaptation of the Fick method using indicators that are more easily collected and measured than elemental oxygen. The basis still lies in the Fick principle and conservation of matter (or thermal energy). With this method an exogenous indicator is injected into the patient's mixed venous blood via a pulmonary artery cath eter (see Chapter 50, Pulmonary Artery Catheterization), and the dilution of the indicator is followed continuously until both the original concentration peak associated with injection and a secondary peak due to recirculation are observed. By plotting the concentration of the indicator against time, one can obtain the area under the curve of the concentration ver sus time plot. Cardiac output is determined by taking the known amount of indicator and dividing it by the area under the curve. Typically, this process is an integrated function of the software packages included with modern cardiac monitor ing equipment. In the laboratory setting the indicator maybe a dye such as indocyanine green; however, this method is sel dom used in clinical patients. The indicator of choice is thermal energy. Modern pul monary artery catheters can be equipped with a sensitive thermocouple that can give highly accurate continuous mea surements of blood temperature. This type of pulmonary artery catheter has been termed a Swan-Ganz catheter after the physicians who developed it and introduced it into clinical practice in human medicine. Although the technology has advanced, the technique still relies on the Fick principle. By injecting a known volume of saline at a known temperature (typically room temperature; chilling is no longer needed with modern catheters) into the right-sided circulation, one can use the thermocouple to fol low the dilution of this cool sample in the larger, warmer blood volume of the patient. Integration of this temperature signal can provide the clinician with a reliable measure of cardiac output. Recorded values are usually the average of three measurements taken in a short time, one after another. Good agreement is considered to be values that don't vary by more than 10%. One difference in this method relative to other indicatordilution techniques is that the indicator is injected into the right atrium and dilution is measured in the pulmonary artery. Dye dilution is performed by injecting into the pul monary artery and measuring the dilution at an arterial site. The thermodilution method is by far the most widely used method in practice today and is at least as reliable as either of the two other methods discussed above. Advances in ion-specific electrode technology have led to novel means of using indicator-dilution principles to 5
determine cardiac output in humans and animals. One such advance is the development of an electrode for lithium ions that can be introduced into the patient's arterial bloodstream via an indwelling arterial catheter. Such an electrode can be used to record the dilution of small doses of lithium chloride injected into the venous circulation at either a peripheral or central site. Cardiac output determination by this method has been studied in both dogs and cats, and agreement with cardiac output values obtained via thermodilution methods has generally been good. ' The lithium dilution method holds great promise because it does not require that a pulmonary artery catheter be in place. As clinical experience with the technique and evi dence of the method's reliability grows, the lithium dilution method (or similar technology) may replace thermodilution as the method of choice for cardiac output determination in small animal practice. 6 7
Noninvasive Methods of Determining Cardiac Output Although the lithium dilution method for determining car diac output can be termed minimally invasive, it is not truly noninvasive because it requires placement of both venous and arterial catheters. For patients requiring long-term intensive care and cardiac output monitoring, the availabil ity of patent peripheral arteries can become limited and lim iting. Truly noninvasive methods of real-time continuous monitoring of cardiac output continue to be sought and will be discussed briefly here. Transesophageal echocardiography has been used in man and a number of animal species as a minimally invasive means of tracking changes in cardiac output and performance. Mea surement of blood velocity (using Doppler) and aortic diame ter (using echocardiography) allow estimates of stroke volume to be obtained. To obtain truly reliable and quantifiable mea surements of cardiac output, transesophageal echocardiogra phy measurements should be initially (and periodically) calibrated against measurements obtained by one of the more invasive methods discussed above. The utility of this method is somewhat limited in small animal practice because of equip ment limitations, the time required to obtain acceptable stud ies, patient tolerance of the probe, and the need for highly trained personnel to be on hand to make the measurements. However, it does hold promise in limited application (e.g., anesthetized patient evaluation and monitoring). Thoracic electrical bioimpedance is a noninvasive method of evaluating changes in the conductivity of the thorax result ing from the pulsatile flow of blood within the thoracic cavity. Sets of electrodes similar to electrocardiogram electrodes are located superficially on the thorax. Although electrocardio gram electrodes simply measure voltage changes resulting from the intrinsic electrical activity of the heart, thoracic elec trical bioimpedance utilizes electrodes that both measure and apply voltage. The principle is that by applying a small known voltage to the patient's thorax and then measuring what por tion of that initial voltage reaches a distant sensing electrode, the conductivity (and impedance) of the thorax to flow of cur rent can be determined. Changes in thoracic blood volume (blood and tissue are good conductors, air-filled lungs are not) can be detected, and estimates of stroke volume and car diac output can be made using computer algorithms. Although this method holds promise in humans where the size and shape of the thorax is somewhat uniform, the variety of species and
breeds presented to the small animal clinician may make any single algorithm of limited utility, and estimates may require comparison with invasive methods with some frequency. Analysis of the arterial pressure waveform is an additional form of algorithm-dependent monitoring that is minimally invasive (requires an indwelling arterial catheter). Changes in the conformation of the arterial pressure waveform can provide insights into alterations in the performance of the heart and the tone of the vascular tree. Although qualitative evaluation of arterial waveforms has been standard practice for decades, it is only fairly recently that efforts have been made to provide quantitative information from this source. One promising prospect is the use of lithium dilution meth ods to calibrate arterial waveform analyses, which may then provide continuous read-outs of cardiac performance. This is an active area of research in both humans and animals.
NORMAL VALUES The normal values for cardiac output (and related and derived indexes) for dogs and cats are presented in Table 212-1. Values other than cardiac output and cardiac index are presented for the reader's consideration but are discussed in greater detail elsewhere (see Chapters 50, 64, and 203, Pulmonary Artery Catheterization, Daily Intra venous Fluid Therapy, and Hemodynamic Monitoring, respectively). The normal values presented in Table 212-1 represent composite values obtained from the literature and measurements made on clinical patients and research animals at the School of Veterinary Medicine at the Univer sity of California, Davis. These composites include values from animals that were sedated, as well as lightly anesthe tized animals. Values for fully awake animals might be con sidered true "normal" values but would not represent normal values for the setting in which clinical measurements are generally obtained. 2
POTENTIAL CAUSES OF ERROR Any form of measurement of any parameter carries an intrinsic degree of error. It is the responsibility of the
clinician and the nursing staff to avoid compounding this form of uncertainty by introducing additional sources of error (Table 212-2). To this end, clinicians seeking to mea sure cardiac output using any of the techniques discussed above should ensure that they have been trained by experi enced personnel and have suitable "hands-on" experience with the method before using it in clinical decision making. Misuse of data from Swan-Ganz catheters by insufficiently trained personnel has on occasion led to iatrogenic injury and poor outcomes, and subsequently the devices have fallen out of favor in some segments of human medicine. All of the methods for measuring cardiac output that have been discussed rely on the patient having stable hemo dynamics throughout the study period (typically several minutes). In the case of the Fick method, reliable measure ments also require that the patient have only small fluctua tions in metabolic rate during the study period. With each of the methods discussed, the serial evaluation of measure ments is of greater use than any single measurement.
DISEASE STATES AND CARDIAC OUTPUT MEASUREMENT Cardiac output is the product of stroke volume and heart rate. Disease processes that alter either of these factors may alter cardiac output (unless the disease affects both in oppo site directions and to equal degrees). Decreasing heart rates may either improve or worsen cardiac output depending on the individual patient. Patients with stiff, noncompliant ventricles or tachyarrhythmias, for example, may benefit from a reduction in heart rate via greater filling during dias tole. Alternatively, a patient with advanced atrioventricular node disease may have reduced cardiac output due to low (ventricular) heart rate. Generally, any condition that reduces stroke volume will reduce cardiac output if heart rate changes are minimal. Stroke volume is determined by preload, afterload, and con tractility. Preload is determined largely by cardiac compli ance and filling pressures. Any disease state that reduces filling pressures (e.g., hemorrhage, dehydration) or ventricu lar compliance (e.g., pericardial tamponade) can reduce
Table 212-1
Normal Cardiopulmonary Values for Dogs and Cats
Table 212-1
Normal Cardiopulmonary Values for Dogs and Cats -1
Heart rate (min ) Mean arterial pressure (mm Hg) Cardiac output (ml/kg/min)
100 to 140
110 to 140
80 to 120
100 to 150
125 to 200
2
Cardiac index (L/min/m )
3.5 to 5.5
Stroke volume (ml/beat/kg)
40 to 60
Systemic vascular resistance (mm Hg/ml/kg/min)
0.5 to 0.8
Mean pulmonary artery pressure (mm Hg) Pulmonary vascular resistance (mm Hg/ml/kg/min)
10 to 20 0.04 to 0.06
120
-
Central venous pressure (cm H 0)
Oto 10
Pulmonary artery wedge pressure (mm Hg)
-
5 to 12
-
2
Oxygen delivery (ml/kg/min) Oxygen consumption (ml/kg/min) Oxygen extraction (%)
20 to 35 4 to 11 20 to 30
3 to 8
-
Table 212-2
Sources of Error in Cardiac Output Measurement (Thermodilution)
Error Source
Brief Description
Adjustments
Respiratory cycle
Pulmonary artery blood cools during inspiration
Make measurements at end expiration
Venous return varies with intrathoracic pressure
Arrhythmias
Cause rapid and marked variations in stroke volume
Treat arrhythmias as indicated
Altered intracardiac flow
Shunting and regurgitation can cause some of the injectate to bypass the thermistor or delay arrival of some of the bolus volume
Thermodilution technique may be invalid in patients with significant flow abnormalities
Low cardiac output
Slow ejection causes warming of the injectate before it reaches the thermistor
Further therapeutic interventions will be required to increase cardiac output before values will be valid or repeatable
Injectate factors
Wrong solution, wrong volume, wrong temperature
Triple check all aspects of the bolus before injecting
Thermistor factors
Thrombus on the catheter tip
Check position and reposition or replace catheter as needed
Catheter migration Catheter defect
Additional infusions
Simultaneous infusion of large volumes of crystalloid or colloid solutions can interfere with thermistor detection of the bolus
preload and cardiac output. Afterload is a complex determi nant of stroke volume and is largely dependent on the tone of the vasculature (particularly arterioles), but in some patients is influenced by physical abnormalities in the vasculature (e.g., aortic stenosis, arteriovenous fistulas). Any process that increases afterload may reduce cardiac output (e.g., a-adrenergic stimulation), and processes that reduce afterload (e.g., reduced blood viscosity, arteriolar dila tion) may increase cardiac output. Contractility is a measure of the myocardium's ability to eject blood independent of preload. Contractility may, for example, be depressed by circulating mediators (e.g., sepsis, pancreatitis) or enhanced by P-adrenergic stimulation. Any alteration in a patient's cardiac output should prompt a careful consideration of how disease states may be altering heart rate, preload, afterload, and contractility. Factors known to adversely effect these determinants of cardiac output should be addressed whenever possible.
POTENTIAL COMPLICATIONS The vast majority of patients in which cardiac output measure ments are made experience no direct complications due to the instrumentation or procedures required. However, many com plications can occur when hemodynamic data are misinter preted, and this issue has been discussed earlier in this chapter. A small subset of patients in whom Swan-Ganz or other
Either interrupt the fluid bolus or postpone cardiac output measurements as dictated by patient's needs
pulmonary artery catheters are placed will experience complica tions related to the placement, presence, or maintenance of the catheter. These complications include, but are not limited to, the following: catheter-related sepsis, pulmonary artery rup ture, damage to cardiac structures, catheter knotting (possibly requiring thoracotomy), hemorrhage, and embolization. For these reasons and others, it is stressed that pulmonary artery catheter placement is not a technique to be learned without the guidance of experienced personnel. Complications from lithium chloride injection have not been reported in dogs or cats. The other methods of cardiac output determination discussed above also are considered to have a very large measure of safety. 8
SUGGESTED FURTHER READING* Haskins S, et al: Reference cardiopulmonary values in normal dogs, Comp Med 55:156, 2005. An excellent reference article reporting data collected from 97 healthy, unsedated, normovolemic dogs. Mean cardiac index for these dogs reported to be 4.44 L/min/m . Mellema MS: Cardiac output, wedge pressure, and oxygen delivery, Vet Clin North Am Small Anim Pract 31(6):1175, 2001. A more detailed presentation of the topic by this author. Although lacking a dis cussion of newer minimally invasive methods of cardiac output measure ment, contains a more detailed discussion of relevant cardiovascular physiology for the interested reader. 2
*See the C D - R O M for a complete list of references.
Part XX MECHANICAL VENTILATION Chapter 213
BASIC MECHANICAL VENTILATION
Chapter 214
ADVANCED MECHANICAL VENTILATION
Chapter 215
JET VENTILATION
Chapter 216
CARE OF THE VENTILATOR PATIENT
Chapter 217
DISCONTINUING MECHANICAL VENTILATION
Chapter 213 BASIC MECHANICAL VENTILATION Kate Hopper,
BVSC, MVSC, DACVECC
KEY POINTS • Mechanical ventilation involves a machine that performs some or all of the work of breathing. • The three indications for mechanical ventilation are severe hypoxemia despite therapy, severe hypoventilation despite therapy, and excessive respiratory effort. • The goal of mechanical ventilation is to maintain adequate arterial blood gases (partial pressure of arterial carbon dioxide of 35 to 50 mm Hg, partial pressure of arterial oxygen of 80 to 120 mm Hg) with the least aggressive ventilator settings. • Animals requiring mechanical ventilation suffer from either lung disease or neurologic or muscular dysfunction, or both. • Animals with lung disease generally require more aggressive ventilator settings and have a poorer prognosis than animals with neuromuscular diseases. • The "ideal" ventilator settings for a given patient can be determined only by trial and error. • Positive end-expiratory pressure (PEEP) increases the oxygenating efficiency of diseased lungs by preventing alveolar collapse and reducing ventilator-induced lung injury. PEEP is also used to prevent atelectasis in animals requiring prolonged anesthesia and mechanical ventilation. • Complications of mechanical ventilation include ventilatorassociated pneumonia, ventilator-induced lung injury, and pneumothorax.
breaths occur when the patient determines the respiratory rate but the tidal volume is generated by the machine. Dur ing controlled ventilation the machine determines both the respiratory rate and the tidal v o l u m e . The ventilator can generate a breath i n one of two basic ways. It can deliver a preset tidal volume over a given inspi ratory time (volume control), or the machine can provide and maintain a preset airway pressure for a given inspiratory time (pressure control). W h e n delivering a volume-controlled breath, the peak airway pressure generated will be dependent o n the preset tidal volume chosen and the compliance of the respiratory system. W h e n a pressure-controlled breath is delivered, the tidal volume will depend o n the preset airway pressure chosen and the compliance of the respiratory sys t e m . ' The more basic machines tend to be either volumecontrol ventilators or pressure-control ventilators. More modern, advanced machines have the capability to generate several different breath types. 3
1
3
COMPLIANCE Compliance is a measure of the distensibility of the lung and is defined as the change in lung volume for a given change in pressure. A lung with high compliance w i l l have a large increase i n volume for a small pressure change, whereas low compliance w o u l d be characterized as requiring a large pressure change to create a small increase i n volume. The normal, healthy lung is very compliant and, as a result, should require small airway pressures for adequate mechan ical ventilation. In contrast, most pulmonary disease pro cesses c o m m o n to veterinary medicine w i l l reduce pulmonary compliance and require higher airway pressures to adequately oxygenate and ventilate the patient. 2
INTRODUCTION A ventilator is a machine that performs some or all of the work of breathing. In veterinary medicine conventional pos itive-pressure ventilation is used most commonly. These machines utilize an increase in airway pressure to move gas into the lungs, i n contrast to spontaneous breathing where airway pressure decreases below atmospheric pressure i n order to generate the inspiratory phase o f a breath. The respiratory function of the lungs is to oxygenate the arte rial blood and remove carbon dioxide from the venous blood. Oxygenation refers to the movement of oxygen from the alveoli into the pulmonary capillaries and is primarily dependent on the surface area available for gas exchange and preservation of the delicate structure of the gas-exchange barrier. Removal of carbon dioxide is primarily dependent o n fresh gas movement into the alveoli; this process is ventilation. W h e n managing patients on mechanical ventilation it is useful to think of oxyge nation and ventilation as two separate processes.
1
1
2
VENTILATOR BREATH Ventilator breaths can be spontaneous, assisted, or con trolled. Spontaneous breaths occur when the patient deter mines the respiratory rate and tidal volume. Assisted
VENTILATOR SETTINGS Every model has a different range of settings. The more modern and advanced the machine, the more options it will provide for the operator to manipulate the ventilator breath. Despite the apparent complexity o f modern ventilators, only a few impor tant ventilator settings, available o n almost all machines, allow an effective ventilation protocol to be determined for a patient. These include respiratory rate, tidal volume, peak inspiratory pressure, inspiratory time, inspiratory-to-expiratory ratio, trigger sensitivity, and positive end-expiratory pressure (PEEP) (Table 213-1). The parameters that can be preset will depend o n the type of ventilation being used. W i t h volumecontrolled ventilation the tidal volume or minute ventilation is preset by the operator and peak airway pressure is a depen dent variable. Rather a peak airway pressure alarm limit is set
Table 213-1 Important Characteristics of a Ventilator Breath Parameter
Definition
Fraction of inspired Concentration of oxygen in the inhaled oxygen gas Respiratory rate Number of breaths per minute
INDICATIONS FOR MECHANICAL VENTILATION There are three m a i n indications for mechanical ventilation: (1) severe hypoxemia despite therapy, (2) severe hypoventila t i o n despite therapy, and (3) excessive respiratory effort. ' Hypoxemia is defined as a partial pressure o f arterial oxygen ( P a 0 ) o f less than 80 m m H g or a hemoglobin saturation ( S p 0 ) of less than 95%. A P a 0 o f less than 60 m m H g or an S p 0 o f less than 90% is considered severe hypoxemia. 1 5
2
Tidal volume
Volume of a single breath (ml)
Total minute ventilation
Total volume of breaths in a minute (ml) (V = TV x RR)
Inspiratory time
Duration of inspiration (sec)
Inspiratory-toexpiratory ratio
Duration of inspiration versus duration of expiration Peak pressure measured in the proximal airway (cm H 0) during inspiration
Peak airway pressure Positive endexpiratory pressure
T
2
Positive airway pressure maintained during exhalation
2
2
2
W h e n patients have severe hypoxemia despite oxygen therapy and specific treatment o f the primary disease, mechanical ventilation is indicated. M o s t o f these animals have primary lung disease. Inspired oxygen concentrations of greater than 60% for a prolonged period (24 to 48 hours) can lead to oxygen toxicity and subsequent p u l m o n a r y dam age. Therefore animals that require high concentrations o f inspired oxygen for longer than 24 hours i n order to achieve adequate oxygenation may also benefit from mechanical ventilation. 2,4
4
1
RR, Respiratory rate; TV, tidal volume; V , total minute ventilation. T
Hypoventilation is defined as an elevation i n the partial pressure o f carbon dioxide ( P a C 0 ) . Severe hypoventilation is defined as a P a C 0 higher than 60 m m H g and is an i n d i cation for mechanical ventilation i f the patient is unrespon sive to therapy for the p r i m a r y disease. Hypercapnia is a consequence o f reduced effective alveolar ventilation. This may be due to increased dead space i n a breathing circuit, upper airway obstruction, sedative overdose, or neuromus cular diseases that impair respiratory rate or chest wall movement. ' M o s t patients w i t h increased apparatus dead space, upper airway obstruction, or sedative overdoses w i l l respond to therapy and w i l l not require mechanical ventila tion. Patients requiring ventilation i n this category have neu rologic, muscular, or neuromuscular disease processes such as brain disease, high cervical spinal cord disease, peripheral neuropathies, neuromuscular junction abnormalities, o r p r i mary myopathies. F o r simplicity, this group o f disease pro cesses w i l l be considered neuromuscular diseases. Animals w i t h brain disease may not tolerate small elevations i n P C 0 , and mechanical ventilation may be indicated i n these patients i f the P a C 0 is higher than 45 m m H g . 2
to alert the operator o f excessive airway pressures. If pressure control is used, the peak airway pressure is preset and tidal v o l ume is a dependent variable. In some cases the parameters can be set directly or are indirectly determined by other settings. For example, the inspiratory-to-expiratory ratio can be preset directly o n some ventilators, but with many machines it is the consequence of the inspiratory time and respiratory rate that is chosen b y the operator. ' 1 3
The trigger variable is the parameter that initiates inspira tion, that is, how the ventilator determines when to deliver a breath. In animals that are not making respiratory efforts o f their own, the trigger variable is time and is determined from the set respiratory rate. If the animal is making respiratory efforts, the trigger variable may be a change i n airway pressure or gas flow i n the circuit resulting from the patient attempting to initiate inspiration. The trigger variable o r sensitivity o f the machine is set by the operator. A n airway pressure drop o f 2 c m H 0 or gas flow change of 2 L / m i n is an appropriate trig ger sensitivity i n most patients. It is important to always set the trigger sensitivity so that any genuine respiratory efforts made by the patient are detected by the machine and thus obvious to the operator. This is because an increase i n respiratory rate may be the only mechanism by which a ventilated patient can indicate that there is a problem. The trigger variable can be too sensitive, such that nonrespiratory movement such as patient handling may initiate breaths. This should be avoided. 3,5
2
P E E P is available o n many ventilators. If not provided by the machine, P E E P can be added by attaching a tube to the exhalation port o f the ventilator. This can then be attached to a P E E P valve or the end o f the tube can be submerged in the desired depth o f water. PEEP, as the name suggests, maintains positive pressure during exhalation that prevents the lung from emptying completely. A s a result the lung is "held" at a higher volume and pressure during exhala tion. ' P E E P is thought to increase the oxygenating effi ciency o f diseased lungs by recruiting previously collapsed alveoli, preventing further alveolar collapse, and reducing ventilator-induced lung i n j u r y . The appropriate magni tude o f P E E P depends o n the severity o f the lung disease and the clinical response o f the patient. Initially it may be set between 2 and 5 c m H 0 and then titrated appropriately. 1
3,4
1,3,5
2
2
2
4
2
4
2
A n i m a l s w i t h p u l m o n a r y disease may be able to maintain adequate oxygenation and ventilation b y increasing respira tory effort. If respiratory effort is marked, patients can become exhausted and respiratory arrest can occur despite acceptable b l o o d gas values. Intervention before arrest and initiation o f mechanical ventilation may successfully stabilize these patients. ' There are no objective measures o f respira tory effort and impending fatigue; therefore this evaluation is one o f clinical judgment. 1 5
APPROACH TO INITIATION OF MECHANICAL VENTILATION Before initiating mechanical ventilation, appropriate machine setup and monitoring is required. The "ideal" ventilator set tings for a given patient can be determined only by a process of trial and error. The initial ventilator settings are based o n guidelines such as those given i n Table 213-2. The operator should anticipate that animals with diseased lungs will require more aggressive ventilator settings and higher inspired oxygen concentrations than patients with neuromuscular disease.
Table 213-2
Suggested Initial Ventilator Settings
Ventilator Parameter
Initial Setting
Fraction of inspired oxygen
100%
Tidal volume
5 to 15 ml/kg
Respiratory rate
8 to 30 breaths/min
Minute ventilation
150 to 250 ml/kg
Peak inspiratory pressure
10 to 15 cm H 0
Positive end-expiratory pressure
0 to 5 cm H 0
Inspiratory time
«1 second
Inspiratory-to-expiratory ratio
1:2
Inspiratory trigger
-1 to - 2 cm H 0
2
2
2
The machine should be turned o n and tested w i t h a rebreathing bag to be sure it is functioning properly. It is advisable to always start mechanical ventilation with 100% oxygen until appropriate ventilator function and patient sta bility can be confirmed. Following initial stabilization, the F i 0 can be tailored appropriately. A separate source o f 100% oxygen should be available at all times to provide manual ventilation i n case o f machine failure. Constant, intensive m o n i t o r i n g is essential for patients that are being ventilated, because they are completely dependent on their caregivers for survival. Problems may be masked by anesthe sia or the primary disease process, and respiratory rate is no longer an indication o f life; ventilators w i l l easily ventilate a dead patient. Electrocardiography, core body temperature, arterial b l o o d pressure, end-tidal carbon dioxide levels, and pulse oximetry m o n i t o r i n g ideally are provided for every ventilator patient. Arterial b l o o d gas measurements are o f great benefit for patients w i t h p u l m o n a r y disease.
The ventilator settings should be adjusted i f the chest wall movements appear excessive or inadequate. Auscultation should then be performed to confirm the presence of breath sounds bilaterally. If breath sounds are not audible bilaterally, endobronchial intubation may have occurred and the endo tracheal tube should be retracted. Auscultation over the larynx may help detect tracheal cuff leaks that can compromise the effectiveness of ventilation. Tra cheal cuff pressures should not exceed 25 m m H g ; cuff pressure manometers help to prevent tracheal necrosis (i.e., Posey Cuffiator). Parameters such as electrocardiography, pulse oximetry, end-tidal carbon dioxide level, and arterial blood pressure should then be evaluated and significant abnormalities addressed immediately. Once the patient is considered stable, arterial blood gases are evaluated while the animal is still receiv ing 100% oxygen, and the ventilator settings should be modi fied accordingly. In the absence o f arterial blood gases, ventilator management is based o n physical examination find ings, venous P C 0 levels, and pulse oximetry. 2
GOALS
2
Patients w i l l require general anesthesia i n order to start mechanical ventilation unless they have severe neurologic defi cits. Anesthesia is required both to secure the airway and to allow the patient to tolerate positive-pressure ventilation. Anes thesia induction should be rapid to allow immediate control o f the airway and initiation o f manual ventilation. A l l patients should receive high levels o f inspired oxygen before and during induction. This is best provided by a tightly fitting face mask. Following induction, maintenance anesthesia will be required. Inhalant anesthetics are not recommended, because most ventilator patients require long-term anesthesia (hours to days) and these agents raise serious personnel safety con cerns. In addition, the inhalant anesthetics tend to have signifi cant cardiovascular depressant effects that may be poorly tolerated by critically i l l patients. The anesthetic protocol for maintaining ventilated patients w i l l depend somewhat on the animal's clinical state. The combination o f a benzodiazepine infusion with a second injectable agent may offer the advantages of balanced anesthesia. Anesthetic drug options are discussed further i n Chapter 216, Care o f the Ventilator Patient. For animals that are unable to fight the ventilator, such as patients w i t h respiratory paralysis, a temporary tracheos t o m y tube w i l l allow the reduction or even removal o f anes thetic agents and make neurologic evaluation and patient treatment simpler. Patients w i t h n o r m a l neurologic function cannot be ventilated without anesthesia, even w i t h a tempo rary tracheostomy tube. Immediately after the patient is connected to the ventilator, the chest should be observed for appropriate movements.
The goal o f mechanical ventilation is to maintain adequate arterial b l o o d gas levels ( P a C 0 o f 35 to 50 m m H g , P a 0 of 80 to 120 m m Hg) w i t h the least aggressive ventilator set tings. If b l o o d gas values are inadequate using the initial ven tilator settings, the machine is first inspected to ensure that it is functioning correctly. Patient-ventilator asynchrony needs to be resolved and significant issues such as pneumo thorax or hyperthermia ruled out. The final option is to adjust the ventilator settings to improve oxygenation and ventilation accordingly. It is always simpler to make one change at a time in the ventilator settings so that the effect of each change can be interpreted accurately. Careful record ing o f ventilator settings with the concurrent arterial blood gas values, end-tidal carbon dioxide levels, and pulse oxime try readings is essential i n evaluating and modifying the ventilator protocol. 2
2
Carbon Dioxide Total minute ventilation ( V ) is equal to the product of the respiratory rate and the tidal volume. C a r b o n dioxide levels are controlled primarily by the alveolar minute ventilation ( V = V — dead-space volume). Dead space is any portion of the tidal volume that does not participate i n gas exchange; increases i n dead space result in decreases i n effective alveolar ventilation and subsequent hypercapnia. In small patients excess tubing length between the breathing circuit Y-piece and the animal's m o u t h can cause significant increases in dead space and a subsequent elevation i n P C 0 . This may be a con sequence o f excessive endotracheal tube length, extension pieces, or m o n i t o r i n g devices connected to the end of the endotracheal tube. Endotracheal tube obstruction from kink ing or the accumulation o f airway secretions may also reduce the volume o f effective alveolar ventilation. In the absence of these equipment issues, hypercapnia is considered to be a result o f inadequate V . Because minute ventilation is equal to the product o f the respiratory rate and tidal volume, one or both o f these ventilator settings can be increased and the P C 0 concentration reevaluated to determine i f the new ven tilator protocol is adequate. Alternatively, i f the P C 0 is low, V should be decreased. T
A
T
2,4
2
A
2
2
A
Oxygen
1 2
The initial arterial blood gas result is evaluated while the patient is breathing 100% oxygen. The first priority is to reduce the F i 0 to less than or equal to 60% as soon as pos sible to reduce the risk of oxygen toxicity. The degree to which the F i 0 can be reduced w i l l be dictated by the measured P a 0 . After any reduction i n oxygen concentra tion, the P a 0 should be reevaluated. If this is not feasible, constant pulse oximetry monitoring is essential to ensure that the animal does not develop hypoxemia. 2
2
2
2
Once the F i 0 can be reduced to less than 60%, the focus then becomes reducing the aggressiveness o f the ventilator settings, namely P E E P and the peak inspired airway pressure, in an attempt to minimize the likelihood of ventilatorinduced lung injury (see Chapter 26, Ventilator-Associated Lung Injury). In patients with significant pulmonary disease, the P a 0 obtained with the initial ventilator settings may not allow sufficient reductions i n F i 0 . In severe cases hypoxemia will persist despite ventilation with 100% oxygen. In these animals an increase i n the aggressiveness of the ventilator settings is required. Increases in PEEP, peak inspired airway pressure, or respiratory rate may help improve the oxygenating efficiency of the l u n g . The following chapter on advanced mechanical ventilation will discuss aggressive ventilator protocols i n more detail. Prone positioning will maximize lung function i n most patients, and animals with hypoxemia should be maintained in sternal recumbency until stabilized. 2
2
pneumonia. ' Patients should be monitored continuously for evidence of infection and changes i n pulmonary function. Early signs of pneumonia are an indication for antibiotic administration; culture and sensitivity from an endotracheal lavage or bronchoalveolar lavage sample is always desirable. Pneumothorax is a well-reported complication o f mechani cal ventilation, especially when high airway pressures and large tidal volumes are used. M i n i m i z i n g the aggressiveness of ven tilator settings should be the constant goal o f ventilator man agement. Pneumothorax should be a primary consideration when a patient has an acute decline i n oxygenating ability, ele vation i n P C 0 , decreased chest wall movement and compli ance, and patient-ventilator asynchrony. If not diagnosed and treated rapidly, a tension pneumothorax can prove rapidly fatal in animals receiving positive-pressure ventilation. Unilateral or bilateral thoracostomy tubes with continuous drainage are indicated when managing these ventilated animals. 1,2
2
2
1
MAINTENANCE OF MECHANICAL VENTILATION Short-term mechanical ventilation (less than 24 hours) requires appropriate m o n i t o r i n g and nursing care but is feasible i n most practice situations. Long-term mechanical ventilation is far more challenging and requires a wellstaffed, 24-hour facility. Patient care issues such as cardio vascular support, nutritional support, airway care, and pre vention of decubitus ulcers require continuous evaluation and treatment i n order to prevent significant, life-threaten ing complications (see Chapter 216, Care o f the Ventilator Patient).
COMPLICATIONS Mechanical ventilation is not benign; cardiovascular c o m promise, ventilator-induced lung injury, ventilator-asso ciated pneumonia, and pneumothorax are all c o m m o n issues for ventilator patients. ' ' Cardiovascular compromise by impairment of intrathoracic blood flow is often an issue for patients with cardiovascular instability or when aggres sive ventilator settings are necessary. Cardiovascular m o n i toring is recommended for all ventilator patients and is essential when high P E E P levels or more aggressive ven tilator settings are used. Volutrauma and repetitive alveolar collapse are believed to be the major causes of ventilatorinduced lung injury and may be reduced with protective ventilation strategies (see Chapter 214, Advanced Mechani cal Ventilation) 7 Aseptic airway procedures, intensive oral care, and reducing the incidence of gastric regurgi tation are all important in preventing ventilator-associated
TROUBLESHOOTING Patient-ventilator asynchrony, called bucking the ventilator, is a c o m m o n issue and should be considered a sign of patient distress. Evaluation of the causes o f distress should begin with the most life-threatening problems. Issues for consider ation include airway patency, oxygenation and ventilation status, body temperature, anesthetic depth, patient comfort, and the suitability o f the ventilation protocol. If a sudden decrease i n oxygenation occurs, the oxygen supply to the machine should be checked as well as confir mation that the breathing circuit is intact and the ventilator is delivering breaths as desired. The patient should then be examined to rule out a pneumothorax. In the absence of mechanical failure or a pneumothorax, deterioration i n oxy genation is a sign o f progression of pulmonary disease or the acquisition o f a new pulmonary disease process. If the patient has become hypoxemic, the F i 0 should be increased immediately to 100% and the animal placed i n sternal recumbency until the condition is improved. 2
Sudden elevations i n P C 0 can occur as a consequence of increased apparatus dead space, occlusion of the breath ing circuit or endotracheal tube, pneumothorax, patientventilator asynchrony, and reductions i n effective alveolar ventilation. If no mechanical abnormalities are evident and pneumothorax is ruled out, then the ventilator settings can be changed to increase minute ventilation. Hypercapnia may be an acceptable consequence o f some protective ventilation strategies. ' ' 2
1,2
5
7
PROGNOSIS
1 2 6
Prognosis for successful weaning from mechanical ventila tion is largely dependent o n the primary disease process. H u m a n and veterinary clinical studies have repeatedly reported lower weaning rates for patients requiring ventila tion for pulmonary parenchymal disease (inability to oxy genate) compared with patients with neuromuscular disease processes (inability to ventilate). F r o m the few veter inary studies available it appears that approximately 30% of patients ventilated for pulmonary parenchymal disease are successfully weaned compared with 50% or more of patients with neuromuscular disease processes (see Chapter 217, Discontinuing Mechanical Ventilation).
SUGGESTED FURTHER READING* Haskins SC, King LG: Positive pressure ventilation. In King L G , editor: Text book of respiratory disease in dogs and cats, St Louis, 2004, Saunders. A detailed discussion of mechanical ventilation in veterinary patients in the context of an excellent reference textbook on respiratory disease. Maclntyer N R , Branson R D : Mechanical ventilation, Philadelphia, 2001, Saunders. One of the few textbooks available that is dedicated to mechanical ventilation and provides a comprehensive review of the relevant topics. A human medi cal textbook, so some of the information is not relevant to veterinary patients.
Tobin MJ: Mechanical ventilation, New Engl J Med 330:1056, 1994. An excellent review of mechanical ventilation. Easy to read and a good supple ment to other resources but lacks depth and addresses only some of the major issues. West JB: Respiratory physiology: the essentials, ed 7, Baltimore, 2005, Lippincott Williams & Wilkins. A simple, short, easy-to-understand presentation of respiratory physiology. An essential "first" hook for anyone interested in this area. *See the C D - R O M for a complete list of references.
Chapter 214 ADVANCED MECHANICAL VENTILATION Kate Hopper, BVSC, MVSC, DACVECC
KEY POINTS • The ventilator mode is defined by the control variable, breath pattern, and phase variables selected. • Ventilator breaths can be volume controlled or pressure controlled. The three main breath patterns are continuous mandatory ventilation, continuous spontaneous ventilation, and intermittent mandatory ventilation. • The goal of selection of the ventilator mode is to provide adequate gas exchange while preventing ventilator-induced lung injury. • Lung-protective strategies may be important for treatment of severe, diffuse lung disease such as acute respiratory distress syndrome. •
Patient-ventilator asynchrony is a common, often unrecognized problem that can impair effective gas exchange, increase work of breathing, and create patient discomfort. • Ventilator waveforms and loops can provide valuable information about ventilator function, patient physiology, and the patientventilator interaction.
Figure 214-1
The respiratory cycle.
A n understanding o f ventilator function requires an appreci ation o f h o w the machine is generating and controlling a given breath. This requires knowledge of what is determining each phase o f the breath and where the energy for that breath is derived (i.e., patient or ventilator).
define c o m m o n ventilator parameters. For example, peak airway pressure is the maximal airway pressure measured during the inspiratory flow phase. The plateau pressure is the airway pressure measured at the end o f the inspiratory pause. The difference between the peak inspiratory pressure and plateau pressure is usually m i n i m a l i n patients with nor mal lungs. Some pulmonary disease processes that increase airway resistance (e.g., asthma) can cause significant differ ences between the peak and plateau pressures.
Respiratory Cycle
Equation of Motion
The respiratory cycle can be divided into four phases: (1) the inspiratory flow phase, (2) the inspiratory pause phase, (3) the expiratory flow phase, and (4) the expiratory pause phase (Figure 2 1 4 - 1 ) . B y defining h o w each respiratory phase is determined, the ventilator mode can be described. The respiratory phases also provide a context i n which to
Patient-ventilator interactions can be described by the equation o f motion. This equation is built into the ventilator software and is the basis for machine operation (Box 214-1 ). " The equation o f m o t i o n states that the pressure required to deliver a breath depends o n the tidal volume and flow o f the breath i n addition to the resistance and compliance o f the system.
VENTILATOR CONCEPTS
1,2
2
4
Box 214-1 Equation of Motion Pressure = (tidal volume •¥ compliance) + resistance x
flow
The resistance and compliance are determined largely b y the characteristics o f the patient while pressure, volume, and flow are the three interdependent variables that may be manipulated by the machine. To understand a ventilator breath, knowledge o f changes i n airway pressure, volume, and flow during each respiratory phase is required.
DEFINING THE VENTILATOR MODE The ventilator mode is defined by nature o f the breath type and pattern, control variable, and phase variables used.
Breath Types
ventilator maintains gas flow at a preset pressure for a given time. W h e n that time has elapsed, inspiration is terminated and exhalation begins, so time is the cycle variable. T i m e is the most c o m m o n cycle variable and will be determined b y the preset respiratory rate and the inspiratory-to-expiratory (I:E) ratio. A n inspiratory time o f approximately 1 second is a c o m m o n guideline.
Trigger Variable This is the parameter that initiates inspiration. It is how the ventilator determines when to deliver a breath. " I n animals that are not m a k i n g respiratory efforts of their own, the trig ger variable w i l l be time and is determined from the set respi ratory rate. If the a n i m a l is m a k i n g respiratory efforts, the trigger variable may be a change i n airway pressure o r gas flow i n the circuit resulting from the patient attempting to initiate inspiration. The trigger sensitivity o f the machine usually can be set by the operator. A n airway pressure drop of 2 c m H 0 o r gas flow change o f 2 L / m i n are usually effec tive trigger sensitivities. Appropriate trigger sensitivity is essential to ensure that ventilator breaths are synchronized w i t h genuine respiratory efforts made b y the patient. This increases comfort and allows the patient to increase its respi ratory rate as required. The trigger variable can be too sensi tive, such that nonrespiratory movements such as patient handling may initiate breaths, a n d this should be prevented. 2
4
2
A ventilator breath is one o f two major types: mandatory or spontaneous. D u r i n g a spontaneous breath, the patient is responsible for both initiation and termination o f inspira tion. If the machine controls one or both of these factors, the breath is considered mandatory. W h e n a mandatory breath is initiated b y the patient, it is classified as an assisted breath. A spontaneous breath i n which inspiration is aug mented above baseline by the machine is considered a sup ported breath (Table 214-1). " 2
4
Limit Variable This is a parameter that the breath cannot exceed during inspiration, but it is different from the cycle variable because it does not terminate the breath. " This variable may be found o n modern intensive care ventilators. F o r example, a volume-controlled, pressure-limited breath means that the ventilator w i l l generate the breath by delivering a preset tidal volume, but it w i l l not exceed the limit set for airway pres sure at any time during the delivery. 2
Control Variable The control variable is the primary variable manipulated by the machine to generate an inspiration. " Because flow and volume are interrelated, ventilator breaths are either volume controlled or pressure controlled. In a pressure-controlled breath the machine will maintain airway pressure at a constant, preset (by the operator) level, and inspiration ends when a preset inspiratory time is reached. The tidal volume and gas flow rate generated during this breath are dependent o n the magnitude of the preset airway pressure and the resistance and compliance inherent to that system as per the equation of motion. 2
4
D u r i n g a volume-controlled breath the flow and tidal volume are fixed to a level preset by the operator; the machine will maintain a constant gas flow, and the inspira tion ends when a preset tidal volume is delivered. A s the equation o f motion describes, airway pressure reached dur ing these breaths is dependent o n the magnitude o f the preset tidal volume and the resistance and compliance o f the patient's respiratory system. " The basic waveforms for a pressure-controlled and a volume-controlled breath are shown i n Figure 214-2. Exhalation is passive, and it can be seen that it has an exponential character. 2
4
Phase Variables
4
Baseline Variable This variable is controlled during exhalation; airway pressure is the most c o m m o n baseline variable manipulated. " If air way pressure during exhalation is maintained above atmo spheric pressure, this is referred to as positive end-expiratory pressure (PEEP). 2
Breath Patterns Continuous Mandatory Ventilation In this mode o f ventilation a m i n i m u m respiratory rate is set by the operator. If the trigger sensitivity is set appropriately, the patient can increase the respiratory rate but all breaths delivered will be o f a mandatory type. If the patient is unable to trigger breaths, it is considered controlled ventilation. M o r e c o m m o n l y patients are allowed to trigger their o w n respiratory rate and this is called assist-control ventilation. The terms controlled mechanical and assist-control ventilation generally are used interchangeably. " 2
The respiratory cycle helps define the four phases of a breath that can be controlled by the ventilator (see Figure 214-1): (1) the start o f inspiration, (2) inspiration, (3) the end o f inspiration, and (4) exhalation. ' 2
3
Cycle Variable 2
4
This is the parameter by which inspiration is terminated. " For example, to give a pressure-controlled breath, the
4
4
Intermittent Mandatory Ventilation In this mode a set number o f mandatory breaths is delivered with either pressure o r volume control. Between these breaths patients can breathe spontaneously as often o r as lit tle as they choose. I n modern ventilators the machine tries to synchronize the mandatory breaths with the patient's inspi ratory efforts, a pattern called synchronized intermittent
Table 214-1
Comparison of the Four Clinically Different Ventilator Breath Types
Table 214-1 Comparison of the Four Clinically Different Ventilator Breath Types
Inspiratory Flow
Breath Type Mandatory
Ventilator
Ventilator
Ventilator
Assisted
Patient
Ventilator
Ventilator
Spontaneous
Patient
Patient
Patient
Supported
Patient
Patient
Ventilator
Figure 214-2 Pressure, volume, and flow as related to time waveforms for pressure-controlled and volume-controlled ventilation. (Note the inspi ratory portion of each waveform is in blue.) A, In pressure-controlled ventilation, airway pressure is maintained at a constant level throughout the inspi ration, volume increases with time, and the flow rate of the breath decelerates as the lungs fill with gas. B, In volume-controlled ventilation, the flow rate is held constant throughout inspiration, but tidal volume and airway pressure both increase with time. mandatory ventilation. If no breaths are detected by the machine during the period o f synchronization, a mandatory breath w i l l be given. The operator can control only the m i n i m u m respiratory rate and m i n i m u m minute ventilation; there is no control over the m a x i m u m rate or m a x i m u m minute ventilation. " 2
4
Continuous Spontaneous Ventilation Every breath o f continuous spontaneous ventilation is trig gered and cycled by the patient; consequently this breath pattern can be used only in patients w i t h a reliable respira tory rate. The inspiratory time and tidal volume are also determined by the patient. The two most c o m m o n forms of this mode are continuous positive airway pressure ( C P A P ) and pressure support ventilation (PSV). C P A P provides a constant level o f positive pressure (preset by the operator) throughout the respiratory cycle. C P A P increases functional residual capacity and compliance, enhancing gas exchange and oxygenation; it does not augment airflow during inspiration. C P A P is used most commonly for spontaneous breathing trials i n an attempt to evaluate i f a patient can be disconnected from the ventilator. " 2
4
In P S V the ventilator provides a constant preset level of airway pressure during inspiration. This reduces the effort required to maintain spontaneous breathing i n patients with adequate respiratory drive but inadequate ventilatory strength. The degree o f support provided will depend on the magnitude o f pressure support given. P S V can help over come the resistance o f breathing through the endotracheal tube and ventilator breathing circuit. " It can be used alone, i n conjunction with PEEP, or to augment the spontaneous breaths during synchronized intermittent mandatory venti lation or CPAP. P S V is used most c o m m o n l y as a step-down mode from C M V or synchronized intermittent mandatory ventilation during the weaning process. The cycle variable i n P S V is flow; the ventilator ceases providing inspiratory pressure when it senses a decrease o f 20% to 25% (depend ing o n the machine) i n flow rate, signaling exhalation. 2
4
Ventilator Mode The basic definition o f a ventilator mode requires identifica tion o f the control variable and the breath pattern: pressurecontrolled or continuous mandatory ventilation. A more
detailed definition would include a description o f the nature of any phase variables being used; these include pressurecontrolled, continuous, mandatory, pressure-triggered, and time-cycled ventilation with PEEP.
greatest when pulmonary compliance is high and preexisting cardiovascular compromise is present, such as i n patients with hypovolemia. Hemodynamic monitoring is recommended for all ventilated patients and is essential when high levels o f P E E P or more aggressive ventilator settings are used. " 2
RESPIRATORY RATE AND INSPIRATORYTO-EXPIRATORY RATIO The mandatory respiratory rate can be set o n all ventilators. A normal respiratory rate of 15 to 20 breaths is usually selected when assisted ventilation is initiated. This can then be changed as appropriate. The I:E ratio may be preset by the operator, or i n some older ventilators it is a default setting within the machine. Depending o n the ventilator, the I:E ratio may be set directly or indirectly by manipula tion of inspiratory time, percent inspiratory time, or inspira tory flow rate i n conjunction with the respiratory rate. A n I:E ratio of 1:2 with inspiratory times of approximately 1 second are used to ensure that the patient has exhaled fully before the onset of the next breath. As respiratory rates are increased, the expiratory time will be sacrificed to "squeeze" in the necessary number o f inspirations. H i g h respiratory rates can lead to a situation k n o w n as breath stacking or intrinsic PEEP, because the animal is not able to exhale fully before the start o f the next inspiration. Longer inspiratory times can be used i n an effort to improve oxygenation. In some lung disease processes, a reverse I:E ratio (where inspiration is longer than exhalation) has been found beneficial, but this should be used with caution because associated intrinsic P E E P and hemodynamic c o m promise can have serious consequences. " 2
4
5
LUNG-PROTECTIVE VENTILATION It is n o w recognized that positive-pressure ventilation trig gers an inflammatory response i n the lungs, and the degree of this response is determined by the ventilation strategy employed. It has been well demonstrated that overdistention of alveoli is injurious and should always be prevented. In many patients this can be achieved by maintaining recom mended tidal volumes when designing a ventilation proto col. In patients with severe lung disease such as acute respiratory distress syndrome ( A R D S ) , the normal recom mended tidal volumes may be excessive. A R D S causes col lapse and consolidation of alveoli, leaving fewer aerated lung regions. These regions w o u l d be vulnerable to overdis tention i f a regular tidal volume were delivered. 6
The A R D S Network reported a significant reduction i n mortality of h u m a n patients with A R D S who were ventilated with a tidal volume o f 6 ml/kg compared with 12 m l / k g . This lung-protective ventilation strategy included high P E E P levels and limited plateau pressures (no higher than 30 c m H 0 ) . The role of high levels o f P E E P i n protective lung ventilation remains controversial, and further studies are being performed. A consequence of l o w tidal volume ventila tion is elevations i n P C 0 , which can be addressed with interventions such as tracheal gas insufflation. In human patients high P C 0 levels may be tolerated, a situation referred to as permissive hypercapnia, although these patients tend to need heavier sedation or paralysis. " 6
2
2
2
POSITIVE END-EXPIRATORY PRESSURE PEEP is achieved by maintaining a pressure above atmospheric pressure during the expiratory phase o f the breath. Extrinsic PEEP is a baseline phase variable that can be set on most m o d ern ventilators. In addition, intrinsic P E E P can be developed as a consequence of inadequate time for exhalation. Physiologi cally intrinsic PEEP has effects o n pulmonary function and hemodynamics identical to those o f extrinsic P E E P . " Pulmonary parenchymal disease creates areas o f l o w ven tilation to perfusion (low V / Q ) and areas of alveolar collapse (no V / Q ) , leading to decreased oxygenating or ventilating ability, or both. W h e n pulmonary disease causes severe hy poxemia that will not resolve with oxygen therapy alone, positive-pressure ventilation is indicated (see Chapter 213, Basic Mechanical Ventilation). In patients with acute lung injury, P E E P can open or "recruit" previously collapsed alveoli and prevent further collapse o f unstable alveoli, improving V / Q matching and hence improving oxygenation. Appropriate levels of P E E P can improve pulmonary c o m p l i ance and reduce the work of breathing, although excessive PEEP can decrease compliance. Appropriate use of P E E P is also thought to reduce ventilator-associated lung injury by preventing shear injury associated with the cyclic reopening and collapse of alveoli with each breath (see Chapter 26, Ventilator-Associated Lung Injury). 2
4
5,6
PEEP can also have distention of healthier ance. PEEP may also venous return during
detrimental effects; it can cause overalveoli, which have a higher compli reduce cardiac output by impairing the expiratory phase. This effect is
4
6
The ventilatory strategy of low tidal volumes and moder ate to high PEEP, with or without permissive hypercapnia, is considered lung-protective ventilation. Given the evidence from experimental animal studies and human clinical trials, it w o u l d be reasonable to assume that lung-protective venti lation has a valid role i n veterinary patients. It is important to appreciate that this ventilation strategy is designed for the lung with A R D S and should be applied with caution to those with other disease states.
PATIENT-VENTILATOR ASYNCHRONY Patient-ventilator asynchrony occurs whenever there is a mismatch between the machine settings for the trigger sensi tivity, gas delivery, or breath cycle determinants and the patient's breathing pattern. Patient-ventilator asynchrony can impair gas exchange, increase the work of breathing, and create a sense o f dyspnea for the patient. ' ' A l t h o u g h there are no specific diagnostic criteria for the condition, it is c o m m o n l y evidenced by animals fighting, or "bucking," the ventilator. Less obvious signs o f patient-ventilator asynchrony may be best observed by studying real-time ventilator waveforms and l o o p s . ' ' Studies report that patient-ventilator asyn chrony is underestimated and frequently goes unrecognized in h u m a n patients, so it is likely that more subtle forms are poorly recognized i n veterinary patients as well. In order to try and optimize the patient-ventilator interaction, the 2
2,3
7
8
3
7
Table 214-2
Common Causes of Patient-Ventilator Asynchrony*
Nature of Problem
Diagnostic Approach
Therapeutic Approach
Hypoxemia
Arterial blood gas analysis or pulse oximetry
Increase Fi0 or magnitude of ventilator settings
Hypercapnia
Arterial or venous blood gas analysis
Check endotracheal tube Increase tidal volume or respiratory rate
Hyperthermia
Temperature monitoring
Provide active cooling
Pneumothorax
Auscultation, blood gas analysis, radiographs, thoracentesis
Thoracentesis Thoracic drain
Drug-induced panting (opioids)
Consideration of respiratory pattern and concurrent drug administration
Consider change in anesthetic or sedation protocol
Inadequate anesthesia depth
Palpebral reflex, jaw tone, heart rate
Increase anesthesia depth
Disconnection or circuit leak
Evaluate circuit and endotracheal connection Auscultate neck for cuff leak Observe waveforms
Resolve disconnection or leak
Endotracheal tube kinked, obstructed, dislodged
Observe endotracheal tube position Auscultate chest Evaluate tidal volumes Measure PC0
Reposition or replace endotracheal tube
Inappropriate trigger setting
Observe patient's respiratory efforts compared with ventilator responses
Change trigger setting accordingly
Insufficient tidal volume
Animal appears to try to increase inspiratory effort: observe waveforms
Consider increasing tidal volume (caution in patients with ARDS)
Inspiratory time too short
Animal trying to inspire during exhalation: observe waveforms
Increase inspiratory time
Inspiratory time too long
Animal trying to exhale during inspiration: observe waveforms
Decrease inspiratory time
Patient Related 2
Equipment Related
2
ARDS, Acute respiratory distress syndrome; Fi0 , fraction of inspired oxygen; PCO2, partial pressure of carbon dioxide. *NOTE: Patients may develop more than one problem concurrently. 2
Figure 214-3 An idealized pressure-volume loop. Note that for a positive-pressure breath the loop flows in a counterclockwise direction, with inspiration represented by the lower limb and exhalation represented by the upper limb.
operator must continually match the trigger, gas flow, and cycling o f breaths to the animal. Patient-ventilator asynchrony can have ventilator-related or patient-related causes. Because patient requirements can
be changing constantly, continuous clinical assessment and physiologic monitoring is required i n conjunction with con tinuous manipulation o f the machine settings or patient care i n response to changes observed. " ' Table 214-2 lists 2
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c o m m o n machine-related and patient-related causes o f patient-ventilator asynchrony that should be evaluated when troubleshooting this problem. It is important to avoid the knee-jerk reaction of increasing anesthetic depth, because this may mask a significant underlying problem and increases the risk of anesthetic-related complications.
ventilator settings. The pressure-volume curve can also pro vide information regarding patient-ventilator asynchrony and airway leaks. A full description o f ventilator waveforms and their interpretation is beyond the scope o f this chapter and is provided elsewhere. ' 2,3 8
SUGGESTED FURTHER READING*
VENTILATOR WAVEFORMS M o d e r n ventilators provide real-time graphics o f the ventila tor breath that can be valuable i n assessment o f ventilator performance, patient physiology, and the patient-ventilator interaction. The most clinically useful graphics are the flow, pressure, and volume versus time waveforms, as well as flowvolume and pressure-volume l o o p s . Figure 214-2 shows a simplified version o f flow, pressure, and volume waveforms. Analysis o f these can provide infor mation regarding the mode o f ventilation, patient trigger ing, patient ventilator asynchrony, presence o f intrinsic PEEP, and airway leaks. W h e n evaluating waveforms, it is always important to identify the ventilator mode, because this w i l l determine what " n o r m a l " should be for a given waveform. Figure 214-3 is a pressure-volume loop. The slope o f the pressure-volume curve at a given point reflects the c o m p l i ance of the chest wall and lung at that lung volume. The shape and orientation o f the pressure-volume curve w i l l change with the presence o f lung disease and alterations i n 2,8
A R D S Network: Ventilation with lower tidal volumes as compared with tra ditional tidal volumes for acute lung injury and the acute respiratory dis tress syndrome, N Engl ] Med 342:1301, 2000. The original study documenting the benefits of low tidal volumes in human patients with ARDS. Ventilation with a 6-ml/kg tidal volume compared with a 12-ml/kg tidal volume associated with a reduced mortality and fewer days on the ventilator. Hess DR, Kacmarek R M : Essentials of mechanical ventilation, ed 2, New York, 2002, McGraw-Hill. An excellent general text on mechanical ventilation that contains all the impor tant information in an easy-to-read fashion. Pilbeam SP, Cairo J M : Mechanical ventilation: Physiological and clinical applications, ed 4, St Louis, 2006, Mosby. A great in-depth resource for mechanical ventilation that has a lot of diagrams and human clinical examples. Ideal for true mechanical ventilation enthusiasts. Squadrone V, Gregoretti C , Ranieri V M : Patient-ventilator interaction. In Fink MP, Abraham E , Vincent JL, Kochanek P M , editor: Textbook of criti cal care, Philadelphia, 2005, Saunders. One of several excellent chapters on mechanical ventilation in this textbook. Provides an overview of the major issues contributing to human patientventilator asynchrony. *See the C D - R O M for a complete list of references.
Chapter 215 JET VENTILATION Bruno H. Pypendop, Dr.Med.Vet., Dr.Vet.Sci., DACVA
can be achieved using a high-pressure oxygen source, a valve, a jet injector, a catheter, and noncompliant tubing. A jet injector can be made o f a cut-off 1-ml syringe; the flush valve o f an anesthesia machine can be used as a valve. Ventilation is then provided at a rate o f 12 to 20 breaths/min.
KEY POINTS • Transtracheal jet ventilation can be used for emergency ventilation; high-frequency jet ventilation can be used to ventilate patients when tracheal intubation is not possible or practical. • High-frequency ventilation can produce normoxemia and normocapnia with tidal volumes less than the volume of the dead space. • High-frequency ventilation requires very high minute volumes. • During jet ventilation, distribution of ventilation and tidal volume depend more on airway resistance than on respiratory system compliance. • Tidal volume and end-tidal carbon dioxide concentration cannot be measured accurately during jet ventilation. • Adequacy of ventilation and oxygenation should be assessed using blood gas analysis, particularly if jet ventilation is used for extended periods. • Interpretation of blood gas data should not be influenced by the mode of ventilation (spontaneous versus conventional mechanical versus jet).
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PHYSICS AND PHYSIOLOGY High-frequency ventilation is based on the premise that transpulmonary pressure (i.e., the pressure that distends alveoli) can be divided i n a steady and an oscillatory compo nent. Eucapnia can then be maintained at low tidal volumes by an increase i n the frequency o f oscillation. By decreasing tidal excursion (i.e., transpulmonary pressure excursion above and below its mean), high-frequency ventilation should also limit alveolar derecruitment due to insufficient lung volume. Interestingly, panting i n dogs may be consid ered to represent the physiologic counterpart to mechanical high-frequency, l o w - t i d a l volume ventilation, and has been used as a model to study gas exchange during conditions o f high-frequency ventilation. 7
INTRODUCTION
8
High-frequency ventilation was first explored i n the 1960s, i n an attempt to find a technique o f positive-pressure venti lation that w o u l d have m i n i m a l impact o n circulation. It was assumed that insufflation o f gas at a high frequency, directly into the airway, w o u l d enable a reduction i n tidal volume and thereby i n intrathoracic pressure. Various strategies can be used to deliver high-frequency ventilation. These include high-frequency oscillation, highfrequency jet ventilation (or jet ventilation), high-frequency flow interruption, and high-frequency positive-pressure ven tilation. This chapter w i l l focus o n jet ventilation. Jet ventilation was first used during bronchoscopy. A cannula was placed i n an open-ended bronchoscope, and gas was delivered from a high-pressure source. A m b i e n t air was entrained b y the Venturi effect. The system was later adapted to deliver gas through a ventilating laryngoscope, and through a catheter placed between the vocal cords. Percutaneous transtracheal jet ventilation was introduced i n anesthesia i n the early 1970s. 1
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D u r i n g jet ventilation, pulses o f gas are delivered at high velocity through an orifice i n a T-piece connected to a tracheal tube, through a narrow tube incorporated i n the tra cheal tube, or through a catheter placed i n the upper airway. Typical frequencies are i n the 100 to 300 breaths/min range. The major advantage o f jet ventilation resides i n the flexibility of the patient interface, allowing ventilation i n situations where tracheal intubation is not possible. In addition to high-frequency jet ventilation, transtra cheal jet ventilation can be used for emergency ventilation, if a tracheal tube cannot be placed. Acceptable gas exchange 3
4
The volume o f gas delivered to the alveoli depends on the volume o f gas passing through the jet, the volume o f gas entrained into the tracheal tube or airway, and the volume o f the dead space. A s frequency increases, tidal volume decreases, but dead-space ventilation increases and alveolar ventilation can therefore be maintained only with very high minute ventilation. A t frequencies above 1 H z (60 breaths/ m i n ) , tidal volume is usually less than the volume of the dead space. It has been suggested that when tidal volume is less than 1.2 times the volume o f the dead space, carbon dioxide ( C 0 ) elimination is greatly reduced compared with conventional convective gas exchange, and that the length of the dead space has a larger influence than its volume on C 0 elimination. It may therefore be beneficial to administer jet ventilation as distally as possible or practical. 9
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However, it has been shown that the physical character istics o f a jet depend o n the ratio o f the jet diameter to tube or airway diameter, the ratio o f jet diameter to tube length, the p o s i t i o n o f the jet entrance, and the driving pressure. Injectors can be designed to maximize flow. W i t h distal jet ventilation, o p t i m i z a t i o n o f the injector is not possible, potentially resulting i n decreased efficiency and flow. Although the gas volume o f the jet after a single injection may not travel more than a few diameters, a continuing distal m o t i o n o f previously injected gas occurs with the rep etition o f this jet injection, particularly at high frequencies. High-frequency jet ventilation results i n inhomogeneous ventilation. Regional variation i n gas concentration, air space volumes, and pressures are observed. Caudal lung 10
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lobes usually are ventilated better, due to inertial factors. However, this lack o f uniform ventilation is expected to have m i n i m a l impact o n overall gas exchange. The volume o f the jet impulse (tidal volume) is influ enced by the geometry o f the injector, the amount o f gas entrained, the pressure o f the jet, the back pressure, and the impulse d u r a t i o n . Effective injectors can entrain 4 to 5 times the jet flow during the early part o f i n s p i r a t i o n , ' although some studies suggest that this effect is m i n i m a l . The entrained volume, measured as a fraction o f the tidal volume, is minimally affected by respiratory rate i n the 12 to 200 breaths/min range. Entrainment is optimized by positioning the jet entrance i n the proximal part o f the endotracheal tube. Entrainment is due to a Venturi effect as a high velocity gas stream exits the injector. Entrainment is limited to the early part o f inspiration (first 0.08 second, regardless o f respiratory rate), because as the lungs begin to fill the airway pressure increases, w h i c h opposes, and eventually prevents, entrainment o f gas. 10
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For the remainder o f inspiration, some o f the jet gas comes out o f the airway opening without entering the lungs. The amount o f gas lost this way (spilled volume) decreases as respiratory rate increases. D u r i n g gas entrain ment, there can be no spillage. A s respiratory rate increases, inspiratory time decreases, but the time during w h i c h entrainment occurs remains fairly constant; therefore the time available for spillage decreases. Because high frequen cies are required, expiratory time is short, and end-expiratory lung volume is increased. Therefore end-expiratory pressure is usually positive. This raises the pressure at the beginning of inspiration and may limit gas entrainment when high respiratory rates are used. Because o f the high velocity o f gas flow required to produce adequate ventilation at these high frequencies, changes i n airway resistance w i l l have a larger effect o n tidal volume than respiratory system compliance, especially because volume changes are m i n i m a l . Similarly, distribution o f ventilation w i l l depend more o n airway resis tance than regional compliance, which may be beneficial i n lung diseases that do not affect the airway. 14
16
traditional ventilation. It is indicated i f ventilation is required i n patients w i t h a tracheal lesion secondary to tra cheostomy or prolonged i n t u b a t i o n . Jet ventilation may also be used i f the laryngeal opening is too small to allow intubation. It has been suggested that, because of lower peak airway pressure than i n traditional mechanical ventilation, jet ventilation may be preferable i n airway leak situations. In dogs and cats, high-frequency jet ventilation has been used to maintain oxygenation and ventilation during resec tion and anastomosis of the intrathoracic trachea and during bronchoscopy. ' We mainly use jet ventilation to maintain oxygenation and C 0 elimination during bronchoscopy i n dogs of small size and i n cats. We deliver ventilation through a 14- or 16-gauge catheter positioned i n the trachea (Color Plate 215-1). The bronchoscope can then be passed alongside that catheter (Color Plate 215-1). Transtracheal high-frequency jet ventilation can be used i n emergency situations. A catheter is placed percutaneously through the cricothyroid membrane. The catheter is then secured to the patient's neck. M i g r a t i o n o f the catheter out side o f the trachea w o u l d result i n severe subcutaneous emphysema. 15
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DISADVANTAGES
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Tidal volume is very difficult to measure during jet ventila tion. The high velocity o f the jet and entrainment o f addi tional gas make inspiratory volume measurement very difficult; spillage of gas out of the open airway and the c o m m o n addition o f a bias flow make measurement o f expired volume inaccurate. Similarly, end-tidal carbon dioxide con centration cannot reliably be measured. Therefore adequacy of ventilation should be confirmed b y end-tidal carbon diox ide concentration measurement during intermittent ventila tion w i t h large tidal volume, or by arterial b l o o d gas analysis. 14
3
Jet ventilation may cause fluctuations i n the amplitude of chest excursions, and phasic changes i n heart rate and systemic and pulmonary arterial pressures, resulting i n fluctua tions i n b l o o d flow. The small tidal volumes and therefore low peak airway pressure and possibly mean airway pressure during jet ventilation are expected to limit the cardiovascular effects of this mode o f ventilation. However, compared with conven tional mechanical ventilation, high-frequency jet ventilation may result i n similar, larger, or smaller cardiovascular effects. 20
EQUIPMENT Various devices to administer jet ventilation are commer cially available. They are based o n a high-pressure gas source and solenoid valves to admit and/or interrupt gas flow. Typical settings include peak airway pressure, respiratory rate, and inspiratory time, or inspiratory-to-expiratory time ratio. Some ventilators allow the control o f mean airway pressure, positive end-expiratory pressure, minute volume, and/or driving pressure. Rates usually range from 30 to 150, sometimes as high as 600 breaths/min.
Jet ventilation, particularly during severe bronchoconstriction or other forms o f airway obstruction, may result i n lung overinflation, as gas accumulates because o f short expiratory times. L u n g hyperinflation may also result from steady alveo lar pressure i n excess o f steady airway pressure. This is likely due to unequal inspiratory and expiratory impedances, distri bution o f oscillatory flow, and expiratory flow l i m i t a t i o n . ' In addition, high-velocity gas streams as generated during high-frequency ventilation preferentially follow straight path ways. Because o f the geometry o f the central airway, this may result i n regional differences, w i t h an increased tendency o f the lung base to be overinflated compared w i t h the apex. 7
11
INDICATIONS Jet ventilation is indicated when mechanical ventilation is necessary or beneficial but traditional positive-pressure ventilation cannot be delivered. This may include laryngeal and tracheal surgery, bronchial resection, laryngoscopy, and bronchoscopy, and whenever limitation o f movement asso ciated with respiration is beneficial. In addition, it has been suggested that jet ventilation i n acute respiratory failure w i t h circulatory shock resulted i n higher cardiac output than 15
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Prolonged use (i.e., hours) o f high-frequency jet ventila tion administered i n the trachea v i a a catheter was shown to result i n endoscopic evidence of tracheal injury character ized b y hypervascularity, mucus accumulation, focal hemor rhage, linear epithelial loss, and/or diffuse erythema and epithelial loss. 22
MONITORING OF GAS EXCHANGE DURING JET VENTILATION Despite the technical difficulties limiting the ability to m o n itor the adequacy o f ventilation during high-frequency jet ventilation, the same principles as for conventional mechan ical ventilation apply. Arterial b l o o d gas analysis remains the gold standard to judge adequacy o f oxygenation and ventilation, and should be available i f jet ventilation is used for extended periods. The same normal and abnormal P a 0 and P a C 0 values as during conventional mechanical ventilation should be used when interpreting b l o o d gas data. Similarly, intrapulmonary gas exchange efficiency can be assessed using the alveolar-arterial P 0 difference or (with more limitations) the P a 0 - t o - F i 0 ratio. 23
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normal ventilation i n various situations. O u r clinical expe rience suggests that at a frequency of 180 breaths/min with tidal volumes resulting i n barely detectable chest excursions usually results i n adequate oxygenation and normocapnia to moderate hypocapnia. One study i n dogs and cats reported that w i t h driving pressures of 0.33 k g / c m and an inspira tory-to-expiratory ratio o f 1:2, cats were mildly hyperventi lated at a frequency o f 140 breaths/min; i n dogs, a driving pressure o f 1.3 to 1.8 k g / c m and 120 to 150 breaths/min resulted i n a similar degree of hyperventilation. 2
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2
SUGGESTED FURTHER READING*
2
2
2
VENTILATOR SETTINGS The goal o f jet ventilation is to maintain adequate oxyge nation and C O elimination. However, because of the char acteristics of this method it is difficult to give guidelines for adjusting ventilatory parameters that w i l l result i n z
Bohn D: The history of high-frequency ventilation, Respir Care Clin North Am 7:535, 2001. Good review article on the development of high-frequency ventilation techniques. Haskins SC, Orima H , Yamamoto Y, et al: Clinical tolerance and bronchoscopic changes associated with transtracheal high-frequency jet ventila tion in dogs and cats, / Vet Emerg Crit Care 2:6, 1992. Good research article on the consequences of long-term jet ventilation in dogs and cats. "See the C D - R O M for a complete list of references.
Chapter 216 CARE OF THE VENTILATOR PATIENT Monica C. Clare,
VMD, DACVECC
KEY POINTS • Ventilator patient care requires specialized equipment, extensive monitoring, and dedicated, trained staff. • Inadequate care can lead to life-threatening complications for the ventilator patient. • Oropharyngeal bacterial colonization is a leading cause of ventilator-associated pneumonia and can be minimized by strict adherence to oral care protocols. • Maintenance of airway hygiene is essential; anything entering the upper airway, such as endotracheal tubes or suction catheters, should be sterile.
INTRODUCTION Mechanical ventilation is becoming more c o m m o n i n small animal medicine. These patients are usually anesthetized and are totally dependent o n their caregivers. The major complications seen i n ventilator patients can be m i n i m i z e d or prevented w i t h appropriate nursing care and dedicated, trained caregivers. The challenges o f caring for short-term (1 to 24 hours) and long-term (days to weeks) ventilator
patients are different. Short-term ventilator patients may not require such specialized equipment or intensive care, but those being ventilated over a long term may have unique man agement requirements. Detailed patient records are essential, and a ventilator record sheet is often helpful (Box 216-1). In one small animal study of long-term ventilation, many of the complications seen were related to nursing care issues, including endotracheal (ET) tube occlusion and accidental disconnections, tracheal necrosis, oral and ocular ulcers, pressure sores, muscle atrophy, and peripheral edema. This chapter reviews basic concepts i n ventilator patient care. 1
AIRWAY Intubation Airway management is an essential aspect of ventilator patient care. For most patients this is accomplished via ET intubation and general anesthesia. It is important that ET tubes are sterile and ideally have high-volume, low-pressure cuffs. Tracheal mucosal blood flow can be occluded by pres sures over 25 to 35 m m H g . Ideally cuff pressure should 2
be maintained between 20 and 25 m m H g and measured regularly with a pressure gauge. Higher pressures impede mucosal b l o o d flow and may lead to tracheal necrosis. Lower cuff pressures are associated w i t h an increased risk o f aspira tion. " In practice, the cuff should be inflated while auscul tating the trachea until no leak is heard and then deflated slightly until a small leak can first be detected. Although fre quently used, the pilot balloons do not correlate well w i t h cuff pressure and should not be used as an indicator o f appropriate inflation.
associated distress or discomfort associated w i t h mechanical ventilation. ' Tracheostomy tubes ideally should have an inner cannula that should be cleaned every 4 hours and the entire trache ostomy tube changed every 24 to 48 hours. If there is no cannula, the tube should be suctioned regularly and changed every 24 hours. The tracheostomy tube should also have a cuff to protect the airway from migration o f oral secretions and to allow positive end-expiratory pressure (PEEP) to be used.
Tracheal injury can also be m i n i m i z e d by repositioning the E T tube every 4 hours. This is achieved by deflating the cuff, repositioning the tube slightly to change the pressure point, and then reinflating the cuff. The m o u t h and pharynx should be flushed and suctioned before deflating the cuff. ET tubes should be tied securely w i t h intravenous tubing or another nonporous material, w h i c h is less likely than gauze to become saturated with oral secretions and bacteria. The ties should be moved and secured i n a different position every 4 hours to prevent lip necrosis. The E T tube should be changed every 24 to 48 hours depending on the amount and character o f the secretions. It is important to preoxygenate with 100% oxygen before chang ing the tube and to be prepared for a difficult reintubation. Sterile E T tubes should be used i n all ventilator patients. Patients such as those with neurologic or neuromuscular disease that cannot fight mechanical ventilation often can be managed with a tracheostomy tube and light sedation instead o f ET intubation and general anesthesia. This may provide the benefits of allowing ongoing neurologic evalua tion, decreased need for anesthesia, and the ability o f some patients to eat and drink o n their o w n while being venti lated. It is important to consider that some o f these patients may require anxiolytic and/or analgesic drugs to control
Humidification and Suction
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Box 216-1 Sample Ventilator Patient Treatment Sheet
Anesthetized patients are not able to cough or clear airway secretions effectively, and occlusion o f the tube l u m e n is a c o m m o n and potentially life-threatening p r o b l e m . Pre vention o f airway occlusion requires adequate humidifica tion and suctioning. Gas flow bypasses the nasal passages during mechanical ventilation and is therefore not humidified or filtered by the body. This can lead to a loss o f heat and moisture, which can damage the respiratory epithelium. Humidification is also critical i n making secretions less viscous and easier to remove. ' ' Humidifiers can be divided broadly into two groups: high flow and passive. High-flow humidifiers are connected to the ventilator circuit and generally involve a heated element and a sterile water reservoir to add moisture and heat to the gases. These humidifiers are expensive but are very effective. It is important to m o n i t o r the respiratory circuit for exces sive condensation or heat. 1
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A less expensive method uses heat and moisture exchangers ( H M E ) that act as an "artificial nose." These devices trap exhaled water particles and heat as condensation during exhala tion, helping to conserve airway moisture. Specialized filters also trap exhaled bacteria and viruses. The effectiveness of these devices depends on gas flow rates and the patient's temperature. They should be changed every 24 to 72 hours or if they become saturated with secretions, because this creates resistance to gas flow. H M E s are not recommended i n patients who are hypo thermic or w h o have thick and copious secretions. 2
•
Evaluate and record ventilator settings q2h
•
M o n i t o r depth of anesthesia and adjust infusions q2h
•
Suction endotracheal tube and instill saline if needed q4h
•
Adjust tube ties and cuff q4h
•
Clean tracheostomy tube cannula and site q4h
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Change endotracheal tube q24-48h
•
T u r n patient, record position, and check padding and heat support q4h
•
D o passive range-of-motion exercises q4h
•
Lubricate eyes q2h
•
Flush and suction m o u t h and pharynx q4h
•
Clean mouth with oral chlorhexidine solution q4h
•
Reposition pulse oximetry probe and wrap tongue with saline or glycerine gauzes q2h
•
Palpate bladder and measure urine output q4h
•
Provide urinary catheter care q8h
•
Perform intravenous catheter care q24h
•
Change heat and moisture exchanger and ventilator tubing
•
Monitor continuously and record the following values q2h
q48-72h • Electrocardiogram (heart rate and rhythm) • Blood pressure (direct, Doppler, or oscillometric) • Pulse oximeter • End-tidal carbon dioxide • Rectal temperature • Central venous pressure
Suctioning is another critical aspect o f airway management. There are risks associated with this procedure, and proper tech nique must be followed. The inhaled oxygen concentration should be increased to 100% before and during suctioning. M o n i t o r i n g of the patients oxygenation status with pulse o x i m etry throughout the procedure is recommended. The suction catheter should be sterile, soft, and flexible, w i t h more than one distal opening and a p r o x i m a l thumbhole to control the level o f suction. Sterile gloves should be w o r n and sterile technique observed throughout the pro cedure. Closed suction systems are also available and are helpful i n maintaining sterility and preventing problems associated w i t h tubing disconnection. Suction should be applied while withdrawing the catheter from the airway for no more than 5 seconds at a time. This procedure can be repeated two or three times as l o n g as oxy genation remains adequate and the patient does not seem distressed. If suctioning is productive, it can be performed as frequently as every 2 to 4 hours. The risks o f suctioning include hypoxemia, patient discomfort, damage to the tra cheal mucosa, collapse o f small airways and alveoli, and contamination o f the lower airways. ' ' 2
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If the secretions are too dry to suction well or adequate humidification is not being provided, small aliquots o f
sterile saline (0.2 ml/kg) may be instilled into the airway before suctioning. This practice has been challenged because of the lack o f evidence o f beneficial effects coupled with the risk o f introducing i n f e c t i o n . ' Ventilator circuit tubing is a potential source o f nosoco m i a l infection and should be replaced every 48 to 72 hours. Tubing should be sterile. 2
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ANESTHESIA There is no single ideal protocol for anesthetizing ventilator patients; the best combination for each patient w i l l depend o n the anticipated duration o f ventilation, species, and concurrent diseases (Table 216-1). The anesthesia plan should be tailored to each patient, and a balanced approach should be used to m i n i m i z e the adverse effects o f individual drugs. Patients should be preoxygenated before induction, and induction should provide rapid control o f the airway. Poten tial i n d u c t i o n agents include propofol plus or minus diaze pam, ketamine and diazepam, etomidate, or thiopental. M a s k inductions with inhalants should be a v o i d e d . Short-term ventilation (1 to 24 hours) can be accomplished w i t h combinations o f diazepam, opioids, and propofol. If a patient is ventilated for a longer period, a constant rate infu sion (CRI) of pentobarbital usually i n conjunction w i t h a ben zodiazepine C R I frequently is used instead o f p r o p o f o l . ' Pentobarbital is associated w i t h very slow recoveries, so infu sions should be decreased or stopped 12 to 24 hours before weaning. Pentobarbital infusions o f 3 to 4 days duration can be associated w i t h very rough recoveries, and patients may benefit from a change to a propofol C R I for the final day o f anesthesia to provide a smoother and more predictable 3,5
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recovery. Pentobarbital infusions o f a week or longer can be associated w i t h seizures during the recovery period; phenobarbital should be started several days before recovery. N e u romuscular blockers often are used for treatment o f human patients receiving mechanical ventilation; however, they require specialized monitoring, and i n rare cases these agents can lead to incomplete reversal and prolonged paralysis. ' Regardless o f the anesthesia protocol used, it is important to reassess the patient's level o f sedation frequently and to adjust infusions as needed. 3
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MONITORING Like any patient under anesthesia, ventilator patients need intensive monitoring. Basics monitoring should include con tinuous electrocardiography ( E C G ) , pulse oximetry, capnography, and serial b l o o d pressure measurements. Ideally an arterial catheter should be inserted for direct blood pressure measure ments and frequent (q4h) arterial blood gas analysis. Arterial catheters usually are placed i n the dorsopedal artery, which can be difficult i n cats and small dogs. Cats also have less collat eral circulation and may tolerate an arterial catheter for only 6 to 8 hours. If arterial lines cannot be placed or maintained, then pulse oximetry, jugular venous blood gasses, and lactate levels can be used to assess oxygenation indirectly. Thoracic radiographs are often helpful i n the assessment of patients with deteriorating oxygenation, or when aspiration or pneumotho rax is suspected. 3
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Ventilator settings, including inhaled oxygen concentra tion, pressure and volume settings, respiratory rate, and breath patterns (mode), should be recorded regularly to m o n i t o r trends.
Table 216-1
Anesthetic Agents for Ventilator Patients
Agent
Pros
Cons
Comments
Inhalants
Effective
Needs scavenging system, associated operator health risks Cardiovascular depression
Impairs hypoxic vasoconstriction
Propofol
Rapid onset and recovery
Expensive Causes lipemia, hypotension, respiratory depression
Not recommended for >1 to 2 days because of lipemia Can cause Heinz body anemia in cats
Etomidate
Cardiovascular sparing
Propylene glycol carrier causes hemolysis Expensive Adrenocortical suppression
CRI not recommended because of propylene glycol and high osmolality
Opioids
Cardiovascular sparing Analgesic
Panting may worsen patientventilator asynchrony Ileus Hyperthermia
Intermittent doses or low-dose CRI may be a helpful adjunct in addition to other agents
Pentobarbital
Effective, easy to manage as CRI Good choice for intracranial disease
Prolonged recovery Can cause seizures on recovery after use for >7 days
CRI must be decreased or stopped 12 to 24 hours before weaning
Diazepam
Good as an adjunct
Phlebitis concerns necessitate central catheter
—
Neuromuscular blockade
Risk of incomplete reversal of Reduces patientparalysis ventilator asynchrony Patient cannot signal if problem Muscle atrophy
Requires careful monitoring Should be used only by experienced ICU clinicians
Reprinted with permission from Clare MC, Hopper K: Mechanical ventilation: Ventilator settings, patient management, and nursing care, Comp Cont Educ Pract Vet 27:256, 2005.
CRI, Constant rate infusion; ICU, intensive care unit.
FLUID THERAPY Fluid therapy is essential to optimize perfusion and hydration o f the airways while preventing pulmonary or peripheral edema. The fluid plan needs to be specific for each patient's medical issues and status. In general, animals with exudative processes (e.g., pneumonia) should be kept well hydrated, and a more con servative approach is appropriate for patients with transudative diseases (e.g., congestive heart failure, pulmonary edema). Fre quent physical examinations and serial monitoring of serum electrolytes, lactate, and albumin, urine output, and specific grav ity can all be helpful in adjusting fluid plans. Ventilator patients have a tendency toward peripheral edema and sodium and water retention; fluid intake and output should be monitored closely. Measurement of central venous pressure and colloid osmotic pressure may be also useful in designing a fluid plan. 3
Intravenous catheters should be unwrapped and evalu ated for phlebitis or swelling every 24 to 48 hours.
NUTRITION
These patients require careful padding and attention to positioning to prevent decubitus ulcers. Hypothermia is a c o m m o n problem, because thermoregu lation is depressed under anesthesia and large amounts of heat may be lost from the airway i f heated humidification is not used. Patient temperature should be monitored closely with continuous temperature probes or w i t h frequent intermittent measurements. Circulating water blankets, forced-air warm ing blankets, and adequate padding may help maintain a nor mal body temperature. H o t water bottles should be avoided or used w i t h caution because o f the risks for thermal injury. Hyperthermia can also be a problem i n the ventilated patient. Increased work o f breathing from fighting the venti lator as a result o f patient-ventilator asynchrony is a c o m m o n cause. Excessive active warming, overheating o f the breathing circuit, drug therapy, and primary disease pro cesses are other possible contributors. The increased respira tory rate and effort that occurs i n response to hyperthermia can be a significant cause o f patient-ventilator asynchrony and may result i n hypoxemia and patient deterioration. Active cooling measures may be necessary i n addition to treating primary causes o f hyperthermia. 10
Enteral nutritional support is challenging i n ventilator patients because o f the risks o f regurgitation and aspiration and the high incidence o f ileus. Inadequate nutrition is associated with worsening of respiratory muscle atrophy and increased incidence o f gastrointestinal bacterial translo cation. Excessive feeding can lead to hypercapnia and can exacerbate hypotension because o f redistribution o f b l o o d to the splanchnic circulation. Specialized enteral formulas have been designed to reduce carbon dioxide p r o d u c t i o n . 2
Histamine-2 blocker use i n ventilated humans has been associated with an increased risk o f bacterial pneumonia, because gastric colonization with bacteria occurs at a less acidic p H . Sucralfate has been advocated as an alternative for gastric protection. Enteral nutrition can be provided via a nasogastric tube, gastrotomy tube, or jejunostomy tube. Postpyloric feeding may be correlated with a decreased risk o f aspiration. Gastric residuals should be monitored, although the amount of residual is not well correlated w i t h risk o f aspiration. Promotility agents such as metoclopramide, ranitidine, and cisapride should be considered i n patients receiving enteral feedings. Parenteral nutrition should be considered i n patients that will not tolerate enteral feeding.
EYE CARE Ventilator patients require eye care to prevent corneal drying and ulceration. Artificial tear ointment should be applied at least every 2 hours. If an ulcer is suspected, fluorescein staining should be performed and an antibiotic ophthalmic ointment regimen should be started (see Chapter 172, Ocular Disease i n the Intensive Care U n i t ) .
ORAL CARE
2
2
8
Ventilator patients w i l l inevitably develop oropharyngeal ulceration and frequently develop lingual swelling unless meticulous oral care is performed (and possibly despite meticulous care) (Color Plate 216-1). Bacterial colonization of the oropharynx is believed to be the major cause o f ventilator-associated pneumonia i n h u m a n patients. O r o pharyngeal bacteria can colonize the respiratory tract by migration or by microaspiration o f oropharyngeal secre tions. In addition, oropharyngeal ulceration can be a source of systemic bacteremia. Strict adherence to oral care proto cols is beneficial i n both h u m a n and veterinary patients. ' Oral care includes preventing mechanical trauma and frequent rinsing with dilute antibacterial solutions. A n y sites of consistent pressure should be relieved regularly; for example, the pulse oximeter probe should be repositioned at least every 2 hours, the tongue should be protected against damage from the teeth and the E T tube with an atraumatic m o u t h gag. The tongue can be wrapped with gauze soaked with water or glyc erin to reduce lingual drying and swelling. The m o u t h should be cleaned and suctioned every 4 hours and rinsed with an anti bacterial mouthwash solution such as dilute chlorhexidine. 11
RECUMBENT CARE AND TEMPERATURE SUPPORT Prolonged recumbency can lead to muscle atrophy, pressure sores, peripheral edema, and nerve damage. Patients should be repositioned every 4 hours and should receive passive range-of-motion exercises. Ventilator patients should be kept on sufficient padding that is changed immediately i f soiled. Frequent changes i n body position also help prevent pooling of secretions i n one airway region and reduce atelec tasis o f the dependent lung lobes. Oxygenation should be monitored carefully after changes i n position. Turning may be associated with desaturation i n animals w i t h substantial pulmonary pathology; some patients w i l l not tolerate lateral recumbency, i n which case they may have to be maintained in sternal recumbency with only their hips turned regularly. 9
12
12
URINARY AND FECAL CARE Quantification o f urine output and prevention o f urine scald can be accomplished by using diapers (which can be weighed) or by inserting a urinary catheter w i t h a sterile
collection system. If diapers are used, the bladder should be palpated and expressed every 4 hours. Urinary catheters require aseptic placement and regular cleaning to reduce the risk of ascending infection (see Chapter 138, Urinary Catheterization). The colon should be palpated regularly and enemas should be used i f necessary.
SUGGESTED FURTHER READING* Clare M C , Hopper K: Mechanical ventilation: ventilator settings, patient management, and nursing care, Comp Cont Educ Pract Vet 27:256, 2005. A general review of veterinary patient ventilator management.
Haskins SC, King LG: Positive pressure ventilation. In King L G , editor: Textbook of respiratory disease in dogs and cats, St Louis, 2004, Saunders. A comprehensive chapter on ventilation in dogs and cats providing a general overview of patient care. Hendricks JC: Airway hygiene. In King L G , editor: Textbook of respiratory disease in dogs and cats, St Louis, 2004, Saunders. A chapter that discusses general principles of airway management and humidification techniques. Mellema MS, Haskins SC: Weaning from mechanical ventilation, Clin Tech Small Anim Pract 15:157, 2000. A paper that provides a good discussion about weaning techniques and ventilator complications. "See the C D - R O M for a complete list of references.
Chapter 217 DISCONTINUING MECHANICAL VENTILATION Kate Hopper,
BVSC, MVSC, DACVECC
KEY POINTS • A patient must attain certain physiologic goals to be weaned from mechanical ventilation. • Weaning can be achieved by a gradual reduction in the level of ventilator support or by using a specific weaning method. • There are three main weaning methods: spontaneous breathing trials, pressure support ventilation, and synchronized intermittent mandatory ventilation. • Close monitoring is necessary after disconnecting a patient from mechanical ventilation. Weaning failures require immediate action to maximize future success.
INTRODUCTION Mechanical ventilation is not benign and the a i m is to discon tinue it as soon as possible. The process o f discontinuing venti lator support is called weaning and has been the focus of a great deal of study i n h u m a n medicine, although little information is available i n the veterinary literature. In many patients receiving short-term ventilator support that have rapidly resolving dis ease processes, discontinuation is simply a matter of discon necting the patient from the ventilator. Patients receiving mechanical ventilation for longer periods and those with c o m plex disease processes may require a true weaning process. A patient must attain certain physiologic goals to be weaned from the ventilator. These include adequate gas
exchange without the support of aggressive ventilator settings, an appropriate ventilatory drive, and recovery from signifi cant systemic disease such as cardiovascular instability or organ failure. However, attaining these goals does not guaran tee that the patient can be weaned successfully. Prolonged mechanical ventilation (longer than 48 hours) can cause inspiratory muscle weakness that is proportional to the dura tion o f ventilation. In addition, short-term controlled mechanical ventilation can cause decreased diaphragmatic force-generating capacity, also k n o w n as ventilator-induced diaphragmatic dysfunction. As a result, sudden discontinua tion of mechanical ventilation may be poorly tolerated despite adequate gas exchange. 1
2
The weaning process must force the patient to assume some of the work of breathing to recondition the inspiratory muscles. Patients must be monitored closely subsequent to discontinuation o f ventilation i n case respiratory muscle fatigue develops. Weaning from mechanical ventilation i n human medicine is largely protocol driven; the weaning process is started only after specific criteria of readiness are fulfilled, respiratory performance is tested regularly i n an effort to predict the likelihood o f successful weaning, and management of the ventilator settings d u r i n g weaning follows preset guidelines. In veterinary medicine discontinuation of mechanical ventilation is a trial-and-error process that depends largely
Box 217-1 Criteria for Readiness to Wean
correlation with successful weaning i n adults. It is calculated as the ratio o f respiratory rate (f) and tidal volume ( V ) . Those patients who develop increased rapid shallow breathing during a spontaneous breathing trial (SBT) (marked by a higher f / V ratio) are more likely to fail the weaning trial. A ratio o f less than 100 is used i n human medicine to identify patients that can be weaned. Unfortunately, even this ratio has not been a consistently reliable predictor o f weaning out come. In veterinary medicine this ratio may be difficult to adapt to our patients given the variability i n normal respira tory rates, but it does suggest that a fast, shallow breathing pattern during an SBT may be a poor prognostic indicator. T
•
Improvement in the primary disease process
•
Pa0 :Fi0
•
P E E P 150-200 with F i 0
2
50%), high peak inspired airway pressures (>25 c m H 0 ) , and high positive end-expiratory pressure levels (>5 c m H 0 ) to maintain oxygenation should preclude any weaning attempts. Weaning is not advised in animals that are hemo dynamically unstable or have severe systemic disease such as organ dysfunction. The final stage o f weaning includes disconnection from the ventilator and extubation. 2
2
2
2
ANESTHETIC CONSIDERATIONS As soon as the patient fulfills the weaning criteria, rapid extubation is desirable. Long-acting anesthetic agents such as pentobarbital are associated with prolonged recoveries (several hours to days). Discontinuing these agents 24 hours or more before weaning is predicted to occur is recom mended to prevent unnecessary prolongation o f the anes thetic period. Changing to constant rate infusions o f a short-acting anesthetic agent, such as propofol or a benzodi azepine, or both, for the last 1 to 2 days o f the ventilation period can provide effective control o f anesthetic depth and may smooth out the rough recovery associated with pentobarbital.
T
D
D
T
5
WEANING A PATIENT FROM MECHANICAL VENTILATION The process o f weaning involves a reduction i n the work o f breathing performed by the machine with a proportional increase i n the work performed by the patient. In veterinary medicine, this sometimes is achieved w i t h assist-control ventilation modes (such as volume assist control or pressure assist control) i n which the magnitude of the ventilator settings is decreased. However, this approach is not recommended, because every breath is generated by the machine; the patient is able only to increase the respiratory rate. This does not increase the patient's work o f breathing adequately and i f the magnitude o f the ventilator settings are lowered excessively, there is a risk of hypoventilation. The three m a i n weaning tech niques are SBT, pressure support ventilation (PSV), and synchronized intermittent mandatory ventilation ( S I M V ) . 6
Spontaneous Breathing Trials A n S B T involves removing all ventilator support and m o n i toring the patient's ability to breathe spontaneously. This can be achieved by disconnecting the animal from the machine and allowing it to breathe an enriched oxygen source (usually w i t h an F i 0 similar to or above the level the patient was receiving while ventilated) via a breathing circuit (such as a Bain circuit). A n alternative approach is to leave the patient connected to the ventilator and switch to a low level (2 to 5 c m H 0 ) o f continuous positive airway pressure ( C P A P ) . The advantage o f using C P A P is that all m o n i t o r i n g and ventilator alarms can remain attached and if the patient fails the SBT, ventilatory support can be rees tablished rapidly. The endotracheal tube and ventilator breathing circuit increase the work o f spontaneous breathing compared with the extubated state; a l o w level o f C P A P may compensate for this effect and prevent unnecessary weaning failures. 2
2
7
WEANING PREDICTION In human medicine many indexes have been evaluated as potential predictors o f weaning success. The rapid shallow breathing index ( f / V ) is the only one shown to have some T
The concept behind SBTs is to use it almost as a training exercise for the patient as soon as it is considered sufficiently stable; there may be no expectation that the patient w i l l be weaned w i t h the initial trial. In h u m a n medicine it is c o m m o n l y recommended to perform a 30- to 120-minute SBT daily from the time the patient attains adequate
physiologic goals. SBTs may be a superior method o f wean ing from mechanical ventilation compared w i t h P S V or S I M V i n h u m a n medicine. In veterinary medicine, it is more c o m m o n to place patients o n an S B T when they are considered ready to be removed completely from ventilator support. Evidence from the h u m a n literatures suggests that daily S B T to improve respiratory muscle strength as a pre lude to successful weaning could be o f benefit to many long-term ventilated small animal patients. 8
Pressure Support Ventilation
Box 217-2 Criteria for Failure of a Spontaneous Breathing Trial •
Tachypnea (RR
•
Pa0
•
PaC0
2
>50)
60 m m H g or E T C 0
2
>50
mm Hg •
Tachycardia
•
Hypertension
•
Anxiety
ETCO2, End tidal carbon dioxide; Pa0 , partial pressure of arterial oxygen; PaC0 , partial pressure of arterial carbon dioxide; P v C 0 , partial pressure of venous carbon dioxide; RR, respiratory rate; Sp0 , oxygen saturation. 2
2
P S V is a pressure-limited spontaneous breathing mode; the breath is triggered and terminated by the patient. As such, it can be used only i n patients with a normal respiratory drive. The inspiration is augmented by additional inspiratory pressure as preset by the operator, but the patient controls the respiratory rate, inspiratory flow, and tidal volume of each breath. The level of pressure support can be decreased gradually as the patient improves. W h e n the patient is stable o n a low level o f pressure support (i.e.,