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

doi:10.1016/S0140-6736(97)80087-6

The Lancet

Volume 349, Issue 9051, 22 February 1997, Pages 535-537

https://doi.org/10.1016/S0140-6736(97)80087-6 Get rights and content

Summary

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 doubleblind 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%) epinephrinetreated 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 treated 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.

Introduction

Intravenous epinephrine is currently the recommended drug of choice for the treatment of ventricular fibrillation when direct-current shock therapy is ineffective.1, 2 Because of the poor clinical outcome in patients in cardiac arrest who require epinephrine treatment, other pharmacological therapies have been examined. Interest in the possible value of vasopressin treatment during cardiopulmonary resuscitation arose after the observation that there is a large release of vasopressin immediately after a cardiac arrest.³ We have previously reported that the higher the endogenous vasopressin concentration, the greater the chances of restoration of spontaneous circulation.⁴ In cardiac arrest of long duration associated with severe hypoxia and acidosis, vasopressin seems to be more effective than epinephrine in restoration of spontaneous cardiovascular function.⁵ These findings are consistent with data from studies in animals, demonstrating greater efficacy of vasopressin than of optimum doses of epinephrine in restoration of vital-organ blood flow.6, 7 In a randomised, double-blind study, we have directly compared vasopressin (40 U) with epinephrine (1 mg) as the initial intravenous drug therapy for treatment of out-of-hospital ventricular fibrillation.

Section snippets

Methods

The study was approved by the Institutional Review Board of Ulm University. Waiver of informed consent was accepted under the requirements of German law. Patients were prospectively enrolled in the study if they were treated for out-of-hospital cardiac arrest by the Emergency Rescue Team of Ulm University and if they required epinephrine, according to standard treatment protocols, for advanced cardiac life support according to the guidelines of the European Resuscitation Council and the

Results

40 consecutive patients (29 men, 11 women) with a mean age of 65 (SE 4) years and out-of-hospital ventricular-fibrillation cardiac arrest resistant to direct-current shocks were enrolled into the investigation during an 18-month period (figure). Table 1 shows the demographic characteristics of the patients and response times of the emergency medical services system. Eight patients in the epinephrine group and seven in the vasopressin group had a history of myocardial infarction. Seven other

Discussion

Consistent with previous studies in animals and in patients with refractory cardiac arrest, in this study, among patients with out-of-hospital ventricular fibrillation resistant to direct-current shocks, a significantly higher proportion of those treated with vasopressin than those given epinephrine as the initial vasopressor during cardiopulmonary resuscitation and advanced cardiac life support survived for 24 h.

The results of this preliminary study are encouraging, especially because there is

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Cited by (385)

Epinephrine in Out-of-Hospital Cardiac Arrest: A Network Meta-analysis and Subgroup Analyses of Shockable and Nonshockable Rhythms
2023, Chest
Epinephrine is the most commonly used drug in out-of-hospital cardiac arrest (OHCA) resuscitation, but evidence supporting its efficacy is mixed.
What are the comparative efficacy and safety of standard dose epinephrine, high-dose epinephrine, epinephrine plus vasopressin, and placebo or no treatment in improving outcomes after OHCA?
In this systematic review and network meta-analysis of randomized controlled trials, we searched six databases from inception through June 2022 for randomized controlled trials evaluating epinephrine use during OHCA resuscitation. We performed frequentist random-effects network meta-analysis and present ORs and 95% CIs. We used the the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate the certainty of evidence. Outcomes included return of spontaneous circulation (ROSC), survival to hospital admission, survival to discharge, and survival with good functional outcome.
We included 18 trials (21,594 patients). Compared with placebo or no treatment, high-dose epinephrine (OR, 4.27; 95% CI, 3.68-4.97), standard-dose epinephrine (OR, 3.69; 95% CI, 3.32-4.10), and epinephrine plus vasopressin (OR, 3.54; 95% CI, 2.94-4.26) all increased ROSC. High-dose epinephrine (OR, 3.53; 95% CI, 2.97-4.20), standard-dose epinephrine (OR, 3.00; 95% CI, 2.66-3.38), and epinephrine plus vasopressin (OR, 2.79; 95% CI, 2.27-3.44) all increased survival to hospital admission as compared with placebo or no treatment. However, none of these agents may increase survival to discharge or survival with good functional outcome as compared with placebo or no treatment. Compared with placebo or no treatment, standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm (OR, 2.10; 95% CI, 1.21-3.63), but not in those with shockable rhythm (OR, 0.85; 95% CI, 0.39-1.85).
Use of standard-dose epinephrine, high-dose epinephrine, and epinephrine plus vasopressin increases ROSC and survival to hospital admission, but may not improve survival to discharge or functional outcome. Standard-dose epinephrine improved survival to discharge among patients with nonshockable rhythm, but not those with shockable rhythm.
Center for Open Science: https://osf.io/arxwq
Meta-Analysis of Efficacy of Vasopressin During Cardiopulmonary Resuscitation
2022, American Journal of Cardiology
Randomized controlled trials evaluating the efficacy of vasopressin versus standard of care during cardiopulmonary resuscitation (CPR) have yielded conflicting results. An electronic search of MEDLINE, Cochrane, and Embase databases was conducted through February 2022 for randomized controlled trials that evaluated the outcomes of vasopressin versus standard of care during CPR among patients with cardiac arrest. The primary outcome was the likelihood of spontaneous circulation (ROSC) return. Data were pooled using the random-effects model. The final analysis included 11 trials with 6,609 patients. The weighted mean age was 65.5 years, and 68.2% were men. There was no significant difference between the vasopressin and control groups in the likelihood of ROSC (33.1% vs 31.9%, odds ratio [OR] 1.23, 95% confidence interval [CI] 0.98 to 1.55). Subgroup analyses suggested that the use of vasopressin versus control increased the likelihood of ROSC when used in combination with steroids (p_interaction = 0.01) and in cases of in-hospital cardiac arrest (p_interaction = 0.01). There was no significant difference between the vasopressin and control groups in the likelihood of favorable neurological outcome (OR 1.14, 95% CI 0.75 to 1.71), in-hospital mortality (OR 0.89, 95% CI 0.60 to 1.31), or ventricular arrhythmias (OR 0.93, 95% CI 0.44 to 1.97). In conclusion, compared with the standard of care, the use of vasopressin during CPR did not increase the likelihood of ROSC among patients with cardiac arrest. There was no difference between the vasopressin and control groups in the likelihood of the favorable neurological outcome, in-hospital mortality, or ventricular arrhythmias.
Influence of the prehospital administered dosage of epinephrine on the plasma levels of catecholamines in patients with out-of-hospital cardiac arrest
2021, Heliyon
This study evaluated whether the prehospital administered dosage of epinephrine (Ep) influences the plasma levels of catecholamines in patients with out-of-hospital cardiac arrest (OHCA).
This was a prospective, observational clinical study. Patients with OHCA transferred to our hospital between July 2014 and July 2017 were analyzed. The plasma levels of catecholamines were measured using blood samples obtained immediately upon arrival at the hospital and before the administration of Ep. Patients were divided into three groups based on the prehospital administered dosage of Ep: no prehospital administration (group Z); 1 mg of Ep (group O); and 2 mg of Ep (group T). The levels of catecholamines, as well as the conditions of resuscitation prior to and after arrival at the hospital were compared between the three groups.
We analyzed 145 patients with OHCA (96, 38, and 11 patients in groups Z, O, and T, respectively). Group T exhibited the highest plasma levels of Ep with a statistically significant difference, however, there were no significant differences in the plasma levels of norepinephrine (Nep), dopamine (DOA) and vasopressin (ADH) among the three groups.
The prehospital administered dosage of Ep influences the plasma levels of Ep; however, it does not contribute to the plasma levels of Nep, DOA and ADH in patients with OHCA.
Analysis of the 2019 American Heart Association (AHA) Focused Update on Advanced Cardiovascular Life Support
2021, Journal of Cardiothoracic and Vascular Anesthesia
Citation Excerpt :
There were no studies that compared vasopressin with placebo. A 2019 meta-analysis evaluating this question identified 3 RCTs that compared initial vasopressin versus initial epinephrine after cardiac arrest.10-12 There was no statistically significant difference between the groups on any outcomes, including survival to hospital discharge and survival to hospital discharge with a favorable neurologic outcome.
Updates in Cardiac Arrest Resuscitation
2020, Emergency Medicine Clinics of North America
Epinephrine for out of hospital cardiac arrest: A systematic review and meta-analysis of randomized controlled trials
2019, Resuscitation
Citation Excerpt :
Six studies compared patients receiving SDE versus HDE randomly,9–14 whereas six studies compared SDE versus Epi + Vaso.15–20 Five studies considered more than one primary outcome.10,13–15,17. According to the FI, only three studies had an FI > 0.8,10,14
To evaluate the effectiveness of epinephrine, compared with control treatments, on survival at admission, ROSC, survival to discharge, and a favorable neurologic outcome in adult patients during OHCA.
MEDLINE and PubMed from inception to August 2018.
Randomized controlled trials (RCTs) on adult patients after out-of-hospital cardiac arrest (OHCA) treated with epinephrine versus controls.
Independent, double-data extraction; risk of bias assessment with Cochrane Collaboration’s criteria.
15 RCTs representing 20,716 OHCA adult patients. When epinephrine was compared with a placebo/no drugs, survival to hospital discharge (RR: 1.34, 95% CI: 1.08–1.67), ROSC (RR: 2.03, 95% CI: 1.18–3.51) and survival to hospital admission (RR: 2.04, 95% CI: 1.22–3.43) were increased, but favorable neurologic outcome was not significantly different (RR: 1.22, 95% CI: 0.99–1.51). Patients treated with the high-dose epinephrine (HDE) had a higher rate of ROSC (standard-dose epinephrine (SDE) versus HDE, RR: 0.85, 95% CI: 0.74–0.97, p = 0.01) and increased survival to hospital admission (SDE versus HDE, RR: 0.86, 95% CI: 0.75–0.99, p = 0.04) compared with those treated with SDE. No considered treatments improved the neurological outcome after OHCA.
In OHCA, standard or high doses of epinephrine should be used because they improved survival to hospital discharge. There was also a clear advantage of using epinephrine over a placebo or no drugs in the considered outcomes.

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

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Methods

Results

Discussion

Ann Emerg Med

Resuscitation

Chest

Adult advanced cardiac life support: the European resuscitation guidelines 1992

BMJ

Guidelines for cardiopulmonary resuscitation and emergency cardiac care, III: adult advanced cardiac life support

JAMA

Stress hormone response during and after cardiopulmonary resuscitation

Anesthesiology

Release of endogenous vasopressors during and after cardiopulmonary resuscitation

Br Heart J

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