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Evevident
Original paper
2013NEJMEmergency Medicine

TTM

Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest

RCTCardiac arrest

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Overview

After out-of-hospital cardiac arrest, targeting 33 degrees C did not improve outcomes compared with 36 degrees C when fever was actively prevented.

Clinical takeaway

TTM shifted practice away from mandatory deep hypothermia for all post-arrest patients and toward controlled temperature/fever prevention.

Key result

All-cause mortality was 50% at 33 degrees C vs 48% at 36 degrees C (HR 1.06; not significant).

Practice impact

Post-arrest temperature management should prevent fever; exact target depends on protocol and patient context.

Evidence

Study design

Randomized, assessor-blinded controlled trial.

Enrollment

950

Follow-up

Mortality through end of trial; neurologic outcome assessed at 180 days.

Geography

Europe, Australia

Clinical question

Is targeted temperature management at 33 degrees C superior to 36 degrees C after out-of-hospital cardiac arrest?

Population

  • Unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause.

Intervention

Targeted temperature management at 33 degrees C.

Comparator

Targeted temperature management at 36 degrees C (active fever prevention).

Primary outcome

All-cause mortality through the end of the trial.

Targeting 33 degrees C conferred no survival or neurologic benefit over 36 degrees C when fever was actively prevented in both arms.

Hazard ratio / 1.06 / CI 95% CI 0.89-1.28 / p=0.51

Key results

  • All-cause mortality: 50% at 33 degrees C vs 48% at 36 degrees C; HR 1.06 (95% CI 0.89-1.28; p=0.51).
  • Poor neurologic outcome (CPC 3-5 or mRS 4-6) at 180 days did not differ between groups.
  • Both arms actively controlled temperature and prevented fever.

Harms

  • Overall serious adverse events did not differ significantly between the temperature targets.
  • Hypokalemia and shivering are recognized consequences of deeper cooling.

Clinical Use

When to cite

  • When managing temperature after out-of-hospital cardiac arrest and emphasizing fever prevention rather than routine deep hypothermia for every patient.

Practice impact

  • Post-arrest temperature management should prevent fever; exact target depends on protocol and patient context.

Applicability

  • Most applicable to unconscious adults resuscitated from out-of-hospital cardiac arrest of presumed cardiac cause.

Limitations

  • Compared two actively controlled temperature targets, not hypothermia versus no temperature control.
  • Enrolled mostly presumed cardiac-cause, shockable-rhythm arrests.
  • The later TTM2 trial reinforced that 33 degrees C offers no benefit over targeted normothermia (fever prevention).

Common misinterpretations

  • TTM does not show cooling is useless; it shows deep hypothermia is not superior to controlled normothermia with fever prevention.
  • The comparator was not 'no treatment'; both arms received strict temperature management.

Citation

Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013;369(23):2197-2206. doi:10.1056/NEJMoa1310519

In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33 degrees C did not confer a benefit as compared with a targeted temperature of 36 degrees C.