Karl H. Lindner

Randomised comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation

BACKGROUND Studies in animals have suggested that intravenous vasopressin is associated with better vital-organ perfusion and resuscitation rates than is epinephrine in the treatment of cardiac arrest. We did a randomised comparison of vasopressin with epinephrine in patients with ventricular fibrillation in out-of-hospital cardiac arrest. METHODS 40 patients in ventricular fibrillation resistant to electrical defibrillation were prospectively and randomly assigned epinephrine (1 mg intravenously; n = 20) or vasopressin (40 U intravenously; n = 20) as primary drug therapy for cardiac arrest. The endpoints of this double blind study were successful resuscitation (hospital admission), survival for 24 h, survival to hospital discharge and neurological outcome (Glasgow coma scale). Analyses were by intention to treat. FINDINGS Seven (35%) patients in the epinephrine group and 14 (70%) in the vasopressin group survived to hospital admission (p = 0.06). At 24 h, four (20%) epinephrine-treated patients and 12 (60%) vasopressin-treated patients were alive (p = 0.02). Three (15%) patients in the epinephrine group and eight (40%) in the vasopressin group survived to hospital discharge (p = 0.16). Neurological outcomes were similar (mean Glasgow coma score at hospital discharge 10.7 [SE 3.8] vs 11.7 [1.6], p = 0.78). INTERPRETATION In this preliminary study, a significantly larger proportion of patients created with vasopressin than of those treated with epinephrine were resuscitated successfully from out-of-hospital ventricular fibrillation and survived for 24 h. Based upon these findings, larger multicentre studies of vasopressin in the treatment of cardiac arrest are needed.

Vasopressin administration in refractory cardiac arrest

In studies done in pigs, the administration of exogenous vasopressin during closed- and open-chest cardiopulmonary resuscitation has been shown to be more effective than optimal doses of epinephrine in improving vital organ blood flow and increasing perfusion pressure [1, 2]. Interest in the potential value of vasopressin administration during cardiopulmonary resuscitation also stems from human studies showing high levels of circulating vasopressin in patients in cardiac arrest [3, 4]. Higher levels of endogenous vasopressin are associated with greater chances for survival, and higher endogenous levels of epinephrine and norepinephrine are associated with decreased chances for survival [4]. To date, no case reports or controlled studies have addressed the potential value of exogenous vasopressin for the treatment of patients having cardiac arrest. In light of the data from the animal studies, eight patients having refractory in-hospital cardiac arrest were treated with vasopressin after standard therapies, including intravenous administration of epinephrine, had failed. Methods In a final effort to resuscitate patients in whom standard American Heart Association Advanced Cardiac Life Support therapies after in-hospital cardiac arrest had failed, arginine vasopressin was administered centrally as an initial 40-U bolus. Each patient had received standard manual cardiopulmonary resuscitation with at least 1 mg of epinephrine and an attempt at direct-current shock before receiving vasopressin through either a femoral or jugular vein. Table 1 lists patient demographic characteristics, and Table 2 provides some details of therapy and outcome after cardiac arrest. One of eight patients (patient 2) had an unwitnessed arrest. Cardiopulmonary resuscitation was initiated less than 1 minute after arrest in the remaining patients; cardiopulmonary resuscitation and advanced cardiac life support were done on all patients for at least 12 minutes (mean SD, 21.6 11.8 minutes) before vasopressin was administered. Three patients were discharged from the hospital with good neurologic recovery. Table 1. Demographic Characteristics of Patients Having In-Hospital Cardiac Arrest Refractory to Epinephrine*. Table 2. Time Intervals and Outcome in Patients Having In-Hospital Cardiac Arrest Refractory to Epinephrine*. Case Highlights Patient 4 Four days after having a hemicolectomy, a 78-year-old woman developed pulmonary emboli and ventricular fibrillation. Defibrillation (200 J) led to asystole. The patient received cardiopulmonary resuscitation and epinephrine (1-mg, 3-mg, and 5-mg doses administered 3 minutes apart). After the 5-mg bolus, ventricular fibrillation evolved but was resistant to repeated direct-current shocks and to lidocaine (100 mg). Central administration of vasopressin (40 U) followed by direct-current shock (360 J) resulted in a supraventricular rhythm with a palpable carotid pulse. A systolic blood pressure of approximately 100 mm Hg was maintained with a norepinephrine infusion of 0.15 g/kg of body weight per minute. After uncomplicated embolectomy, the patient was transferred to the intensive care unit for 3 days and was discharged without neurologic deficit 4 weeks later. Patient 5 A 71-year-old woman developed ventricular fibrillation while her chest was being scrubbed before implantation of a permanent pacemaker. Closed-chest cardiac massage was initiated within seconds. After three successive direct-current shocks (200 J, 300 J, and 300 J) followed by epinephrine (1 mg) and another direct-current shock (300 J), the patient remained in ventricular fibrillation. Examination of arterial blood gases showed a pH of 7.33 and a Po 2 of 60 mm Hg before endotracheal intubation. Additional epinephrine (1 mg) and defibrillation efforts were unsuccessful. Vasopressin (40 U) was administered 50 minutes after the arrest, and spontaneous circulation returned immediately after a 300-J direct-current shock. Immediately before vasopressin administration, the patients arterial blood had a pH of 7.18 and a Po 2 of 543 mm Hg. The patient was treated with dopamine (10 g/kg per minute) intravenously. Forty-five minutes later, she again developed hypotension followed by ventricular fibrillation. Cardiopulmonary resuscitation was reinitiated, but direct-current shock (300 J), epinephrine (1 mg), and another direct-current shock (300 J) failed to revive her. Vasopressin (20 U) followed 30 seconds later by direct-current shock (300 J) was unsuccessful; more vasopressin (20 U) was administered 2 minutes after the first 20-U dose. Thirty seconds later, a direct-current shock (300 J) led to an immediate return of spontaneous circulation. The patients pulmonary capillary wedge pressure at this time was 25 mm Hg, and her pulmonary systolic pressure was 35 mm Hg. Twenty minutes after her second and final resuscitation effort, she became hypotensive and bradycardic and died secondary to pulseless electrical activity. Patient 6 Immediately after induction with a standard cardiac general anesthetic for placement of an implantable cardioverter-defibrillator, a 45-year-old man developed pulseless electrical activity. Standard closed-chest manual cardiopulmonary resuscitation was started immediately. The patient received fluids (500 mL of normal saline), atropine (1 mg intravenously), and epinephrine (1 mg intravenously). After 10 minutes and another 1-mg epinephrine dose, he developed ventricular fibrillation. Several efforts to defibrillate failed. Twenty minutes after cardiac arrest, the patient received vasopressin (40 U); after a single 360-J transthoracic direct-current shock, spontaneous circulation promptly returned. The patient remained hemodynamically stable for 30 minutes. Despite intravenous fluids, dopamine (10 g/kg per minute), and placement of an intra-aortic balloon pump, he again developed hypotension, followed by ventricular fibrillation. After an effort to resuscitate the patient with standard cardiopulmonary resuscitation, epinephrine (1 mg), and direct-current shock was unsuccessful, the patient was given vasopressin (40 U) and was successfully resuscitated with direct-current shock. An angiogram showed a large thrombus at the site of an angioplasty done 2 weeks earlier; the vessel was again dilated. Within 30 minutes, the patient developed polymorphous ventricular tachycardia and had another cardiac arrest. Standard manual cardiopulmonary resuscitation, intravenous vasopressin (40 U), and direct-current shock were not effective. The patient received active compression-decompression cardiopulmonary resuscitation and vasopressin (40 U). Systolic arterial pressure increased to more than 100 mm Hg; when active compression-decompression cardiopulmonary resuscitation was stopped, the patient spontaneously convertedwithout direct-current shockto sinus tachycardia. One hour later, ventricular fibrillation again developed. Resuscitation efforts were terminated. Patient 8 A 31-year-old man had several internal injuries after a car accident. He developed ventricular fibrillation on the way to the operating room for emergent repair of a ruptured aorta. Fibrillation persisted despite many direct-current shocks and the administration of epinephrine (2 1 mg repeated after 3 minutes). After 4 minutes of closed-chest cardiopulmonary resuscitation, examination of the arterial blood showed a pH of 7.16, a Pco 2 of 54 mm Hg, a Po 2 of 49 mm Hg (fraction of inspired oxygen, 1.0), a potassium level of 2.8 mmol/L, and a hemoglobin level of 9.1 g/L. Despite treatment with epinephrine, diastolic arterial pressures remained less than 15 mm Hg. Administration of vasopressin (40 U) increased the diastolic arterial pressure to 30 mm Hg, and a subsequent direct-current shock (360 J) restored a stable heart and blood pressure. After the operation, the patient was transferred to the intensive care unit. Discussion These cases show that in patients in cardiac arrest who are receiving closed-chest cardiopulmonary resuscitation and have not responded to the standard doses of epinephrine recommended by the American Heart Association, spontaneous circulation can be restored by intravenous administration (through the femoral or jugular vein) of 40 U of vasopressin. These results are consistent with recent data from animals showing that vasopressin has greater efficacy than epinephrine during cardiopulmonary resuscitation [1, 2]. Although the prognosis was poor in all cases and all conventional measures had failed, spontaneous circulation was restored in all eight patients after vasopressin administration. Three patients survived to hospital discharge with minimal or no neurologic deficit. In addition, when active compression-decompression cardiopulmonary resuscitation was combined with the use of vasopressin, one patient had spontaneous conversion to sinus rhythm without the use of direct-current shock. Although the optimal dose of vasopressin in humans is not known, 40 U was effective in all of our patients. In one patient, a dose of 20 U was not effective. In the eight patients studied, an initial dose of 1 mg of epinephrine was administered. In four of these eight patients, an escalating dose of epinephrine (from 1 mg to 3 mg to 5 mg) was used but was similarly ineffective. In humans having cardiac arrest, epinephrine therapy is used on the basis of case reports and animal studies [5, 6]. Recent clinical trials comparing low-dose with high-dose epinephrine show that the latter has no significant advantage [7, 8]. A more recent placebo-controlled trial showed that neither high- nor low-dose epinephrine had benefit compared with placebo [9]. In our patients, vasopressin may have been more effective because of several factors. Vasopressin exerts a greater vasoconstrictive effect under conditions of hypoxia and acidosis than does epinephrine, and the effects of vasopressin last longer [1, 2]. Vasopressin causes a greater increase in arterial tone than does epine

Stress Hormone Response during and after Cardiopulmonary Resuscitation

The purpose of this study was to assess whether plasma adrenocorticotropin, cortisol, vasopressin, and renin concentrations are higher in resuscitated than in nonresuscitated patients during cardiopulmonary resuscitation, and whether there are possible correlations between these hormones and blood pressure or heart rate in the immediate postresuscitation phase. Of 34 consecutive patients (36-85 yr of age) with out-of-hospital cardiac arrest, 20 could be successfully resuscitated and admitted to hospital, whereas in the remaining 14 patients restoration of spontaneous circulation could not be achieved. During cardiopulmonary resuscitation, median adrenocorticotropin, cortisol, vasopressin, and renin concentrations in the external jugular vein were 237 pg/ml, 32.6 micrograms/dl, 122 pg/ml, and 46.5 ng/l, respectively, in resuscitated patients, and 45 pg/ml (P = 0.018), 18.4 micrograms/dl (P = 0.481), 88 pg/ml (P = 0.049), and 11 ng/l (P = 0.017), respectively, in nonresuscitated patients. Median adrenocorticotropin, cortisol, vasopressin, and renin concentrations were 101 pg/ml, 34.6 micrograms/dl, 22 pg/ml, and 25 ng/l, respectively, 60 min after successful resuscitation. No significant correlations were found between hormone levels and blood pressure or heart rate, but there was a significant negative correlation between the interval from collapse to the start of cardiopulmonary resuscitation and plasma cortisol concentrations during cardiopulmonary resuscitation (Spearman rank correlation coefficient = -0.967, P less than 0.001), indicating an impaired cortisol release from the adrenal cortex. The lower hormone concentrations of the nonresuscitated patients measured during cardiopulmonary resuscitation might indicate an impairment in neuroendocrine response.

Repeated Administration of Vasopressin but Not Epinephrine Maintains Coronary Perfusion Pressure After Early and Late Administration During Prolonged Cardiopulmonary Resuscitation in Pigs

BACKGROUND It is unknown whether repeated dosages of vasopressin or epinephrine given early or late during basic life support cardiopulmonary resuscitation (CPR) may be able to increase coronary perfusion pressure above a threshold between 20 and 30 mm Hg that renders defibrillation successful. METHODS AND RESULTS After 4 minutes of cardiac arrest, followed by 3 minutes of basic life support CPR, 12 animals were randomly assigned to receive, every 5 minutes, either vasopressin (early vasopressin: 0.4, 0.4, and 0.8 U/kg, respectively; n=6) or epinephrine (early epinephrine: 45, 45, and 200 microg/kg, respectively; n=6). Another 12 animals were randomly allocated after 4 minutes of cardiac arrest, followed by 8 minutes of basic life support CPR, to receive, every 5 minutes, either vasopressin (late vasopressin: 0.4 and 0.8 U/kg, respectively; n=6), or epinephrine (late epinephrine: 45 and 200 microg/kg, respectively; n=6). Defibrillation was attempted after 22 minutes of cardiac arrest. Mean+/-SEM coronary perfusion pressure was significantly higher 90 seconds after early vasopressin compared with early epinephrine (50+/-4 versus 34+/-3 mm Hg, P<0.02; 42+/-5 versus 15+/-3 mm Hg, P<0.0008; and 37+/-5 versus 11+/-3 mm Hg, P<0. 002, respectively). Mean+/-SEM coronary perfusion pressure was significantly higher 90 seconds after late vasopressin compared with late epinephrine (40+/-3 versus 22+/-4 mm Hg, P<0.004, and 32+/-4 versus 15+/-4 mm Hg, P<0.01, respectively). All vasopressin animals survived 60 minutes, whereas no epinephrine pig had return of spontaneous circulation (P<0.05). CONCLUSIONS Repeated administration of vasopressin but only the first epinephrine dose given early and late during basic life support CPR maintained coronary perfusion pressure above the threshold that is needed for successful defibrillation.

Effects of active compression-decompression resuscitation on myocardial and cerebral blood flow in pigs.

BACKGROUND This study was designed to assess the effects of a modified cardiopulmonary resuscitation (CPR) technique that consists of both active compression and active decompression of the chest (ACD CPR) versus standard CPR (STD CPR) on myocardial and cerebral blood flow during ventricular fibrillation both before and after epinephrine administration. METHODS AND RESULTS During a 30-second period of ventricular fibrillation cardiac arrest, 14 pigs were randomized to receive either STD CPR (n = 7) or ACD CPR (n = 7). Both STD and ACD CPR were performed using an automated pneumatic piston device applied midsternum, designed to provide either active chest compression (1.5 to 2.0 in.) and decompression or only active compression of the chest at 80 compressions per minute and 50% duty cycle. Using radiolabeled microspheres, median total myocardial blood flow after 5 minutes of ventricular fibrillation was 14 (7 to 30, minimum to maximum) STD CPR versus 30 (9 to 46) mL.min-1 x 100 g-1 with ACD CPR (P < .05). Median cerebral blood flow was 15 (10 to 26) mL.min-1 x 100 g-1 with STD CPR and 30 (21 to 39) with ACD CPR (P < .01). When comparing STD with ACD CPR, aortic systolic (62 mm Hg [48 to 70] vs 80 [59 to 86]) and diastolic (22 [18 to 28] vs 28 [21 to 36]) pressures, calculated coronary systolic (30 [22 to 36] vs 49 [37 to 56]) and diastolic (18 [16 to 23] vs 26 [21 to 31]) perfusion pressures, end-tidal CO2 (1.4% [0.8 to 1.8] vs 2.1 (1.8 to 2.4]), cerebral O2 delivery (3.1 mL.min-1 x 100 g-1 [1.5 to 4.5] vs 5.3 [3.8 to 7.5]), and cerebral perfusion pressure (14 mm Hg [4 to 22] vs 26 [6 to 34]) were all significantly higher with ACD CPR: To compare these parameters before and after vasopressor therapy, a bolus of high-dose epinephrine (0.2 mg/kg) was given to all animals after 5 minutes of ventricular fibrillation. Organ blood flow and calculated perfusion pressures increased significantly in both the STD and ACD groups after epinephrine. The differences observed between STD and ACD CPR before epinephrine were diminished 90 seconds after epinephrine but were again statistically significant when assessed 5 minutes later, once the acute effects of epinephrine had decreased. No difference in short-term resuscitation success was found between the two groups. CONCLUSIONS We conclude that ACD CPR significantly increases myocardial and cerebral blood flow during cardiac arrest in the absence of vasopressor therapy compared with STD CPR:

Comparison of Standard Cardiopulmonary Resuscitation Versus the Combination of Active Compression-Decompression Cardiopulmonary Resuscitation and an Inspiratory Impedance Threshold Device for Out-of-Hospital Cardiac Arrest

Background—Active compression-decompression (ACD) CPR combined with an inspiratory impedance threshold device (ITD) improves vital organ blood flow during cardiac arrest. This study compared survival rates with ACD+ITD CPR versus standard manual CPR (S-CPR). Methods and Results—A prospective, controlled trial was performed in Mainz, Germany, in which a 2-tiered emergency response included early defibrillation. Patients with out-of-hospital arrest of presumed cardiac pathogenesis were sequentially randomized to ACD+ITD CPR or S-CPR by the advanced life support team after intubation. Rescuers learned which method of CPR to use at the start of each work shift. The primary end point was 1-hour survival after a witnessed arrest. With ACD+ITD CPR (n=103), return of spontaneous circulation and 1- and 24-hour survival rates were 55%, 51%, and 37% versus 37%, 32%, and 22% with S-CPR (n=107) (P =0.016, 0.006, and 0.033, respectively). One- and 24-hour survival rates in witnessed arrests were 55% and 41% with ACD+ITD CPR versus 33% and 23% in control subjects (P =0.011 and 0.019), respectively. One- and 24-hour survival rates in patients with a witnessed arrest in ventricular fibrillation were 68% and 58% after ACD+ITD CPR versus 27% and 23% after S-CPR (P =0.002 and 0.009), respectively. Patients randomized ≥10 minutes after the call for help to the ACD+ITD CPR had a 3 times higher 1-hour survival rate than control subjects (P =0.002). Hospital discharge rates were 18% after ACD+ITD CPR versus 13% in control subjects (P =0.41). In witnessed arrests, overall neurological function trended higher with ACD+ITD CPR versus control subjects (P =0.07). Conclusions—Compared with S-CPR, ACD+ITD CPR significantly improved short-term survival rates for patients with out-of-hospital cardiac arrest. Additional studies are needed to evaluate potential long-term benefits of ACD+ITD CPR.

Vasopressin improves vital organ blood flow after prolonged cardiac arrest with postcountershock pulseless electrical activity in pigs

OBJECTIVE Although a benefit of vasopressin when compared with epinephrine was shown during cardiopulmonary resuscitation (CPR) after a short duration of ventricular fibrillation cardiac arrest, the effect of vasopressin during prolonged cardiac arrest with pulseless electrical activity is currently unknown. DESIGN Prospective, randomized laboratory investigation using an established porcine model with instrumentation for measurement of hemodynamic variables, vital organ blood flow, blood gases, and return of spontaneous circulation. SETTING University hospital laboratory. SUBJECTS Eighteen domestic pigs. INTERVENTIONS After 15 mins of cardiac arrest and 3 mins of chest compressions, 18 animals were randomly treated with either 0.8 units/kg vasopressin (n = 9) or 200 microg/kg epinephrine (n = 9). MEASUREMENTS AND MAIN RESULTS Compared with epinephrine, vasopressin resulted, at both 90 secs and 5 mins after drug administration, in significantly higher (p < .05) median (25th-75th percentiles) left ventricular myocardial blood flow (120 [range, 96-193] vs. 54 [range, 11-92] and 56 [range, 41-80] vs. 21 [range, 11-40] mL/min/100 g, respectively) and total cerebral blood flow (85 [78-102] vs. 24 [18-41] and 50 [44-52] vs. 8 [5-23] mL/min/100 g, respectively). Spontaneous circulation was restored in eight of nine animals in the vasopressin group and in one of nine animals in the epinephrine group (p = .003). CONCLUSIONS Compared with a maximum dose of epinephrine, vasopressin significantly increased left ventricular myocardial and total cerebral blood flow during CPR and return of spontaneous circulation in a porcine model of prolonged cardiac arrest with postcountershock pulseless electrical activity.

Survival with full neurologic recovery and no cerebral pathology after prolonged cardiopulmonary resuscitation with vasopressin in pigs

OBJECTIVES We sought to determine the effects of vasopressin and saline placebo in comparison with epinephrine on neurologic recovery and possible cerebral pathology in an established porcine model of prolonged cardiopulmonary resuscitation (CPR). BACKGROUND It is unknown whether increased cerebral blood flow during CPR with vasopressin is beneficial with regard to neurologic recovery or detrimental owing to complications such as cerebral edema after return of spontaneous circulation. METHODS After 4 min of cardiac arrest, followed by 3 min of basic life support CPR, 17 animals were randomly assigned to receive every 5 min either vasopressin (0.4, 0.4 and 0.8 U/kg; n = 6), epinephrine (45, 45 and 200 microg/kg; n = 6) or saline placebo (n = 5). The mean value +/- SEM of aortic diastolic pressure was significantly (p < 0.05) higher 90 s after each of three vasopressin versus epinephrine versus saline placebo injections (60 +/- 3 vs. 45 +/- 3 vs. 29 +/- 2 mm Hg; 49 +/- 5 vs. 27 +/- 3 vs. 23 +/- 1 mm Hg; and 50 +/- 6 vs. 21 +/- 3 vs. 16 +/- 3 mm Hg, respectively). After 22 min of cardiac arrest, including 18 min of CPR, defibrillation was attempted to achieve return of spontaneous circulation. RESULTS All the pigs that received epinephrine and saline placebo died, whereas all pigs on vasopressin survived (p < 0.05). Neurologic evaluation 24 h after successful resuscitation revealed only an unsteady gait in all vasopressin-treated animals; after 96 h, magnetic resonance imaging revealed no cerebral pathology. CONCLUSIONS During prolonged CPR, repeated vasopressin administration, but not epinephrine or saline placebo, ensured long-term survival with full neurologic recovery and no cerebral pathology in this porcine CPR model.

Cerebral Oxygenation During Cardiopulmonary Resuscitation With Epinephrine and Vasopressin in Pigs

BACKGROUND AND PURPOSE Administration of vasopressin during cardiopulmonary resuscitation (CPR) improves vital organ blood flow compared with epinephrine, but the effect of vasopressin on cerebral oxygenation and cerebral venous hypercarbia during CPR has not previously been studied. METHODS Fourteen pigs were allocated to receive either epinephrine (0.2 mg/kg) or vasopressin (0.4 U/kg) after 4 minutes of ventricular fibrillation and 3 minutes of CPR. Cerebral blood flow was determined by radiolabeled microspheres, and arterial and cerebral venous blood gases were measured. RESULTS Cerebral blood flow, measured before and 90 seconds and 5 minutes after drug administration, was 9 (3; 12), 25 (19; 27), and 18 (10; 23) mL/min per 100 g (median and 25th and 75th percentiles, respectively) in the epinephrine group and 12 (5; 16), 51 (48; 70), and 53 (45; 63) mL/min per 100 g in the vasopressin group (P<.05 at 90 seconds, P<.01 at 5 minutes between groups). Five minutes after drug administration, cerebral venous Pco2 was 63 (59; 68) mm Hg in the epinephrine group and 47 (43; 55) mm Hg in the vasopressin group (P<.01); at the same time cerebral venous pH was 7.18 (7.17; 7.20) and 7.26 (7.22; 7.36) (P<.01) in the epinephrine and vasopressin groups, respectively. Cerebral oxygen extraction ratio, calculated before and 90 seconds and 5 minutes after drug administration, was 0.42 (0.32; 0.57), 0.47 (0.41; 0.57), and 0.56 (0.56; 0.64) in the epinephrine group and 0.43 (0.38; 0.45), 0.38 (0.25; 0.44), and 0.35 (0.33; 0.49) in the vasopressin group (P<.05 at 90 seconds and 5 minutes). CONCLUSIONS Compared with epinephrine, vasopressin not only increases cerebral blood flow but also improves cerebral oxygenation and decreases cerebral venous hypercarbia when administered during CPR in pigs.

Effect of vasopressin on hemodynamic variables, organ blood flow, and acid-base status in a pig model of cardiopulmonary resuscitation

Based upon the hypothesis that vasopressin (antidiuretic hormone) may increase vascular resistance during ventricular fibrillation, the effects of this potent vasoconstrictor were studied in a porcine model of ventricular fibrillation. Vasopressin therapy was compared to epinephrine by randomly allocating 14 pigs to receive either 0.045 mg/kg of epinephrine (n = 7) or 0.8 U/kg of vasopressin (n = 7) after 4 min of ventricular fibrillation and 3 min of open-chest cardiopulmonary resuscitation. During cardiopulmonary resuscitation, myocardial blood flow before and 90 s and 5 min after drug administration was 57 +/- 11, 84 +/- 11, and 59 +/- 9 mL.min-1 x 100 g-1 (mean +/- SEM) in the epinephrine group, and 61 +/- 5, 148 +/- 26, and 122 +/- 22 mL.min-1 x 100 g-1 in the vasopressin group (P < 0.05 at 90 s and 5 min). At the same times, mean cardiac index was not significantly different between the groups. After drug administration, coronary venous PCO2 was significantly higher and coronary venous pH was significantly lower in the epinephrine as compared to the vasopressin group. All pigs in both groups were resuscitated and survived the 2-h observation period. We conclude that vasopressin improves vital organ perfusion during ventricular fibrillation and cardiopulmonary resuscitation. Vasopressin seems to be at least as effective as epinephrine in this pig model of ventricular fibrillation.