Conclusion: Targeted hypothermia to 33°C does not improve mortality in patients with out of hospital cardiac arrest when compared to normothermia
My take away: Target normothermia post cardiac arrest to prevent secondary insult, as this study adds to the literature that there is no good evidence of benefit with for cooling. Hyperthermia is known to be detrimental and should be actively avoided
- Background : The TTM (2013) study compared a targeted temperature of 33°C vs. 36°C in patients with an out-of-hospital cardiac arrest from a presumed cardiac cause. There was no significant difference in all-cause mortality
- This was an international, multicentre, parallel group, randomised superiority trial conducted across 14 countries and 61 institutions in Europe
- They enrolled patients with admitted to hospital following OHCA of presumed cardiac or unknown cause who were unconscious (score of <4 on the Full Outline of Unresponsiveness scale) with more than 20 minutes of spontaneous circulation after resuscitation
- Exclusion criteria included:
- Unwitnessed cardiac arrest with systole as initial rhythm
- Not randomised within 3hrs of arrest
- Hypothermia T <30°C on admission
- Intracranial haemorrhage
- Pregnancy
- A total of 1900 patients were enrolled between November 2017 and January 2020
- Patients randomised to the intervention group received 40 hours of intervention:
- Immediate cooling with a surface or intravascular temperature-management device to a target core temperature of 33°C, then maintained at this temperature for 28 hours
- After 28 hours rewarming to 37°C began in hourly increments of one third of a degree
- Patients randomised to the normothermia group had a target temperature 36.5°C – 37.7°C with cooling therapies commenced if T > 37.8°C
- From 40 to 72 hours both groups were maintained at normothermia 36.5°C – 37.7°C
- The primary outcome was death from any cause at 6 months
- Secondary outcomes included:
- Poor functional status at 6 months (mRankin 4-6)
- Number of days the patient was alive and out of the hospital until day 180
- Survival determined in a time-to-death analysis
- Health-related quality of life
- Secondary outcomes included:
- Results: A total of 1,861 patients were enrolled. There was no significant difference at in mortality at 6 months – 465 of 925 patients (50%) in the hypothermia group and 446 of 925 patients (48%) in the normothermia group had died (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37)
- There were no differences in any secondary outcomes
- There were higher rates of arrhythmias with haemodynamic instability in the hypothermia group 24% vs 16% (RR 1.45, 95% CI 1.21 – 1.75, p<0.001)
- Strengths:
- Large well conducted study with low risk of bias and near complete data set (very low rate of loss to follow up (<1%)
- Outcome assessors were blinded
- Interventions were protocolised and therefore reduced individual practitioner variability
- Multinational nature of the study with consistency of results across regions increases external validity
- Limitations:
- Treating clinicians were aware of patient group allocation (practicably unavoidable)
- There was no control group – it is unclear whether any temperature management is better than no temperature management (though previous evidence would suggest that hyperthermia is detrimental to an injured brain)
Reference: TTM2 Trial Investigators. Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest. N Engl J Med. 2021 Jun 17;384(24):2283-2294.
