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Original Article
CPR/Resuscitation Esmolol in the management of refractory ventricular fibrillation: a systematic review and meta-analysis
Acute and Critical Care 2026;41(3):598-607.
DOI: https://doi.org/10.4266/acc.001675
Published online: August 19, 2026

1Department of Pharmacy, St. Paul’s Hospital, Vancouver, BC, Canada

2Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada

3Department of Pharmacy, Vancouver General Hospital, Vancouver, BC, Canada

4Department of Emergency Medicine, Vancouver General Hospital, Vancouver, BC, Canada

5Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada

6Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada

7Department of Emergency Medicine, St. Paul’s Hospital, Vancouver, BC, Canada

8Department of Emergency Medicine, University of British Columbia, Vancouver, BC, Canada

9Woodward Library, University of British Columbia, Vancouver, BC, Canada

Correspondence To: Anthony Lau Department of Emergency Medicine, Vancouver General Hospital and Faculty of Pharmaceutical Sciences, University of British Columbia, 855 West 12th Ave. Vancouver, BC V5Z 1M9, Canada Tel: +1-604-875-4111 Fax: +1-604-875-5267. Email: Anthony.Lau@vch.ca
*These authors contributed equally to this study as co-first authors.
• Received: June 1, 2025   • Revised: May 2, 2026   • Accepted: May 27, 2026

© 2026 The Korean Society of Critical Care Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Background
    Refractory ventricular fibrillation (rVF) presents a significant challenge in advanced cardiovascular life support (ACLS), with traditional antiarrhythmics showing limited success in improving long-term survival and neurological function. Esmolol, a beta-1 selective adrenergic receptor antagonist, might offer benefits due to its rapid onset and catecholamine-suppressing effects during cardiac arrest.
  • Methods
    This systematic review and meta-analysis (SRMA) evaluates the effectiveness of esmolol in improving the temporary return of spontaneous circulation (ROSC), sustained ROSC, survival to discharge, and survival to discharge with favorable neurological outcomes in rVF patients. This SRMA reviewed Medline (Ovid), Embase (Ovid), and Cochrane Central (Ovid) from their inception until October 2, 2025, for full-text clinical or observational studies assessing esmolol use alongside standard ACLS in adult rVF in both prehospital and in-hospital settings.
  • Results
    The risk of bias was independently assessed using the Newcastle-Ottawa Scale. Pooled risk ratios (RRs; 95% CI) are reported. Analyses in which I² >50% used a random-effects model; otherwise, a common-effect model was used. Four studies (n=273) are included. Esmolol was associated with an increased temporary ROSC (RR, 1.80; 95% CI, 1.09–2.98), and although the links were not statistically significant, esmolol trended toward a benefit in sustained ROSC (RR, 1.25; 95% CI, 0.28–5.66), survival to discharge (RR, 1.08; 95% CI, 0.57–2.03), and survival to discharge with favorable neurological outcomes (RR, 2.08; 95% CI, 0.83–5.24).
  • Conclusions
    Esmolol was associated with improved temporary ROSC in rVF. The sensitivity analysis suggests potential benefits for sustained ROSC and neurological survival, but more data are needed. Further research is needed to clarify its role.
  • Key Words: advanced cardiac life support; esmolol; heart arrest; meta-analysis; systematic review; ventricular fibrillation
In shock-refractory ventricular fibrillation (rVF) or pulseless ventricular tachycardia (pVT), the role of antiarrhythmic pharmacologic therapies such as amiodarone and lidocaine in facilitating successful defibrillation and reducing the risk of recurrent arrhythmias is well-described in advanced cardiovascular life support (ACLS) guidelines [1]. In randomized controlled trials (RCTs), amiodarone improved survival to hospital admission in patients with rVF/pVT who received at least three shocks and epinephrine, compared with placebo and lidocaine, respectively [2,3]. However, none of those antiarrhythmic therapies have been associated with significant improvement in survival with favorable neurological outcomes or survival to hospital discharge [1-3].
Esmolol is a beta-1 selective adrenergic receptor antagonist which, due to its rapid onset and ultra-short half-life (approximately nine minutes), has found increasing favor in emergency departments for patients with VF refractory to guideline-recommended antiarrhythmics [4]. In rVF, high levels of circulating endogenous and exogenous catecholamines (i.e., from administered epinephrine) increase the myocardial oxygen demand, worsen ischemia, and lower the VF threshold [4]. By inhibiting some of that adrenergic drive, esmolol might increase the fibrillation threshold and potentially terminate the electrical storm, as has been shown in both small human and animal trials [5,6]. Esmolol has been shown to improve the return of spontaneous circulation (ROSC) and survival, with statistical significance in animal models [7]. Small retrospective studies have also demonstrated improvement in ROSC and survival to discharge in patients who received esmolol with ACLS, compared with controls who received standard ACLS care [4,8].
Additionally, esmolol has shown promising neuroprotective effects in animal models, including reduced impairment of cerebral microcirculation blood flow and cerebral edema, improved nerve function, and reduced neuronal necrosis [9-11]. However, differences between animals and humans in the activities and functions of beta-adrenergic receptors make it difficult to generalize those neurological benefits to humans [12].
Given the increasing clinical interest in esmolol, the failure of other ACLS medications to affect long-term outcomes, the lack of large RCTs that specifically examine esmolol in rVF/pVT, and the small sample sizes of existing clinical studies, the addition of any new data could significantly improve understanding of esmolol’s efficacy, particularly its effects on key outcomes such as survival to discharge with favorable neurological function. Therefore we conducted a systematic review and meta-analysis (SRMA) on the use of esmolol for rVF/pVT. Although both rVF and pVT are included under the umbrella of shockable cardiac arrest, the available clinical data on esmolol use predominantly involve patients with rVF. Therefore, the findings of this review emphasize relevant outcomes in rVF. Our study uniquely incorporates the latest evidence by Stupca et al. [13], adds a sensitivity analysis not performed in prior reviews, and evaluates our hypothesis that esmolol as an adjunct to standard ACLS in patients with rVF could be associated with improved key resuscitation and survival outcomes.
Institutional research ethics board review was not required for this study pursuant to section 4.3.1 of national guidance policy, which states that “REB review is not required for research that relies exclusively on publicly available information.”
Search Strategy
The review question was formulated following the PICO method Population [P], Intervention [I], Comparator [C], and Outcomes [O]: What are the rates of temporary ROSC, sustained ROSC, survival to discharge, and survival to discharge with favorable neurological outcomes in patients with rVF/pVT before or during hospital admission who were treated with esmolol, compared with those receiving standard ACLS care without esmolol?
We reviewed multiple electronic databases: Medline (Ovid), Embase (Ovid), and Cochrane Central (Ovid) from database inception until October 2, 2025. A global approach was adopted based on the PICO model to capture a broad range of relevant publications. The search strategy, which used the terms “esmolol” or “beta blocker” and (“ventricular fibrillation” or “rVF” or “ventricular tachycardia” or “rVT”), was developed in consultation with a medical librarian and can be found in Supplementary Material 1. We also screened the references of applicable articles to identify additional relevant studies not captured in the initial search.
Inclusion and Exclusion Criteria
Preset criteria were established before search initiation to guide article selection. Articles were deemed appropriate if they met the following criteria: (1) articles published between database inception and October 2, 2025, that discussed the use of esmolol in the management of rVF/pVT in adults; (2) Full-text articles, without language restrictions; and (3) In-hospital and out of hospital cardiac arrest (OHCA). Systematic reviews, meta-analyses, scoping reviews, narrative reviews, case reports, case series, editorials/commentaries, books, book chapters, pediatric studies, animal studies, and in vitro studies were excluded.
Study Screening and Data Extraction
The study selection process was conducted independently by four reviewers. Titles and abstracts were screened based on the inclusion and exclusion criteria (Figure 1). Any differences in selection were discussed and resolved by consensus at all stages. The process was performed on the Covidence systematic review management platform [14]. Three reviewers independently extracted data using a standardized chart for consistency. The following data were extracted: (1) publication details; (2) study design; (3) outcomes; (4) patient characteristics (sample size, sex, age); (5) intervention; and (6) control. Table 1 summarizes the characteristics of the included studies [4,8,13,15].
Outcome Definitions
To ensure consistency across studies, outcomes were standardized as follows: (1) temporary ROSC: Return of spontaneous circulation lasting less than 20 minutes; (2) sustained ROSC: return of spontaneous circulation lasting 20 minutes or longer; (3) survival to discharge: patient survival measured at the time of hospital discharge; and (4) favorable neurological outcome: Cerebral Performance Category score ≤ 2 at the time of hospital discharge. For studies without explicit ROSC definitions, all initial ROSC events were classified as temporary unless sustained ROSC was explicitly reported. These criteria were applied consistently across studies to ensure comparability.
Assessment of the Risk of Bias and Statistical Analysis
The risk of bias in the included studies was evaluated using the Newcastle-Ottawa Scale for observational studies across selection, comparability, and outcome domains. Because this study is a meta-analysis, a formal a priori sample size calculation was not applicable. The total number of subjects reflects the aggregate sample sizes of all eligible studies, which allows for a reasonably precise estimation of the pooled effect. We performed analyses in R using the meta package (R Foundation for Statistical Computing) [16,17]. The t-tests were used to compare age between subgroups, and Fisher’s exact test was used for categorical variables. Pooled risk ratios (RRs) and 95% CIs are reported, with statistical significance defined as a CI that does not include 1. Heterogeneity was assessed using the I² statistic, with I² >50% or P<0.10 indicating significant heterogeneity. A random-effects model was used when I² >50%; otherwise, a common-effect model was applied. Given anticipated clinical heterogeneity in Stupca et al. [13] (including mixed rhythms and bundled interventions), a sensitivity analysis excluding this study was performed to explore sources of heterogeneity.
Study Selection
Figure 1 illustrates the study screening process. In total, 2,888 articles were identified, of which 2,884 were excluded, leaving four retrospective studies for inclusion in this SRMA.
Baseline Characteristics
The baseline characteristics of the study participants are presented in Table 2. Patients were predominantly male (72%–100%) across both the esmolol and control arms, and the median age range was from the mid-50s to the 70s. Most patients who received esmolol presented with VF as their initial rhythm (80%) and received bystander cardiopulmonary resuscitation (CPR) (74.6%). Patients in the control group presented similarly with VF as their initial rhythm (85.3%), and most of them also received bystander CPR (74.1%). Three studies evaluated esmolol as a standalone intervention, whereas Stupca et al. [13] used a bundled protocol (esmolol, vector-change defibrillation, and capped epinephrine). The overall risk of bias for each study was deemed to be low to moderate (Supplementary Material 2).
Temporary ROSC
Esmolol was associated with a higher incidence of temporary ROSC than the control (RR, 1.80; 95% CI, 1.09–2.98; 273 patients; I²=51%), which suggests an increased likelihood of an initial resuscitation response (Figure 2A).
Sustained ROSC
Esmolol demonstrated a non-significant trend toward improved sustained ROSC (RR, 1.25; 95% CI, 0.28–5.66; 149 patients), with substantial heterogeneity among studies (I²=91%) (Figure 2B).
Survival to Discharge
A non-significant trend toward improved survival to discharge was observed (RR, 1.08; 95% CI, 0.57–2.03; 273 patients; I²=47%) (Figure 3).
Favorable Neurological Outcomes
A non-significant trend favoring esmolol for survival with favorable neurological outcomes was observed (RR, 2.08; 95% CI, 0.83–5.24; 149 patients; I²=6%) (Figure 4).
Sensitivity Analysis
When we excluded Stupca et al. [13], esmolol was associated with significant improvements in temporary ROSC (RR, 1.95), sustained ROSC (RR, 2.84), and favorable neurological outcomes (RR, 3.26), with reduced heterogeneity. A non-significant trend toward improved survival to discharge persisted (RR, 1.68) (Supplementary Figures 1-3).
Interpretation of Findings
Our SRMA provides an updated evaluation of the clinical effects of esmolol in rVF. Esmolol was associated with a significant improvement in temporary ROSC (RR, 1.80; 95% CI, 1.09–2.98), and although the associations were not statistically significant, point estimates also favored esmolol for sustained ROSC (RR, 1.25), survival to discharge (RR, 1.08), and survival to discharge with favorable neurological outcomes (RR, 2.08). The sensitivity analysis excluding Stupca et al. [13] strengthened those findings, demonstrating significant improvements in temporary ROSC (RR, 1.95; 95% CI, 1.32–2.86), sustained ROSC (RR, 2.84; 95% CI, 1.44–5.61), and favorable neurological outcomes (RR, 3.26; 95% CI, 1.06–10.07), along with a continued positive trend in survival to discharge (RR, 1.68; 95% CI, 0.78–3.63).
Although studies on both rVF and pVT were eligible for our SRMA, the pooled population predominantly reflects rVF, with pVT comprising only a small proportion. Findings differed between the studies that evaluated esmolol alone and the one that used a bundled intervention. Lee et al. [8], Driver et al. [4], and Patrick et al. [15] favored the use of esmolol, whereas Stupca et al. [13] favored standard ACLS care. This discrepancy appears to be largely attributable to baseline clinical differences, rather than the bundled intervention itself.
Patients in Stupca et al. [13] were older than those in the other included studies, with mean ages of 70.8 years in the esmolol group and 68.6 years in the control group. Age is an independent predictor of mortality in OHCA, particularly in patients older than 70 years [18]. In addition, the esmolol group had a substantially higher proportion of non-shockable rhythms (19.1% vs. 5.6%), a pattern not observed in other studies [13]. This distinction is clinically important because non-shockable rhythms are associated with significantly worse outcomes and are not appropriate targets for esmolol therapy. In contrast, the other studies more strictly reflected rVF populations, aligning with current practice [4,8]. Furthermore, compared with the patients in the other studies, the esmolol group in Stupca et al. [13] experienced longer prehospital times, which are associated with increased immediate mortality and poor neurological outcomes [19].
Differences in intervention design might also have contributed to the differences among the studies. Stupca et al. [13] used a bundled protocol with lower-dose esmolol and vector-change defibrillation, which could have introduced heterogeneity. Evidence suggests that vector-change defibrillation does not consistently improve ROSC, survival, or neurological outcomes in rVF patients [20,21].
Taken together, those factors provide a strong rationale for our sensitivity analysis. Excluding Stupca et al. [13] reduced heterogeneity and revealed more consistent and clinically meaningful effect estimates across outcomes. Importantly, the overall direction of the effects remained favorable even when all studies were included, consistent with prior meta-analyses by Miraglia et al. [22] and Hasegawa et al. [23].
Esmolol’s potential benefit is supported by its physiologic mechanism. By attenuating the catecholamine surge associated with prolonged VF and repeated epinephrine administration, esmolol might reduce myocardial oxygen demand and increase the likelihood of successful defibrillation [24]. Although epinephrine improves coronary perfusion pressure, excessive exposure can worsen myocardial function, reduce survival, and negatively affect neurological outcomes [8,15,25,26]. Although retrospective clinical studies have evaluated neurological outcomes as secondary endpoints and suggested a possible signal toward improved neurological function, those findings were observational and do not establish a direct neuroprotective effect. Evidence supporting neuroprotection is therefore largely derived from preclinical animal models, and its applicability to human cardiac arrest remains uncertain. Epinephrine use varied across the studies: Driver et al. [4] reported continued use in approximately half of the esmolol group. Lee et al. [8] and Patrick et al. [15] did not limit epinephrine in either group, and Stupca et al. [13] capped epinephrine at 3 mg. This variability might have influenced the observed outcomes. Collectively, the findings support esmolol as a physiologically targeted adjunct in rVF, rather than a universal therapy for all cardiac arrest rhythms.
Emerging evidence highlights the ongoing exploration of esmolol within broad resuscitation strategies. For example, Slagt et al. [27] evaluated a helicopter emergency medical service protocol that incorporated esmolol alongside vasoactive agents, adjunct medications, and alternative defibrillation strategies. Among 19 patients, 47% achieved ROSC, and 42% survived to discharge with favorable neurological outcomes. However, due to the use of combined interventions, the observed outcomes cannot be attributed exclusively to esmolol, which is why that study was not included in our meta-analysis.
Strengths
This SRMA synthesizes the best available evidence evaluating esmolol in rVF and incorporates clinically meaningful outcomes: ROSC, survival to discharge, and neurological recovery. Given the challenges of conducting randomized trials in cardiac arrest, this approach provides valuable insight to inform clinical practice. Additional strengths include a rigorous methodology and collaboration with a medical librarian.
Limitations
This study was not prospectively registered, which might limit transparency and increase the potential for reporting bias. However, given the narrowly defined clinical context and small pool of eligible studies, the risk of selective reporting is likely low. All eligibility criteria, outcomes, and analyses were predefined and conducted in accordance with the PRISMA guidelines. All included studies were retrospective, introducing potential selection bias, confounding, and limitations in causal inference. Variability in CPR quality, adjunctive therapies, and the baseline patient characteristics of age, initial rhythm, and comorbidities might also have influenced the outcomes [28-31]. The reporting of key variables, such as CPR duration and use of adjunct medications (e.g., calcium, sodium bicarbonate), was inconsistent across studies [4,8,13,15]. Additionally, unmeasured pre-arrest factors, such as comorbidities, might further confound survival outcomes [31].
Small sample sizes and predominantly single-center designs limit statistical power and generalizability. Although ACLS protocols are widely standardized, variation in implementation across settings might still contribute to heterogeneity. Follow-up duration was limited to in-hospital or short-term outcomes, restricting the assessment of long-term survival and neurological recovery. Finally, current evidence for esmolol is limited to rVF, so its role in pVT and non-shockable rhythms remains uncertain.
Clinical Application and Research Implications
Esmolol may be considered as a salvage therapy for adult patients with rVF who do not achieve ROSC after standard ACLS, particularly during a VF storm that continues despite repeated defibrillation and epinephrine [32]. Consideration should be given to adult patients with shockable rhythms, ideally excluding those with predominant non-shockable rhythms or prolonged downtime because the current evidence is limited to rVF. Optimal use, including timing, dosing, and the selection of patients most likely to benefit, remains undefined and should be guided by institutional protocols and clinical judgment.
In this setting of limited effective treatment options and poor prognosis, even modest improvements in ROSC, survival, or neurological outcomes can be clinically meaningful. Ultimately, resuscitation decision-making must balance aggressive life-saving interventions with the consideration of long-term outcomes and patient quality of life [32]. Further prospective multicenter studies are needed to refine the criteria for patient selection and standardized esmolol administration.
Conclusion
In observational study data, esmolol was associated with improved rates of temporary ROSC in the emergency management of rVF. A sensitivity analysis suggests possible associations with sustained ROSC and survival to discharge with favorable neurological outcomes. However, the effect on sustained ROSC and survival to discharge alone were not statistically significant, and the overall evidence remains sparse and subject to the inherent constraints of retrospective study designs. These findings support a further investigation into esmolol as a possible adjunct in rVF, with prospective studies needed to clarify its effects on long-term survival and neurological outcomes.
▪ Esmolol is a rapid-onset, ultra-short-acting beta-1 blocker that might help to terminate refractory ventricular fibrillation (rVF) or pulseless ventricular tachycardia by attenuating excessive catecholamine activity, both endogenous and exogenous (e.g., epinephrine), when standard antiarrhythmics fail.
▪ Amiodarone and lidocaine have not demonstrated improvements in long-term survival or neurological function in rVF, whereas esmolol has shown potential to improve return of spontaneous circulation (ROSC), survival, and neurological function in preclinical models and small clinical studies.
▪ Esmolol was associated with improved temporary ROSC in rVF, with possible benefits in sustained ROSC and neurological survival, although further research is needed.

CONFLICT OF INTEREST

No potential conflict of interest relevant to this article was reported.

FUNDING

None.

ACKNOWLEDGMENTS

None.

AUTHOR CONTRIBUTIONS

Conceptualization: AL. Data curation: KL, YLC, UE, AL. Data analysis: AL, KL, YLC, DY. Writing - original draft: KL, YLC, AL, TC, ML. Writing - review & editing: KL, YLC, AL, DY, TC, ML, UE. All authors read and agreed to the published version of the manuscript.

Supplementary materials can be found via https://doi.org/10.4266/acc.001675.
Supplementary Material 1.
Database search strategies
acc-001675-Supplementary-Material-1.pdf
Supplementary Material 2.
Quality assessment of included observational studies using the Newcastle-Ottawa Scale
acc-001675-Supplementary-Material-2.pdf
Supplementary Figure 1.
Forest plots comparing esmolol vs. no esmolol for return of spontaneous circulation (ROSC) outcomes: (A) temporary ROSC and (B) Sustained ROSC. RR: risk ratio.
acc-001675-Supplementary-Figure-1.pdf
Supplementary Figure 2.
Esmolol vs. no esmolol: survival to discharge. RR: risk ratio.
acc-001675-Supplementary-Figure-2.pdf
Supplementary Figure 3.
Esmolol vs. no esmolol: survival with favorable neurological outcomes. RR: risk ratio.
acc-001675-Supplementary-Figure-3.pdf
Figure 1.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of the study selection process.
acc-001675f1.jpg
Figure 2.
Forest plots showing esmolol vs. no esmolol for (A) temporary return of spontaneous circulation (ROSC) and (B) sustained ROSC. We derived temporary ROSC by subtracting the number of sustained ROSC cases from the total cases of any ROSC. RR: risk ratio.
acc-001675f2.jpg
Figure 3.
Esmolol vs. no esmolol: survival to discharge. RR: risk ratio.
acc-001675f3.jpg
Figure 4.
Esmolol vs. no esmolol: survival with favorable neurological outcomes. RR: risk ratio.
acc-001675f4.jpg
Table 1.
Characteristics of the studies included in the SRMA
Author (year)/location Design and participants Intervention Key Results
Driver et al. (2014)/USA [4] A single-center retrospective study performed in an urban academic ED investigating patients experiencing out of hospital cardiac arrest or ED cardiac arrest with an initial rhythm of VF/VT who were refractory to at least three defibrillation attempts, 300 mg of amiodarone and 3 mg of adrenaline during the period of Jan 2011 to Jan 2014 Patients received a 500 μg/kg esmolol bolus, followed by a maintenance infusion of 0–100 μg/kg/min. Six patients who received esmolol were compared to nineteen patients who did not.
Those who received esmolol had higher rates of achieving temporary ROSC, sustained ROSC, survival to ICU, survival to hospital discharge, and survival to discharge with good neurological outcomes, although none of these results were statistically significant.
Lee et al. (2016)/South Korea [8] A single-center retrospective study evaluating patients with rVF originating from initial VF/ VT in out of hospital cardiac arrest refractory to three or more defibrillation attempts, 3 mg of epinephrine, 300 mg of amiodarone, and had no ROSC after 10 min of cardiopulmonary resuscitation between Jan 2012 and Dec 2015 Patients received a loading dose of 500 μg/kg esmolol, followed by an infusion of 0–100 μg/kg/min. Sixteen patients who received esmolol were compared to twenty-five patients who did not. The intervention group had a significantly higher rate of sustained ROSC and better rates of temporary ROSC and survival to ICU admission. There were no significant differences in rate of survival and survival to discharge with good neurological outcomes compared to the control group.
Patrick et al. (2022)/USA [15] A retrospective study of a large suburban emergency medical services evaluating the effects of esmolol in patients with rVF. Control cases were from Oct 2017 to Sep 2018, while intervention cases were from Oct 2018 to Oct 2020. Patients received a 0.5 mg/kg single bolus of esmolol. Sixty-one patients who received esmolol were compared to sixty-three patients in the control group. In the intervention group, there was a higher rate of prehospital ROSC and similar rates of survival at 24 hr and survival to hospital discharge, although these were not statistically significant.
Stupca et al. (2023)/USA [13] A multicenter retrospective study evaluating patients with prehospital cardiac arrest with rVF/pVT, originating from an initial rhythm of VF/pVT. Patients who received at least 3 defibrillations, at least 3 mg of epinephrine, and 300 mg amiodarone from Oct 2017 to Nov 2019 were included in the control group. Patients in the intervention group were included from Dec 2019 to Mar 2022. Patients received an Emergency Medical Service bundle, which consisted of esmolol (40 mg IV push, average 0.435 mg/kg) followed by 60 mg IV infusion over 10 min), vector change defibrillation, and dose-capped epinephrine at 3 mg. Forty-seven patients who received the interventions were compared to thirty-six patients who received standard advanced cardiovascular life support care. The control group achieved significantly higher rates of sustained ROSC, any ROSC, and survival to hospital arrival. However, the rates of survival to hospital discharge and neurologically intact survival at hospital discharge were not statistically significant.

SRMA: systematic review and meta-analysis; ED: emergency department; VF: ventricular fibrillation; VT: ventricular tachycardia; ROSC: return of spontaneous circulation; ICU: intensive care unit; rVF: refractory ventricular fibrillation; pVT: pulseless ventricular tachycardia; IV: intravenous.

Table 2.
Baseline characteristics between the esmolol group and control group of the included studies
Author (year) Patient group Age (yr) Male Initial rhythm VF Bystander CPR Defibrillation attempts
Esmolol Control Esmolol Control Esmolol Control Esmolol Control Esmolol Control Esmolol Control
Driver et al. (2014)/ [4] 6 19 54.5 (47–59) 56 (48–66.2) 6 (100) 18 (94.7) 6 (100) 18 (94.7) 3 (75) 14 (77.8) 6.5 (5–9.5) 7 (5–8)
Lee et al. (2016) [8] 16 25 58 (45.8–72) 52 (43.6–64.5) 14 (87.5) 19 (76.0) 14 (87.5) 21 (84.0) 11 (68.8) 16 (64) 6 (6–8.75) 5 (5–6.5)
Patrick et al. (2022) [15] 61 63 67 (57–76) 67 (55–77) 44 (72.1) 45 (71.4) 44 (72.1) 52 (82.5) 47 (77.1) 48 (76.2) 5 (4–7) 6 (5–9)
Stupca et al. (2023) [13] 47 36 70.8±12.8 68.6±14.7 40 (85.1) 29 (80.6) 40 (85.1) 31 (86.1) 36 (76.6) 28 (77.8) 8.6±3.4 5.8±2.9

Values are presented as median (interquartile range), number (%), or mean±standard deviation.

CPR: cardiopulmonary resuscitation.

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        Esmolol in the management of refractory ventricular fibrillation: a systematic review and meta-analysis
        Acute Crit Care. 2026;41(3):598-607.   Published online August 19, 2026
        DOI: https://doi.org/10.4266/acc.001675
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      Esmolol in the management of refractory ventricular fibrillation: a systematic review and meta-analysis
      Image Image Image Image
      Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of the study selection process.
      Figure 2. Forest plots showing esmolol vs. no esmolol for (A) temporary return of spontaneous circulation (ROSC) and (B) sustained ROSC. We derived temporary ROSC by subtracting the number of sustained ROSC cases from the total cases of any ROSC. RR: risk ratio.
      Figure 3. Esmolol vs. no esmolol: survival to discharge. RR: risk ratio.
      Figure 4. Esmolol vs. no esmolol: survival with favorable neurological outcomes. RR: risk ratio.

      Figure 1.

      Figure 2.

      Figure 3.

      Figure 4.

      Esmolol in the management of refractory ventricular fibrillation: a systematic review and meta-analysis
      Author (year)/location Design and participants Intervention Key Results
      Driver et al. (2014)/USA [4] A single-center retrospective study performed in an urban academic ED investigating patients experiencing out of hospital cardiac arrest or ED cardiac arrest with an initial rhythm of VF/VT who were refractory to at least three defibrillation attempts, 300 mg of amiodarone and 3 mg of adrenaline during the period of Jan 2011 to Jan 2014 Patients received a 500 μg/kg esmolol bolus, followed by a maintenance infusion of 0–100 μg/kg/min. Six patients who received esmolol were compared to nineteen patients who did not.
      Those who received esmolol had higher rates of achieving temporary ROSC, sustained ROSC, survival to ICU, survival to hospital discharge, and survival to discharge with good neurological outcomes, although none of these results were statistically significant.
      Lee et al. (2016)/South Korea [8] A single-center retrospective study evaluating patients with rVF originating from initial VF/ VT in out of hospital cardiac arrest refractory to three or more defibrillation attempts, 3 mg of epinephrine, 300 mg of amiodarone, and had no ROSC after 10 min of cardiopulmonary resuscitation between Jan 2012 and Dec 2015 Patients received a loading dose of 500 μg/kg esmolol, followed by an infusion of 0–100 μg/kg/min. Sixteen patients who received esmolol were compared to twenty-five patients who did not. The intervention group had a significantly higher rate of sustained ROSC and better rates of temporary ROSC and survival to ICU admission. There were no significant differences in rate of survival and survival to discharge with good neurological outcomes compared to the control group.
      Patrick et al. (2022)/USA [15] A retrospective study of a large suburban emergency medical services evaluating the effects of esmolol in patients with rVF. Control cases were from Oct 2017 to Sep 2018, while intervention cases were from Oct 2018 to Oct 2020. Patients received a 0.5 mg/kg single bolus of esmolol. Sixty-one patients who received esmolol were compared to sixty-three patients in the control group. In the intervention group, there was a higher rate of prehospital ROSC and similar rates of survival at 24 hr and survival to hospital discharge, although these were not statistically significant.
      Stupca et al. (2023)/USA [13] A multicenter retrospective study evaluating patients with prehospital cardiac arrest with rVF/pVT, originating from an initial rhythm of VF/pVT. Patients who received at least 3 defibrillations, at least 3 mg of epinephrine, and 300 mg amiodarone from Oct 2017 to Nov 2019 were included in the control group. Patients in the intervention group were included from Dec 2019 to Mar 2022. Patients received an Emergency Medical Service bundle, which consisted of esmolol (40 mg IV push, average 0.435 mg/kg) followed by 60 mg IV infusion over 10 min), vector change defibrillation, and dose-capped epinephrine at 3 mg. Forty-seven patients who received the interventions were compared to thirty-six patients who received standard advanced cardiovascular life support care. The control group achieved significantly higher rates of sustained ROSC, any ROSC, and survival to hospital arrival. However, the rates of survival to hospital discharge and neurologically intact survival at hospital discharge were not statistically significant.
      Author (year) Patient group Age (yr) Male Initial rhythm VF Bystander CPR Defibrillation attempts
      Esmolol Control Esmolol Control Esmolol Control Esmolol Control Esmolol Control Esmolol Control
      Driver et al. (2014)/ [4] 6 19 54.5 (47–59) 56 (48–66.2) 6 (100) 18 (94.7) 6 (100) 18 (94.7) 3 (75) 14 (77.8) 6.5 (5–9.5) 7 (5–8)
      Lee et al. (2016) [8] 16 25 58 (45.8–72) 52 (43.6–64.5) 14 (87.5) 19 (76.0) 14 (87.5) 21 (84.0) 11 (68.8) 16 (64) 6 (6–8.75) 5 (5–6.5)
      Patrick et al. (2022) [15] 61 63 67 (57–76) 67 (55–77) 44 (72.1) 45 (71.4) 44 (72.1) 52 (82.5) 47 (77.1) 48 (76.2) 5 (4–7) 6 (5–9)
      Stupca et al. (2023) [13] 47 36 70.8±12.8 68.6±14.7 40 (85.1) 29 (80.6) 40 (85.1) 31 (86.1) 36 (76.6) 28 (77.8) 8.6±3.4 5.8±2.9
      Table 1. Characteristics of the studies included in the SRMA

      SRMA: systematic review and meta-analysis; ED: emergency department; VF: ventricular fibrillation; VT: ventricular tachycardia; ROSC: return of spontaneous circulation; ICU: intensive care unit; rVF: refractory ventricular fibrillation; pVT: pulseless ventricular tachycardia; IV: intravenous.

      Table 2. Baseline characteristics between the esmolol group and control group of the included studies

      Values are presented as median (interquartile range), number (%), or mean±standard deviation.

      CPR: cardiopulmonary resuscitation.

      Table 1.

      Table 2.

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