June 17, 2021
Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest.
What was the research question?
In survivors of out-of-hospital cardiac arrest, does targeted hypothermia impact all-cause mortality compared to targeted normothermia?
How did they do it?
An open-label trial with blinded assessment of outcomes in 14 countries, 61 institutions.
1861 adults with coma after resuscitation from out-of-hospital cardiac arrest were randomized to undergo targeted hypothermia at 33°C for 28 hours, followed by controlled rewarming at 0.3°C per hour until 40 hours ( 930 patients), or targeted normothermia with early treatment of fever (body temperature, ≥37.8°C) (931patients).
The primary outcome was death from any cause at 6 months.
Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale.
What did they find?
All-cause mortality at 6 months was not significantly different between the hypothermia group and the normothermia group (50% vs, 48%, p = 0.37).
Rate of patients with poor functional status (modified Rankin scale 4 to 6) was not significantly different between the hypothermia group and the normothermia group (55% vs. 55%, P=1.09).
Hypothermia group had more arrhythmias compared to normothermia group (24% versus 17%, P <0 .001).
Are there any limitations?
Results cannot be generalized to in-hospital cardiac arrest.
Cooling to a target temperature occurred at a median of 3 hours. Therefore, cannot rule out a benefit effect of earlier.
The trial used an absolute risk reduction of 7.5% in mortality based on the Hypothermia After Cardiac arrest trial, this may have been very ambitious and may subject the trial to type II error.
What does it mean?
Among survivors of out-of-hospital cardiac arrest, outcomes of targeted hypothermia are not different compared to targeted normothermia in terms of all-cause mortality and neurological functional status at six months.
The trial supports the notion that active temperature management and avoidance of hyperthermia are the most the most important factors determining the outcome of survivors of out-of-hospital cardiac arrest rather than hypothermia.