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

Description:

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.

Hypothesis:

 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

Exclusions:

  • >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).

Interpretation:

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.

References:

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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