its based on refractory VF

2. Title they have not used PICO format

3. • Journal name – NEJM
• Impact Factor – 176
• Indexing - PubMed

5. BACKGROUND
• 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

6. Problem statement, conceptual framework and
Research question
• Introduction builds a logical case and context for the problem
statement : YES
• The problem statement is clearand well articulated : YES
• The conceptual framework is explicit and justified : YES
• The variables being investigated are clearly identified and presented :
YES

7. DESIGN
• 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%

8. • 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 clinicaltrials.gov
• Blinding of outcome assessors
• Outcomes assessed until hospital discharge

9. • Research design is defined and clearly described : YES
• The design is appropriate for research question : YES
• The design has internal validity, potential confounding variables or
biases are addressed : YES
• The design has external validity, including subjects, setting and
conditions : YES
• The design and conduct of study are plausible : YES

10. SETTING
• 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

11. INCLUSION CRITERIA
• ≥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

12. 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

13. SAMPLE SIZE
• The sample size calculated and submitted in the protocol was 930 (150 pilot study
participants and 780 RCT participants).
• This was calculated based on the observed difference of 8% in survival rate with a
power of 80% and alpha error of 5 %.
But they had to stop the trail early due to COVID pandemic as there was a
paramedic shortage.
Final patients included in the study - 405 patients

14. After 3rd Shock, the patients were randomised
to either:

17. OUTCOME
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

18. Secondary outcome
• 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)

19. • 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)

20. • 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)

21. STRENGTHS
• 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

22. WEAKNESSES
• 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.

23. • 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