The Dose of Epinephrine during Cardiopulmonary Resuscitation in Humans: What Should it Be?

Abstract

The objective of vasopressor therapy during closed-chest cardiopulmonary resuscitation (CPR) is to augment coronary perfusion pressure so that spontaneous circulation can be reestablished. Epinephrine, an endogenous catecholamine with both alpha- and beta-adrenergic activity, is the vasopressor of choice for use during CPR. Epinephrine's potent alpha,- and alpha2-adrenergic effects improve cerebral and myocardial blood flow by preventing arterial collapse and by increasing peripheral vasoconstriction. The optimal dose of epinephrine in humans during closed-chest CPR is unknown. Studies suggest that the dose of epinephrine currently recommended during CPR may be five to ten times lower than the dose required to produce the beneficial pharmacologic effects observed in animal models of closed-chest CPR. Data from patients with prehospital cardiac arrest indicate that a 5-mg dose of epinephrine may be required to increase diastolic blood pressure above 30 mm Hg. Until additional data are available, our clinical experience suggests that all patients should receive at least one 1-mg dose of epinephrine. If the patient fails to respond, the administration of 3–5 mg of epinephrine every five minutes or the use of continuous infusions of epinephrine (0.2–0.6 mg/min) may be indicated. The results of ongoing clinical trials comparing conventional epinephrine regimens with high-dose regimens will provide valuable information and will assist clinicians in establishing an optimal dosage range for epinephrine during CPR in humans. What is the best vasopressor regimen to use during CPR in humans? Although dopamine, methoxamine, phenylephrine, or norepinephrine have been used during resuscitation, epinephrine is still the vasopressor agent of choice.5 The optimal dose of epinephrine during CPR in humans remains to be determined. It is likely that a range of dosages will be needed to account for differences in vascular reactivity between prehospital cardiac arrest victims with prolonged down-times and inpatients with witnessed cardiac arrest and immediate ACLS. The use of high-dose epinephrine is not without risks. Epinephrine may precipitate myocardial ischemia, tachyarrhythmias, hypertensive crisis, pulmonary edema, digitalis toxicity, and cardiac arrest.5 Antidepressants, anesthetics, sympathomimetics, bretylium, and phosphodiesterase inhibitors potentiate epinephrine's arrhythmogenic effect.50 Until definitive data are available, our clinical experience suggests that all patients should receive at least one dose of epinephrine 1 mg. If the patient fails to respond, the administration of epinephrine 3–5 mg every five minutes or the use of continuous infusions of epinephrine (0.2–0.6 mg/min) may be indicated. Whenever possible the administration of epinephrine, especially at a higher dose or by continuous infusion, should be accomplished through an indwelling central venous catheter.