Episode 21- Esmolol in refractory VF arrest


Episode Summary:

This week we review a meta-analysis that looked at the use of esmolol in patients in refractory VF/pVT arrest. Will this change your practice?

Show Notes:

Key Points:

Esmolol in refractory VF arrest”:
– Esmolol has been shown to increase rates of return of spontaneous circulation (ROSC) in some animal models, case reports/series, and retrospective studies
– Esmolol is a very quick (90 second onset) and short (9 minute half-life) acting cardio-selective beta-blocker. It is thought to work in this setting by reducing the sympathetic surge that occurs during ACLS measures
– It is given to patients who have failed 3 defibrillation attempts, 3 mg of epinephrine, and 300 mg of amiodarone
– The dose used is 500 mcg/kg as a bolus followed by a continuous infusion of 0-100 mcg/kg/min
– A recent meta-analysis showed that esmolol given in this setting increases survival to discharge, survival with favorable neurological outcomes, increases the rates of ROSC, and increases rates of ICU/hospital admission
– However, the authors advise caution as only two studies were included in the analysis, both of which were small and observational in nature
ER-Rx Episode 21


Miraglia D, Miguel LA, Alonso W. Esmolol in the management of pre-hospital refractory ventricular fibrillation: a systematic review and meta-analysis. Am J Emerg Med. 2020; 38: 1921-1934

Driver BE, Debaty G, Plummer DW, et al. Use of esmolol after failure of standard cardiopulmonary resuscitation to treat patients with refractory ventricular fibrillation. Resuscitation. 2014; 85: 1337-1441

Lee, YH, Lee KJ, Min YH, et al. Refractory ventricular fibrillation treated with esmolol. Resuscitation. 2016; 107: 150-155


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.

As always, thank you so much for your time. If you are on social media, take a second to follow us on InstaGram @errxpodcast.

Leave a Reply

Your email address will not be published. Required fields are marked *

Recent Reviews/ Comments

“Love this podcast for anyone working in an ER or ICU. If you aren’t a pharmacist you will still get tons of useful information to improve your practice. Adis has a knack for finding a happy balance between explaining the pharmacokinetics and practical use for patients at the bedside. Highly recommend!”

–  NotAPharmacist, Apple Podcasts review 

“Perfect amount of knowledge in a great length to refresh ICU and ED topics. Explains concepts in an easy to understand fashion”

–  RxLaura, Apple Podcasts review

“I love listening to this podcast because I can listen to 1 or 2 on my way to work and it provides great info! As a paramedic, this podcast has really helped me understand the “why” we give certain meds.”

cresjr, Apple Podcasts review

“Ideal podcast to listen on the way to my shift. Learning points throughout!”

andmatjos, Apple Podcasts review

“I’m currently in my last year of pharmacy school […] I just happen to come across your podcast on YouTube as I was trying to find a good explanation regarding the misleading sulfa allergy in non-antibiotic sulfonamides. Your explanation was great. I can’t believe I’m only now finding out about your podcasts but please continue to make them for as long as you can. Prospective pharmacists, such as myself, really appreciate you taking the time to put such great educational content out there.”

– S.P., Pharmacy Student

“Adis does a wonderful job of gathering the evidence-based answers to the hard questions that we all get as pharmacists and putting them into a nice, neat package.”

– rebroush1, Apple Podcasts review

“This is a great podcast to listen to at work and is not too overwhelming and well put together. Highly recommended for anyone in healthcare, even outside of emergency medicine.”

Peelage, Apple Podcasts review

“Great reviews on drug-related topics with useful details on drug mechanisms, pharmacodynamics and administration considerations as well as data to support recommendations. Great for pharmacists, providers and learners!”

-JaayyZzee, Apple Podcasts review

“I found the topics very helpful. I have been recommending this show to pharmacy students and residents, who are also enjoying it.”

hvgjnfd, Apple Podcasts review

“As a PA, I found this very informative. I like that the episodes are short, making them easy to listen to on my way to and from work. Would love to hear more pediatric topics!”

-Pediatric PA, Apple Podcasts review

“Good podcast thats very informative for all healthcare providers. Very easy to listen to and enjoy.”

-Bradlley88, Apple Podcasts review