Double Sequential External Defibrillation: What the Science Says

Anyone who has worked on the road long enough can remember a patient who, despite their best attempts at resuscitation, stubbornly remained in ventricular fibrillation (VF). Patients who present to emergency medical services in shockable rhythms are considered to have a high probability of survival. But what happens when these patients don’t respond to initial care? 

According to advanced cardiac life support (ALCS) algorithms, if we perform CPR and defibrillation, administer antiarrhythmics and epinephrine, and a patient remains in VF, then we do it again. If that doesn’t work, we do it again and again, hoping with enough attempts it will result in a return of spontaneous circulation (ROSC).

We know, however, that approximately 20% of patients with initial VF don’t respond to initial defibrillation attempts, and the more shocks required to terminate VF, the worse a patient does.^1,2 

Einstein noted that insanity is doing the same thing over and over and expecting different results. So why do we continue to repeat the same treatments during cardiac arrest, yet expect anything different?

Previous Research and Limitations

Double sequential external defibrillation (DSED) has been touted as the next promising treatment for refractory VF patients, but what does the science say? Recently the authors of this article published the DOSE VF (Double Sequential External Defibrillation for Refractory Ventricular Fibrillation) pilot randomized controlled trial.³ This was the first RCT to examine the use of DSED for out-of-hospital cardiac arrest and overcame many of the methodological deficiencies of previous research.  

The exact mechanism behind DSED is not known. There are multiple hypotheses, including additional energy, the alternative vector of energy created by a change in pad position, and changes in impedance threshold based on the delivery of two sequential shocks.⁴ 

Prior to this study there were a number of case reports and case series, as well as five observational comparison studies. The previous research consisted of a number of case reports and case series, as well as five comparison studies.^5–9 Case reports and case series, while interesting, typically represent nothing more than selection bias of unique cases and are unable to provide evidence to the benefit or risk of DSED. 

This leaves us with a small handful of observational studies that demonstrated the use of DSED had no association or was associated with worse clinical outcomes (e.g., ROSC, survival, and neurological outcome) compared to standard practice. These studies, however, have limitations that hinder interpretation of the effect of the intervention. These limitations are important to our current understanding of DSED. 

Double sequential defibrillation is generally performed in observational studies as a rescue therapy when patients do not respond to standard resuscitation treatment. This often results in a delay to treatment, creating a biased comparison to patients who only received standard defibrillation attempts. This effect has been called resuscitation time bias.¹⁰

Resuscitation time bias occurs in observational cardiac arrest research when the probability of receiving an intervention increases the period of time a patient is in cardiac arrest. This occurs with placement of an advanced airway, administration of epinephrine, and in this case the use of DSED. 

The problem in these cases is that the patient outcome may have more to do with the duration of the cardiac arrest than the intervention itself, falsely diminishing the effect of the intervention. Without properly controlling for the time of the intervention or other variables that may impact survival, it is challenging to make sense of these studies. 

Pilot Study

One of the other questions with DSED that observational studies can’t answer involves its application. There are differences in the technique used to perform DSED (pressing the two shock buttons simultaneously versus sequentially), the energy delivered, and placement of the defibrillator pads. These are all questions to which we do not yet have answers in terms of optimizing DSED. 

Perhaps more important is the variability in the timing of the initial DSED shock across the observational studies. In some studies the initial DSED shock is performed after the third standard defibrillation, in others after the sixth, and in still others after 10 or more standard defibrillation attempts.^5,6,11 This makes it almost impossible to compare the use of DSED across different studies. 

The DSED pilot study attempted to answer some of these unknowns by applying strict protocols and techniques of application. The pilot study was a three-arm cluster RCT. Each paramedic service involved was randomly assigned to one of three study arms: standard defibrillation, vector change (VC) defibrillation, or double sequential defibrillation. Paramedic services were randomly assigned to a different intervention (crossed over) at six-month intervals throughout the trial (a total of six different intervention periods).

Patients were assumed to be in refractory VF and included in the trial if they were found in an initial shockable rhythm and had three consecutive shocks delivered. These patients were then enrolled in the DOSE VF RCT, and the intervention was ideally applied at the fourth rhythm analysis. 

All defibrillator pads were initially placed in the anterior-lateral (AL) position as per standard practice. Vector change defibrillation was applied by changing pads from the AL position to the anterior-posterior (AP) position, and DSED was applied by adding a second set of pads in the AP position.

DSED was performed by a single paramedic pressing the shock button of the first, then second defibrillator in rapid succession. This technique was felt to be important to ensure the shock buttons were not pressed simultaneously, minimizing the rare likelihood of defibrillator damage during DSED. 

The main outcome of the pilot study was to examine the feasibility of performing the trial in the prehospital setting. The secondary outcomes were ROSC, termination of VF, and ROSC at ED arrival. 

Results

The pilot study found performing the study in the field was feasible, with high rates of compliance with the study intervention arm (around 90%) and intervention shocks given at shock number four or five in 89% of cases. This suggests paramedics performed the trial intervention very well during the pilot study. 

Of secondary outcomes, termination of VF was higher in both intervention arms compared to standard defibrillation (76% DSED, 82% VC, and 66% standard). Similarly, rates of ROSC (40% DSED, 39% VC, 25% standard) and ROSC at ED arrival (33% DSED, 25% VC, 19% standard) were also higher for both intervention arms compared to standard defibrillation. Interestingly the DSED appeared to have a higher ROSC at ED arrival than both VC and standard defibrillation. 

It is important that this study was not designed to statistically compare patient outcomes across the three groups—as it is an internal pilot study, the patients will be included as part of the ongoing full RCT, and so survival to hospital discharge could not be reported for these patients. 

Key Differences

While this wouldn’t be the first time we’ve seen a treatment improve ROSC without having a meaningful effect on survival to hospital discharge, there are some key differences in this study.

In studies examining epinephrine and antiarrhythmics for OHCA, the intervention was not applied until an average of 20 minutes into the cardiac arrest.^12,13

In the case of DSED, it is applied at the fourth rhythm analysis, which would occur approximately seven minutes into a resuscitation. We know one of the biggest determinants of survival is the duration of cardiac arrest, and in this case DSED is associated with early ROSC.^14,15 

There are still many unanswered questions related to the use of DSED. While it is essential that we wait for the results of the full RCT to determine its true impact on patient survival, this study does provide us with some evidence that DSED may have a role in the treatment of patients in refractory VF cardiac arrest.

Instead of continuing to repeat the same treatments without success, DSED may offer us a way to stop the insanity and perform additional therapy for patients who do not respond to standard defibrillation.

References

1. Sakai T, Iwami T, Tasaki O, et al. Incidence and outcomes of out-of-hospital cardiac arrest with shock-resistant ventricular fibrillation: Data from a large population-based cohort. Resuscitation, 2010 Aug; 81(8): 956–61.

2. Holmen J, Hollenberg J, Claesson A, et al. Survival in ventricular fibrillation with emphasis on the number of defibrillations in relation to other factors at resuscitation. Resuscitation, 2017 Apr; 113: 33–8.

3. Cheskes S, Dorian P, Feldman M, et al. Double sequential external defibrillation for refractory ventricular fibrillation: The DOSE VF pilot randomized controlled trial. Resuscitation, 2020 May; 150: 178–84.

4. Ramzy M, Hughes PG. Double Defibrillation. StatPearls, 2019 Jun 28; www.ncbi.nlm.nih.gov/books/NBK544231/.

5. Beck LR, Ostermayer DG, Ponce JN, Srinivasan S, Wang HE. Effectiveness of Prehospital Dual Sequential Defibrillation for Refractory Ventricular Fibrillation and Ventricular Tachycardia Cardiac Arrest. Prehosp Emerg Care, 2019 Sep–Oct; 23(5): 597–602.

6. Cheskes S, Wudwud A, Turner L, et al. The impact of double sequential external defibrillation on termination of refractory ventricular fibrillation during out-of-hospital cardiac arrest. Resuscitation, 2019 Jun; 139: 275–81.

7. Emmerson AC, Whitbread M, Fothergill RT. Double sequential defibrillation therapy for out-of-hospital cardiac arrests: The London experience. Resuscitation, 2017 Aug; 117: 97–101.

8. Mapp JG, Hans AJ, Darrington AM, et al; Prehospital Research and Innovation in Military and Expeditionary Environments (PRIME) Research Group. Prehospital Double Sequential Defibrillation: A Matched Case-Control Study. Acad Emerg Med, 2019 Sep; 26(9): 994–1,001.

9. Ross EM, Redman TT, Harper SA, et al. Dual defibrillation in out-of-hospital cardiac arrest: A retrospective cohort analysis. Resuscitation, 2016 Sep; 106: 14–7.

10. Andersen LW, Grossestreuer AV, Donnino MW. “Resuscitation time bias”—A unique challenge for observational cardiac arrest research. Resuscitation, 2018 Apr; 125: 79–82.

11. Cabanas JG, Myers JB, Williams JG, De Maio VJ, Bachman MW. Double Sequential External Defibrillation in Out-of-Hospital Refractory Ventricular Fibrillation: A Report of Ten Cases. Prehosp Emerg Care, 2015 Jan–Mar; 19(1): 126–30.

12. Kudenchuk PJ, Daya M, Dorian P; Resuscitation Outcomes Consortium Investigators. Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. N Engl J Med, 2016 Aug 25; 375(8): 802–3.

13. Perkins GD, Ji C, Deakin CD, et al; PARAMEDIC2 Collaborators. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. N Engl J Med, 2018 Aug 23; 379(8): 711–21.

14. Drennan IR, Case E, Verbeek PR, et al; Resuscitation Outcomes Consortium Investigators. A comparison of the universal TOR Guideline to the absence of prehospital ROSC and duration of resuscitation in predicting futility from out-of-hospital cardiac arrest. Resuscitation, 2017 Feb; 111: 96–102.

15. Reynolds JC, Grunau BE, Rittenberger JC, et al. Association Between Duration of Resuscitation and Favorable Outcome After Out-of-Hospital Cardiac Arrest: Implications for Prolonging or Terminating Resuscitation. Circulation, 2016 Dec 20; 134: 2,084–94.

Ian R. Drennan, ACP, PhD(c), is a paramedic, educator, and researcher in Ontario, Canada. He’s a PhD candidate at St. Michael's Hospital and the Institute of Medical Science at the University of Toronto. 

Sheldon Cheskes, MD, CCFP (EM), FCFP, is medical director for Halton and Peel Region Paramedic Services Sunnybrook Centre for Prehospital Medicine, and associate professor of emergency medicine at the University of Toronto.