February 2017

Esmolol and Dual Defibrillation for Refractory V-Fib



You're working a busy TCC shift one weekend when you get a page that EMS is bringing in a fiftyish year old man in cardiac arrest.  You prep the room and discuss the plan with the team, emphasizing high-quality CPR with minimal interruptions.

The patient arrives with a King tube in place, in ventricular fibrillation.  EMS reports the patient was in V-fib on their arrival about 15 minutes earlier.  They have attempted defibrillation twice, have given three rounds of epinephrine, and have given 150 mg of amiodarone, all with no change in rhythm.  You immediately attempt defibrillation for a third time, with no change in the patient's condition, and give an additional 150 mg of amiodarone.  Two mintes later, the patient remains in v-fib.

When the patient remains in v-fib after two additional attempts, you and the attending exchange a, "Well, what now?"  look.  You begin to wonder if there are additional medicaitons or maneuvers for patients in refractory v-fib.  You later begin searching for answers online, and stumble upon a write-up from R.E.B.E.L EM (http://rebelem.com/september-2016-rebel-cast-refractory-ventricular-fibrillation/) on this very topic.  The authors evaluate the evidence for esmolol and dual sequential defibrillation.  Being wary of other's opinions, and being adept at appraising the medical literature yourself, you perform your own literature search and begin evaluation the evidence on your own.

PICO Question #1

Population: Adult patients with refractory ventricular fibrillation or pulseless ventricular tachycardia

Intervention: IV esmolol

Comparison: Standard ACLS

Outcome: ROSC, survival to hospital admission, survival to discharge, and neurologically intact survival


PICO Question #2

Population:  Adult patients with refractory ventricular fibrillation or pulseless ventricular tachycardia

Intervention:  Dual defibrillation

Comparison:  Standard ACLS

Outcome:  ROSC, survival to hospital admission, survival to discharge, and neurologically intact survival


Search Strategy
Three of the articles (PGY-2, PGY-3, and PGY-4) were selected from the above referenced post on the topic at RebelEM’s website. PubMED was searched using the strategy “refractory ventricular fibrillation AND esmolol” (http://tinyurl.com/zjo9zeh) which resulted in 9 citations, from which the PGY-1 article was chosen. An additional search was conducted using the strategy “refractory ventricularfibrillation AND ("dual defibrillation" or "sequential defibrillation")” (http://tinyurl.com/jb63l5m) which resulted in 6 articles. No additional, higher quality studies were found among these.


Article 1: 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 Oct;85(10):1337-41.


Article 2: Lee YH, Lee KJ, Min YH, Ahn HC, Sohn YD, Lee WW, Oh YT, Cho GC, Seo JY, Shin DH, Park SO, Park SM. Refractory ventricular fibrillation treated with esmolol. Resuscitation. 2016 Oct;107:150-5.

Article 3:  Cortez E, Krebs W, Davis J, Keseg DP, Panchal AR. Use of double sequential external defibrillation for refractory ventricular fibrillation during out-of-hospital cardiac arrest. Resuscitation. 2016 Nov;108:82-86.

Article 4:  Ross EM, Redman TT, Harper SA, Mapp JG, Wampler DA, Miramontes DA. Dual defibrillation in out-of-hospital cardiac arrest: A retrospective cohort analysis. Resuscitation. 2016 Sep;106:14-7.

Bottom Line

Electrical defibrillation, long the mainstay of treatment for ventricular fibrillation (VF), often successfully converts the heart to a sinus rhythm with return of spontaneous circulation (ROSC). Unfortunately, some cases of VF are refractory to multiple attempts at defibrillation, despite the additional use of the anti-arrhythmic Amiodarone. Such patients have an excess of circulating catecholamines due to both the exogenous administration of IV epinephrine as a part of routine ACLS, and as a result of increases in endogenous catecholamines resulting from the body’s natural stress response (Bassiakou 2009). This has led some to advocate the use of betablockers (typically cardiac-selective esmolol) to decrease adrenergic stimulation of the heart, and hence potentially facilitate conversion to a sinus rhythm (de Oliveira 2012).

Two small retrospective observational studies of esmolol use in refractory VF have shown promising results.  In one study of 25 patients (Driver 2014), those receiving esmolol were nearly five times more likely to survive with a good neurologic outcome (RR of 4.8, 95% CI 1.0 to 22).  The other study (Lee 2016) also enrolled 25 patients and also demonstrated slightly higher rates of long-term survival with good nurologic outcomes (RR 2.3, 95% CI 0.4 to 12.5), though in this case statistical significance was not achieved.  These two studies were, unfortunately, both retrospective and both very small with a high risk of bias (particularly selection bias) making these results less robust.

Other have suggested the use of two sets of defibrillator pads in either a dual or double sequential defibrillation attempt in order to convert refractory VF.  There are several theories as to how this may increase defibrillation success in such cases, including "optimization of the electrical vector direction, increased myocardial surface area affected, and increased power delivered.  In one recent case series on 12 patients in refractory VF (Cortez 2016), double sequential defibrillation resulted in ROSC in 3 patients (25%, 95% CI 9% to 53%), all of whom survived to hospital discharge.  Two of these patients had good neurologic outcomes at discharge (CPC scores of 1 and 2) while the third had a CPC score of 3.  Unfortunately, a recent retrospective, observational study comparing outcome sin patients receiving and not receiving dual defibrillation (Ross 2016) found no benefit to this treatment, with a statistically  non-significant trend toward harm (OR 0.50, 95% CI 0.15-1.72).

While both of these treatments for refractory VF seem promising, this discussion,s, unfortunately, lacking in robust evidence.  Three of the studies reviewed were retrospective and observational, and the fourth was merely a case series.  While the two studies addressing esmolol use were both positive, they were very small studies subject to multiple sources of bias.  For double sequential or dual defibrillation, the evidence is even more suspect, with the single observational study demonstrating no benefit.  Refractory VF, being rather rare, would be difficult to study in large, randomized controlled trials, and the evidence we have may be all the evidence we get.  Given the dismal prognosis of refractory VF, consideration of any alternative treatment (especially the two suggested here) seems very reasonable, even if there is insufficient evidence to make a firm recommendation.

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