TTM (2014)

Therapeutic hypothermia was established as a neuroprotective intervention after cardiac arrest, but the optimal target temperature remained uncertain. Previous studies suggested benefit, but the precise degree of cooling and its impact on outcomes needed further investigation.

The TTM trial was a randomized, controlled, assessor-blinded, multicenter study comparing targeted temperature management at 33°C versus 36°C in 950 comatose adult survivors of out-of-hospital cardiac arrest. The primary outcome was all-cause mortality at 180 days, and a secondary outcome was neurologic function assessed by the Cerebral Performance Category (CPC) scale.

There was no significant difference in mortality at 180 days between the 33°C group (50%) and the 36°C group (48%), with a relative risk of 1.06 (95% CI 0.89-1.28, p=0.51). Similarly, there was no significant difference in poor neurologic outcome (CPC 3-5) at 180 days (54% in the 33°C group vs. 52% in the 36°C group, p=0.69). Adverse events were similar between the groups, with slightly more arrhythmias in the lower temperature group.

Targeted temperature management at 36°C is non-inferior to 33°C for mortality and neurologic outcome after out-of-hospital cardiac arrest, suggesting that avoiding fever is paramount, but deeper hypothermia may not offer additional benefit.

The study primarily included patients with out-of-hospital cardiac arrest with a shockable rhythm, limiting generalizability to other cardiac arrest etiologies or in-hospital arrests. The definition of 'poor neurologic outcome' may also be considered a limitation by some.