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Three Part Question

Does [esmolol] [decrease mortality] in [any patient experiencing cardiac arrest]?

Clinical Scenario

A 60-year-old man is brought to the emergency department (ED) via Emergency Medical Services (EMS) after a fall with vital signs absent. EMS provided Cardiopulmonary Resuscitation (CPR) and was able to achieve return of spontaneous circulation (ROSC) on route, however the patient became pulseless again. In the ED the patient was assessed, CPR was initiated and he was intubated; ROSC is achieved once more. Shortly thereafter the patient is found to be pulseless and CPR is restarted. The ACLS algorithm has been followed and all standard resuscitation practices have been implemented. You wonder if the use of Esmolol could have helped you achieve sustained ROSC.

Search Strategy

Medline 1946 – March, 2020 using the OVID interface.
[({Esmolol.mp. OR brevibloc.mp.}) AND ({cpr.mp. or Cardiopulmonary Resuscitation/} OR {cardiac arrest.mp. or Heart Arrest/} OR {ventricular fibrillation.mp. or Ventricular Fibrillation/} OR {Ventricular Fibrillation/ or VF.mp. or Tachycardia, Ventricular/} OR {vsa.mp.} OR {vital signs absent.mp.} OR {code blue.mp.})]

Search Outcome

114 papers were found of which 83 were irrelevant, six removed as they were case studies or case reports, one was a letter to the editor, 19 were based on animal models or experiments, and three were literature reviews. The remaining two papers are outlined on the table below.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Lee et al. 2016 Republic of Korea	Patients presenting to the ED between January 2012 and December 2015 with refractory ventricular fibrillation (RVF) in out-of-hospital cardiac arrest (OHCA).	16 patients in RVF received the same dose of Esmolol after 3 SD shocks, 3 mg of epinephrine and 300mg of amiodarone vs. 25 patients who just received standard ACLS (control).	Sustained ROSC	Sustained ROSC was significantly more common in the Esmolol group, compared to the control group (56% vs. 16%, p = 0.007). Nine of 16 (56.3%) of those in the Esmolol group sustained ROSC and survival to intensive care unit (ICU) admission compared to 4 of 25 (16%) (p = 0.007) who did not receive Esmolol.	Retrospective study. Pre- post-treated group may have selection bias. The study was only performed at a single hospital and included very small sample of patients despite a long study period. Disproportionately predominant male population used. Results may have limited generalizability
			Survival	There was found to be no statistically significant survival at 30 days, 3 months and at 6 months in the Esmolol group as compared to the non-Esmolol group; 3 of 16 (18.8%) vs. 2 of 25 (8%) respectively.
Driver et al. 2014 USA	Patients presenting between January 1, 2011 and January 31, 2014 to an ED with a diagnosis of cardiac arrest (CA), ventricular fibrillation (VF), or pulseless ventricular tachycardia (VT).	Patients were included if: 1. the initial rhythm was VF or VT, AND 2. they had CA in the ED or had CA pre-hospital and remained in arrest upon ED arrival, AND 3. they received at least three defibrillation attempts, 300 mg of amiodarone, and 3 mg of adrenaline. Esmolol (6) ACLS only (19) NB. Those that received Esmolol before CA were excluded; those that received Esmolol after sustained ROSC were included in the group that did not receive Esmolol.	Achievement of ROSC.	Four of six patients with refractory VF achieved sustained ROSC after receiving Esmolol 500 mcg/kg IV bolus followed by a slow drip of a maximum of 100 mcg/kg/min and standard ACLS when compared with 19 patients who just received standard ACLS. ‘Near significant’ increase in ROSC (OR = 17.59; 95% CI = 0.87-356.81; p = 0.06).	Retrospective study. Small sample size. Disproportionately predominant male population used. No statistically significant differences between the two groups (6 of Esmolol group vs. 19 of control group).
			Survival to admission.	No significant difference in survival to admission (OR = 4.33; 95% CI – 0.61 – 30.57; p = 0.14).
			Survival to hospital discharge	Survival to hospital discharge was 50% in the Esmolol group vs. 16% in those that received standard ACLS. (OR =5.33; 95% CI = 0.71 – 40.22; p = 0.10).

Comment(s)

There is a paucity of literature on this topic owing to small study sizes and the inherent difficulty in studies relating to cardiac arrest and subsequent resuscitation, relating to the rarity of these events and their inherent emergent nature. Due to the aforementioned, the potential for being unethical, and because universally, comprehensive evidence based treatments available should be used in all cardiac arrest resuscitations, study designs can be problematic and difficult. The plethora of new research based on animal models may provide valid evidence in support of, or to refute, the use of Esmolol in improving mortality in individuals experiencing cardiac arrest. This may lead to further human studies and possible utilization of Esmolol as an adjunct in ACLS in cardiac arrest in the future.

Clinical Bottom Line

Currently, there is insufficient evidence in the existing literature to support the regular use of Esmolol in resistant cardiac arrest; additional research is warranted to evaluate the effects of Esmolol against the best current standard of care – standard CPR in conjunction with the current ACLS algorithm.

Level of Evidence

Level 3 - Small numbers of small studies or great heterogeneity or very different population.

References

1. Lee et al. Refractory ventricular fibrillation treated with Esmolol Resuscitation 2016; 107:150-5.
2. Driver et al. Use of Esmolol after failure of standard cardiopulmonary resuscitation to treat patients with refractory ventricular fibrillation. Resuscitation 2014; 85(10):1337-41.