Refractory ventricular fibrillation (VF) is very difficult to manage. Up until recently, emergency providers were limited to defibrillation and delivery of high quality CPR as well as amiodarone administration. However, a couple of recent trials have given us food for thought about two possible additional treatments. The first treatment, dual sequential defibrillation has been investigated in retrospective case series and has shown potential for benefit. The second treatment, esmolol infusion, may result in a higher rate of return of spontaneous circulation (ROSC) although without a significant change in neurological outcomes.

The definition of refractory VF varies depending on the source quoted but for the purpose of this review, we will define it as VF resistant to at least three defibrillations, 3 mg of epinephrine and 300mg of amiodarone with high quality CPR over 10 minutes. Esmolol is thought to help counter the huge amount of circulating catecholamines (endogenous as well as from multiple rounds of epinephrine). Epinephrine works by primarily improving coronary flow however there are also some, deleterious side effects of this medication. Epinephrine stimulates the beta receptors causing increased myocardial oxygen demand and disequilibrium between 02 demand and supply. Epinephrine also causes hyperphosporylation of Ryanodine receptor 2 (RyR2) in the myocardium, causing an influx of calcium and increased electrical instability. Beta blockers administration may protect the myocardium from these effects and, increase the chance of successful defibrillation.

Clinical Question

Is esmolol efficacious in achieving ROSC and survival with good neurologic outcome in treatment of refractory VF?


Adults >18 with an out-of-hospital cardiac arrest (OHCA) and an initial rhythm of VF or ventricular tachycardia (VT) who had refractory VF defined as resistant to >3 defibrillations, 3mg of epinephrine, 300mg of amiodarone and no ROSC after10 mins of CPR.


Patients received 500 mcg/kg bolus followed by a 0-100 mcg/kg/min infusion


Placebo bolus and infusion


Primary: Sustained ROSC (>20 min of spontaneous circulation without recurrence of cardiac arrest).

Secondary: Survival to ICU admission, survival to hospital discharge, and survival with favorable neurological outcomes at 30 days, 3 months, and 6 months. 


Single center, retrospective pre-post study


Severe head trauma or acute active bleeding, severe sepsis, VF that developed during resuscitation for initial asystole or PEA, terminal stage malignancy, history of severe neurological deficits (i.e. Dementia, ICH, ischemic stroke with bedridden status) and patients who had received beta-blocker therapy before the cardiac arrest.

Primary Results

  • 41 patients were included in the study
    • 16 patients in the esmolol group
    • 25 patients in the no esmolol group
  • No significant difference in baseline demographic characteristics between the two groups
  • No significant difference in ACLS treatment between the two groups

Critical results

  • Those in the esmolol group (9/16, 56.3%) were statistically significantly more likely to achieve ROSC and survival to an ICU than those who did not receive esmolol (4/25, 16%).
  • There was no statistical difference in good neurological outcomes in the esmolol group (3/16, 18.8%) as opposed to the no esmolol group (2/25, 8%)


No esmolol

P value


Number of patients



Sustained ROSC

9 (56.3%)

4 (16%)



Survival to ICU admission

9 (56.3%)

4 (16%)



Survival at 30days

3 (18.8%)

2 (8%)


Good neurological outcome at 30 days

3 (18.8%)

2 (8%)


Survival at 3 months

3 (18.8%)

2 (8%)


Good neurological outcome at 3 months

3 (18.8%)

2 (8%)



  • Study investigated a clinically important question
  • Baseline characteristics were balanced between groups
  • No significant difference in baseline ACLS treatment between the groups 


  • Single center study
  • Small sample size
  • Retrospective nature of study can introduce bias and is prone to confounding
  • No blinding or randomization
  • Unable to assess quality of CPR
  • Unclear timing of esmolol administration 
  • The authors did not discuss methods of their chart review, blinding of chart reviewers to treatment arms, completeness of charts etc.
  • Primary outcome (ROSC) not a patient centered outcome. Good neurologic outcome would have been a more patient centered outcome

Author's Conclusions

“The findings of our study suggest that administration of esmolol may increase the rate of sustained ROSC and ICU survival among patients with RVF in OHCA.  Further larger-scale, prospective studies are necessary to determine the effect of esmolol for RVF in OHCA.”

Our Conclusions

The study suggests esmolol is efficacious in increasing the rate of sustained ROSC for patients with refractory VF. However, larger prospective studies need to be performed to assess whether the benefit persists and if there is a significant improvement in neurological outcomes.

Potential Impact To Current Practice

Based on the available data, we cannot recommend routine use of esmolol in refractory VF. However, it should be noted that refractory VF is an uncommon clinical scenario with few treatment recommendations and so the benefit of achieving ROSC must be weighed against the harm of increasing ROSC without improving neurologic outcomes.

Bottom Line

Esmolol represents a possible adjunct treatment for patients with refractory VF. Studies to date do not demonstrate a clear improvement in patient centered outcomes but, this study does show a promising increase in ROSC. Additional, larger, prospective studies with an outcome of good neurologic function are needed.

Read More

REBEL EM: Refractory ventricular fibrillation

Resus.ME: (Esmolol for Refractory VF

Cortez E et al. Use of Double Sequential External Defibrillation for Refractory Ventricular Fibrillation During Out-of-Hospital Cardiac Arrest. Resuscitation 2016; S0300-9572(16): 30398 – 7. PMID: 27521470