Episode 21- Esmolol in refractory VF arrest

Hello and welcome back to Episode 21 of ER-Rx. In this episode, we review a recent study that was published in the American Journal of Emergency medicine. This study is entitled “Esmolol in the management of pre-hospital refractory ventricular fibrillation,” and this was a systematic review and meta-analysis.

Pre-hospital cardiac arrest is associated with high mortality rates, especially for patients with refractory ventricular fibrillation/ pulseless ventricular tachycardia (VF/ pVT). Although early defibrillation is the best care for patients in refractory VF/pVT, there exists a subgroup of patients who do not respond to this therapy. In an attempt to improve outcomes for these and other patients, we started doing some interesting things such as ECMO and giving beta-blockers like esmolol.

During prolonged resuscitation, sympathetic tone goes on overdrive due in part to all of that epinephrine that was given. Although epinephrine can increase coronary blood flow through activation of alpha-receptors, it may also increase myocardial oxygen consumption and the risk of myocardial ischemia by activating beta-receptors. So this is where esmolol comes in. Esmolol is thought to reduce the sympathetic overdrive we see in VF/ pVT by blocking beta receptors, but keeping the beneficial effects of alpha activation. Esmolol is very cardio selective for beta-1 receptors and has a very short half-life (9 min) and a very quick onset (90 seconds), which means it has a low risk of prolonged effects during and after resuscitation. Based off of animal models, esmolol administration improved resuscitation and survival, reduced the number of shocks required for successful defibrillation, and improved rates of ROSC. But to be clear, other animal studies found no benefit with esmolol. On the contrary, some showed worse myocardial performance- and that is the concern that we have with esmolol; its negative inotropic properties. The good news is that we have not seen an overall harmful effect of esmolol in animal experiments.

As a matter of fact, we have a small amount of data in humans (mostly case reports and case-series) that esmolol can help abort VF/pVT and increase the rates of ROSC. That is why the authors of this systematic review and meta-analysis set out to answer a few specific questions; in the pre-hospital setting, how does esmolol affect rates of survival to discharge, survival with a favorable neurological outcome, rates of sustained ROSC, and survival to hospital admission when compared to no esmolol in patients who were resuscitated from prehospital cardiac arrest.

After excluding a number of studies, only two were included in this meta-analysis. These studies by Driver, et al and Lee et al, are some of the most frequently cited studies that address this issue. Both studies enrolled patients with refractory VF/pVT who failed 3 defibrillation attempts, 3 mg of epinephrine, and 300 mg of amiodarone and who remained in arrest upon ER arrival. All patients received a loading dose of esmolol of 500 mcg/kg which was then followed by a continuous infusion of 1-100 mcg/kg/min. The median age was 54-58 years, > 80% were male, and VF was the initial document rhythm in >85% of patients.

In terms of results, esmolol had a positive effect on survival to discharge (RR 2.82, 95% CI 1.01-7.93, p = 0.05), survival with favorable neurological outcome (RR 3.44, 95% CI 1.11-10.67, P=0.03), increased rates of ROSC (RR 2.63, 95% CI 1.37-5.07, p = 0.004), and survival to ICU/hospital admission (RR 2.63, 95% CI 1.37-5.07, p=0.004). In all of the results, there was no statistical difference at the individual study level but there was significance at the meta-analysis level. However, the authors reiterate that they are uncertain of the true effects of esmolol on these outcomes as the quality of evidence from the two studies was very low. This is because the studies were observational in nature, had high risks of bias, and only included a small number of patients.

In conclusion, although promising, and we really want esmolol to work, this meta-analysis had a lot of limitations and larger studies are needed before this becomes widespread practice. It was also kind of a disappointing study as it did not add much that we didn’t already know. In my ER, we have started stocking vials of esmolol in one Pyxis machine for ease of access in case a provider decides to try esmolol. Esmolol vials cost only a few dollars, whereas the infusions cost more than 100. Personally, I’ve only seen it given a handful of times and without success. We just gave the bolus out of the vial and did not start the continuous infusion. Also, note that usually when we consider esmolol, we are also doing dual sequential defibrillation at the same time. My thought overall is if you are already at the “kitchen-sink” point of the cardiac arrest, this is an easy and cheap intervention we can try to give our patients the best chance at survival.

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