Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013;369(23):2197-206.
What we already know about the topic: Patients generally have poor survival and neurologic outcomes after out-of-hospital cardiac arrest. After two studies in 2002 showed improved outcomes in patients with out-of-hospital arrest (of a presumed cardiac cause, with an initial shockable rhythm) when they were cooled for a period following their arrest, therapeutic hypothermia became a standard part of international resuscitation guidelines.
Why this study is important: Therapeutic hypothermia is now standard for patients who have ROSC after out-of-hospital arrest with an initial shockable rhythm, and this protocol has been extended to patients who have had in-hospital arrests, initial non-shockable rhythms, and arrests of non-cardiac origin. However, we don’t know at what temperature this benefit begins.
Brief overview of the study: This international, multicenter, randomized controlled trial took place in 36 ICUs in Europe and Australia. Eligibility criteria included age of 18 years or older, Glasgow Coma Scale < 8 on admission to the hospital, and at least 20 consecutive minutes of spontaneous circulation. Exclusion criteria included time from ROSC to screening of > 240 minutes, unwitnessed arrest with asystole as the presenting rhythm, suspected or confirmed ICH or stroke, or body temperature of less than 30°C. Patients were consecutively screened and randomized to be cooled to either 33°C (473 patients) or 36°C (466 patients) for 28 hours and then gradually rewarmed, after which they underwent neurologic assessment by blinded physicians. The primary outcome measure was all-cause mortality through the end of the trial. Results showed no significant difference in all-cause mortality or poor neurologic outcome between patients in the two groups. Hypokalemia was more frequent in the 34°C group.
Limitations: While the physicians performing neurologic exams were blinded to patient group, the ICU doctors were not (they needed to know the goal temperatures of their patients). The types of sedation and paralytic agents used were not protocolized, and were therefore uncontrolled.
Take home points: This RCT on targeted temperature management suggests that cooling patients to 36°C is non-inferior to cooling them to 34°C. These results suggest that prevention of fever may be the true benefit of temperature management, as opposed to aggressive cooling.