ReviewBeta-blockade for the treatment of cardiac arrest due to ventricular fibrillation or pulseless ventricular tachycardia: A systematic review and meta-analysis
Introduction
There are approximately 356,000 patients each year that experience out-of-hospital cardiac arrest (OHCA) with over 20% of them presenting in a shockable rhythm.1 Patients presenting in ventricular fibrillation/ventricular tachycardia (VF/VT) have a higher chance of survival to hospital discharge.1 However, there continues to be a subset of these patients who are not successfully resuscitated using standard Advanced Cardiovascular Life Support (ACLS) care and that remain in VF/VT, with an incidence ranging from 2% to 28%.2, 3, 4 This increasingly recognized group of patients with a shockable rhythm that does not respond to traditional ACLS therapies (e.g. defibrillation, epinephrine, antiarrhythmic medications) have been labeled as ‘refractory VF/VT’. While 30% of patients presenting in a shockable rhythm responding to ACLS therapies survive with a favorable neurological outcome, those that are refractory have a survival rate of 3%–15% with only 5% of these patients surviving with good neurologic outcomes.5 The most recent update to the American Heart Association (AHA) ACLS guidelines in 2018 recognized the growing evidence of using novel therapies such as beta-blockade in refractory VF/VT but provided no formal recommendations for their use.6 Prior literature has primarily focused on animal data.7, 8 However, there have been several recent human studies which have evaluated the impact of beta-blockers on refractory VF/VT prompting the need for the current systematic review and meta-analysis.9, 10, 11
The primary aim of this study was to evaluate the effect of beta-blockade compared with control in patients with refractory VF/VT arrest for the primary outcome of return of spontaneous circulation (ROSC). Secondary outcomes included survival-to-admission, survival-to-discharge, survival with a favorable neurologic outcome, and adverse events.
Section snippets
Methods
Our study conforms to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews and was performed in accordance with best practice guidelines.12 This review was registered with PROSPERO (CRD42019126902). In conjunction with a medical librarian, we conducted a search of PubMed, Scopus, the Cumulative Index of Nursing and Allied Health (CINAHL), the Latin American and Caribbean Health Sciences Literature database (LILACS), Google Scholar,
Results
A total of 3,682 studies were identified with the search strategy. PubMed identified 1972 studies, Scopus yielded 857 studies, CINAHL discovered 317 studies, LILACS found 14, the Cochrane Database of Systematic Reviews identified 323 studies, and the Cochrane Central Register of Controlled Trials yielded 2 studies. In addition, the initial 200 studies from Google Scholar were also included as recommended by Bramer and colleagues.20 After removing duplicates, 2824 original abstracts were
Discussion
In this systematic review and meta-analysis, we investigated the efficacy of beta-blockade compared with control in patients with refractory VF/VT arrest. The data suggests that beta-blockade may lead to improved outcomes, including temporary and sustained ROSC, survival-to-admission, survival-to-discharge, and survival with a favorable neurologic outcome.
To our knowledge, this is the first systematic review and meta-analysis on this topic focusing on human studies. Two prior systematic reviews
Limitations
It is important to consider several limitations with regard to the current study. All studies were observational in nature and there were no randomized controlled trials. As such, it is possible that unidentified confounders may have been present, which may have influenced the findings. Future randomized controlled trials are recommended to further assess this intervention. Additionally, while all studies assessed esmolol, Nademanee and colleagues included LSGB which may have led to some
Conclusion
Beta-blockade may be associated with improved outcomes including ROSC, survival-to-discharge, survival-to-admission, and survival with a favorable neurologic outcome. Future randomized controlled trials are needed to further evaluate this approach to refractory VF/VT.
Author contributions
MG, SPD, and GDP contributed to the study concept and design.
MG, SPD, and GDP contributed to the acquisition of the data.
MG, SPD, and GDP contributed to the analysis and interpretation of the data.
MG, SPD, and GDP contributed to drafting of the manuscript.
MG, SPD, and GDP contributed to critical revision of the manuscript for important intellectual content.
MG and GDP contributed to the statistical expertise.
No funding was obtained for this study.
Prior presentations
None.
Conflicts of interest
None.
Acknowledgement
The authors would like to thank Jennifer C. Westrick, MSLIS for her assistance with the literature search.
References (24)
- et al.
Incidence and outcomes of out-of-hospital cardiac arrest with shock-resistant ventricular fibrillation: data from a large population-based cohort
Resuscitation
(2010) - et al.
Managing cardiac arrest with refractory ventricular fibrillation in the emergency department: conventional cardiopulmonary resuscitation versus extracorporeal cardiopulmonary resuscitation
Resuscitation
(2015) - et al.
Use of double sequential external defibrillation for refractory ventricular fibrillation during out-of-hospital cardiac arrest
Resuscitation
(2016) - et al.
Management of refractory ventricular fibrillation (Prehospital and Emergency Department)
Cardiol Clin
(2018) - et al.
beta-Blockers for the treatment of cardiac arrest from ventricular fibrillation?
Resuscitation
(2007) - et al.
Use of beta-blockers for the treatment of cardiac arrest due to ventricular fibrillation/pulseless ventricular tachycardia: a systematic review
Resuscitation
(2012) - et al.
Use of esmolol after failure of standard cardiopulmonary resuscitation to treat patients with refractory ventricular fibrillation
Resuscitation
(2014) - et al.
Refractory ventricular fibrillation treated with esmolol
Resuscitation
(2016) - et al.
COSCA (core outcome set for cardiac arrest) in adults: an advisory statement from the International Liaison Committee on Resuscitation
Resuscitation
(2018) - et al.
European Resuscitation Council and European Society of Intensive Care Medicine Guidelines for Post-resuscitation Care 2015: section 5 of the European Resuscitation Council Guidelines for Resuscitation 2015
Resuscitation
(2015)
Heart disease and stroke statistics—2018 update: a report from the American Heart Association
Circulation
2018 American Heart Association focused update on advanced cardiovascular life support use of antiarrhythmic drugs during and immediately after cardiac arrest: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care
Circulation
Cited by (17)
The Pharmacologic Management of Cardiac Arrest
2023, Emergency Medicine Clinics of North AmericaCardiopulmonary Resuscitation: The Importance of the Basics
2023, Emergency Medicine Clinics of North AmericaDefibrillation in the Cardiac Arrest Patient
2023, Emergency Medicine Clinics of North AmericaEsmolol, vector change, and dose-capped epinephrine for prehospital ventricular fibrillation or pulseless ventricular tachycardia
2023, American Journal of Emergency MedicineCitation Excerpt :While our study evaluated multiple interventions, these results contrast with the findings from earlier studies that suggest benefit of the individual interventions within the bundle, such as esmolol or vector change in cases of refractory VF/pVT. Unlike our study, previous literature evaluating esmolol utilization in patients with refractory VF/pVT have demonstrated higher rates of sustained ROSC in those who received esmolol compared to those who received standard interventions [3,4,9]. Furthermore, our study did not replicate the findings from recent meta-analyses that demonstrated beta blockade was associated with increased rates of ROSC, survival to hospital discharge, and neurologically intact survival [13,15]. Our EMS protocol bundle utilized a fixed esmolol bolus dose of 40 mg.
Drug use during adult advanced cardiac life support: An overview of reviews
2021, Resuscitation PlusCitation Excerpt :Chowdhury et al. reported a non-significant favourable trend towards beta-blockade, although this is based on one study by Driver et al.42 In 2019, Gottlieb et al. performed a meta-analysis investigating beta-blockade versus placebo in shock refractory VF/VT with a larger sample size. They found a significant beneficial effect for all outcomes.53 In contrast, Lundin et al. described no differences in rates of ROSC and intact neurological survival.20
Resuscitation highlights in 2020
2021, ResuscitationCitation Excerpt :The precise role and value of both vasopressors (adrenaline) and antiarrhythmic drugs (amiodarone or lidocaine) during cardiac arrest remains controversial and the evidence suggests that they are most likely to beneficial when given early after cardiac arrest.3,58,59 A systematic review and meta-analysis of beta-blockade for refractory VF/pulseless ventricular tachycardia (pVT) cardiac arrest identified three observational studies with a total of 115 patients.60 Proponents of beta-blockade state that beta-blockade will prevent the harmful beta-agonist effects of adrenaline given during CPR.