Epinephrine in Resuscitation: Curse or Cure?

Robert R Attaran; Gordon A Ewy

Future Cardiol. 2010;6(4):473-482.

Epinephrine Dosing

In animal studies, higher doses of epinephrine have been found to cause myocardial necrosis^[48] and to be harmful in resuscitation.^[49,50] Several human studies have evaluated higher doses of epinephrine in human cardiac arrest. Among children with in-hospital cardiac arrest, once standard-dose epinephrine had failed, rescue high doses of epinephrine did not alter ROSC or survival compared with a standard dose.^[51]

Woodhouse et al. evaluated 194 patients with cardiac arrest.^[52] A total of 94 patients were randomized to receive two ampoules of 10 mg intravenous epinephrine 5–10 min apart versus 100 patients who received placebo. Both groups could subsequently be administered 1-mg doses of epinephrine, as per American Heart Association guidelines. In addition, 145 patients who met the inclusion criteria were not randomized, as the supervising medical staff chose to administer open-label 1 mg epinephrine ampoules rather than risk using placebo. Data from this group was retrospectively included in the analysis (as a registry). There was no significant difference in the rate of survival or hospital discharge between initial high-dose epinephrine versus placebo. The authors also found no difference in survival or hospital discharge in the open-label standard epinephrine (registry) group compared with the early high-dose epinephrine and early placebo groups. Despite the several limitations of this study, high-dose epinephrine is not recommended.

1 2 3 4 5 6 7 8 9 10 11 12

Next Section

Cite this: Epinephrine in Resuscitation: Curse or Cure? - Medscape - Jul 01, 2010.

Sidebar

Executive Summary

Introduction

Epinephrine administration has been advocated in resuscitation for decades and forms a key component of published guidelines. Its usage is based chiefly on animal studies, and human trial evidence is scant.

Pharmacologic & physiologic considerations: the importance of coronary perfusion pressure

There are subtypes of both the α- and β-adrenergic receptors, and that epinephrine's effects are mediated through α ₁ -, α ₂ -, β ₁ - and β ₂ -receptors.
The key to successful resuscitation is to achieve a high aortic diastolic pressure and, by extension, coronary perfusion pressure.
High coronary perfusion pressures have been associated with improved return of spontaneous circulation (ROSC) in human and animal studies and with improved survival in animal studies.
Epinephrine can also have adverse effects including increased myocardial oxygen consumption and necrosis, postresuscitation myocardial dysfunction and ventricular arrhythmias.

Epinephrine dosing

Higher-dose epinephrine has been found to be harmful in animal studies.
Limited human trial data show no benefit to higher-dose epinephrine over standard dosing.

Human studies of epinephrine in cardiac arrest

To date, no randomized controlled human trial has specifically evaluated early epinephrine administration in cardiac arrest.
One recent randomized controlled trial (RCT) from Norway evaluated early administration of epinephrine and other intravenous drugs (atropine and amiodarone) in out-of-hospital cardiac arrest (OHCA). The group treated with early intravenous drugs had higher ROSC and survival to hospital admission, but there was no difference in survival to discharge, survival with good neurological function or longer-term survival. This RCT did not find epinephrine use to be an independent predictor of poor outcome.

Intraosseous administration of epinephrine

Animal studies support early administration of vasopressors for improving neurologically intact survival.
Vasopressor administration times in animal studies are often less than 10 min.
By contrast, in human studies, the first drugs are administered at 10–25 min (mean: 17.7 min) post-emergency medical services dispatch. This can explain the lack of observed benefit of epinephrine usage in human OHCA.
One way to administer epinephrine quicker is with intraosseus access.

Deleterious effects of multiple-dose epinephrine

Epinephrine is not always the ideal vasopressor and this may be attributable to its β-adrenergic effects.
Epinephrine usage may result in increased recurrent VF and in electrical storm, β-blockade is the preferred treatment.
Future human RCTs should evaluate epinephrine combined with β-blockers and pure α-adrenergic drugs.
Epinephrine usage is so engrained in the current guidelines that it would take compelling evidence to remove it, evidence that to this day does not exist.

Quality of resuscitation is critically important

The message regarding optimal care in cardiac arrest, in particular OHCA, should not be lost in the debate over the use of epinephrine. It is the quality of the basic and advanced resuscitation efforts that determines survival.
During early cardiac arrest, interventions that have been shown to improve survival must be emphasized: early and continuous chest compressions, early defibrillation and delaying endotracheal intubation.
Interruptions to chest compressions to obtain intravenous access may be counterproductive. Intraosseus administration of epinephrine can minimize the interruption and allow for quicker drug delivery.
Cardiocerebral resuscitation, a system that prohibits early endotracheal intubation, advocates 200 chest compressions before and immediately after a single shock and advocates the early administration of epinephrine, significantly improves survival of patients with OHCA who have a witnessed arrest and a shockable rhythm on arrival of the paramedics.

Conclusion

Epinephrine can be either a curse or a cure in cardiac arrest.
Its value depends on the dosage given, the timing of administration, and the initiating factor of the cardiac arrest.
Epinephrine can be a curse in excessive doses or if used too late in resuscitation efforts, resulting in ROSC without improved (and neurologically intact) survival.
Despite the demonstrated benefit of epinephrine in animal studies, human trials have failed to show a benefit. The two major explanations for this disparity are: epinephrine in animal trials is given approximately 10 min sooner; and the initiating factor of the VF arrest in animal studies is often different.
Nevertheless, earlier administration of epinephrine (e.g., via the intraosseus route) is not the cure by itself. Its usage should be integrated into a series of essential steps including cardiocerebral resuscitation and postresuscitation care.

Comments

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.