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Double Sequential External Defibrillation for Refractory Ventricular Fibrillation: It’s All About the Timing

Double sequential external defibrillation (DSED) for refractory ventricular fibrillation (VF) has generated a great deal of interest, excitement and confusion as a treatment option for patients who present in refractory VF. Our research team was delighted by the invitation by JEMS to describe our findings from the 2019 NAEMSP annual meeting in this edition of the journal. In this article, we will also discuss controversies surrounding the practice of DSED and highlight some of the previous research into the effectiveness of DSED for refractory VF.

The Background

DSED has been studied for decades in the electrophysiology lab for patients in both refractory atrial fibrillation and refractory VF.1-8 Why do ongoing defibrillation attempts in refractory VF fail to terminate VF? The reason is believed to be at least twofold. As VF persists, the energy required to defibrillate increases as a function of time, due to ischemia induced changes in conduction velocity and refractoriness. Second, if the initial shocks fail to terminate VF, the energy supplied to the fibrillating heart may be insufficient to terminate VF. Finally, as resuscitation progresses, ongoing hypoxia, acidosis and exogenous and endogenous catecholamine surges increase myocardial oxygen consumption, making the ventricle more difficult to successfully defibrillate.1-4

Defibrillatory shocks effectively depolarize most of the fibrillating myocardium and allows coordinated muscle contraction of the heart to begin. When a shock fails to terminate VF, fibrillation invariably resumes or re-initiates starting in the region of lowest voltage and current gradient in the myocardium. Given the usual position of the defibrillation pads (anterior-anterior), this region will be the postero-lateral region of the left ventricle, where the shock vector results in the lowest voltage gradient. Considering the anatomical location of the left ventricle, a posterior structure, this region is furthest from the direct line between the electrode pads. As a consequence, there are multiple reasons why alternative methods of defibrillation may be more successful.     

Recently published case reports and multiple case series have described conflicting outcomes for patients treated with DSED for refractory VF.9-15 In a retrospective analysis of 50 DSED cases over a three-year time frame, Ross et al., reported no improvement in the primary outcome of neurologically intact survival with DSED, but did not include data regarding the timing of the DSED shock or CPR quality.10 Similar findings were noted by Beck et al., but failed to report the critical issue of the timing of DSED in refractory VF and also did not include data regarding the CPR quality provided.11 The authors note that “DSD may be more efficacious if used earlier and by standing protocol.” Cabanas et al., were able to demonstrate improved termination of VF employing a prehospital protocol using DSED, but reported no improvement in hospital survival, likely due to late application of the intervention.9 On the contrary, Lybeck et al., and Johnson et al., both described case reports of early use of DSED with successful outcomes of neurologically intact survival to hospital discharge.12,13 Most uses of DSED have been employed as an ad-hoc final effort to convert refractory VF, as opposed to a planned early application during the resuscitation.

Our Research            

The objective of our study was to explore the relationship between type of defibrillation (standard vs DSED), the number of defibrillation attempts provided and the outcomes of VF termination and VF termination with return of spontaneous circulation (ROSC) for out-of-hospital cardiac arrest (OHCA) patients presenting in refractory VF.

We performed a retrospective review of prospectively collected data on treated adult (≥ 18 years) OHCA who presented in VF and received a minimum of three successive standard defibrillations over a three-year period beginning on January 1, 2015 in four EMS agencies in Ontario, Canada. The agencies (Peel Regional Paramedic Service, Halton Region Paramedic Service, Simcoe Paramedic Service and Toronto Paramedic Service) provide emergency care and transport to a population of 4.8 million people in both urban and rural settings within a geographic area of 7,680 km2. To assess the relationship between number of defibrillation attempts, mode of defibrillation (standard vs DSED) and our outcome measures of VF termination and VF termination to ROSC, we performed a shock-sequence analysis. We first divided our overall cohort into two groups, those who only received standard defibrillation throughout their resuscitation, and those who received at least one DSED as part of their resuscitation. To assess the impact of mode of defibrillation on a shock-by-shock basis, we analyzed what type of defibrillation (standard or DSED) was provided to every patient at each defibrillation attempt. This allowed us to account for the variable time at which the initial DSED was provided during each individual resuscitation.

Our Results

During the study period, 252 patients met inclusion criteria. Of the 252 patients included in the analysis, 201 (79.8%) received standard defibrillation and 51 (20.2%) patients received DSED. Age, sex, location of arrest, EMS witnessed arrest, bystander witnessed status and rate of bystander CPR were similar between standard and DSED groups.

Overall, VF termination was similar between standard and DSED cohort (78.1% vs. 76.5%; RR: 1.0; 95% CI: 0.8 to 1.2). In our shock-sequence analysis, when early defibrillation attempts were considered (defibrillation attempt 4-8), VF termination was higher for those receiving DSED compared to standard defibrillation (29.4% vs. 17.5%; RR: 1.7; 95% CI: 1.1 to 2.6). When late defibrillation attempts were considered (defibrillation attempt 9-17), VF termination was higher for those receiving DSED compared to standard defibrillation (31.2% vs. 17.1%; RR: 1.8; 95% CI: 1.1 to 3.0). Overall, ROSC was similar between the standard and DSED groups (21.4% vs. 17.6%; RR: 0.8; 95% CI: 0.4 to 1.6). When early defibrillation attempts were considered (defibrillation attempt 4-8), ROSC was higher for those receiving DSED compared to standard defibrillation (15.7% vs. 5.4%; RR: 2.9; 95% CI: 1.4 to 5.9). When late defibrillation attempts were considered (defibrillation attempt 9-17), ROSC rates were similar for those receiving DSED compared to standard defibrillation (1.3% vs. 0.8%; RR: 1.6; 95% CI: 0.1 to 25.2). For cases where DSED terminated VF into ROSC, the median (interquartile range) number of standard defibrillations prior to DSED was 4 (4, 6), compared to 7 (6, 9) defibrillations when DSED did not result in ROSC. When DSED terminated VF into ROSC, it did so with a single DSED in 66.7% of cases. These results suggest that successful resuscitation with DSED may be time-sensitive, with greater success early in the resuscitation.

THE CONTROVERSIES

Timing of the intervention

A limitation of previous research is the omission of data surrounding the time to DSED for patients in refractory VF. In the vast majority of described cases, DSED is applied late as it is often used only after failed standard defibrillation attempts. With ongoing resuscitation efforts, conditions for successful defibrillation deteriorate, as hypoxia, acidosis and increased administration of epinephrine ensue. Our colleagues at the Minnesota Resuscitation Consortium have also suggested the timing of an intervention in refractory VF is critical to success. In an innovative approach to refractory VF, patients who present in refractory VF and have fail three defibrillation attempts are transferred from the field with mechanical CPR directly to the cardiac catheterization lab, where they are placed on extracorporeal membrane oxygenation (ECMO) and undergo percutaneous coronary intervention (PCI) for the critical coronary lesion producing the cardiac arrest in a vast majority of cases.16 While producing outstanding results in this subset of patients, it is critical to understand these results not only are based on superb prehospital and PCI/ECMO care, but exemplary ongoing inpatient care, as 100% of these patients sustain multisystem failure. Therefore, the generalizability of the Minnesota approach to refractory VF may be a challenge for the vast majority of EMS agencies. What has been shown to be critical is the element of time. For ECMO to be successful, it must be done early. In the Minnesota consortium, neurologically intact survival to hospital discharge is nearly 100% if ECMO is started within 30 minutes of cardiac arrest. Unfortunately, success drops by 25% for every ten minute delay over the original 30 minutes and is essentially 0% at one hour.17 Additionally, if ECMO was applied after multiple failed defibrillation attempts in the field, the likelihood of success would be far lower than currently reported.

Refractory or Recurrent VF: Does it Matter?

Research in the area of refractory VF has been complicated by the lack of a concrete definition of this condition. Similar controversies exist in the definition of VF termination. What matters most is how this difference impacts paramedics in their care of patients in a pragmatic manner. It is commonly quoted that biphasic defibrillation will terminate VF in greater than 90% of defibrillation attempts.18 What is obscure is how we describe “successful” defibrillation. Most would agree that defibrillation of VF into asystole or PEA would not be considered “successful,” yet up to 60% of defibrillation attempts result in these non-perfusing rhythms. Similarly, VF termination has been defined as VF terminated within five seconds of defibrillation.19 This historical definition dates back to 2005, prior to multiple changes in the provision of CPR. Recent focus on high quality CPR has resulted in extremely short post-shock pauses. CPR artifact makes the use of this historical definition problematic even when reviewing these cases in retrospect. For paramedics providing care, all that matters is what rhythm the patient is in after defibrillation and two minutes of CPR. The rhythm that occurred transiently after shock delivery has no role in their current management of refractory VF. As such, historical descriptions of refractory VF may include a heterogeneous collection of cases which include both refractory and recurrent VF.

Pooled Data from Heterogeneous Studies: Beware the Interpretation of the Results

Meta-analysis is the statistical procedure for combining data from multiple studies. A key benefit of this approach is the aggregation of information leading to a higher statistical power and more robust point estimate than is possible from the measure derived from any individual study. However, in performing a meta-analysis, an investigator must make choices which can affect the results, including deciding how to search for studies, selecting studies based on a set of objective criteria, dealing with incomplete data, analyzing the data, and accounting for or choosing not to account for publication bias. Unfortunately, the vast majority of studies in prehospital care, and most certainly those of DSED and refractory VF are not randomized controlled trials, but rather case series, case reports and observational cohort studies. Combining the results of these study designs in a meta-analysis can be problematic as heterogeneity may be a significant issue.20 Even a good meta-analysis cannot correct for poor design or bias in the original studies. Therefore, when interpreting results of a meta-analysis of DSED in refractory VF, look closely at the original study designs and use caution when interpreting the pooled results.

Research vs Real World Application: What is the Optimal Time Interval Between DSED Shocks?

Animal studies suggest that DSED may be successful by lowering the defibrillation threshold.3 Previous research suggests the optimal timing of the two shocks may be as short as 10 milliseconds (ms), or between 75-125 ms with a period of increased defibrillation threshold existing between 50 and 75 ms. Periods longer than 125 ms were not studied. The known refractory period of ventricular muscle is between 50-75 ms, which may be a particularly vulnerable period to reintroduce ventricular fibrillation.21 Contrasting these findings and those of earlier animal studies, Hoch et al., have demonstrated successful use of DSED in refractory VF with shocks separated by 0.5 to 4.5 seconds with no pharmacological therapy provided between unsuccessful and successful (DSED) shocks.1 For those doing DSED in the prehospital field, the timing of the shocks is generally heterogeneous as the application of the intervention is often varied between simultaneous (directly pressing the shock button on two defibrillators at the same time) and sequential (pressing the shock button of two defibrillators in a sequential manner). As such, it is often difficult to pragmatically determine the relationship between the exact timing of the DSED shocks and outcomes of interest. Our research group has developed a technique to retrospectively calculate the timing of the DSED shocks during a resuscitation. Future research will explore whether optimizing the time frame between the DSED attempts may improve outcomes of VF termination and ROSC. If the timing of DSED shocks in real life are related to DSED efficacy, technology could be developed that would optimize the timing of the DSED shocks by two defibrillators.

Defibrillator Damage – Myth vs Reality

One of the most common concerns of those wanting to start DSED is the potential to damage the defibrillator. Although rare, it is possible that damage to the defibrillator may occur when simultaneous (to the millisecond) defibrillation is employed.22 The mechanism of this damage is poorly understood. In fact, many EMS agencies have not been prepared to attempt DSED as some defibrillator manufacturers will not cover the warranty of the defibrillator if it is damaged during DSED.23 What I did find remarkable is the number of EMS agencies who approached me after our presentation at NAESP who are performing DSED with simultaneous defibrillation despite the warning of the defibrillator manufacturer. In reality, the likelihood of this occurring is remote as the ability for humans to provide shocks within this exact time frame is close to zero. To our knowledge, there has never been a case of defibrillator damage when sequential shocking has occurred, and rapid sequential defibrillation has not been associated with defibrillator damage/malfunction.

Double Sequential External Defibrillation: Is it the Energy or the Vector?

In theory, the application of DSED leads to the provision of more energy to overcome the increasing defibrillatory threshold observed as standard defibrillation attempts continue to fail. However, the issue may not be an energy problem. The efficacy of DSED may simply be the alternate plane or vector of defibrillation provided by the anterior-posterior pad placement added to standard anterior-anterior pad placement. The vector or pathway of flow of defibrillatory energy may be a factor in vector change success, as shocks incorporating a pathway that includes the interventricular septum may require lower energy levels to defibrillate, and different pathways can result in increased current density (voltage gradients) in the lowest voltage areas after standard shocks.24 Additional research is required to determine whether the potential benefit of DSED is related to energy, vector or both.

A New Trial to Help Address Some of These Issues: Double Sequential External Defibrillation in Refractory VF: The DOSE VF Randomized Controlled Trial

            The DOSE VF pilot study is a cluster randomized crossover study designed to determine the feasibility of conducting a full-scale randomized trial in this patient population. Specifically, patients who present in VF and fail three successive defibrillation attempts are randomized to receive one of three therapies: (1) continued resuscitation using standard defibrillation; (2) resuscitation involving DSED; or (3) resuscitation involving vector change (change of defibrillation pads from anterior-anterior to an anterior-posterior pad position) defibrillation. The primary outcome will be survival to hospital discharge. To date, we have trained over 2,300 paramedics in Ontario in the technique of DSED and vector change defibrillation. Training videos for the DOSE VF RCT study used by the Peel Regional Paramedic Services are attached below. All paramedics underwent in-person training using a combination of didactic, video and simulated scenarios prior to the study launch. All eligible patients with refractory VF (n=128 to date) in four participating EMS agencies have been enrolled, and paramedics have successfully applied both vector change and DSED with no reported issues. We have demonstrated our protocol is feasible and well accepted by paramedics in the field. It is our hope that the DOSE VF pilot study and the expansion of this trial to more sites will provide high level evidence as to the potential benefit of alternate defibrillation strategies for patients presenting in refractory VF.

In conclusion, DSED remains a potential exiting alternative therapy for patients presenting in refractory VF. Although controversy exists as to the mechanism of effect, current and future high-quality research trials may clarify the pragmatic effectiveness of DSED for refractory VF in the prehospital setting.

VIDEO

Training video: Peel Regional Paramedic Services

IMAGES

DS Dose VF

Dose VF Launch

DS Dose VF Defib

Defib Card Vector

REFERENCES

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23.       Communication. Physio-Control, Inc.

24.       Marrouche NF, Bardy GH, Frielitz HJ, Gunther J, Brachmann J. Quadruple pads approach for external cardioversion of atrial fibrillation. Pacing Clin Electrophysiol. 2001;24:1321–1324.

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