DSED: 8 Questions to the Principal Investigator of DOSE VF

In November 2022, the New England Journal of Medicine published the DOSE VF trial, the first randomized controlled trial to compare double sequential external defibrillation (DSED) and vector change defibrillation versus standard defibrillation for refractory ventricular fibrillation during out-of-hospital cardiac arrest. The results were significant: DSED was the only strategy to statistically significantly improve both survival to hospital discharge and survival with favorable neurological outcome.

Since then, DSED has sparked one of the most active debates in resuscitation science, which we had already discussed last year in this article.

Several European trials are underway, guideline-writing bodies have issued conflicting recommendations, and prehospital systems worldwide are grappling with the question of whether and how to implement the technique.

This interview stems from a real case. In recent months, our team in Valle d'Aosta performed DSED on a patient in refractory ventricular fibrillation during an out-of-hospital cardiac arrest. There was no protocol in our system. There was no institutional mandate. There was the evidence from the DOSE VF trial, two Zoll X Series on scene, and a clinical decision. The patient survived. When I shared the case on LinkedIn, Dr. Cheskes himself commented and contacted me. This article was born from that conversation.

I am truly honored to host Dr. Sheldon Cheskes on the EMSy blog. The goal is simple: to bring his expertise closer to the Italian prehospital community and to every clinician who will read these lines, so that what we know about DSED does not remain confined to scientific journals and conference halls. In many European systems, DSED is not yet protocolized. Awareness is the first step. My hope is that this interview, together with ongoing scientific studies, will contribute to an open and rigorous debate on how we defibrillate refractory VF in the field.

His answers are direct, evidence-based, and at times provocatively honest about the current state of science and the politics surrounding it.

1. The DOSE VF trial focused specifically on refractory VF. In your conversation with Scott Weingart on EMCrit, you drew an important distinction between refractory VF and recurrent VF. For clinicians who may not be familiar with this nuance, how do you define each, and does DSED have a role in both?

In the DOSE VF trial we defined refractory VF pragmatically as VF persisting after three shocks, each separated by two minutes of CPR. From an electrophysiological standpoint, shock-refractory VF identifies those patients who present in VF and never exit it during the first three shocks, while recurrent VF identifies those patients who during the first three shocks exit VF for at least five seconds but then re-enter it.

Defibrillator manufacturers have long led us to believe that if VF is terminated even for a brief period, the problem is not a "defibrillation problem" but rather a left anterior descending artery lesion that needs to be opened, or a problem with resuscitation. Those who contest DSED therefore believe that in recurrent VF, DSED is not needed, because it would not be a defibrillation problem, and most cases in DOSE VF, using an electrophysiological definition, would fall into the recurrent category.

We tested this hypothesis in the per-protocol population of the DOSE VF trial by applying an electrophysiological definition to all cases and found that not a single individual survived refractory VF when treated with standard defibrillation (survival with DSED 29%). Furthermore, importantly, in the recurrent VF group survival with DSED was 27% vs 17% in the standard group and survival with favorable neurological outcome was 25% vs 14.4%. Although the recurrent group did not reach statistical significance due to sample size, we believe that an almost doubling of survival and neurologically intact survival in recurrent VF is clinically relevant.

For this reason we believe that, regardless of whether refractory VF is defined pragmatically, as shock-refractory or as recurrent, DSED is a superior strategy.

2. Rahimi et al. demonstrated that a DSED interval of less than 75 milliseconds is associated with better VF termination rates. In practical terms, what technique do you recommend to crews to achieve this interval on scene?

This is a somewhat complicated issue. From a safety standpoint, sequential DSED (one person presses the shock button on each defibrillator in rapid sequence) has never been shown to damage a defibrillator. However, it is associated with a longer DSED interval. Therefore, simultaneous DSED (one person presses both shock buttons simultaneously) is probably associated with better outcomes and a 1/1000 risk of defibrillator damage.

In DOSE VF, where the DSED interval between shocks was approximately 600 ms, we may have only seen the tip of the iceberg of DSED effectiveness. Future defibrillators, with four pads (or one large pad) on a single defibrillator with a single button and sequential shocks at approximately 70 ms (or less), will optimize DSED effectiveness. Stay tuned!

3. Your recent review in the Journal of Electrocardiology describes the standard DSED configuration as antero-lateral plus antero-posterior pad placement. How critical is the position of the second set of pads for the technique's success, and what should crews avoid?

I think the critical point is that both sets of pads, the antero-lateral and the antero-posterior, must be positioned correctly. The lateral pad of the antero-lateral set is the most inconsistently positioned pad during resuscitation, so one must take the time to ensure it is in the correct position. Conversely, the vast majority of people know where to place the AP pads, but because it is not done as commonly, rescuers should verify that this is also positioned correctly. Once both sets of pads are in the correct position, DSED is ready.

4. In a LinkedIn comment under one of my posts, you mentioned performing DSED with two manual defibrillators, two AEDs and mechanical compression. How does the integration of mechanical compression change the DSED workflow, and is there a preferred equipment combination?

In DOSE VF we always started with pads in the antero-lateral position even with mechanical compression. This can be complicated, but generally the application of mechanical compression occurred after three shocks.

Many services, particularly in the US, perform DSED with mechanical compression and place the AP pads first. They position the posterior pad simultaneously with the posterior portion of the LUCAS device or AutoPulse (the same could be done with the Corpuls device) and then position the anterior pad. After three failed shocks, placement of the antero-lateral pads can occur while mechanical compression is ongoing, without interrupting compressions.

This is probably the best method to perform DSED with mechanical compression, with the caveat that this is not the protocol we studied in DOSE VF, so I cannot comment on effectiveness, but I believe it is at least as effective as our protocol in the study.

5. Your case report in JACC describes DSED used as an initial defibrillation strategy, not after three failed standard shocks. Is this the direction the field is moving, and what should change in protocols to support earlier use?

The interest in almost all DSED studies in Europe concerns the concept of early DSED. The reasoning is: if DSED is so effective, why not use it earlier?

The Swedish group led by Gabriel Riva and Akil Awad is studying DSED vs standard after a single failed EMS shock in the DoubleD trial. They presented their feasibility study, soon to be published, last year at ERC, in which 40 patients were randomized 3:1 to DSED vs standard. 80% received DSED before the second shock, with survival in the DSED arm of 41% and 9% in the standard arm. Results were even more marked in patients presenting in VF (criteria similar to DOSE VF). Although the numbers are small, a clear signal is present, consistent with our research.

Lars Wiuff Andersen and the Danish group are studying DSED vs standard vs vector change after a single failed EMS shock in the STRAT-DEFI trial. My only concern about this trial is that it includes all patients indiscriminately, and we found that DSED is less effective for those patients who present in asystole or PEA and then go into VF, consistent with previous research. This is a different inclusion criterion, and we await the results.

In Norway, Jostein Brede is evaluating DSED as an initial defibrillation strategy compared to standard defibrillation in the Dual Defib Trial.

And finally, Stephan Katzenschlager and his team in Germany are evaluating the impact of DSED vs standard after three failed EMS shocks, similar to DOSE VF, in the DOSEVF 2 trial.

So most of the interest in ongoing trials is focused on early DSED, a different research question from that studied in DOSE VF. We look forward to the results of all ongoing DSED research.

6. You wrote that "the key is to have a protocol in place." For a European prehospital system that currently does not have a DSED protocol, what are the minimum essential elements to get started?

For me it's all about training, training, training. It doesn't have to be long and laborious, but practice on protocols similar to those in the videos I shared is fundamental. Equally critical is the anticipation of performing DSED early and in a protocolized manner, rather than as a desperate attempt when everything else fails, and knowledge of how to use the second defibrillator if it is not a service manual defibrillator.

All these nuances must be resolved before proceeding with a DSED strategy. Otherwise, all that will be done is late DSED, which will likely lead to poor outcomes.

7. You said it's a shame that DSED is not practiced more in Europe. From your perspective, what are the main barriers to adoption, and what would help accelerate it?

Having given many lectures in Europe, I can say there is enormous interest and many centers are already practicing DSED. The problem, for me, is that Europe is very guideline-focused, and if DSED is not in the guidelines, some are afraid to implement it.

The truth is that some of the detractors of DSED sit on guideline panels and, despite also sitting on the ILCOR panel (which issued a positive recommendation for DSED), have bewilderingly chosen vector change over DSED, citing a lack of evidence for DSED (despite all the evidence for vector change coming from the same trial) and logistical challenges. Guidelines should focus on science and leave logistics to EMS services. I can say without any doubt that bringing two defibrillators to the scene is much simpler than organizing a system-wide ECPR program.

The idea of "equivalence between DSED and vector change" is frankly laughable. In DOSE VF, all point estimates favored DSED, all sensitivity analyses favored DSED, re-arrest was higher in the vector change arm during the trial, vector change produced an improvement in survival but not in ROSC suggesting unmeasured confounding confirmed by a fragility index of 1 for vector change in the trial, and finally neurologically intact survival improved only for DSED, not for vector change. In summary, they are not the same thing.

Our system never uses vector change defibrillation. We start in AP position and after three failed shocks we move to DSED. Considering some of the individuals present in these guideline-writing bodies, I suspect a confirmatory RCT will be needed to change the guidelines, and even then, who knows. I've seen stranger things in the resuscitation world.

The preliminary results of the Swedish study certainly suggest we won't have to wait too long. I can say without hesitation: no one who is practicing DSED has stopped because of ERC or AHA guidelines. They followed the ILCOR Review of Science, implemented, and never looked back.

8. What is the single most important unanswered question about DSED that you would like to see addressed in future research?

I think the question of early DSED is probably the most important question, and it will be answered in due time. Our current research is focusing on the interaction between DSED and ECPR in a system that can perform both interventions, and on the optimal timing of scene transfer for ECPR, whether DSED is successful or not. Stay tuned!

The other aspect is not really a question but more of a technological issue: producing a single defibrillator capable of performing DSED. The technology is simple, but it will probably never be realized until a confirmatory study on DSED is published.

This interview was conducted via written exchange. Dr. Cheskes reviewed and approved the final text.

Dr. Sheldon Cheskes is Professor at the University of Toronto, Division of Emergency Medicine, Medical Director of the Sunnybrook Center for Prehospital Medicine and Researcher at the Li Ka Shing Knowledge Institute, St. Michael's Hospital. He is the Principal Investigator of the DOSE VF trial and will present a pro/con debate on DSED at ERC 2026 in Milan.