article51

TTM2

"Hypothermia vs. Normothermia after Out-of-Hospital Cardiac Arrest".

The New England Journal of Medicine. Full Article can be accessed through NEJM.org

Clinical Question

Does targeted hypothermia improve survival and functional outcomes in adults with coma who have experienced out-of-hospital cardiac arrest compared with targeted normothermia?

Bottom Line

Targeted hypothermia did not result in a lower incidence of death at 6 months compared to targeted normothermia in patients with coma after out-of-hospital cardiac arrest.

Major Points

Guidelines

Design

- Open-label, randomized, superiority trial with blinded outcome assessment
- N=1,900 adults in coma after out-of-hospital cardiac arrest of presumed cardiac or unknown cause
- Targeted hypothermia at 33°C with controlled rewarming (n=930)
- Targeted normothermia with early treatment of fever (n=931)
- Enrollment: November 2017 – January 2020
- Primary outcome: All-cause mortality at 6 months
- Secondary outcomes: Functional outcomes at 6 months using the modified Rankin scale, number of days alive and out of the hospital, survival analysis, and quality of life assessed by EQ-5D-5L
- Prespecified adverse events: Pneumonia, sepsis, bleeding, arrhythmia with hemodynamic compromise, skin complications
- Analysis: Intention-to-treat

Population

- Inclusion criteria: Adults ≥18 years of age with presumed cardiac or unknown cause out-of-hospital cardiac arrest, coma, and no ability to obey verbal commands post-resuscitation
- Exclusion criteria: More than 180 minutes from return of spontaneous circulation to screening, unwitnessed cardiac arrest with initial asystole, care limitations

Interventions

- Hypothermia group: Immediate cooling to target temperature of 33°C, maintained until 28 hours, followed by rewarming
- Normothermia group: Temperature maintained at ≤37.5°C, with temperature management devices initiated if body temperature reached ≥37.8°C

Outcomes

- Primary: At 6 months, death occurred in 50% of patients in the hypothermia group and 48% in the normothermia group (relative risk with hypothermia, 1.04; 95% CI, 0.94 to 1.14; P=0.37).
- Modified Rankin scale scores (0-6) indicating functional outcome were similar between groups at 6 months, with 55% in both groups experiencing moderately severe disability or worse.
- Outcomes were consistent across prespecified subgroups.
- Arrhythmias resulting in hemodynamic compromise were more common in the hypothermia group compared to the normothermia group.

Criticisms

- The trial did not include a control group without any temperature management, leaving unanswered whether any management is superior to none.
- ICU staff were aware of temperature targets, which may have influenced care outside of the study parameters.
- The study was limited to out-of-hospital arrests due to presumed cardiac or unknown cause, so the results may not be fully generalizable to other types of cardiac arrest.

Funding

Supported by independent research grants from various nonprofit and governmental agencies, with no commercial funding.