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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

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% eliminating in the urine
Adverse Effects
- Bradyarrhythmias
- Hypotension
- Infusion site reaction
- Nausea + vomiting
Drug Interactions and
warnings
- Drug interaction: Rivastigmine, calcium channel blockers, beta
blockers
- Warning: Extravasation can lead to skin necrosis and sloughing
Compatibility
-
Antibiotics: acyclovir, ciprofloxacin
-
Dexamethasone, barbituates,
-
Diazepam, furosemide, milrinone
Pharmacy Friday
evidence-based medicine
Other pearls found at:
-
https://sites.google.com/presby.edu/pharmacy-friday

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

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

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