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