A Commentary on the Effect of Targeted Temperature Management in Patients Resuscitated from Cardiac Arrest

The members of the International Liaison Committee on Resuscitation (ILCOR) Advanced Life Support Task Force have written a comprehensive summary of trials of the effectiveness of induced hypothermia (IH) or targeted temperature management (TTM) in comatose patients after cardiac arrest (CA). However, in-depth analysis of these studies is incomplete, especially since there was no significant difference in primary outcome between hypothermia versus normothermia in the recently reported TTM2 trial. We critically appraise trials of IH/TTM versus normothermia to characterize reasons for the lack of treatment effect, based on a previously published framework for what to consider when the primary outcome fails. We found a strong biologic rationale and external clinical evidence that IH treatment is beneficial. Recent TTM trials mainly included unselected patients with a high rate of bystander cardiopulmonary resuscitation. The treatment was not applied as intended, which led to a large delay in achievement of target temperature. While receiving intensive care, sedative drugs were likely used that might have led to increased neurologic damage as were antiplatelet drugs that could be associated with increased acute stent thrombosis in hypothermic patients. It is reasonable to still use or evaluate IH treatment in patients who are comatose after CA as there are multiple plausible reasons why IH compared to normothermia did not significantly improve neurologic outcome in the TTM trials.