Does Vasopressin Improve Survival?

The American Heart Association (AHA) has estimated that the probability of survival diminishes 7%-10% for each minute an individual is in a state of ventricular fibrillation (VF) sudden cardiac arrest (SCA).1 If ventricular fibrillation is not reversed, the heart progresses into a state of asystole.1 Survival from asystolic cardiac arrest is estimated to be approximately 2%.2 Historically, survival rates from SCA have been reported to range between 1% and 30%, depending on the circumstances of the event.3,4 Put into context, SCA claims approximately 250,000 lives per year in the United States.5 The poor outcome of SCA patients drives the continuous research, development and implementation of new therapeutic approaches in emergency cardiac care.

     In 2000, the AHA Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care incorporated the addition of vasopressin in conjunction with current acceptable therapeutic interventions.6 This systematic review and meta-analysis utilized an evidence-based medicine (EBM) methodology to evaluate the existing clinical evidence toward assessing whether vasopressin improved survival in the setting of adult SCA.

Background

     Victims of SCA present with two major categories of electrical heart activity observed on electrocardiogram: shockable and nonshockable rhythms. The shockable rhythm category includes ventricular fibrillation and pulseless ventricular tachycardia. These are classified as shockable because the definitive treatment is direct-current shock (defibrillation). Pharmacological interventions are initiated if defibrillation is not initially successful. The nonshockable rhythm category includes asystole and pulseless electrical activity (PEA). These rhythms are not shockable and are treated with pharmacological or other invasive interventions.

     The AHA has established treatment algorithms for each rhythm disturbance.6 The Comprehensive Emergency Care Algorithm outlines the treatment guidelines for patients in sudden cardiac arrest. There are specific treatment guidelines for subclassifications of rhythm disturbances of sudden cardiac arrest (pulseless ventricular fibrillation/ventricular tachycardia, asystole and PEA). Therapeutic interventions are classified based on the level of evidence and critical appraisal. The current scheme for the classification of therapeutic interventions includes Class I (excellent intervention), Class IIa (good to very good intervention), Class IIb (fair to good intervention), Class Indeterminate (preliminary research stage) and Class III (an unacceptable intervention).

     Prior to the publication of the AHA's Guidelines 2000, the first-line pharmacological intervention for cardiac arrest patients was epinephrine. With publication of the Guidelines 2000, the addition of vasopressin was incorporated into the ventricular fibrillation/ventricular tachycardia treatment algorithm (Class IIb) only. Insufficient evidence establishing the effectiveness of vasopressin versus epinephrine in asystolic and PEA categories of cardiac arrest resulted in the decision to exclude the drug in those treatment algorithms (Class Indeterminate). Additionally, epinephrine was reclassified as Class Indeterminate in all cardiac arrest treatment algorithms due to insufficient clinical data; however, it still remains incorporated in the treatment protocols.

     Epinephrine, a naturally occurring catecholamine, is a á1, â1, and â2 adrenergic agonist.7 In cardiac arrest, the á1 agonist action of epinephrine causes peripheral vasoconstriction,7 which is desirable during cardiopulmonary resuscitation because it improves cerebral perfusion, coronary perfusion and VF median frequency (increases response to defibrillation).7-11 The â1 effects include increased heart rate (chronotropic), contractility (inotropic) and conduction (dromotropic).7 The consequences of â1 stimulation include increased myocardial workload and reduced endocardial perfusion with a net increasing oxygen demand.7,10 The standard dosage of epinephrine is 1 mg intravenous push (IVP) every 3-5 minutes for patients in cardiac arrest.10,12 Epinephrine is conveniently packaged in a prefilled syringe of 1 mg per 10 ml normal saline, at an average price of $2.59.