The ambiguous role of epinephrine in ventricular fibrillation

Cardiac arrest affects more than 250,000 people per year in the USA. Ventricular Fibrillation (VF) is the rhythm observed in up to 40% of the cases, when help arrives. Current guidelines recommend initiation of immediate bystander cardiopulmonary resuscitation (CPR), electrical defibrillation and epinephrine (adrenaline) administration. Since the restoration of threshold levels of coronary perfusion pressure (CPP) has been found to be the only independent determinant of return of spontaneous circulation (ROSC), the use of a vasopressor agent has been considered indispensable for successful CPR. Epinephrine holds a predominant role as the drug of choice for more than 100 years. However, recent studies have shown that eventhough the use of epinephrine increases the possibility of ROSC, it does not result in higher hospital discharge rates when compared to placebo in VF cardiac arrest setting. Epinephrine is an endogenous catecholamine which possesses both alpha and beta adrenergic actions. Its beneficial effects are assumed to be primarily due to its a2 action leading to peripheral arteriolar vasoconstriction, increasing thus the aortic pressure and consequently myocardial and cerebral perfusion. On the other hand, epinephrine's a1, β1 and β2 actions have serious arrhythmogenic effects originated from the resulting increase of oxygen demands in an already fasting myocardium, the increase of myocardial lactate levels and the decrease of myocardial ATP reserves, increasing thus the severity of post-resuscitation myocardial dysfunction. Furthermore, epinephrine is very sensitive to the effects of acidosis, which is the case in VF setting. Lastly, in cardiac arrest victims, endogenous catecholamine levels have been found to be in extremely elevated concentrations. Therefore, it is possible that almost all the catecholamine receptors have been already been stimulated and an epinephrine administration will not have the expected impact.The aforementioned data have oriented CPR research to the quest for alternative pharmacologic agents which will either replace epinephrine or attenuate its undesired effects.