RCT

TTM2

Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

NEJM, 2021 · Multicenter randomized open-label trial with blinded outcome assessment (n=1900)

Clinical question

Does targeted hypothermia at 33°C improve 6-month survival and functional outcome compared with targeted normothermia (<=37.5°C) with early fever treatment in comatose post-cardiac arrest adults?

Population: Adults with out-of-hospital cardiac arrest of presumed cardiac or unknown cause who remained comatose after ROSC
Intervention: Targeted hypothermia at 33°C for 28 hours followed by controlled rewarming
Comparator: Targeted normothermia with early fever treatment (temperature maintained <= 37.5°C with device cooling if >= 37.8°C)
Primary outcome: All-cause mortality at 6 months
Result: 6-month mortality was 50% in the hypothermia group and 48% in the normothermia group (relative risk 1.04; 95% CI, 0.94 to 1.14; P=0.37). Functional outcome (modified Rankin Scale score 0-3) was identical (45% vs 45%, P=0.76). Arrhythmias causing hemodynamic compromise were significantly more common with hypothermia (24% vs 17%, P<0.001).

What the trial found

Targeted hypothermia at 33°C did not improve survival or functional neurological outcome compared with targeted normothermia and active fever prevention.

Current guideline position

Class I recommendation in ILCOR and ERC 2022 post-resuscitation updates.

Clinical interpretation

Shifted international post-ROSC practice from mandatory 33°C hypothermia toward strict targeted normothermia (<= 37.5°C) with rapid fever prevention.

Clinical Context & Relevant Topics (1)

Disease Reference

Cardiac Arrest & Post–Cardiac Arrest Care

Multimodal resuscitation, post-cardiac arrest syndrome management, targeted temperature control, and delayed neuroprognostication.

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