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"Targeted Temperature Management at 33°C Versus 36°C after Cardiac Arrest". The New England Journal of Medicine. 2013. 369:2197-2206. PubMed•Full text•PDF

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcome
8.2 Secondary Outcomes
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

Does targeted temperature management at 33°C provide any benefit compared with a target of 36°C in unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause?

Bottom Line

Targeting a body temperature of 33°C did not reduce mortality or improve neurologic outcomes compared with a target of 36°C in unconscious patients after out-of-hospital cardiac arrest.

Major Points

Hypothermia at 33°C is no more effective than 36°C in preventing death or poor neurologic function at 180 days in survivors of out-of-hospital cardiac arrest of presumed cardiac cause.

Guidelines

Current international resuscitation guidelines recommend therapeutic hypothermia for unconscious adult patients with return of spontaneous circulation after out-of-hospital cardiac arrest. Decisions about the target temperature should now consider the evidence from this trial.

Design

- Multicenter, randomized, parallel-group, unblinded clinical trial
- N=950 unconscious adults after out-of-hospital cardiac arrest
- Targeted temperature management at 33°C (n=473)
- Targeted temperature management at 36°C (n=466)
- Setting: 36 ICUs in Europe and Australia
- Enrollment: November 2010 to January 2013
- Mean follow-up: 256 days
- Analysis: Modified intention-to-treat
- Primary outcome: All-cause mortality through the end of the trial

Population

Inclusion Criteria

- Age ≥18 years, unconscious after out-of-hospital cardiac arrest of presumed cardiac cause
- More than 20 minutes of spontaneous circulation after resuscitation

Exclusion Criteria

- Interval from return of spontaneous circulation to screening >240 minutes
- Unwitnessed arrest with asystole as initial rhythm, suspected intracranial hemorrhage or stroke, body temperature <30°C

Baseline Characteristics

- Mean initial recorded body temperature: 35.2°C in the 33°C group; 35.3°C in the 36°C group

Interventions

- Randomization to targeted body temperature of either 33°C or 36°C
- Aim to achieve target temperature as rapidly as possible using ice-cold fluids, ice packs, intravascular or surface temperature management devices
- Mandatory sedation maintained for the 36-hour intervention period
- Temperature-controlled rewarming commenced after 28 hours

Outcomes

Primary Outcome

- All-cause mortality at the end of the trial: 50% in the 33°C group vs. 48% in the 36°C group (HR 1.06; 95% CI 0.89-1.28; P=0.51)

Secondary Outcomes

- Poor neurologic function or death at 180 days according to CPC and modified Rankin scale: 54% vs. 52% with CPC (RR 1.02; 95% CI 0.88-1.16; P=0.78); 52% vs. 52% with modified Rankin scale (RR 1.01; 95% CI 0.89-1.14; P=0.87)

Criticisms

- Lack of blinding for ICU staff managing the patients' temperature
- Some patients in the 33°C group were rewarmed earlier than intended by protocol

Funding

Funded by the Swedish Heart–Lung Foundation, Arbetsmarknadens Försäkringsaktiebolag Insurance Foundation, Swedish Research Council, Region Skåne, National Health Service, Thelma Zoega Foundation, Krapperup Foundation, Thure Carlsson Foundation, Hans-Gabriel and Alice Trolle-Wachtmeister Foundation for Medical Research, Skåne University Hospital, TrygFonden, and European Clinical Research Infrastructures Network.

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