ESMOLOL-ACLS

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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. (85):1337-1345.
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Clinical Question

In patients with a cardiac arrest with an initial rhythm of ventricular fibrillation (VF), or pulseless ventricular tachycardia (VT) pre-hospital or in the emergency department, who were refractory to treatment after receiving at least three defibrillation attempts, 300 mg of amiodarone, and 3 mg of adrenaline in the emergency department, would the addition of esmolol prior to return of spontaneous circulation (ROSC) improve the chances of sustained ROSC, survival to hospital discharge, and improved congnitive function compared to standard of care alone.

Bottom Line

Patients following failure of standard of care who present with VF/VT may benefit from beta-blockade, potential harm is unclear. More study is required.

Major Points

VF is the most common arrhythmia recorded during cardiac arrest.[1] In patients with shock and refractory VF, no pharmacologic agents have been shown to increase long term survival.

A systematic review of animal trials[2] and human case reports suggest that beta-blackade may abort VF and increase survival.[3] [4] [5]

This small, observational case series suggests a survival and ROSC benefit, however, there was at least one brady-arrest in the treatment group suggesting that harm cannot be excluded.

Guidelines

As of July 2015, no guidelines have been published that reflect the results of this trial.

Design

  • Single center (USA), retrospective, observational, chart review, case series
  • N=25
    • Esmolol (n=6)
    • No esmolol [standard of care] (n=19)
  • Setting: Level 1 trauma centre, academic urban county hospital,capable of 24hour PCI and therapeutic cooling
  • Enrollment: January 2011 to January 2014
  • Mean follow-up:
  • Analysis: Intention-to-treat
  • Primary outcome: Note: this was very unclear
    • Timing of ROSC
    • Temporary ROSC (non-fleeting spontaneous circulation lasting >30sec but <20min)
    • Sustained ROSC (20min of spontaneous circulation without cardiac arrest)
  • Secondary outcomes
    • Survival to discharge
    • STEMI
    • Emergent PCI
    • Cerebral Performance Category / Good Neurologic Outcome

Population

Inclusion Criteria

  • Patient's initial rhythm was VF or VT
  • Cardiac Arrest in the ED or had Cardiac Arrest pre-hospital and remained in arrest upon ED arrival
  • received >=3 defibrillation attempts, 300 mg of amiodarone, and 3 mg of epinephrine (adrenaline)
  • (patients that received esmolol following ROSC were included in the no esmolol group)

Exclusion Criteria

  • Patients that received esmolol prior to cardiac arrest

Baseline Characteristics

Presented as esmolol (n=6) vs. no esmolol (n=19)

  • Age, year; median (IQR) 54(47-59) vs. 56(48-56)
  • Male gender (%) 6(100) vs. 18(95)
  • Initial rhythm VF (%) 5(83) vs. 18(95)
  • Witnessed arrest (%) 5(83) vs. 16(84)
  • Bystander CPR (%) 3/4(75) vs. 14/18(78)
  • Time from call to EMS arrival, min; median (IQR) 7(3-9) vs. 6(6-7.5)
  • Total pre-hospital Time, min; median (IQR) 25(18-29 vs. 42(25-51)

Pre-Esmolol Interventions

Presented as esmolol (n=6) vs. No esmolol (n=19)

  • Mechanical CPR with LUCAS device (%) 6(100) vs. 16(84)
  • Impedance threshold device used (%) 6(100) vs. 18(95)
  • Epinephrine (adrenaline), mg; median (IQR) 6(5-7.75) vs. 6(5-7)
  • Amiodarone, mg; median (IQR) 375(300-450) vs. 450(300-450)
  • Sodium bicarbonate, meq; median (IQR) 225(200-287) vs. 150(100-250)
  • Defibrillation attempts; median (IQR)
    • in the esmolol group, one patient's ICD fired approximately every 2–3 min until it failed 30 min after ED arrival

Interventions

Esmolol 500 mcg/kg IV loading dose, then infusion of 0-100 mcg/kg/min

Outcomes

  • N=90 met inclusion criteria
    • 65 excluded:
      • 45 Pre-hospital ROSC
      • 13 received <300mg amiodarone
      • 4 had mission information
      • 2 had <3 defibrillation attempts
      • 1 received <3mg epinephrine (adrenaline)

Comparisons are esmolol (n=6) vs. No esmolol (n=19)

Primary Outcomes

Achieved Temporary ROSC (non-fleeting spontaneous circulation lasting >30sec but <20min)
4(66.7) vs. 8(42.1)
Achieved Sustained ROSC (20min of spontaneous circulation without cardiac arrest)
4(66.7) vs. 6(31.6)
Time to ROSC following esmolol (n=4)
13.5 min (range 9-31min)

Secondary Outcomes

Total ED CPR time, min; median (IQR)
39.5 (31-59) vs. 16 (13-25)
Total CPR time, min; median (IQR)
63 (57-83) vs. 57 (39-66)
STEMI (%)
3/5(60) vs. 1/7(14.3) Note: unknown if remaining patients also had a STEMI
Emergent cardiac catheterization from the ED (%)
5(83.3) vs. 3(15.8)
Survival to ICU admission (%)
4(66.7) vs. 6(31.6)
Therapeutic hypothermia (%)
4(66.7) vs. 5(26.3) Note: one (1) No Esmolol Patient not cooled as Core Temp already 33DegC
Survival to hospital discharge (%)
3(50) vs. 3(15.8)
Survival to discharge with good neurologic outcome (%)
3(50) vs. 2(10.5)

Adverse Events

One (1) patient in Esmolol group achieved Temporary ROSC then had a subsequent bradycardic-PEA arrest. No other adverse effects were reported.

Criticisms

  • Patients that received Esmolol after ROSC were included in the control group (not reported)
  • Small sample size, potentially under-powered
  • Patients without Esmolol had a longer pre-hospital time, indicating more stable patients?
  • Patients were exposed to a mixed bag of treatments, making comparison between treatment and control groups difficult to interpret
  • Outcomes for No Esmolol group not reports/tracked
  • Aggressive resusitation may have skewed results in either group
  • Esmolol used as a salvage therapy after failure of other treatments, unclear if earlier treatment would have different outcomes.

Funding

No funding source was reported nor were any conflict of interest by the authors.

Further Reading

  1. McNally B, Robb R, Mehta M, et al; Centers for Disease Control and Prevention. Out-of-hospital cardiac arrest surveillance- Cardiac Arrest Registry to Enhance Survival (CARES), United States, October 1, 2005-December 31, 2010. MMWR Surveill Summ. 2011 Jul 29;60(8):1-19.
  2. de Oliveira FC, Feitosa-Filho GS, Ritt LE. Use of beta-blockers for the treatment of cardiac arrest due to ventricular fibrillation/pulseless ventricular tachycardia: a systematic review. Resuscitation. 2012 Jun;83(6):674-83
  3. Bassiakou E, Xanthos T, Papadimitriou L. The potential beneficial effects of betaadrenergic blockade in the treatment of ventricular fibrillation. Eur J Pharmacol2009;616:1–6
  4. de Oliveira FC, Feitosa-Filho GS, Ritt LE. Use of beta-blockers for the treatment ofcardiac arrest due to ventricular fibrillation/pulseless ventricular tachycardia: asystematic review. Resuscitation 2012;83:674–83.
  5. Bourque D, Daoust R, Huard V, Charneux M. beta-Blockers for the treatment of cardiac arrest from ventricular fibrillation? Resuscitation 2007;75:434–44.