Targeted hypothermia as good as normothermia in reducing mortality among cardiac arrest survivors: NEJM

Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Last month results from the CAPITAL-CHILL trial (presented at ACC 2021) suggested no additional benefit of achieving hypothermia at 31°C rather than the usual 34°C for improving survival among cardiac arrest victims. The surprising results from TTM2 trial now show that targeted hypothermia (34°C) doesnot lower mortality even in comparison to targeted normothermia (37.5°C). The trial results were published this week in NEJM.

Although guidelines strongly recommend targeted temperature management with a constant target between 32°C and 36°C, they also state that the overall evidence is of low certainty.

Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial was planned to assess the beneficial and harmful effects of hypothermia as compared with normothermia and early treatment of fever (including the use of acetaminophen) in patients after cardiac arrest.

Nineteen hundred adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33°C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, ≥37.8°C). 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.

Carefully designed targeted temperature management protocols involved the use of surface or intravascular temperature-management devices in both assigned groups, as well as standard care for patients who had had cardiac arrest.

1. There was no significant difference in survival at 6 months with hypothermia (33°C target), as compared with normothermia (≤37.5°C) (both groups reported a survival of approx. 50%).

2. 55% in each group had moderately severe disability or worse (modified Rankin scale score ≥4).

3. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group. Other adverse effects were similar in both groups.

Do these results suggest that the deliberate care bundles involved in targeted temperature management, as guided by the protocol, are not needed?

This would be a misinterpretation trial findings. 46% of the patients in the normothermia group received cooling with a temperature management device (31% with an intravascular device and 69% with a surface device).

These findings underscore the need for close temperature monitoring, pharmacotherapy, and device cooling in keeping with a targeted temperature management protocol, regardless of the target temperature.

The overall survival at 6 months among patients who had had out-of-hospital cardiac arrest was approximately 50%. This is a remarkable achievement as compared with the historical value of approximately 25%, and it may be attributed to advances in critical care, the implementation of targeted temperature management, and a uniform approach to neurologic prognostication.

The key take-away message is that post cardiac arrest care should be personalised. Although the target temperature may vary for each patient but achieving a particular "Target temperature" is essential using pharmacotherapy, device cooling, and timely neurologic prognostication.

"The target temperature, at the discretion of the clinician, could be 33°C, 36°C, or 37.5°C or less", conclude Morrison et al in an accompanying editorial.

Source: NEJM: DOI: 10.1056/NEJMe2106969