Defibrillation Strategies for Refractory Ventricular Fibrillation

@DrCheskes. NEJM 2022 DOI: 10.1056/NEJMoa2207304

Clinical Question

  • In patients with refractory VF, does Double Sequential External Defibrillation or Vector-change Defibrillation compared to standard defibrillation improve survival to hospital discharge?


  • Refractory VF occurs in up to half of patients following an out-of-hospital VF arrest
  • Anti-arrhythmics are commonly used in this setting. However the ALPS study reported no significant improvement in survival to discharge or good neurological outcome with the use of either amiodarone or lignocaine
  • Case series have suggested a potential benefit with the use of Double Sequential External Defibrillation or Vector-change defibrillation to treat patients with refractory VF. These strategies may enable a greater or different part of the ventricle to be defibrillated


  • Randomised controlled trial
  • 3 group cluster randomisation with cross-over
  • Each cluster crossed over every 6 months
  • Randomisation performed at level of paramedic service
  • Random treatment sequences were computer-generated
  • Power calculation: 930 patients would provide 80% power to detect an 8% absolute improvement in the primary outcome from a baseline of 12%, with a false positive rate of 5%
  • Trial terminated early by data and safety monitoring board due to paramedic staffing shortages affecting timely delivery of assigned defibrillation strategy
  • Intention to treat analysis used for primary analysis
  • Treatment received analysis also reported
  • Registered on
  • Blinding of outcome assessors
  • Outcomes assessed until hospital discharge


  • 6 paramedic services, Ontario, Canada, included ~4000 paramedics
  • Data collection:
    • Pilot trial: March 2018 – September 2019 (n=152) – results also included in this analysis
    • Planned trial: September 2019 – May 2022 (n=253)
    • Study paused April – September 2020 due to COVID pandemic
  • Inclusion:
    • ≥18 years
    • Out-of-hospital-VF arrest of presumed cardiac cause
    • Refractory VF
      • Defined as initial presenting rhythm of VF/VT that was still present after 3 consecutive rhythm checks and standard defibrillations
  • Exclusion:
    • Non-VF/VT as presenting rhythm
    • Non-cardiac cause
    • Traumatic cardiac arrest, drowning, hypothermia, hanging, or suspected drug overdose
    • DNAR order
    • Patients initially treated by non-participating fire or EMS agencies
  • 405 patients randomised
  • Comparing baseline characteristics of standard vs. VC vs. DSED groups
    • Age: 64 vs. 64 vs. 63
    • Male: 80% vs. 88% vs. 85%
    • Bystander witnessed cardiac arrest: 60% vs. 76% vs. 66%
    • Bystander CPR: 54% vs. 63% vs. 57%
    • Median response time: 7.4 vs. 7.4 vs. 7.8min
    • Median time from initial call to 1st shock: 10 vs. 10 vs. 10min
    • Pre-hospital intubation: 38% vs 50% vs 42%
    • Anti-arrhythmic dose administered: 81% vs. 74% vs. 74%
    • Adrenaline administered: 95% vs. 92% vs. 86%


  • Patients randomised to either:
    • Vector-change (VC) Defibrillation
      • All subsequent defibrillations performed with Anterior-Posterior pad placement
      • 144 patients assigned to VC defibrillation
        • 113 patients received VC defibrillation
        • 31 patients received standard defibrillation
    • Double Sequential External Defibrillation (DSED)
      • All subsequent shocks performed using DSED
      • 2nd defibrillator attached in AP position. Single operator pressed shock button on anterior-lateral followed immediately (<1sec) by anterior-posterior defibrillation
      • 125 patients assigned to DSED
        • 107 patients received DSED
        • 16 patients received standard defibrillation
        • 2 patients received VC defibrillation


  • Standard defibrillation
    • All defibrillation attempts occurred in standard anterior–lateral position
    • 136 patients assigned to standard defibrillation
      • 135 received standard defibrillation
      • 1 received DSED

Management common to both groups

  • Resuscitation followed standard AHA guidelines
  • The 1st 3 defibrillation attempts occurred with the pads in standard anterior–lateral position


  • Primary outcome: Survival to hospital discharge
    • Significantly increased using:
      • DSED vs. standard care
        • 30.4% vs. 13.3%
        • RR 2.21, 95% CI. 1.33-3.67
        • Fragility index 9 patients
      • VC vs. standard care
        • 21.7% vs. 13.3%
        • RR 1.71, 95% CI. 1.01-2.88
        • Fragility index 1 patient
  • Secondary outcomes:
  • Comparing DSED vs. standard care
    • Significantly higher:
      • Termination of VF
        • 84.0% vs. 67.6%
        • Adjusted RR 1.25 (95% CI. 1.09-1.44)
      • ROSC
        • 46.4% vs. 26.5%
        • Adjusted RR 1.72 (95% CI. 1.22-2.42)
      • Survival with good neurological outcome – Modified Rankin Score ≤2
        • 27.4% vs 11.2%
        • Adjusted RR 2.21 (95% CI. 1.26-3.88)
  • Comparing VC vs. standard care
    • Significantly higher:
      • Termination of VF
        • 79.9% vs. 67.6%
        • Adjusted RR 1.18 (95% C.I. 1.03-1.36)
    • No significant difference in:
      • ROSC
        • 35.4% vs 26.5%
        • Adjusted RR 1.39 (95% CI. 0.97-1.99)
      • Survival with good neurological outcome – Modified Rankin Score ≤2
        • 16.2% vs 11.2%
        • Adjusted RR 1.48 (95% CI 0.81-2.71)
  • Treatment received analysis for survival to hospital discharge
    • No significant difference comparing:
      • DSED vs. standard defibrillation
        • RR 1.38 (95% CI. 0.90-2.11)
      • VC vs. standard defibrillation
        • RR1.13 (95% CI. 0.72-1.78)

Authors’ Conclusions

  • Survival to hospital discharge appeared higher with DSED and VC defibrillation that with standard defibrillation among patients with refractory VF


  • Randomised controlled trial
  • Crossover which decreases risk of bias from high/low performing paramedic teams
  • Assessed quality of CPR
  • Standard protocol for resuscitation and use of DSED and VC defibrillation
  • Blinding of outcome assessors


  • Trial stopped early before it reached planned sample size. There were a low number of outcome events. Both of these are likely to result in an overestimate of the effect size being reported
  • Outcomes assessed only until hospital discharge. For neurological outcomes longer follow up may be beneficial
  • DSED requires 2 defibrillators. It is unclear if this meant that more paramedics were called to cardiac arrests when DSED were used. If so this may introduce bias
  • Results from pilot trial were included in this analysis. This was not planned for in the trial registration on
  • The median time from initial call to 1st shock was 10 minutes. These results may not be generalisable to setting that do not achieve this
  • There are some baseline differences between the treatment groups that may lead to confounding bias
  • There were differences in the amount of crossovers between services, suggesting that bias from individual treating services may not have been completely eliminated
  • Blinding of treatment was not possible

The Bottom Line

  • In this randomised trial of patients with refractory VF following out-of-hospital cardiac arrest, the use of DSED or VC defibrillation resulted in significantly higher survival to hospital discharge. The use of DSED was also reported to lead to a significant increase in survival with a good neurological outcome
  • These results should be interpreted with caution as
    • The trial was stopped early and there were a low number of outcome effects, and therefore the effect size is likely to be overestimated
    • The analysis using treatment received reported no significant difference in the primary outcome
  • Further trials should therefore be performed. In the mean time, if you are unable to randomise a patient to a trial, the use of DSED or VC defibrillation would be a reasonable treatment option to try for refractory VF, with the knowledge that the research is not definitive and the outcome benefits are unclear

External Links


Summary author: @davidslessor
Summary date: 9th November 2022
Peer-review editor: @iceman_ex



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