Target Temperature Management 33°C Versus 36°C After Out-of-Hospital Cardiac Arrest - TTM


The goal of the trial was to evaluate a targeted temperature of 33°C compared with 36°C among unconscious patients after an out-of-hospital cardiac arrest.


 Hypothermia to 33°C will improve survival.

Study Design

  • Randomized
  • Parallel
  • Stratified

Patient Populations:

  • Patients ≥18 years of age who were unconscious after an out-of-hospital cardiac arrest ≥20 minutes of spontaneous circulation after resuscitation

    Number of enrollees: 939 patients
    Duration of follow-up: mean 256 days
    Mean patient age: 64 years
    Percentage female: 17% women


  • >240 minutes from ROSC to screening
  • Asystole as initial rhythm
  • Suspected intracranial hemorrhage or stroke
  • Body temperature <30°C

Primary Endpoints:

  • All-cause mortality

Secondary Endpoints:

  • Poor neurologic function or death at 180 days

Drug/Procedures Used:

 Unconscious patients after an out-of-hospital cardiac arrest were randomized to 33°C hypothermia (n = 473) versus 36°C (n = 466).

The method of hypothermia was at the discretion of the individual sites: cold fluids, ice packs, intravascular devices, and/or surface cooling systems.

Gradual rewarming was commenced at 28 hours.

Concomitant Medications:

Sedation was mandated in both groups during the intervention period.

Principal Findings:

Overall, 939 patients were randomized. The mean age was 64 years, 17% were women, 23% had a previous myocardial infarction, 13% had diabetes, 40% presented as ST-segment elevation myocardial infarction, the first monitored rhythm was ventricular fibrillation in 74%, and return of spontaneous circulation (ROSC) occurred at a median of 25 minutes.

The primary outcome of all-cause mortality occurred in 50% of the 33°C group versus 48% of the 36°C group (p = 0.51). Results were similar in prespecified subgroups.

Death or poor neurological function at 180 days was similar between the two groups (hazard ratio, 1.02; p = 0.78).


Among unconscious patients after an out-of-hospital cardiac arrest, hypothermia to 33°C was not beneficial compared to a target temperature of 36°C. Outcomes (survival and good neurological function) remain abysmal in this cohort of patients. Despite a relative paucity of data, hypothermia has been recommended for patients with coma after cardiac arrest. The recommendation for hypothermia will likely need to be tempered, pending further data.


Nielsen N, Wetterslev J, Cronberg T, et al., on behalf of the TTM Trial Investigators. Targeted Temperature Management at 33°C Versus 36°C After Cardiac Arrest. N Engl J Med 2013;369:2197-2206.

Presented by Dr. Niklas Nielsen at the American Heart Association Scientific Sessions, Dallas, TX, November 17, 2013.

Keywords: Coma, Myocardial Infarction, Resuscitation, Follow-Up Studies, Out-of-Hospital Cardiac Arrest, Rewarming, Hypothermia, Ventricular Fibrillation, Diabetes Mellitus

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