Does the outcome from refractory VF differ from recurrent VF in DOSE-VF patients?

Out-of-hospital cardiac arrest (OHCA) remains a leading cause of mortality worldwide. Despite low overall survival rates, patients presenting with an initial rhythm of ventricular fibrillation (VF) have a higher likelihood of survival with the primary and most effective intervention for improving survival being early external defibrillation. However, a subset of patients experiences refractory VF (RVF), where the VF persists despite multiple standard defibrillation attempts, significantly decreasing survival rates. The Double Sequential External Defibrillation for Refractory Ventricular Fibrillation (DOSE VF^​1,2​) randomized controlled trial (RCT) explored alternative defibrillation strategies, such as double sequential external defibrillation (DSED) and vector change defibrillation (VC), demonstrating a survival benefit for patients with RVF. We reviewed this paper on the blog, and it’s arguably one of the most influential resuscitation papers of the last few years. This week we are looking at a reanalysis of the DOSE-VF trial^​3​ that hopes to distinguish between shock-refractory VF and recurrent VF and evaluate the efficacy of these defibrillation strategies in each scenario.

The abstract is below, but as always please read the full paper and make your own mind up.

Background – The DOSE VF randomized controlled trial (RCT) employed a pragmatic definition of refractory ventricular fibrillation (VF after three successive shocks). However, it remains unclear whether the underlying rhythm during the first three shocks was shock-refractory or recurrent VF.

Objective – To explore the relationship between alternate defibrillation strategies employed during the DOSE VF RCT and the type of VF, either shock-refractory VF or recurrent VF, on patient outcomes.

Methods – We performed a secondary analysis of the DOSE VF RCT. We categorized cases as shock-refractory or recurrent VF based on pre-randomization shocks (shocks 1–3). We then analyzed all subsequent (post-randomization) shocks to assess the impact of standard, vector change (VC) or double sequential external defibrillation (DSED) shocks on clinical outcomes employing logistic regression adjusted for Utstein variables, antiarrhythmics, and epinephrine.

Results – We included 345 patients; 60 (17%) shock-refractory VF, and 285 (83%) recurrent VF. Patients in recurrent VF had greater survival than shock-refractory VF (OR: 2.76 95% CI [1.04, 7.27]). DSED was superior to standard defibrillation for survival overall, and for patients with shock-refractory VF (28.6% vs 0%, p = 0.041) but not for those in recurrent VF. DSED was superior to standard defibrillation for return of spontaneous circulation (ROSC) and neurologic survival for shock-refractory and recurrent VF. VC defibrillation was not superior for survival or ROSC overall, for shock-refractory, or recurrent VF groups, but was superior for VF termination across all groups.

Conclusion – DSED appears to be the superior defibrillation strategy in the DOSE VF trial, irrespective of whether the preceding VF is shock-refractory or recurrent.

What kind of study is this

This study is a secondary analysis of the DOSE VF cluster-randomised controlled trial. The original trial was conducted across six paramedic services in Ontario, Canada, and compared standard defibrillation with DSED and VC defibrillation in adult patients with RVF during OHCA. That paper showed a significant improvement in outcome (hospital dischgarge) for DSD and trends for Vector change (VC) in the primary outcome (discharge), and significantly improved ROSC for VC and DSED. This secondary analysis categorizes patients into shock-refractory or recurrent VF based on their response to the first three pre-randomization shocks. The analysis then evaluates the impact of the allocated defibrillation strategy on clinical outcomes, employing logistic regression adjusted for Utstein variables, antiarrhythmics, and epinephrine.

Tell me about the patients

The analysis included 345 patients from the DOSE VF RCT. These patients were adults (≥18 years) who experienced non-traumatic OHCA and were enrolled in the original study. The exclusion criteria were the same as in the DOSE VF RCT, excluding patients with traumatic cardiac arrest, do-not-resuscitate directives, and cardiac arrest due to drowning, hypothermia, hanging, or suspected drug overdose. Of the included patients, 60 (17%) were classified as having shock-refractory VF, while 285 (83%) had recurrent VF. Both groups were comparable in terms of Utstein characteristics, such as age, sex, bystander CPR, and EMS response times.

What were the measured outcomes in this study

The primary outcome measured was survival to hospital discharge. Secondary outcomes included VF termination, return of spontaneous circulation (ROSC), and neurologically intact survival, defined as a modified Rankin Score (mRS) ≤ 2. The analysis also evaluated differences in event characteristics, such as the time from the initial call to the first shock, prehospital intubation, pre- and post-shock pauses, chest compression quality, and the administration of antiarrhythmics and epinephrine.

What are the main results

• Survival to Hospital Discharge: Patients with recurrent VF had a higher survival rate than those with shock-refractory VF (OR: 2.76, 95% CI [1.04, 7.27]). DSED was superior to standard defibrillation for overall survival (27.2% vs 14.0%; OR: 2.18, 95% CI [1.05, 4.51]) and for patients with shock-refractory VF (28.6% vs 0%, p = 0.041).
• ROSC and Neurologic Survival: DSED was superior to standard defibrillation for ROSC and neurologically intact survival in both shock-refractory and recurrent VF groups. VC defibrillation was not superior to standard defibrillation for overall survival or ROSC but was superior for VF termination across all groups.
• Event Characteristics: Higher doses of antiarrhythmics and epinephrine were more commonly given to those with shock-refractory VF. Time intervals for administration of these medications were similar between the two groups.

Are the methods definitive?

This is a reasonably sized (but not large), well-characterized dataset from the DOSE VF RCT. However, it is a secondary analysis, and it should therefore largely be regarded as hypothesis generating rather than definitive. There are a number of other concerns.

• Sample Size: The smaller sample size in the shock-refractory VF group limits the power of some analyses, and overall it’s not a very large study.
• Definition of VF Types: The pragmatic definition of RVF, while easier to apply in real-time resuscitation, may not capture the full complexity of VF dynamics.
• Unmeasured Variables: Factors such as body mass index (BMI) and changes in defibrillation impedance, which could affect shock success, were not assessed.

Despite these limitations, the findings suggest that DSED is a superior strategy for both shock-refractory and recurrent VF, challenging the traditional approach of using standard defibrillation.

Should we change practice based on this study

Based on the results of this secondary analysis, there is good evidence to support the adoption of DSED as a preferred defibrillation strategy for patients with RVF, regardless of whether the VF is shock-refractory or recurrent. The significantly higher survival rates and improved neurologic outcomes associated with DSED highlight its potential to improve patient outcomes in OHCA. While VC defibrillation showed some benefits in VF termination, it did not translate into better survival or neurologic outcomes, suggesting that DSED should be prioritized when feasible.

In the UK, the use of DSED has not been widely adopted and is not included in the national ambulance service guidelines. However, I do know of some air ambulances and in hospital settings that have used it. Personally, I have certainly had patients with successful outcomes with DSED, and at the moment, I think the balance of evidence is in favour of using it. Similarly as PHEM teams and in the ED we often see people who have already had three shocks before we arrive and so we should be doing something different (as plan A is currently not working otherwise ROSC will already have been achieved). I do wonder whether the lack of adoption is about concerns around equipment damage rather than patient outcomes (maybe???).

Summary

This secondary analysis of the DOSE VF trial provides more nuance on the effectiveness of double sequential external defibrillation (DSED) over standard and vector change (VC) defibrillation for patients with refractory ventricular fibrillation (RVF). Patients with recurrent ventricular fibrillation exhibited better survival rates compared to those with shock-refractory VF, and DSED significantly improved survival and neurologic outcomes across both groups. These findings advocate for the implementation of DSED in prehospital cardiac arrest protocols to enhance survival rates and neurological recovery in patients experiencing refractory ventricular fibrillation. While further research is needed to refine ventricular fibrillation categorization and explore additional factors affecting defibrillation success, the current evidence strongly supports a shift towards DSED in clinical practice.

Further reading

1. Simon Carley, “JC: Alternate defibrillation strategies in refractory VF. The DoseVF trial. St Emlyn’s,” in St.Emlyn’s, November 10, 2022, https://www.stemlynsblog.org/jc-alternate-defibrillation-strategies-in-refractory-vf-the-dosevf-trial-st-emlyns/.
2. The Resus Room. Papers of May 2024. https://www.theresusroom.co.uk/courses/papers-of-may-2024/
3. Simon Carley, “Dual Axis Defibrillation & #ResusFriday at St.Emlyn’s,” in St.Emlyn’s, May 21, 2017, https://www.stemlynsblog.org/dual-axis-defibrillation-resusfriday-at-st-emlyns/.
4. Boehm K, Keyes D, Mader L, Moccia J. First Report of Survival in Refractory Ventricular Fibrillation After Dual-Axis Defibrillation and Esmolol Administration. West J Emerg Med. 2016;17(6):762-765. [PubMed]
5. Leacock B. Double simultaneous defibrillators for refractory ventricular fibrillation. J Emerg Med. 2014;46(4):472-474. [PubMed]
6. Hoch D, Batsford W, Greenberg S, et al. Double sequential external shocks for refractory ventricular fibrillation. J Am Coll Cardiol. 1994;23(5):1141-1145. [PubMed]
7. Cabañas J, Myers J, Williams J, De M, Bachman M. Double Sequential External Defibrillation in Out-of-Hospital Refractory Ventricular Fibrillation: A Report of Ten Cases. Prehosp Emerg Care. 2015;19(1):126-130. [PubMed]
8. Hoch DH, Batsford WP, Greenberg SM, et al. Double sequential external shocks for refractory ventricular fibrillation. Journal of the American College of Cardiology. 1994;23(5):1141-1145. doi: 10.1016/0735-1097(94)90602-5 [Source]
9. Lybeck AM, Moy HP, Tan DK. Double Sequential Defibrillation for Refractory Ventricular Fibrillation: A Case Report. Prehospital Emergency Care. 2015;19(4):554-557. doi: 10.3109/10903127.2015.1025155

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