Extensive epidural anesthesia with sympathetic blockade leads to arterial vasodilation, and therefore, decreased mean arterial pressure. Furthermore, sympathetic blockade prevents effective baroreceptor-driven cardiocirculatory compensation, rendering a low mean arterial pressure that is not accompanied by a rapid heart rate likely. Venodilation, especially of the splanchnic circulation, decreases cardiac filling, and may even further trigger sympathetic withdrawal and vagal hyperactivity (1,2). These mechanisms may lead to sudden cardiovascular collapse during epidural blockade, reflecting a catastrophic complication of regional anesthesia (3).
Accordingly, with the sympathetic nervous system blocked, resuscitation is considered difficult because of a diminished coronary perfusion pressure during cardiopulmonary resuscitation (CPR) (4,5). Also, the role of the standard vasopressor epinephrine during CPR is controversial. In laboratory CPR studies, epinephrine is associated with an increase in myocardial oxygen consumption (6), ventricular arrhythmia (7), ventilation-perfusion defect (8), and a more severe postresuscitation myocardial dysfunction (9). In one clinical trial, normal and large dosages of epinephrine did not result in better outcome compared with saline placebo (10). A number of fundamental endocrinologic responses of the human body to cardiac arrest and CPR have been investigated (11–13). Exogenous vasopressin in pharmacological doses leads to massive peripheral vasoconstriction via V1-receptors (14). In comparison with epinephrine, laboratory investigations show that vasopressin significantly increases vital organ blood flow during ventricular fibrillation (15) and pulseless electrical activity cardiac arrest (16). The efficacy of epinephrine and vasopressin during CPR in epidural anesthesia with a diminished sympathetic response is unknown.
Optimal timing of defibrillation during CPR may increase the likelihood of successful defibrillation (17), and prevent thermal injury of the heart (18). Mean frequency of ventricular fibrillation has been shown in laboratory and clinical studies (19,20) to be a valuable noninvasive monitoring tool in predicting successful countershocks (21). However, nothing is known about ventricular fibrillation mean frequency during cardiac arrest with epidural anesthesia.
Accordingly, the purpose of the present investigation was to evaluate the effects of repeated dosages of epinephrine versus vasopressin in a porcine cardiac arrest model with and without epidural anesthesia, on coronary perfusion pressure, and on return of spontaneous circulation rate. Furthermore, we wanted to evaluate the ability of ventricular fibrillation mean frequency to reflect coronary perfusion pressure and to predict CPR outcome during sympathetic blockade.
Material and Methods
This project was approved by the Austrian Federal Animal Investigational Committee and was performed according to Utstein-style guidelines (22) on 28 healthy, 12–16 wk-old swine (Tyrolean domestic pigs) of either gender weighing 35–45 kg. Animal anesthesia and instrumentation was performed as previously described (23). After instrumentation, animals were put in the prone position, and a 19-gauge soft spring-wound epidural catheter (Racz-model; Medic. Inc., Gloversville, NY) was inserted into the epidural space through a 17-gauge Tuohy needle at the L3-4 level; and advanced under fluoroscopic guidance until the tip reached T15/L1 interspace. The distribution of 1 mL iodinated contrast (Omnipaque, 300 mg/mL; Schering, Vienna, Austria) was examined under fluoroscopic guidance to ensure epidural distribution of the contrast agent. The catheter was secured to the back, and the animals were returned to the supine position.
After hemodynamic variables were stable for at least 20 min, baseline data were recorded and 28 animals were randomly allocated to receive either an epidural bupivacaine administration (Epidural Animals, n = 16) or an epidural saline administration (Control Animals, n = 12). Normal saline was injected intramuscularly (IM) in the Epidural Animals and epidurally in the Control Animals (Table 1). Epidural Animals received an epidural drug administration consisting of a mixture of 0.75% bupivacaine and iodinated contrast (Omnipaque, 300 mg/mL; Schering), rendering a final bupivacaine concentration of 0.5%. Eight milliliters of this mixture were administered over 1 min under fluoroscopic guidance to ensure adequate epidural distribution and spread to cover at least the C7 through L1 levels. The Epidural Animals received 8 mL of IM saline. Control Animals received 8 mL IM 0.5% bupivacaine and saline placebo mixed with contrast epidurally as described above. These doses were chosen to produce thoracolumbar blockade of all vertebral segments with preganglionic sympathetic outflow in the Epidural Animals and to produce comparable serum bupivacaine concentrations.
Heparin 5000 U IV was then administered to prevent intracardiac clot formation during CPR. Thirty minutes after administration, hemodynamic variables and blood gases were measured. Anesthesia was stopped, and a 50-Hz, 60-V alternating current was applied via two subcutaneous needle electrodes to induce ventricular fibrillation. Cardiopulmonary arrest was defined as the point at which the aortic pulse pressure decreased to zero and the electrocardiogram (ECG) showed ventricular fibrillation; mechanical ventilation was continued with 100% oxygen. After 1 min of untreated ventricular fibrillation, closed-chest CPR was performed manually, always by the same investigator at a rate of 80/min guided by audible timer. All investigators were blinded to hemodynamic and end-tidal carbon dioxide monitor tracings.
After 1 min of ventricular fibrillation and an additional 3 min of basic life-support CPR, the Epidural Animals were randomly assigned to receive either IV vasopressin (0.4, 0.4, and 0.8 U/kg;n = 8) or epinephrine (45, 45, and 200 μg/kg;n = 8) after 3, 8, and 13 min of CPR, respectively. The Control Animals were also randomly assigned to receive either vasopressin (0.4, 0.4, and 0.8 U/kg;n = 6), or epinephrine (45, 45, and 200 μg/kg;n = 6) after 3, 8, and 13 min of CPR, respectively. Thus, Epidural Animals received epidural blockade, IM saline, and either IV epinephrine or vasopressin, whereas Control Animals received epidural saline, IM bupivacaine, and either IV epinephrine or vasopressin.
Vasopressin and epinephrine were diluted to 10 mL with normal saline and subsequently injected into the right atrium, which was followed by a 20-mL saline flush. Investigators collecting data and performing CPR were blinded to the identity of the vasopressor. Hemodynamic variables were measured before induction of cardiac arrest, after 3 min of CPR, and 90 s and 5 min after each drug administration, respectively. After 19 min of cardiac arrest, including 18 min of CPR, up to 5 countershocks were administered with an energy of 3, 4, 6, 6, and 6 Joules/kg, respectively. If asystole or pulseless electrical activity was present after defibrillation, the experiment was terminated. Return of spontaneous circulation was defined as an unassisted pulse with a systolic arterial pressure of ≥80 mm Hg, and pulse pressure of ≥40 mm Hg, lasting for at least 5 min. After the first 5 min of return of spontaneous circulation, further postresuscitation management was guided by the American Heart Association guidelines (24). In the postresuscitation period, hemodynamic variables were measured at 5, 15, 30, and 60 min after return of spontaneous circulation, respectively. After finishing the experimental protocol, the animals were killed and necropsied to verify correct positioning of the catheters and identify injuries to the rib cage or thoracic organs.
ECG signal recording and analysis was performed as previously reported (20). Briefly, the ECG signal (standard lead III) was digitized (sampling rate 1000 Hz; amplitude resolution 12 bit), and recorded continuously by PC-based data acquisition. ECG signal analysis was performed by dividing the signal into consecutive 10-s epochs and transforming it into the frequency domain by Fourier transformation. Using the transformed ECG signal, the maximum of ventricular fibrillation mean frequency within 30 s before and 90 s after each drug administration during CPR was calculated.
The comparability of weight and baseline data and ventricular fibrillation mean frequency was tested by using Student’s t-tests for continuous variables. One-way analysis of variance was used to determine statistical significance between groups, and this was corrected for multiple comparisons by using the Bonferroni method. Analysis of variance was used to identify statistically significant differences of mean frequency between the two epinephrine groups and between the two vasopressin groups. We considered a two-tailed P < 0.05 statistically significant. We tested the null hypothesis that the number of surviving animals is independent of treatment by using Fisher’s exact test.
Before administration of the epidural block, there were no differences in weight, hemodynamic variables, and blood gases between groups. Thirty minutes after epidural administration of bupivacaine or saline, mean arterial pressure, coronary perfusion pressure, and systemic vascular resistance decreased approximately 20%–30% in animals receiving epidural bupivacaine and these values were significantly lower in comparison with those seen in animals receiving epidural saline (Table 2). During 3 min of basic life-support CPR, coronary perfusion pressure and mean arterial pressure were significantly lower after epidural bupivacaine compared with values seen after administration of epidural saline. In Control Animals, the initial dose of vasopressin produced a significantly larger increase in coronary perfusion pressure than epinephrine did. Coronary perfusion pressure was also significantly greater in animals receiving vasopressin 5 min after the first, second, and third vasopressor administrations, compared with epinephrine at those times (Fig. 1). After 18 min of CPR, 6 of 6 Vasopressin-Treated Animals and 2 of 6 Epinephrine-Treated Animals (P = NS) had return of spontaneous circulation and survived the 60 min postresuscitation phase.
In animals receiving epidural bupivacaine (Table 2, Fig. 2), the increase in coronary perfusion pressure after the first vasopressor dose was comparable for epinephrine and vasopressin. Five minutes after the first vasopressor dose, coronary perfusion pressure was significantly higher with vasopressin than with epinephrine, although the reverse was true 90 s after the third vasopressor dose. After 18 min of CPR, 7 of 8 Vasopressin-Treated Animals and 3 of 8 Epinephrine-Treated Animals (P = NS) had return of spontaneous circulation and survived the 60 min postresuscitation phase. In comparing drug responses between Epidurally Anesthetized and Control Animals, it is noted that the third administration of epinephrine increased coronary perfusion pressure significantly more during epidural blockade than in Control Animals. After vasopressin treatment and resuscitation, five of the seven surviving animals with epidural block required atropine because of bradycardia, whereas none of the six unblocked animals needed atropine after return of spontaneous circulation (P = 0.02). Atropine was not used in any of the five animals surviving after epinephrine treatment.
Compared with vasopressin, administration of epinephrine revealed a significantly more severe metabolic acidosis during CPR in both the Epidural and the Control Animals (Table 3). Although hemodynamic and blood gas variables were measured in the postresuscitation phase, results were similar in all groups and were not statistically analyzed because of the small sample size (Table 2). Sympathetic blockade resulted into a profound decrease in ventricular fibrillation mean frequency values immediately after induction of cardiac arrest and basic life-support CPR when compared with nonblocked animals (Figs. 3, 4). Ventricular fibrillation mean frequency increased after administration of both epinephrine and vasopressin, resulting in comparable ventricular fibrillation mean frequency values immediately before defibrillation. Before successful or unsuccessful defibrillation, ventricular fibrillation mean frequency was 8.2 ± 1.1 vs 7.1 ± 0.5 Hz (P < 0.05), respectively. Ten of 14 (71%) pigs with ventricular fibrillation mean frequency >7.4 Hz were defibrillated successfully, whereas defibrillation was successful in 4 of 9 (44%) pigs with ventricular fibrillation mean frequency <7.4 Hz. Necropsy confirmed appropriate catheter positions and revealed no injuries to the rib cage or intrathoracic organs in all animals.
This study shows that closed-chest CPR is minimally effective after epidural anesthesia, but both epinephrine and vasopressin produce initial increases in coronary perfusion pressure in this setting. Compared with vasopressin, however, administration of epinephrine is accompanied by more severe metabolic acidosis in Control Animals and those with epidural blockade.
The present model simulates sudden cardiac arrest during epidural anesthesia with 1 min of ventricular fibrillation followed by 3 min of basic and 15 min of advanced cardiac life support. We omitted defibrillation attempts on starting CPR and immediately after drug administration to study the hemodynamic effects of the study drugs during prolonged resuscitation with repeated vasopressor administration, as is often clinically necessary. Although the 45-μg/kg epinephrine dose used in our porcine study is larger than the 15-μg/kg dose recommended for clinical use (24,25), the first two dosages of both vasopressin and epinephrine reflect an established optimal dose in this pig model (15,26). The escalating dose of 0.8 U/kg vasopressin and 200 μg/kg epinephrine are the maximum effective dosages in pigs (15,27).
In control animals, vasopressin produced a larger first-dose increase in coronary perfusion pressure than did epinephrine, but the responses were the same in the context of epidural blockade by bupivacaine. This indicates that epinephrine may be a suitable drug for initial resuscitation if used in adequate doses. Dependence on neural blockade may be explained by an altered neuroendocrine reaction during epidural anesthesia. For example, in unblocked animals and humans, activation of the adrenal medulla during cardiac arrest results in endogenous catecholamine discharge (28), with epinephrine plasma levels increasing from approximately 20 pg/mL at prearrest to 100,000 pg/mL during CPR before drug administration (29). As such, it has been suggested that increased endogenous catecholamine plasma levels actually limit the effectiveness of additional exogenous epinephrine given during advanced cardiac life support because of a down-regulation or uncoupling of receptors and/or low bioavailability (30). Epidural blockade decreases catecholamine levels (31) and diminishes the adrenergic response to cardiac arrest (5), resulting in lower epinephrine plasma levels and more adrenergic receptors that are still sensitive to exogenous epinephrine. Additionally, hypotension during epidural blockade is accompanied by increased endogenous vasopressin levels (32). Thus, there might be an additive effect of increased vasopressin levels and more sensitive adrenergic receptors, rendering exogenous epinephrine especially effective during epidural anesthesia.
There was a decremental of response to epinephrine during repeated administration in Control Animals but not in animals with epidural blockade, such that the third administration of epinephrine increased coronary perfusion pressure significantly more during epidural blockade than in Control Animals. This may indicate that escalating epinephrine doses might be more effective for prolonged resuscitation efforts during epidural anesthesia than without blockade. This beneficial effect of sympathetic blockade may result from the same neuroendocrine differences addressed above.
A decremental vasopressin response on coronary perfusion pressure was observed in animals with and without epidural block, although pressures were lower overall in the blocked animals. This may be because of the initial lower pressures in the blocked animals, and the unopposed parasympathetic activation during ischemia in the presence of a blocked sympathetic system. This is in agreement with easier resuscitation observed in dogs undergoing vagotomy compared with those with an intact parasympathetic system (33). In our study, this was evident by the increased need for atropine in the postresuscitation phase when vasopressin was used during epidural block compared with unblocked animals.
In both Epidural and Control Animals, the coronary perfusion pressure response to epinephrine vanished within 5 min, but the vasopressin response was sustained. Therefore, vasopressin may be the favored resuscitation drug on the basis of this desirable feature. We observed a trend toward better survival in animals treated with vasopressin, regardless of epidural block status. This is consistent with previous laboratory investigations demonstrating that epinephrine fueled cardiac oxygen consumption, which subsequently resulted in severe mismatch of cardiac oxygen delivery and consumption during CPR (34). In a laboratory investigation (35), vasopressin administration resulted in higher systemic blood pressure but a transiently lower cardiac index during early postresuscitation when compared with epinephrine. In the present investigation, myocardial function after vasopressin was comparable with prearrest values, whereas blocked and unblocked epinephrine animals were tachycardic and hypertensive during the postresuscitation period, probably because of the excessive β-stimulation.
Our findings show that there may be a connection between ventricular fibrillation mean frequency and coronary perfusion pressure during CPR with high epidural block. Because sympathetic activity per se has direct influences on ventricular impulse generation (36) and ventricular fibrillation mean frequency pattern (37–39), it could be expected that the previously established relation between coronary perfusion pressure and ventricular fibrillation mean frequency would be altered under these conditions (40). Evidently, however, myocardial perfusion pressure seems to be the dominant determinant regulating fibrillation frequency because we observed a strong connection between the two. Also, ventricular fibrillation mean frequency differed only minimally between blocked and control animals at the outset of cardiac arrest but decreased profoundly during basic life-support CPR; this can be reversed by both vasopressin and epinephrine during CPR. The difference in ventricular fibrillation mean frequency between successful and unsuccessful defibrillation is significant but small.
There are some limitations in the clinical applicability of this study to humans. The pathophysiologic cause of epidural cardiac arrest in the clinical setting may differ from our laboratory model. In patients, cardiac arrest caused by epidural anesthesia is often induced by asystole. Because this cannot be reliably reproduced in a laboratory model, we have induced cardiac arrest electrically. However, we want to point out that ventricular fibrillation can occur during combined regional and light general anesthesia when an unrelated event (for example, myocardial infarction) leads to cardiac arrest. In addition, pig vasopressin (lysine vasopressin) differs from human vasopressin (arginine vasopressin), so our exogenous arginine vasopressin may produce different responses in pigs than when used in humans under comparable conditions. However, the circulatory effects of arginine vasopressin may also be greater in humans than in pigs. It should be noted that young, healthy pigs free from atherosclerotic disease were used for this experiment and that the use of potent anesthetics and muscle relaxation may have affected cardiovascular function and autonomic control. Limitations of the study design include lack of assessment of bupivacaine levels and lack of dose-response data. This last limitation means we are unable to report the minimal effective vasopressin or epinephrine dose.
In conclusion, our results demonstrate that CPR during epidural anesthesia is possible, although the underlying pathophysiology has to be carefully considered. Epidural blockade profoundly decreases ventricular fibrillation mean frequency during basic life-support CPR and is reversed by both epinephrine and vasopressin. If our findings can be extrapolated to a clinical setting, advanced cardiac life support should be started immediately, and vasopressor drugs should not be withheld. In the context of epidural anesthesia, both epinephrine and vasopressin increase coronary perfusion pressure sufficiently during CPR. During epidural block, muscarinic blockade may be needed after vasopressin resuscitation. Vasopressin may be a more desirable vasopressor for resuscitation during epidural block because the response to a single dose is longer lasting, and acidosis after multiple doses is less severe compared with epinephrine.
1. Hogan QH, Stadnicka A, Stekiel TA, et al. Effects of epidural and systemic lidocaine on sympathetic activity and mesenteric circulation in rabbits. Anesthesiology 1993; 79: 1250–60.
2. Jacobsen J, Sofelt S, Brocks V, et al. Reduced left ventricle diameters at onset of bradycardia during epidural anesthesia. Acta Anaesthiolol Scand 1992; 36: 831–6.
3. Caplan RA, Ward RJ, Posner K, Cheney FW. Unexpected cardiac arrest during spinal anesthesia: a closed claims analysis of predisposing factors. Anesthesiology 1988; 68: 5–11.
4. Rosenberg JM, Wahr JA, Sung CH, et al. Coronary perfusion pressure during cardiopulmonary resuscitation after spinal anesthesia in dogs. Anesth Analg 1996; 82: 84–7.
5. Rosenberg JM, Wortsman J, Wahr JA, et al. Impaired neuroendocrine response mediates refractoriness to cardiopulmonary resuscitation in spinal anesthesia. Crit Care Med 1998; 2: 533–7.
6. Ditchey RV, Lindenfeld JA. Failure of epinephrine to improve the balance between myocardial oxygen supply and demand during closed-chest resuscitation in dogs. Circulation 1988; 78: 382–9.
7. Niemann JT, Haynes KS, Garner D, et al. Postcountershock pulseless rhythms: response to CPR, artificial cardiac pacing, and adrenergic agonists. Ann Emerg Med 1986; 15: 112–20.
8. Tang W, Weil MH, Gazmuri R, et al. Pulmonary ventilation/perfusion defects induced by epinephrine during cardiopulmonary resuscitation. Circulation 1991; 84: 2101–7.
9. Tang W, Weil MH, Sun S, et al. Epinephrine increases the severity of postresuscitation myocardial dysfunction. Circulation 1995; 92: 3089–93.
10. Woodhouse SP, Cox S, Boyd P, et al. High dose and standard dose adrenaline do not alter survival, compared with placebo, in cardiac arrest. Resuscitation 1995; 30: 243–9.
11. Prengel AW, Lindner KH, Ensinger H, et al. Plasma catecholamine concentrations after successful resuscitation in patients. Crit Care Med 1992; 20: 609–14.
12. Lindner KH, Strohmenger HU, Ensinger H, et al. Stress hormone response during and after cardiopulmonary resuscitation. Anesthesiology 1992; 77: 662–8.
13. Schultz CH, Rivers EP, Feldkamp CS, et al. A characterization of hypothalamic-pituitary-adrenal axis function during and after human cardiac arrest. Crit Care Med 1993; 21: 1339–47.
14. Vallotton MB. At the cutting edge: the multiple faces of the vasopressin receptors. Mol Cell Endocrinol 1991; 78: C73–6.
15. Lindner KH, Prengel AW, Pfenninger EG, et al. Vasopressin improves vital organ blood flow during closed-chest cardiopulmonary resuscitation in pigs. Circulation 1995; 91: 215–21.
16. Wenzel V, Lindner KH, Prengel AW, et al. Vasopressin improves vital organ blood flow after prolonged cardiac arrest with post-countershock pulseless electrical activity in pigs. Crit Care Med 1999; 27: 486–92.
17. Weaver WD, Copass MK, Bufi D, et al. Improved neurologic recovery and survival after early defibrillation. Circulation 1984; 69: 943–8.
18. Xie J, Weil MH, Sun S, et al. High-energy defibrillation increases the severity of postresuscitation myocardial dysfunction. Circulation 1997; 96: 683–8.
19. Strohmenger HU, Lindner KH, Keller A, et al. Spectral analysis of ventricular fibrillation and closed-chest cardiopulmonary resuscitation. Resuscitation 1996; 33: 155–61.
20. Achleitner U, Wenzel V, Strohmenger HU, et al. Effects of repeated doses of vasopressin or epinephrine on mean fibrillation frequency in a porcine model of prolonged cardiopulmonary resuscitation. Anesth Analg 2000; 90: 1067–75.
21. Amann A, Mayr G, Strohmenger HU. N(alpha)-histogram analysis for the ventricular fibrillation ECG-signal as predictor of countershock success. Chaos, Solitons and Fractals 2000;11:1205–12.
22. Idris AH, Becker LB, Ornato JP, et al. Utstein-style guidelines for uniform reporting of laboratory CPR research. Circulation 1996; 94: 2324–36.
23. Wenzel V, Lindner KH, Krismer AC, et al. Repeated administration of vasopressin but not epinephrine maintains coronary perfusion pressure after early and late administration during prolonged cardiopulmonary resuscitation in pigs. Circulation 1999; 99: 1379–84.
24. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 1998; 102: I–384.
25. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Resuscitation 2000; 46: 1–447.
26. Lindner KH, Ahnefeld FW, Bowdler IM. Comparison of different doses of epinephrine on myocardial perfusion and resuscitation success during cardiopulmonary resuscitation in a pig model. Am J Emerg Med 1991; 9: 27–31.
27. Brown CG, Werman HA, Davis EA, et al. The effects of graded doses of epinephrine on regional myocardial blood flow during cardiopulmonary resuscitation in swine. Circulation 1987; 75: 491–7.
28. Wortsman J, Frank S, Cryer PE. Adrenomedullary response to maximal stress in humans. Am J Med 1984; 77: 779–84.
29. Wenzel V, Lindner KH, Baubin MA, et al. Vasopressin decreases endogenous catecholamine plasma levels during CPR. Crit Care Med 2000; 28: 1096–100.
30. Gonzalez ER, Ornato JP, Garnett AR, et al. Dose-dependent vasopressor response to epinephrine during CPR in human being. Ann Emerg Med 1989; 18: 920–6.
31. Ecoffey C, Edouard A, Pruszczynski W, et al. Effects of epidural anesthesia on catecholamines, renin activity, and vasopressin changes induced by tilt in elderly men. Anesthesiology 1985; 62: 294–7.
32. Peters J, Schlaghecke R, Thouet H, et al. Endogenous vasopressin supports blood pressure and prevents severe hypotension during epidural anesthesia in conscious dogs. Anesthesiology 1990; 73: 694–702.
33. DeBehnke DJ. Effects of vagal tone on resuscitation from experimental electromechanical dissociation. Ann Emerg Med 1993; 22: 1789–94.
34. Ditchey RV. The choice of vasopressor agents in cardiopulmonary resuscitation. Curr Opin Crit Care 1996; 2: 170–5.
35. Prengel AW, Lindner KH, Keller A, et al. Cardiovascular function during the postresuscitation phase after cardiac arrest in pigs: a comparison of epinephrine versus vasopressin. Crit Care Med 1996; 24: 2014–9.
36. Hogan QH, Novalija E, Kulier AH, et al. Effect of thoracic epidural anesthesia on spontaneous postinfarction ventricular dysrhythmia in awake dogs. Reg Anesth 1997; 22: 318–24.
37. Leclercq JF, Rosengarten MD, Kural S, et al. Effects of intrinsic sympathetic activity of beta-blockers on SA and AV nodes in man. Eur J Cardiol 1981; 12: 367–75.
38. Noc M, Weil MH, Gazmuri RJ, et al. Ventricular fibrillation voltage as a monitor of the effectiveness of cardiopulmonary resuscitation. J Lab Clin Med 1994; 124: 421–6.
39. Wit AL, Cranefield PF. Triggered and automatic activity in the canine coronary sinus. Circ Res 1977; 41: 434–45.
40. Price HL, Ohnishi ST. Effects of anesthetics on the heart. Fed Proc 1980; 39: 1575–9.
© 2001 International Anesthesia Research Society
41. Kern KB, Niemann JT. Coronary perfusion pressure during cardiopulmonary resuscitation. In: Paradis NA, Halperin HR, Nowak RM, eds. Cardiac arrest: the science and practice of resuscitation medicine. Baltimore: Williams & Wilkins, 1996: 270–85.