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.

Spectral analysis of ventricular fibrillation and closed-chest cardiopulmonary resuscitation.

This study was designed to assess the interference by closed-chest cardiopulmonary resuscitation (CPR) on the ventricular fibrillation (VF) ECG signal in a porcine model of cardiac arrest and to elucidate which variable of VF spectral analysis reflects best myocardial blood flow and resuscitation success during CPR. Fourteen domestic pigs were allocated to receive either 0.4 U/kg vasopressin (n = 7) or 10 ml saline (n = 7) after 4 min of VF and 3 min of CPR. Using radiolabeled microspheres, myocardial blood flow was determined during CPR before, and 90 s and 5 min after, drug administration. Using spectral analysis of VF, the median frequency, dominant frequency, edge frequency and amplitude of VF were determined simultaneously and before the first defibrillation attempt. Using filters in order to specify frequency ranges, stepwise elimination of mechanical artifacts resulting from CPR revealed that at a frequency bandpass of 4.3-35 Hz, median fibrillation frequency has a sensitivity, specificity, positive and negative predictive value of 100% to differentiate between resuscitated and non-resuscitated animals. The best correlation between myocardial blood flow and fibrillation frequency was found at a median frequency range of 4.3-35 Hz. We conclude that spectral analysis of VF can provide reliable information relating to successful resuscitation. In this model after elimination of oscillations due to mechanical CPR, median fibrillation frequency best reflects the probability of resuscitation success.

Effects of graded doses of vasopressin on median fibrillation frequency in a porcine model of cardiopulmonary resuscitation: results of a prospective, randomized, controlled trial.

OBJECTIVE: To assess the effects of graded doses of vasopressin vs. saline on median fibrillation frequency and defibrillation success in a porcine model of cardiopulmonary resuscitation. DESIGN: Prospective, randomized, controlled trial. SETTING: Animal laboratory in a university medical center. SUBJECTS: Twenty-eight domestic pigs (body weight between 26 and 31 kg), aged 12 to 14 wks. INTERVENTIONS AND MAIN RESULTS: After 4 mins of ventricular fibrillation and 3 mins of closed-chest cardiopulmonary resuscitation, the animals were allocated to receive either 0.2 U/kg of vasopressin (n = 7), 0.4 U/kg of vasopressin (n = 7), 0.8 U/kg of vasopressin (n = 7), or 10 mL of saline (n = 7, control group). Using radiolabeled microspheres, myocardial blood flow rates during cardiopulmonary resuscitation-before drug administration and 90 secs and 5 mins after drug administration-were as follows in the four groups (mean +/- SEM): 18.8 +/- 0.9, 17.2 +/- 1.1, and 14.6 +/- 1.4 mL/min/100 g in the control group; 17.8 +/- 2.2, 49.6 +/- 6.3 (p < .01 vs. control group), and 29.4 +/- 3.1 mL/min/100 g (p < .05 vs. control group) in the group receiving 0.2 U/kg of vasopressin; 17.1 +/- 1.0, 52.4 +/- 7.5 (p < .01 vs. control group), and 52.2 +/- 5.8 mL/min/100 g (p < .001 vs. control group) in the group receiving 0.4 U/kg of vasopressin; and 18.1 +/- 1.6, 94.9 +/- 9.2 (p < .001 vs. control group), and 57.2 +/- 6.3 mL/min/100 g (p < .001 vs. control group) in the group receiving 0.8 U/kg of vasopressin. Using spectral analysis, median frequencies of ventricular fibrillation-before drug administration and 90 secs and 5 mins after drug administration-were as follows in the four groups: 9.6 +/- 0.4, 8.5 +/- 0.8, and 7.2 +/- 1.0 Hz in the control group; 9.7 +/- 0.5, 12.9 +/- 0.8 (p < .01 vs. control group), and 12.7 +/- 0.8 Hz (p < .001 vs. control group) in the group receiving 0.2 U/kg of vasopressin; 10.3 +/- 0.2, 12.7 +/- 0.9 (p < .01 vs. control group), and 12.8 +/- 0.7 Hz (p < .001 vs. control group) in the group receiving 0.4 U/kg of vasopressin; and 10.0 +/- 0.9, 14.1 +/- 0.9 (p < .001 vs. control group), and 12.5 +/- 0.9 Hz (p < .001 vs. control group) in the group receiving 0.8 U/kg of vasopressin at the same points in time. Median frequency before the first defibrillation attempt was 12.3 +/- 0.4 Hz in the resuscitated animals (n = 19) and 8.2 +/- 1.2 Hz in the nonresuscitated animals (n = 9) (p < .001). CONCLUSIONS: This study contributes to the characterization of the effect of increasing global myocardial blood flow on median fibrillation frequency after administration of graded doses of vasopressin in a porcine model of ventricular fibrillation. Interventions such as vasopressor treatment that increase fibrillation frequency improve the chance of successful defibrillation.

Vasopressin administration in refractory cardiac arrest.

BACKGROUND: Successful outcomes after cardiopulmonary resuscitation remain disappointingly infrequent, in animal studies, administration of exogenous vasopressin during closed- and open-chest cardiopulmonary resuscitation has recently been shown to be more effective than optimal doses of epinephrine in improving vital organ blood flow. OBJECTIVE: To describe the clinical effects and outcomes of administering vasopressin to patients in cardiac arrest refractory to current medical therapies. DESIGN: Case reports. SETTING: University hospital. PATIENTS: 8 adults with in-hospital cardiac arrest. INTERVENTIONS: After intravenous epinephrine (administered according to American Heart Association guidelines) and defibrillation efforts had failed, patients in cardiac arrest who were having cardiopulmonary resuscitation received 40 U of vasopressin intravenously and then defibrillation. MEASUREMENTS: Return of spontaneous circulation and hospital discharge rates. RESULTS: After administration of vasopressin, spontaneous circulation was promptly restored in all patients. Three patients were discharged from the hospital with intact neurologic function; the other five lived for between 30 minutes and 82 hours. CONCLUSION: In the presence of ventricular fibrillation with severe hypoxia and acidosis, vasopressin seems to be more potent and effective than adrenergic vasopressors for restoring spontaneous cardiovascular function. These results do not justify the widespread use of vasopressin for refractory cardiac arrest. However, on the basis of these cases, further studies comparing vasopressin with epinephrine are warranted in an effort to improve the currently dismal prognosis of patients after cardiac arrest.

Concentrations of prolactin and prostaglandins during and after cardiopulmonary resuscitation.

OBJECTIVES: To assess differences in plasma prolactin and prostaglandin concentrations in resuscitated and nonresuscitated patients during cardiopulmonary resuscitation (CPR), and to compare changes of prostaglandin and prolactin concentrations with hemodynamic variables in the immediate postresuscitation phase. DESIGN: Prospective, descriptive study. SETTING: Emergency medical service at a university hospital. PATIENTS: Twenty-nine patients ranging in age from 39 to 87 yrs with out-of-hospital cardiac arrest. INTERVENTIONS: Venous blood samples were taken during CPR and at 5, 15, 30, and 60 mins after restoration of spontaneous circulation in order to measure plasma concentrations of prolactin, prostaglandin F2 alpha, 15-keto-13,14-dihydro-prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, and thromboxane B2 by immunoassay. Heart rate and blood pressure were measured at 5, 15, 30, and 60 mins after restoration of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS: In 15 patients, restoration of spontaneous circulation was achieved; in the remaining 14 patients, successful resuscitation was not possible. During CPR, the mean plasma prolactin, prostaglandin F2 alpha, 15-keto-13,14-dihydro-prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, and thromboxane B2 concentrations were 95.9 +/- 13.6 micrograms/L, 357 +/- 61 ng/L, 228 +/- 28 ng/L, 277 +/- 66 ng/L, and 375 +/- 78 ng/L, respectively, in resuscitated patients, and 23.9 +/- 5.6 micrograms/L (p = .0001), 192 +/- 22 ng/L (p = .005), 202 +/- 31 ng/L (p = .528), 221 +/- 40 ng/L (p = .713), and 344 +/- 77 ng/L (p = .780), respectively, in nonresuscitated patients. At 60 mins after restoration of spontaneous circulation, the mean plasma prolactin, prostaglandin F2 alpha, 15-keto-13,14-dihydro-prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, and thromboxane B2 concentrations were 50.1 +/- 9.5 micrograms/L, 306 +/- 42 ng/L, 503 +/- 87 ng/L, 278 +/- 55 ng/L, and 355 +/- 30 ng/L, respectively. Mean values of systolic arterial blood pressure were 114 +/- 12 mm Hg at 30 mins and 123 +/- 18 mm Hg at 60 mins. No significant correlations were found between hemodynamic values and plasma concentrations of prolactin or prostaglandins. CONCLUSIONS: Prolactin and prostaglandin concentrations were increased during cardiac arrest and CPR. Successful initial resuscitation was associated with increased prolactin and prostaglandin F2 alpha concentrations during CPR. Decreased concentrations in non-resuscitated patients may have been a result of exhaustion of the neuroendocrine and eicosanoid systems, or may be due to differences in bioavailability at the site of blood sampling based upon differences in hemodynamics.

Angiotensin II augments reflex activity of the sympathetic nervous system during cardiopulmonary resuscitation in pigs.

BACKGROUND: During hypotensive states, angiotensin II augments reflex activity of the sympathetic nervous system. The purpose of the present study was to assess the effects of this vasoconstrictor on myocardial blood flow and plasma catecholamine concentrations during and after CPR. METHODS AND RESULTS: After 4 minutes of ventricular fibrillation and 3 minutes of open-chest CPR, 14 pigs (24 to 26 kg) were randomized into two groups receiving either saline (n = 7) or 0.05 mg/kg angiotensin II (n = 7). Arterial plasma catecholamine concentration was measured with high-pressure liquid chromatography. Organ blood flow was measured with radiolabeled microspheres. During CPR, after drug administration, left ventricular myocardial blood flow was significantly higher in the angiotensin II-treated group than in the control group. During CPR, median epinephrine concentrations before and 90 seconds and 5 minutes after drug administration were 63.0, 35.2, and 22.5 ng/mL, respectively, in the control group and 63.2, 139.8, and 154.2 ng/mL, respectively, in the angiotensin II group (P < .001 at 90 seconds and P < .01 at 5 minutes). At the same times, median norepinephrine concentrations were 52.6, 59.8, and 33.9 ng/mL, respectively, in the control group and 42.5, 98.7, and 111.3 ng/mL, respectively, in the angiotensin II group (P < .01 at 5 minutes). Restoration of spontaneous circulation was possible in all of the angiotensin II-treated pigs, whereas only 3 of the 7 saline-treated pigs could be resuscitated. At 5 minutes after successful resuscitation, epinephrine was 6.8 ng/mL in the control group and 16.1 ng/mL in the angiotensin II group (P < .05). CONCLUSIONS: During CPR, angiotensin II appears to increase coronary perfusion pressure and myocardial blood flow, not only by direct peripheral arteriolar vasoconstriction via angiotensin II receptors but also by inducing a massive catecholamine release with adrenergic peripheral vasoconstriction.

Vasopressin improves vital organ blood flow during closed-chest cardiopulmonary resuscitation in pigs.

BACKGROUND: This study was designed to compare the effects of epinephrine with those of vasopressin on vital organ blood flow during closed-chest cardiopulmonary resuscitation (CPR) in a pig model of ventricular fibrillation. METHODS AND RESULTS: Vasopressin was compared with epinephrine by randomly allocating 28 pigs to receive either 0.2 mg/kg epinephrine (n = 7), 0.2 U/kg vasopressin (low dose) (n = 7), 0.4 U/kg vasopressin (medium dose) (n = 7), or 0.8 U/kg vasopressin (high dose) (n = 7) after 4 minutes of ventricular fibrillation and 3 minutes of closed-chest CPR. Left ventricular myocardial blood flow, determined by use of radiolabeled microspheres during CPR, before and then 90 seconds and 5 minutes after drug administration was 17 +/- 2, 43 +/- 5, and 22 +/- 3 mL.min-1.100 g-1 (mean +/- SEM) in the epinephrine group; 18 +/- 2, 50 +/- 6, and 29 +/- 3 mL.min-1.100 g-1 in the low-dose vasopressin group; 17 +/- 3, 52 +/- 8, and 52 +/- 6 mL.min-1.100 g-1 in the medium-dose vasopressin group; and 18 +/- 2, 95 +/- 9, and 57 +/- 6 mL.min-1.100 g-1 in the high-dose vasopressin group (P < .001 at 90 seconds and 5 minutes between epinephrine and high-dose vasopressin, and P < .01 at 5 minutes between epinephrine and medium-dose vasopressin). At the same times, calculated coronary systolic perfusion pressures were 12 +/- 2, 36 +/- 5, and 18 +/- 2 mm Hg in the epinephrine group; 10 +/- 1, 39 +/- 6, and 26 +/- 5 mm Hg in the low-dose vasopressin group; 11 +/- 2, 49 +/- 6, and 38 +/- 5 mm Hg in the medium-dose vasopressin group; and 10 +/- 2, 70 +/- 5, and 47 +/- 6 mm Hg in the high-dose vasopressin group (P < .01 at 90 seconds and 5 minutes between epinephrine and high-dose vasopressin); and calculated coronary diastolic perfusion pressures were 15 +/- 2, 24 +/- 2, and 19 +/- 2 mm Hg in the epinephrine group; 13 +/- 1, 25 +/- 2, and 20 +/- 1 mm Hg in the low-dose vasopressin group; 13 +/- 2, 25 +/- 2, and 21 +/- 2 mm Hg in the medium-dose vasopressin group; and 13 +/- 2, 35 +/- 3, and 24 +/- 2 mm Hg in the high-dose vasopressin group (P < .05 at 90 seconds between epinephrine and high-dose vasopressin). Total cerebral blood flow was significantly higher after high-dose vasopressin than after epinephrine (P < .05 at 90 seconds and P < .01 at 5 minutes between groups). Five animals in the epinephrine, 5 in the low-dose vasopressin, 7 in the medium-dose vasopressin, and 6 in the high-dose vasopressin groups were successfully resuscitated and survived the 1-hour observation period. CONCLUSIONS: We conclude that administration of vasopressin leads to a significantly higher coronary perfusion pressure and myocardial blood flow than epinephrine during closed-chest CPR in a pig model of ventricular fibrillation.

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.

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:

Effect of angiotensin II on myocardial blood flow and acid-base status in a pig model of cardiopulmonary resuscitation.

The effect of angiotensin II on myocardial blood flow and acid-base status during cardiopulmonary resuscitation (CPR) was assessed. Fourteen pigs were allocated randomly to receive either 0.9% saline (n = 7) or 0.05 mg/kg angiotensin II (n = 7) after 4 min of ventricular fibrillation and 3 min of open-chest CPR. Total myocardial blood flow (measured with radiolabeled microspheres) before, 90 s, and 5 min following drug administration was 74 +/- 18, 62 +/- 12, and 54 +/- 11 mL.min-1 x 100g-1 (mean +/- SD) in the control, and 72 +/- 17, 125 +/- 25, and 74 +/- 20 mL.min-1 x 100 g-1 in the angiotensin II group (P < 0.001 at 90 s and P < 0.05 at 5 min). The PCO2 of coronary venous blood at 90 s after drug administration was 82 +/- 8 mm Hg in the control group as compared to 47 +/- 9 mm Hg in the angiotensin II group (P < 0.001). Only three of the seven control group animals could be resuscitated successfully, whereas all of the angiotensin II-treated pigs survived the 1-h observation period (P < 0.05), during which neither arterial hypertension nor bradycardia was observed. Angiotensin II was associated with an improvement of myocardial blood flow during CPR and short-term resuscitation success. The increase in myocardial perfusion is associated with a lower coronary venous PCO2 and a higher coronary venous pH. The authors conclude that angiotensin II administration facilitated cardiopulmonary resuscitation.