Introduction

  • 1. Refractory ventricular fibrillation (RVF) is a severe form of electrical storm in which rapidly clustering episodes of ventricular fibrillation (VF) recur or persist after multiple defibrillation attempts, precluding any period of sustained return of spontaneous circulation (ROSC
  • 2. In RVF, there are recommendations outlined in the American Heart Association Advanced Cardiac Life Sup-port (ACLS) guidelines, however mortality remains high in this condition.
  • 3. While the activation of alpha-1 receptors by adrenaline (epinephrine) causes vasoconstriction and increased coronary perfusion pressure, the activation of B-1and B-2 receptors has deleterious effects by increasing myocardial oxygen requirements, worsening ischemic injury, lowering the VF threshold, and worsening post-resuscitation myocardial function.
  • 4. Blocking B-adrenergic receptors has shown promise in terminating electrical storm in recent animal and human trials

Pharmacology

CategoryDetails
Esmolol (Brevibloc)
DoseLoading dose: 500 mcg/kg
IV Infusion: 0-100 mcg/kg/min
AdministrationIV infusion with bolus from bag or vial
FormulationIV premix bag: 2500 mg/250 ml or 2000 mg/100 ml
IV Vial: 100 mg/10 ml
PK/PDOnset: 2-10 minutes ( quickest when loading dose used)
Peak: ~ 5 minutes
Duration: 10-30 minutes
Metabolism: primarily by esterase in blood
Elimination: 1-2% eliminating in the urine
Adverse EffectsBradyarrhythmias
Hypotension
Infusion site reaction
Nausea + vomiting
Drug Interactions and warningsDrug interaction: Rivastigmine, calcium channel blockers, beta blockers
Warning: Extravasation can lead to skin necrosis and sloughing
Compatibility• Antibiotics: acyclovir, ciprofloxacin
• Dexamethasone, barbiturates
• Diazepam, furosemide, milrinone

Evidence

Author, yearDesign & Sample sizeIntervention & ComparisonOutcome
Lee, 2016Single center observation
n= 41		Loading dose 500 mcg/kg
↓
0-100 mcg/kg/min infusion		↑ (ROSC) with esmolol (56% vs16%)
↑ Survival and good neurological outcomes with esmolol
Boehm, 2016Case report/ n=180 mg IVP→100 mcg/kg/min infusionROSC and discharge with good neurological outcome
Driver, 2014Retrospective analysis
n=25		Loading dose 500 mcg/kg
↓
0-100 mcg/kg/min infusion		↑ Temporary ROSC (67% vs 42%)
↑ sustained ROSC (67% vs 32%)
↑ ICU admission (66% vs 32%)
Survival to hospital D/c (50% vs 16%)
Favorable neuro outcome (50% vs 11%)
Bassiakou, 2008Animal study
n=20		Epinephrine 0.02 mg/kg
Vs
Epinephrine + atenolol
(0.02 mg/kg) (0.05 mg/kg)		↑ ROSC with epi+ atenolol (90% vs 40%)
↑ Aortic SBP, DBP, CPP with Epi+atenolol
↓ Post-resuscitation HR with Epi+atenolol
Killingsworth, 2004Animal study
n=16		Epinephrine 0.01 mg/kg + placebo
vs
Epinephrine 0.01 mg/kg + Esmolol 1 mg/kg IV		Esmolol improved ROSC and 4-hour survival
Ditchey, 1994Animal Study (dog)
n=22		Epinephrine (0.015 mg/kg)
vs
Epinephrine + propranolol
(0.015 mg/kg) (2 mg/kg)		↑ Coronary perfusion pressure in Epi + propranolol
↑ successful defibrillation in epi + propranolol

Conclusions

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. The results of the studies above need to be validated in larger, prospective trials with

good neurologic function as primary endpoint.

References

  • Esmolol. Micromedex [Electronic version]. Greenwood Village, CO: Truven Health Analytics. Retrieved October 21, 2018, from http://www.micromedexsolutions.com/
  • Lee YH, et al. Resuscitation. 2016 Oct;107:150-5.
  • Driver BE, et al. Resuscitation. 2014 Oct;85(10):1337-41.
  • Bassiakou E.et al. Am J Emerg Med. 2008 Jun;26(5):578-84.
  • Killingsworth CR, et al. Circulation. 2004 May 25;109(20):2469-74.
  • Ditchey RV, et al. J Am Coll Cardiol. 1994 Sep;24(3):804-12.
Tags: refractory ventricular fibrillation 500 mcg 0-100 mcg/kg/min ROSC