Double Sequential External Defibrillation for Refractory Ventricular Fibrillation: The DOSE VF Pilot Randomized Controlled Trial
Authors: Cheskes S, Dorian P, Feldman M, et al.
Published in: Resuscitation, 2020 Feb 19
Randomized controlled trials (RCTs) are the top level of the evidence scale. RCTs examine cause-and-effect relationships between interventions and outcomes. They can also be complicated, expensive, and hard to manage. So it is important to do everything possible to ensure things like recruitment, the introduction of the intervention into patients’ care, and data collection run smoothly during the trial.
A pilot study of trial logistics is a great way to identify potential issues and correct them before an actual trial begins. This month we review a well-done pilot study with the goal of examining logistics such as “recruitment, intervention delivery, and adherence, with the aim of enhancing the efficiency and internal validity” of a full-scale RCT that will evaluate alternative defibrillation strategies for refractory ventricular fibrillation (VF).
A Sneak Peek
When reviewing a pilot study, we need to focus on the main results describing safety and feasibility. This study was not meant to appropriately evaluate the effects of the alternative defibrillation strategies—it just provides a peek at what we might see in the results of the full-scale RCT.
To ensure they could capture outcome data and help estimate the sample size needed for the full RCT, the authors’ secondary objective was to evaluate the effect of standard defibrillation, vector change defibrillation (VC), and double sequential external defibrillation (DSED) on the outcomes of VF termination and return of spontaneous circulation. VC is the switching of defibrillation pads from anterior-lateral to anterior-posterior after failed defibrillation attempts. DSED provides rapid sequential shocks using two defibrillators with pads placed anterior-lateral and anterior-posterior.
The authors explained that VC may result in a higher voltage gradient in the posterior ventricle, where fibrillation is most likely to restart or fail to terminate after defibrillation pads are placed in standard positions. They further explained the increased voltage and energy delivered by the second DSED shock may be more successful due to changes in wave fronts immediately after an unsuccessful shock. However, these strategies have not been evaluated in an RCT.
This was a three-arm pilot cluster RCT with crossover. The three arms were the interventions, which included standard defibrillation, VC, and DSED. The clusters were paramedic services in four regions in Ontario, Canada, and each “crossed over” from one intervention to another after six months. The services had to cross over at least once during the pilot study and were informed of their randomly assigned strategy one month prior to beginning the trial or crossing over. The study period was from Mar. 8–Sept. 9, 2019.
Prior to beginning the study, all paramedics from each of the four services received three hours of standardized in-person training in VC and DSED. Training included didactic, video, and simulated scenarios. During the pilot study medical directors provided continual feedback on performance and compliance to the study protocol.
All adults over 18 who remained in refractory VF during a nontraumatic out-of-hospital cardiac arrest of presumed cardiac etiology were eligible for inclusion in the pilot study. Patients were excluded if they were in traumatic arrest; if the arrest was secondary to drowning, hypothermia, hanging, or suspected drug overdose; or if they presented in pulseless VT or had a DNR.
For all patients the first three defibrillation attempts occurred with the pads placed in the standard position. Eligible patients who remained in VF after three consecutive shocks and two minutes of CPR received one of the three defibrillation strategies.
The pilot study measures included two feasibility targets. One was successful delivery of the assigned strategy in 80% of eligible patients, and the other was that 80% of enrolled patients would receive an intervention shock prior to the sixth shock. The study also had safety measures that assessed reports for mention of defibrillator damage following DSED, complaints of chest burns, and concerns from paramedics, emergency department staff, patients, or families. Finally, the effect of each strategy on the outcomes of VF termination and ROSC was evaluated.
There were 152 patients enrolled in the study. Of these, 89% received the defibrillation strategy to which they were randomized. All cases randomized to the standard defibrillation group received standard defibrillation, 89% of patients randomized to VC received VC, and 84% randomized to DSED received DSED. With respect to the second feasibility target, 93% received an intervention shock prior to the sixth shock, and 77% received an intervention shock at shock No. 4. Finally, there were no reported cases of defibrillator malfunction, skin burns, difficulty with pad placement, or concerns about the trial expressed by paramedics, ED staff, patients, or families.
The standard defibrillation group had VF termination in 67% of cases. The VC group had VF termination in 82%, and the DSED group in 76%. Further, the standard defibrillation group had ROSC in 25% of patients, the VC group in 39%, and the DSED group in 40%.
In addition to the measures described above, the authors also discovered a critical modification needed to strengthen the RCT: The authors indicated that shocks delivered by fire department first responders need to be included in patients randomized to the VC and DSED group, because firefighters provided shocks to 28% of enrolled patients. By omitting these shocks, the intervention shocks were delivered to the patient later, potentially causing an underestimate of the benefit of VC and DSED.
Read the entire manuscript—this was a great example of why pilot studies should be performed. The authors learned valuable information that will strengthen their full RCT. Also, the outcome results seem promising! I am looking forward to reviewing the full RCT once it is published.
Antonio R. Fernandez, PhD, NRP, FAHA, is a research scientist at ESO and an assistant professor in the department of emergency medicine at the University of North Carolina–Chapel Hill. He is on the board of advisors of the Prehospital Care Research Forum at UCLA.