TTM Trial

What was the research question?

• In patients with out-of-hospital cardiac arrest, does a 36°C targeted temperature management differ from 33°C in terms of mortality at the end of the trial?

How did they do it?

• A multicenter trial in 36 centers in Europe and Australia.

• 939 patients with out-of-hospital cardiac arrest of any initial cardiac rhythm were randomized to undergo therapeutic hypothermia with a target temperature of 33°C (473 patients) or hypothermia with a target temperature of 36°C (466 patients) for 28 hours followed by rewarming at 0.5°C per hour to a temperature of 37°C.

• The primary outcome was all-cause mortality through the end of the trial.

• Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale.

What did they find?

• Mortality rate at the end of the trial was not significantly different between the 33°C group and the 36°C group (50% vs. 48%, P=0.51)

• At 180 days, a composite outcome of mortality or poor neurologic function (using CPC) was not significantly different between the 33°C group and the 36°C group (54% vs. 52%, P=0.78).

• In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87).

Are there any limitations?

• The majority of patients received basic life support, often within one minute of cardiac arrest, which may limit the external validity of the study.

What does it mean?

• There was no difference between hypothermia at a targeted temperature of 33°C compared to 36°C in unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause.

• This trial is complimentary to the previous two landmark hypothermia trials (Hypothermia after cardiac arrest and the Bernard study in Australia). All three studies showed that active temperature management and avoidance of hyperthermia is associated with a better outcome.