Imagine, for a moment, that targeted temperature management (TTM), the standard of care in post cardiac arrest management for more than two decades, was built on a false premise from the very beginning. Not a hypothesis gradually refined by better evidence, but one whose foundation was fundamentally flawed.

The evidentiary basis for TTM rests on two small trials published in the same issue of the New England Journal of Medicine in 2002. The first, Bernard et al¹ enrolled 77 comatose patients following out of hospital cardiac arrest with an initial rhythm of ventricular fibrillation. Patients were allocated by alternating day to either cooling to 33°C using externally applied ice packs or to “normothermia.” Once 33°C was achieved, patients were maintained at that temperature for 12 hours before being actively rewarmed over approximately 6 hours. In the control arm, no active temperature management was provided and, unlike later trials, normothermia was neither targeted nor rigorously maintained. 

The second, the HACA trial², enrolled 275 comatose patients following out of hospital cardiac arrest with an initial rhythm of ventricular fibrillation. Treatment allocation followed a quasi random allocation scheme based on the day of the week, and treating clinicians were not blinded to group assignment.  Patients assigned to TTM were cooled to a target temperature of 32 to 34°C, maintained at that temperature for 24 hours, and then passively rewarmed over approximately 8 hours. As in Bernard et al., the control group received no active temperature management. Normothermia was maintained largely in name only.  Both trials reported remarkably large treatment effects. In Bernard et al., 49% of patients in the hypothermia group achieved a good neurological outcome compared with 26% in the control group. Similarly, the HACA trial reported good neurological outcomes in 55% of patients treated with hypothermia versus 39% of those assigned to the control arm.