A new defibrillation strategy for refractory ventricular fibrillation during out-of-hospital cardiac arrest: are two better than one?

Comment on ‘Defibrillation Strategies for Refractory Ventricular Fibrillation’ which was published in the New England Journal of Medicine,https://doi.org/10.1056/NEJMoa2207304 The Double Sequential External Defibrillation for Refractory Ventricular Fibrillation (DOSE VF) study is a three-group, cluster-randomized, controlled trial with crossover among six Canadian paramedic services to evaluate double sequential external defibrillation (DSED) and vector-change (VC) defibrillation as compared with standard defibrillation in adult patients with refractory ventricular fibrillation (VF) during out-of-hospital cardiac arrest (OHCA).1 A total of 405 participants (mean age, 64 years; 84% male) were randomly assigned in a 1:1:1 ratio to receive standard defibrillation, VC defibrillation or DSED. This population included 152 patients from a randomized, controlled pilot trial.2 Overall, 68% of OHCAs were observed by bystanders and 58% received bystander cardiopulmonary resuscitation. The median time from the initial call to the arrival of paramedics at the scene (∼7.5 min) and the resuscitation characteristics, including doses of epinephrine and antiarrhythmic drugs administered, were similar in the three groups. The trial was interrupted prematurely because of operational challenges resulting from the COVID-19 pandemic, with a total of 136 patients assigned to standard defibrillation, 144 to VC defibrillation, and 125 to DSED. The primary endpoint was survival to hospital discharge. Secondary outcomes included termination of VF, return to spontaneous circulation and a good neurological outcome, defined as a modified Rankin scale score ≤ 2 at hospital discharge. A total of 38 patients (30%) in the DSED group and 31 patients (22%) in the VC group survived to hospital discharge, as compared with 18 patients (13%) in the standard defibrillation group [relative risk (RR), DSED vs. standard, 2.21; 95% confidence interval (CI): 1.33–3.67; RR, VC vs. standard, 1.71; 95% CI: 1.01–2.88). The effect estimates for the primary outcome were consistent across multiple sensitivity analyses. With regard to secondary outcomes, as compared with standard defibrillation strategy, DSED was associated with a significantly higher percentages of patients having VF termination (84% vs. 67%; RR: 1.25; 95% CI: 1.09–1.44), return to spontaneous circulation (46% vs. 26%; RR: 1.72; 95% CI: 1.22–2.42) and a good neurologic outcome at hospital discharge (27% vs. 11%; RR: 2.21; 95% CI: 1.26–3.88). VC defibrillation strategy was associated with a higher percentage of VF termination (79% vs. 67%; RR: 1.18; 95% CI: 1.03–1.36). Approximately 20% of cardiac arrests initially present a shockable rhythm, predominantly VF.1 Of these, ∼20% will remain in VF after five shocks, despite standard resuscitation interventions, and new defibrillation strategies have been proposed.2 DSED refers to rapid sequential shocks provided by two defibrillators, with defibrillation pads placed in two different planes: during the first defibrillation, the shock delivering pads are placed in a standard antero-lateral position, according to current guidelines,3 the additional pads are placed in an antero-posterior position to perform the second near-simultaneous defibrillation shock. VC refers to switching defibrillation pads from antero-lateral to anterior-posterior position. The results of the DOSE VF trial suggest that survival to hospital discharge was higher among patients who received DSED than among patients receiving standard defibrillation for the treatment of refractory VF, defined as the failure to terminate VF after three antero-lateral shocks, during OHCA.1 Moreover, termination of VF, return of spontaneous circulation and a good neurologic outcome were observed more frequently with DSED compared with standard defibrillation.1 In contrast, the benefit of VC defibrillation as compared with standard defibrillation should be interpreted with caution, in view of the marginally significant difference for the primary outcome and a less consistent effect with regard to secondary outcomes and sensitivity analyses. Theoretical reasons as to why DSED might be more effective than standard defibrillation in refractory VF include multiple shock vectors, reduced transthoracic impedance and an additive effect to increase the mass of myocardium exposed to two defibrillating currents.4 In order to be successful, this procedure should be combined with early high-quality compression, appropriate medication, and thorough investigation of the underlying cause of cardiac arrest. Previous, small observational studies showed no clear benefit of DSED defibrillation compared to standard defibrillation, and a systematic review of the International Liaison Committee on Resuscitation concluded in 2020 that the evidence for DSED compared with standard defibrillation was very low.5–8 The authors of the Dose VF trial compared three defibrillation strategies on the hard endpoint of survival to hospital discharge in patients with refractory VF, using multivariable analyses to adjust for imbalances (age, sex, and receipt of bystander cardiopulmonary resuscitation). A strength of this trial is related to its implementation in both urban and rural areas by approximately 4000 paramedics trained in basic and advanced life support with different type of defibrillators. A second positive feature of this trial is the cluster-randomized trial design with crossover of the three defibrillation strategies, that decreases the risk of bias from high/low performing paramedic teams. Moreover, although the treating paramedics had to be aware of the assigned defibrillation strategy, people assessing survival and neurologic outcomes were blinded to the treatment assignments. Study limitations include early termination of the trial (due to the Covid-19 pandemic), which led to reduced sample size (from an expected 930 to the actual 405) and consequent low number of outcome events, possibly overestimating the effect size of the experimental intervention. The second limitation is the combination of data from the pilot feasibility trial9 with data from the subsequent main study, given the different inclusion criteria and intervention personnel. Other limitations resulted from the lack of post-resuscitation care information after hospital discharge (with particular regard to long-term follow-up for the neurologic outcome) and lack of information on patient race/ethnicity, coexisting conditions, medications and length of hospital stay. This trial is an important step in improving the current defibrillation strategy for refractory VF during OHCA, but additional randomized trials are needed to further define the effects of DSED and VC defibrillation in this setting, including trials adequately powered to test the difference in survival and post-resuscitation clinical outcomes between the standard approach and DSED, and to assess feasibility of the latter in less-than-ideal scenarios. No new data were generated or analysed in support of this research. All authors declare no funding for this contribution.