EBQ:TTM Trial
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Clinical Question
Is there a survival benefit to targeted temperature management at 33°C or 36°C in out-of-hospital cardiac arrest patients who remain unconscious after return of spontaneous circulation?
Conclusion
In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit compared with a targeted temperature of 36°C.
Design
Multicenter, International, randomized trial with 1:1 concealed allocation of 950 out-of-hospital cardiac arrest patients to temperature control for 24 hours at 33°C versus 36°C with blinded outcome assessment
Population Studied
Inclusion Criteria
- Age >= 18 years
- Out-of-hospital cardiac arrest of presumed cardiac cause
- Unconsciousness (Glasgow Coma Score <8) after sustained return of spontaneous circulation (ROSC) (20 minutes of circulation)
- ===Exclusion Criteria===
- Conscious patients
- Pregnancy
- Out-of-hospital cardiac arrest of presumed non-cardiac cause
- Cardiac arrest after arrival in hospital
- Known bleeding diathesis
- Suspected or confirmed acute intracranial bleeding
- Suspected or confirmed acute stroke
- Temperature on admission <30°C
- Unwitnessed asystole
- Persistent cardiogenic shock
- Known limitations in therapy
- Known disease making 180 day survival unlikely
- Known pre-arrest cerebral performance category 3 or 4, >240 minutes from ROSC to randomisation
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Baseline Characteristics
- Average Age: 81
- Sex: 83% Male
- Cardiac Arrest Location: 53% at Home, 41% Public location
- Bystander Witness: 89.5%
- Shockable Rhythm: 80%
- Asystole: 56%
- Time from Cardiac Arrest: 1 min
Interventions
Patients were randomized to either 33°C or 36°C The core body temperature was set as quickly as possible at the predefined target temperature, according to intervention allocation, with 4°C intravenous solutions, 43 ice – packs 8, 44 and commercially available cooling devices 45 at the discretion of the treating physician . The target core temperature was then maintained for 24 h. After the maintenance period core temperature was gradually raised to normothermia of 37°C during 8 hours with a rewarming rate of 0.5°C/hour in both groups.
Body temperature was then maintained at normothermia 37 ±0.5°C until 72 hours from sustained ROSC in both treatment groups, as long as the patient was in the ICU, using pharmacological treatment and temperature management systems when applicable
Outcomes
Primary Outcomes
- Survival to end of trial (at least 180 days)
Secondary Outcomes
- Composite outcomes of all-cause mortality and poor neurological function (Cerebral Performance Category (CPC) 3 and 4 and modified Rankin Scale (mRS) 4 and 5) at 180 days.
- All – cause mortality and CPC and mRS at 180 – days
- Adverse events:
- Bleeding
- pneumonia
- sepsis
- electrolyte disorders
- hyperglycaemia
- hypoglycaemia
- cardiac arrhythmia
- renal replacement therapy
Tertiary Outcomes
Complete neurological recovery
- Best neurological outcome during trial period
- Quality of life
- Biomarkers at 24, 48 and 72 hours
Criticism and Discussion
- The EBQ:TTM Trial sucessfully adopted a protocol for handling the problem of withdrawal of life support confounding long term prognosis measurements
- The population in this trial was less selective and included both shockable and nonshockable rhythm which makes delineating a ideal population for temperature ranges impossible to determine. [1]
- Subgroup analysis may be confounded by a trial enrollment of all comers especially if degrees of hypothermia should be adjusted for brain injury severity. [1]
- The prove that temperature control to prevent fever may be more important than the specific target temperature
Funding
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Sources
- ↑ 1.0 1.1 [http://www.nejm.org/doi/pdf/10.1056/NEJMe1312700 Rittenberg, Jon. "Temperature Management and Modern Post-Cardiac Arrest Care" NEJM Editorial. 2013.