Refractory Vfib (RVF) is defined as ventricular fibrillation resistant to at least 3 defibrillation attempts, 3 mg of epinephrine, and 300 mg of amiodarone without ROSC after at least 10 minutes of CPR (1). RVF has also been described as a severe form of electrical storm in which rapidly clustering episodes of Vfib recur or persist after multiple defibrillation attempts (2). Although epinephrine is known to increase ROSC, high levels of endogenous or exogenous catecholamines may have potentially harmful effects on the myocardium via β-1 receptor agonism (3). Notable deleterious effects include increased myocardial oxygen requirements, worsening ischemic injury, lowering of Vfib threshold, and a worsening of post-resuscitation myocardial function (2). It has been theorized that antagonism of β-receptors in the myocardial tissue during cardiac arrest may mitigate the potentially harmful effects of epinephrine, while preserving the beneficial alpha-receptor mediated actions (3).
Animal models experimenting with beta-antagonists during cardiac arrest is not novel. Propranolol was studied in several animal models in 1994 followed by esmolol in 1995. Overall, the animal literature has shown beta-antagonists to reduce myocardial oxygen requirements, decrease the number of defibrillation attempts, improve post-resuscitation myocardial function, diminish arrhythmia recurrence, and prolong survival (4). Esmolol is preferred over propranolol given its faster onset of action and very short half-life should therapy need to be discontinued if the patient exhibits cardiogenic shock (2).
Two case series have been published examining the effects of esmolol on human subjects with RVF. The first, published in 2014, reviewed 6 cases of patients receiving esmolol in the ED compared to 19 control patients also in RVF (see table below for individual patient details) (2). Overall, 4 of 6 patients achieved sustained ROSC after a 500 mcg/kg intravenous bolus of esmolol was administered followed by a continuous intravenous infusion of at most 100 mcg/kg/min. The other 2 patients achieved temporary ROSC after esmolol, but eventually re-arrested and expired. Comparing esmolol versus standard-of-care, patients who received esmolol were more likely to have temporary ROSC (67% versus 42%), sustained ROSC (67% versus 32%), survive to hospital discharge (50% versus 16%), and survive to discharge with a favorable neurologic outcome (50% versus 11%). The authors concluded that beta-blockers “should be considered in patients with RVF in the ED prior to cessation of resuscitative efforts” (2).
In late 2016, a group of investigators from Korea published a pre- and post-cohort study following implementation of esmolol for RVF in out-of-hospital cardiac arrest. Adult patients received an intravenous bolus dose of 500 mcg/kg of esmolol followed by a continuous intravenous infusion of up to 100 mcg/kg/min in patients without ROSC following 3 or more defibrillation attempts, 3 mg of epinephrine, and 300 mg of amiodarone. Patients in the esmolol (n= 16) and non-esmolol (n= 25) groups were well-matched at baseline; however, the details regarding the timing of administration of esmolol were not provided. The esmolol group demonstrated a higher rate of temporary ROSC, sustained ROSC, and survival to the intensive care unit.
In conclusion, esmolol is a β-1 selective antagonist that may mitigate potential negative effects of high levels of epinephrine such as increased myocardial oxygen requirements, lowering of the Vfib threshold, and worsening of post-resuscitation myocardial function. In several animal models, and now human subjects, esmolol has been shown to increase ROSC, improve post-resuscitation myocardial function, diminish arrhythmia recurrence, and most importantly increase the chance of survival to discharge with good neurological function. After failure of standard ACLS measures among patients with refractory Vfib (and potentially pulseless ventricular tachycardia), an intravenous bolus dose of 500 mcg/kg of esmolol can be considered, with or without a continuous infusion, to increase the likelihood of sustained ROSC and survival.
- Lee YH, et al. Refractory ventricular fibrillation treated with esmolol. Resuscitation. 2016;107:150-155.
- Driver BE, Debaty G, Plummer DW, Smith SW. Use of esmolol after failure of standard cardiopulmonary resuscitation to treat patients with refractory ventricular fibrillation. Resuscitation. 2014;85:1337-1341.
- BET 2: Usefulness of epinephrine in out-of-hospital cardiac arrest. Emergency Medicine Journal. 2016;33(5):367-368.
- Oliveira FC, Feitsoa-Filho GS, Ritt LEF. Use of beta-blockers for the treatment of cardiac arrest due to ventricular fibrillation/pulseless ventricular tachycardia: a systematic review. Resuscitation. 2012;83:674-683.
- McNally B et al. Out-of-hospital cardiac arrest surveillance --- Cardiac Arrest Registry to Enhance Survival (CARES), United States, October 1, 2005--December 31, 2010. MMWR Surveill Summ. 2011;60(8):1-19.
- Kudenchuk PJ et al. Amiodarone, lidocaine, or placebo in out-of-hospital cardiac arrest. New England J Med. 2016;374(18):1711-1722.
Scott Dietrich, PharmD (@PCC_PharmD)
Emergency Medicine Clinical Pharmacist
University of Colorado Health - North