Refractory Ventricular Fibrillation: Potential Treatments

Background – What is Double Sequential External Defibrillation?

Out-of-hospital cardiac arrest (OHCA) is a leading cause of morbidity and mortality globally, with a survival rate of less than 10% despite emergency medical services (EMS) interventions. Patients presenting with an initial rhythm of ventricular fibrillation (VF) have the highest chance of neurologically intact survival. However, some patients remain in ventricular fibrillation despite multiple defibrillation attempts, termed refractory VF (RVF). Although there’s no standard definition of refractory ventricular fibrillation, it is generally defined as persistent VF after three successive defibrillation attempts, with or without standard Advanced Cardiac Life Support (ACLS) interventions. RVF patients typically have poor survival and neurological outcomes.

Double sequential external defibrillation (DSED) has emerged as a potential treatment for RVF. Double sequential external defibrillation involves using two defibrillators to deliver two defibrillatory shocks in rapid succession. Previous studies have examined the use of DSED in atrial fibrillation, VF, and RVF with varying outcomes. The recent DOSE-VF trial indicated that survival to hospital discharge was higher among refractory ventricular fibrillation OHCA patients who received DSED than those who received standard defibrillation. However, the mechanism and optimal timing of DSED shocks remain unclear, particularly in human studies.

The Abstract

Background – Animal studies suggest the efficacy of double sequential external defibrillation (DSED) may depend on the interval between the two shocks, or “DSED interval”. No human studies have examined this concept.

Objectives– To determine the relationship between DSED interval and termination of ventricular fibrillation (VFT), return of spontaneous circulation (ROSC), survival to hospital discharge, and favourable neurological status (MRS ≤ 2) for patients in refractory VF.

Methods – We performed a retrospective review of adult (≥18 years) out-of-hospital cardiac arrest between January 2015 and May 2022 with refractory VF who received ≥1 DSED shock. DSED interval was divided into four pre-defined categories. We examined the association between DSED interval and patient outcomes using general estimated equation logistic regression or Fisher’s exact test.

Results – Among 106 included patients, 303 DSED shocks were delivered (median 2, IQR 1–3). DSED intervals of 75–125 ms (OR 0.39, 95% CI 0.16–0.98), 125–500 ms (OR 0.36, 95% CI 0.16–0.82), and >500 ms (OR 0.27, 95% CI 0.11–0.63) were associated with lower probability of VF termination compared to <75 ms interval. DSED interval of >75 ms was associated with lower probability of ROSC compared to <75 ms interval (OR 0.37, 95% CI 0.14–0.98). No association was noted between DSED interval and survival to hospital discharge or neurologic outcome.

Conclusions – Among patients in refractory VF a DSED interval of less than 75 ms was associated with improved rates of VF termination and ROSC. No association was noted between DSED interval and survival to hospital discharge or neurologic outcome.
The impact of double sequential shock timing on outcomes during refractory out-of-hospital cardiac arrest¹. Rahimi M, Drennan I, Turner L.
Resuscitation

What kind of study is this?

This study is a retrospective cohort study using prospectively collected data from six paramedic agencies in Ontario, Canada, covering a population of 4.8 million people. The study aimed to investigate the relationship between the interval of double sequential external defibrillation shocks and patient outcomes, including termination of ventricular fibrillation, return of spontaneous circulation (ROSC), survival to hospital discharge, and favourable neurological status. Data was collected between January 2015 and May 2022, and the study included adult patients (≥18 years) with OHCA who presented in RVF and received at least one DSED shock.

Tell me about the patients

The study included 106 patients who met the criteria for refractory ventricular fibrillation and received double sequential external defibrillation shocks. Among these, 69 patients (65%) were enrolled in the DOSE-VF randomised controlled trial (RCT), while the remaining 37 patients (35%) received double sequential external defibrillation prior to the RCT. Patient characteristics were:

Median age: 63 years (IQR: 24 years)
84% were male
30.2% had a cardiac arrest in a public location
8.5% were witnessed by paramedics
72.4% had bystander-witnessed arrests
57.5% received bystander CPR

Most patients received epinephrine (92.5%) and amiodarone (82.1%) during resuscitation efforts. Chest compression metrics adhered to current guidelines, with a median chest compression rate of 113/min and a chest compression fraction of 82.9%.

Importantly patients in the study were not just those in the DOSE-VF study, but a mix of those and other patients who had DSED performed prior to the study either at the request of paramedics following physician advice, or later under paramedic discretion. This is important as it means the study population is a bit of a mixed bag in terms of selection and that selection bias may therefore be an issue.

What were the measured outcomes in this study?

The primary outcome was the termination of refractory ventricular fibrillation. Secondary outcomes included:

Return of spontaneous circulation (ROSC)
Survival to hospital discharge
Favourable neurological status at discharge, defined as a modified Rankin Scale (mRS) ≤ 2

Double sequential external defibrillation intervals were divided into four categories: <75 ms, 75–125 ms, 125–500 ms, and >500 ms. The association between these intervals and the outcomes was examined using logistic regression models and Fisher’s exact test.

What are the main results?

The main findings of the study are as follows:

A total of 303 double sequential external defibrillation shocks were delivered to 106 patients, with a median of 2 shocks per patient (IQR 1–3).
Double sequential external defibrillation intervals were shorter in the pre-RCT period (simultaneous method) compared to the RCT period (sequential method). This is interesting as in some of the earlier patients DSED was actually simultaneous shocking, and so again a bit of a mixed bag in terms of patients.
Ventricular fibrillation termination was achieved in 26.7% of shocks, with higher success rates for intervals <75 ms (48%) compared to intervals 75–125 ms (24.1%), 125–500 ms (27%), and >500 ms (23.8%).
ROSC was achieved in 11.6% of DSED shocks, with intervals <75 ms showing higher success (24%) compared to intervals >75 ms (10.4%).
No significant difference in survival to hospital discharge or favourable neurological outcome was noted based on DSED interval.

What about the limitations?

The study provides valuable insights into the optimal timing for DSED in RVF patients. However, several limitations should be considered:

Retrospective Design: The study’s retrospective nature introduces potential biases and limits the ability to infer causality.
Data Limitations: Exact DSED intervals <70 ms could not be precisely calculated, impacting the analysis of very short intervals.
Small Sample Size: The sample size may be underpowered to detect significant differences, particularly for survival and neurological outcomes. We would certainly like to see a larger sample size.
Variability in Interventions: Differences in pre-RCT and RCT protocols (simultaneous vs. sequential DSED).
External Validity: The study is based on data from a specific region and EMS system, which may limit its generalisability to other settings. There is always a concern when practice changes based on one group’s research, and it would be good to see changes and improvements in other health economies.

Despite these limitations, the study’s findings align with previous animal research suggesting shorter DSED intervals may improve defibrillation success and ROSC rates.

Should we change practice based on this study?

While the study suggests that shorter double sequential external defibrillation intervals (<75 ms) are associated with better outcomes in terms of ventricular fibrillation termination and ROSC, it is a secondary analysis of data from within and before a study period (DOSE-VF). We should, therefore, consider it hypothesis generating, and I would therefore not change clinical practice immediately. There is also a lack of significant differences in survival and neurological outcomes, which are the important patient outcomes that we would like to see in studies of this type. Specifically, prospective studies with larger sample sizes and more precise interval measurements must confirm these findings and establish clear guidelines for double sequential external defibrillation use in refractory ventricular fibrillation patients.

Summary

This study retrospectively analysed the impact of double sequential external defibrillation shock intervals on outcomes in patients with refractory ventricular fibrillation during out of hospital cardiac arrest. Key findings include:

Shorter double sequential external defibrillation intervals (<75 ms) are associated with higher rates of VF termination and return of spontaneous circulation.
No significant association was found between DSED intervals and survival to hospital discharge or favourable neurological outcomes.

Overall, this study adds to the growing body of evidence on double sequential external defibrillation but highlights the need for further research to optimise defibrillation strategies for RVF patients.

References

1.
Rahimi M, Drennan IR, Turner L, Dorian P, Cheskes S. The impact of double sequential shock timing on outcomes during refractory out-of-hospital cardiac arrest. Resuscitation. Published online January 2024:110082. doi:10.1016/j.resuscitation.2023.110082