TTM & TTM2 Meta-analysis

NEJM Evidence

June 15, 2022

Hypothermic versus Normothermic Temperature Control after Cardiac Arrest.

Summarized by: 

Mazen Kherallah

What was the research question?

  • Does Hypothermia at 33°C decrease 6-month mortality compared with normothermia after out-of-hospital cardiac arrest?


How did they do it?

  • An individual patient data meta-analysis that included patients from the TTM study (Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest) and the TTM2 trial (Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest.

  • Total of 2800 patients were included in the study with 1403 patients in the hypothermia group (target temperature of 33°C), and 1397 patients in the normothermia group (target temperature of 36°C in the TTM trial and <37.8°C in TTM2 trial).

  • The primary outcome was 6-month mortality of all-causes.

  • Secondary outcomes included poor functional outcome (modified Rankin scale score of 4 to 6) at 6 months.

  • Predefined subgroups were tested for interaction with the intervention as follows: Age (older or younger than the median), sex (female or male), initial cardiac rhythm (shockable or nonshockable), time to return of spontaneous circulation (above or below the median), and circulatory shock on admission (presence or absence).


What did they find?

  • 6-month mortality rate was not significantly different in the hypothermia group compared to the normothermia group (49.4% vs. 47.9%, relative risk with hypothermia, 1.03; 95% confidence interval [CI], 0.96 to 1.11; P=0.41).

  • The incidence of a poor functional outcome was not significantly different in the hypothermia group compared to the normothermia group (54.3% vs. 54.0%, relative risk with hypothermia, 1.01; 95% CI, 0.94 to 1.08; P=0.88).

  • There was no evidence of improved outcomes in any of the predefined subgroups including type of rhythm.

  • Potential harm with increased mortality in hypothermia patients who had received bystander cardiopulmonary resuscitation, and potential benefit in hypothermia patients with no bystander cardiopulmonary resuscitation.


Are there any limitations?

  • The study does not rule out a benefit of controlling the temperature between 36-37.8°C as the control groups in both TTM and TTM2 used a temperature control device (100% in the control group of the TTM trial and 46% in the TTM2 trial).


What does it mean?

  • Hypothermia at 33°C does not reduce 6-month mortality and does not improve 6-month neurological outcome compared to normothermia.

  • This high level of evidence provides support to using device-controlled normothermia in patients with out-of-hospital cardiac arrest.

TTM & TTM2 Meta-analysis