Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest

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Nielsen et al. "Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest". The New England Journal of Medicine. 2013;369:2197-206.

Link to Article: https://www.nejm.org/doi/full/10.1056/nejmoa1310519

Supplementary Appendix: https://www.nejm.org/doi/suppl/10.1056/NEJMoa1310519/suppl_file/nejmoa1310519_appendix.pdf


Clinical Question

In adults that suffer an out-of-hospitals (OOH) cardiac arrest of presumed cardiac cause, does induced therapeutic hypothermia targeting 36°C compared to 33°C reduce mortality or reduce neurological deficit?

  • Type of Trial: RCT

  • Blinding:Single blinded

  • Setting: 36 ICUs in Europe and Australia from Nov 2010 - Jan 2013

PICO

  • Population:

    • 950 adult patients who were unconscious (GCS<8) on admission to hospital after out of hospital cardiac arrest of presumed cardiac cause

      • Excluded if:

        • >6 hours from ROSC to screening, unwitnessed arrest w/systole, hypothermia <30C, suspected or known ICH

  • Intervention:

    • 28h of temp management with target of 36C using invasive or surface cooling followed by gradual warming to 37C at 0.5C/hour; avoidance of fever for 72h from randomization

    • Of note: 4 patients did not recieve this intervention as assigned

  • Control:

    • 28h of temp management with target of 33C using invasive or surface cooling followed by gradual warming to 37C at 0.5C/hour; avoidance of fever for 72h from randomization

    • Of note: 3 patients did not recieve this intervention as assigned

  • Outcome:

    • Primary outcome: Mortality

      • No difference in all-cause mortality through to the end of the trial (mean f/u period 256 days)

        • 48% had died in the 36C group and 50% died in 33C group

    • Secondary outcomes:

      • There were no differences between groups regarding their neurological status (as measured by the modified Rankin Scale or Cerebral Performance Category)

Conclusions

In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C


Strengths

  • Well designed methadology

  • Objective outcomes assessed by blinded external physicians

  • Intention-to-treat analysis utilized

Weaknesses

  • Not generalizeable to all arrests: They cannot have unknown or long “downtime”

  • Unwitnessed arrests with systole as initial rhythm were excluded

  • 90% had bystander witness and 73% had bystander CPR

  • Median time to BLS was one minute

  • Follow up was short term; unclear of long term benefit/harm

  • Wide confidence intervals - with 95% certainty, true hazard ratio for 33°C could be anywhere between 0.89 (strong benefit) and 1.28 (strong harm)


Take Note

  • This was only for witnessed cardiac arrests with short downtime

  • Population of patients with cardiac arrest is heterogenous - risks/benefits may not be same across subgroups (age <65 vs >65, gender, time from cardiac arrest to ROSC <25 min vs >25 min, initial rhythm, shock at admission, site category, TTM Trial)

Sources:

https://www.thebottomline.org.uk

Rachel MulderComment