DOuble SEquential External Defibrillation for Refractory Ventricular Fibrillation (DOSE VF): study protocol for a randomized controlled trial

Abstract

Background: Despite high-quality cardiopulmonary resuscitation (CPR), early defibrillation, and antiarrhythmic medications, some patients remain in refractory ventricular fibrillation (VF) during out-of-hospital cardiac arrest. These patients have worse outcomes compared to patients who respond to initial treatment. Double sequential external defibrillation (DSED) and vector change (VC) defibrillation have been proposed as viable options for patients in refractory VF. However, the evidence supporting the use of novel defibrillation strategies is inconclusive. The objective of this study is to compare two novel therapeutic defibrillation strategies (DSED and VC) against standard defibrillation for patients with treatment refractory VF or pulseless ventricular tachycardia (pVT) during out-of-hospital cardiac arrest.

Research question: Among adult (≥ 18 years) patients presenting in refractory VF or pulseless ventricular tachycardia (pVT) during out-of-hospital cardiac arrest, does DSED or VC defibrillation result in greater rates of survival to hospital discharge compared to standard defibrillation?

Methods: This will be a three-arm, cluster randomized trial with repeated crossover conducted in six regions of Ontario, Canada (Peel, Halton, Toronto, Simcoe, London, and Ottawa), over 3 years. All adult (≥ 18 years) patients presenting in refractory VF (defined as patients presenting in VF/pVT and remaining in VF/pVT after three consecutive standard defibrillation attempts during out-of-hospital cardiac arrest of presumed cardiac etiology will be treated by one of three strategies: (1) continued resuscitation using standard defibrillation, (2) resuscitation involving DSED, or (3) resuscitation involving VC (change of defibrillation pads from anterior-lateral to anterior-posterior pad position) defibrillation. The primary outcome will be survival to hospital discharge. Secondary outcomes will include return of spontaneous circulation (ROSC), VF termination after the first interventional shock, VF termination inclusive of all interventional shocks, and number of defibrillation attempts to obtain ROSC. We will also perform an a priori subgroup analysis comparing rates of survival for those who receive "early DSED," or first DSED shock is shock 4-6, to those who receive "late DSED," or first DSED shock is shock 7 or later.

Discussion: A well-designed randomized controlled trial employing a standardized approach to alternative defibrillation strategies early in the treatment of refractory VF is urgently required to determine if the treatments of DSED or VC defibrillation impact clinical outcomes.

Trial registration: ClinicalTrials.gov NCT04080986 . Registered on 6 September 2019.

Keywords: Cardiopulmonary resuscitation; Cluster randomized controlled trial; Double sequential defibrillation; Emergency medical services; Out-of-hospital cardiac arrest; Ventricular fibrillation.

Conflict of interest statement

Dr. Cheskes has received speaking honorarium for educational events on CPR quality from Zoll Medical and Stryker Corporation. Dr. Cheskes has received investigator-initiated grants from the Zoll Medical for AED on the Fly, Community Responder Program for Peel Region and Monitoring Ventilations during OHCA Research Studies. The DOSE VF pilot RCT was funded by the Laerdal Foundation and the DOSE VF RCT was awarded a HSF of Canada GIA grant. Dr. Cheskes has received research funding from the Cardiac Arrhythmia Network of Canada for the AED on the Fly Research Program and sits on the Adivsory Board of Drone Delivery Canada. Dr. Drennan is a member of the ALS Taskforce for the International Liaison Committee on Resuscitation (ILCOR) and the adult writing group for the American Heart Association (AHA) Guidelines for CPR and ECC. No other authors have any conflicts of interest to declare.

Figures

Fig. 1

Pad placement for DSED

Fig. 2

SPIRIT figure