Esmolol in Refractory Ventricular Fibrillation Cardiac Arrest

All Pharmacy Pearls

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

Property	Esmolol (Brevibloc)
Dose	Loading dose: 500 mcg/kg IV infusion: 0–100 mcg/kg/min
Administration	IV infusion with bolus from bag or vial
Formulation	IV premix bag: 2500 mg/250 mL or 2000 mg/100 mL IV vial: 100 mg/10 mL
PK/PD	Onset: 2–10 minutes (quickest when loading dose used) Peak: ~5 minutes Duration: 10–30 minutes Metabolism: primarily by esterase in blood Elimination: 1–2% eliminated in the urine
Adverse Effects	Bradyarrhythmias Hypotension Infusion site reaction Nausea + vomiting
Drug Interactions & Warnings	Drug interactions: 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, Year	Design & Sample Size	Intervention & Comparison	Outcome
Lee, 2016	Single-center observation n = 41	Loading dose 500 mcg/kg → 0–100 mcg/kg/min infusion	↑ ROSC with esmolol (56% vs 16%) ↑ Survival and good neurological outcomes with esmolol
Boehm, 2016	Case report n = 1	80 mg IVP, then 100 mcg/kg/min infusion	ROSC and discharge with good neurological outcome
Driver, 2014	Retrospective analysis n = 25	Loading dose 500 mcg/kg → 0–100 mcg/kg/min infusion	↑ Temporary ROSC (67% vs 42%) ↑ Sustained ROSC (66% vs 32%) ↑ ICU admission (66% vs 32%) Survival to hospital discharge (50% vs 16%) Favorable neuro outcome (50% vs 11%)
Bassiakou, 2008	Animal 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, 2004	Animal 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, 1994	Animal 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

1.
Esmolol . Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved October 21, 2018, from
http://www.micromedexsolutions.com/
2.
Lee YH, et al. Resuscitation. 2016 Oct;107:150-5.
3.
Driver BE, et al. Resuscitation. 2014 Oct;85(10):1337-41.
4.
Bassiakou E.et al. Am J Emerg Med. 2008 Jun;26(5):578-84.
5.
Killingsworth CR, et al. Circulation. 2004 May 25;109(20):2469-74.
6.
Ditchey RV, et. J Am Coll Cardiol. 1994 Sep;24(3):804-12.
Overview of Evidence
Author, year
Design &
Sample size
Intervention & Comparison
Outcome
Lee, 2016
Single 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, 2016
Case report/ n=1
80 mg IVP100
mcg/kg/min infusion
ROSC and discharge with good neurological
outcome
Driver, 2014
Retrospective
analysis
n=25
Loading dose 500 mcg/kg
↓
0-100 mcg/kg/min infusion
↑ Temorary ROSC (67% vs 42%)
↑ sustained ROSC (66% vs 32%)
↑ ICU admission (66% vs 32%)
Survival to hospital D/c (50% vs 16%)
Favorable neuro outcome (50% vs 11%)
Bassiakou, 2008
Animal 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+atentolol
↓ Post-resuscitation HR with Epi+atentolol
Killingsworth,
2004
Animal 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, 1994
Animal Study
(dog)
n=22
Epinephrine (0.015 mg/kg)
vs
Epinephrine + propranolol
(0.015 mg/kg) (2 mg/kg)
↑ Coronary perfusion pressure in Epi + propanol
↑ successful defibrillation in epi + propranolol

Tags: refractory ventricular fibrillation 500 mcg 0-100 mcg/kg/min ROSC

Source PDF

Esmolol in Refractory Ventricular Fibrillation_AUMC_ pharmacy friday-.pdf