Cheskes S, Verbeek PR, Drennan IR, et al. Defibrillation Strategies for Refractory Ventricular Fibrillation. N Engl J Med. 2022 Nov 24;387(21):1947-1956. doi: 10.1056/NEJMoa2207304. Epub 2022 Nov 6. PMID: 36342151.
Double sequential (DSED) and vector change (VC) defibrillation have been in use for many years. In observational studies and case reports, these strategies have been tried out mainly as a last resort in refractory ventricular fibrillation. Early application of DSED or VC may lead to improved rates of defibrillation and return of spontaneous circulation, and thereby, lead to more favorable clinical outcomes. The left ventricle lies posteriorly; hence, a shock delivered through anterior pads may not have an effective impact on some parts of the left ventricle. Fibrillation is most likely to return or fail to terminate after defibrillation in these areas of the left ventricle when standard pad position is used. Change of vector may result in a higher voltage and offers the potential to defibrillate parts of the ventricle that may be relatively inaccessible to conventional pad positioning.
Population and setting
The study was conducted across six paramedic services in Ontario, Canada between March 2018 and May 2022. Adult patients above 18 years of age, who suffered out of hospital cardiac arrest and experienced refractory ventricular fibrillation (VF) were included. Refractoriness was defined as VF or pulseless ventricular tachycardia as the initial rhythm that did not respond to three standard defibrillation attempts between 2-min intervals of cardiopulmonary resuscitation (CPR). Cardiac arrest due to trauma, drowning, hanging, suspected drug overdose, and hypothermia were excluded.
This was a three-group, cluster randomized trial. The study patients received one of three types of defibrillation – conventional, vector-change, or double-sequential defibrillation, based on the randomly assigned intervention for the cluster. Each cluster crossed over to one of the other strategies every 6 months. Each cluster was meant to undergo each of the three strategies at least once.
The three strategies
- Conventional defibrillation with pads in the antero-lateral position
- Double-sequential defibrillation: Two shocks administered one after the other with a gap of less than 1 second, with pads in the antero-lateral and antero-posterior positions
- Vector-change defibrillation: The pad position switched to the antero-posterior position after 3 conventional shocks
Chest compressions were carried out before placement of pads. Rhythm analysis was performed every 2 minutes. All patients received three standard antero-posterior defibrillations. Subsequent defibrillation was based on assignment to one of the three strategies.
The authors assumed a 12% incidence of the primary outcome, the survival to hospital discharge. Based on a difference of 8 percentage points in the primary outcome with the modified defibrillation strategies, they calculated a sample size of 930 patients, with 310 in each group.
Results (Table 1)
The study was ceased prematurely after enrolment of 405 patients due to the spread of Covid-19. Out of 405 patients who were randomized, 136 were assigned to conventional, 144 to VC, and 125 to DSED.
Overall, 67.9% of out-of-hospital cardiac arrests were witnessed and 58.0% of the patients received bystander CPR. Other baseline characteristics, including the median response time, the time to administration of the first shock, the duration and number of shocks administered before return of spontaneous circulation were similar. The dose of epinephrine, amiodarone, and lignocaine administered were also similar between the three groups.
Table 1. Primary and secondary outcomes.
|Endpoint||Standard||VC||DSED||DSED vs. standard(Adjusted RR)||VC vs. standard (Adjusted RR)|
|Survival to hospital discharge||18/135 (13.3%)||31/143 (21.7%)||38/125 (30.4%)||2.21 (1.33–3.67)|
|VF termination||92/136 (67.6%)||115/144 (79.9%)||105/125 (84.0%)||1.25 (1.09–1.44)|
|ROSC||36/136 (26.5%)||51/144 (35.4%)||58/125 (46.4%)||1.72 (1.22–2.42)|
|Modified Rankin Score 2 or less||15/134 (11.2%)||23/142 (16.2%)||34/124 (27.4%)||2.21 (1.26–3.88)|
Abbreviations: VC, vector change defibrillation; DSED, double sequential external defibrillation; ROSC, return of spontaneous circulation; RR: risk ratio
Primary outcome: Survival to hospital discharge was significantly higher with both DSED and VC compared to standard defibrillation
Secondary outcomes: Termination of VF was significantly higher with DSED and VC compared to standard defibrillation. Attainment of ROSC was significantly higher with DSED, but not with VC. More favorable neurological outcomes at hospital discharge, assessed using the Modified Rankin Scale was observed with DSED, but not with VC.
- Addresses an important clinical question of the defibrillation strategy in refractory VF, considering observational studies that suggest efficacy of early application of alternate defibrillation strategies, compared to the standard antero-posterior approach
- The cluster randomized crossover design is most appropriate for a study of this nature
- The quality of CPR was uniform across different groups
- A standard protocol was followed in all three groups
- Outcome assessors were blinded to the defibrillation strategy
- The study did not reach the projected sample size due to the spread of Covid-19 during the study period (only 405 patients were enrolled; the calculated sample size was 930)
- Blinding not possible, and hence, there is a likelihood of investigator bias. Termination of resuscitation may have occurred more often with standard care. The study does not provide details regarding the duration of resuscitation and the total number of shocks delivered
- The number of patients who survived to hospital discharge were few: 18/135, 31/143, and 38/125 patients in the conventional, vector-change, and double-sequenced defibrillation arms respectively. The small numbers may have led to an overestimation of effect
- The outcomes were assessed only until hospital discharge; this may be less than ideal, especially for neurological evaluation
- Bystander CPR was carried out in 58% of cases and the median time between emergency call and first shock was 10 minutes. Other health care settings may not accomplish these endpoints.
- The impact on the primary endpoint of an 8% increase in survival to hospital discharge with the alternate strategies of defibrillation may have been overly optimistic
- For vector-change defibrillation, the fragility index was 1 for survival to hospital discharge, the primary outcome.
- No data were available for co-morbidities, and pre-existing therapies
- Failure to follow the assigned strategy occurred in a few cases
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