For comatose survivors of out-of-hospital cardiac arrest (OHCA), moderate hypothermia to a target body temperature of 31°C did not improve outcomes, compared with guideline-recommended mild hypothermia (target temp 34°C) in the CAPITAL CHILL study.
The results “do not support the use of moderate therapeutic hypothermia to improve neurologic outcomes in comatose survivors of out-of-hospital cardiac arrest,” write the investigators led by Michel Le May, MD, from the University of Ottawa Heart Institute, Ontario, Canada.
The CAPITAL CHILL results were first presented at the American College of Cardiology (ACC) 2021 Scientific Sessions in May and reported by Medscape Medical News at that time.
They have now been published online, October 19, in JAMA.
High Rates of Brain Injury and Death
Comatose survivors of OHCA have high rates of severe brain injury and death. Current guidelines recommend targeted temperature management at 32°C to 36°C for 24 hours. However, small studies have suggested a potential benefit of targeting lower body temperatures.
In the CAPITAL CHILL study of 367 OHCA patients who were comatose on admission, there were no statistically significant differences in the primary composite outcome of all-cause mortality or poor neurologic outcome at 180 days with mild-versus-moderate hypothermia.
The primary composite outcome occurred in 89 of 184 (48.4%) patients in the moderate hypothermia group and 83 of 183 (45.4%) patients in the mild hypothermia group — a risk difference of 3.0% (95% confidence interval [CI], 7.2% – 13.2%) and relative risk of 1.07 (95% CI, 0.86 – 1.33; P = .56).
There was also no significant difference when looking at the individual components of mortality (43.5% vs 41.0%) and poor neurologic outcome (Disability Rating Scale score >5: 4.9% vs 4.4%).
The baseline characteristics of patients were similar in the moderate and mild hypothermia groups. The lack of a significant difference in the primary outcome was consistent after adjusting for baseline covariates as well as across all subgroups.
The rates of secondary outcomes were also similar between the two groups, except for a longer length of stay in the intensive care unit in the moderate hypothermia group compared with the mild hypothermia group, which would likely add to overall costs.
The researchers note that the Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial recently reported that targeted hypothermia at 33°C did not improve survival at 180 days compared with targeted normothermia at 37.5°C or less.
The CAPITAL CHILL study “adds to the spectrum of target temperature management, as it did not find any benefit of even further lowering temperatures to 31°C,” the study team says.
They caution that most patients in the trial had cardiac arrest secondary to a primary cardiac etiology and therefore the findings may not be applicable to cardiac arrest of all etiologies.
It’s also possible that the trial was underpowered to detect clinically important differences between moderate and mild hypothermia. Also, the number of patients presenting with a nonshockable rhythm was relatively small, and further study may be worthwhile in this subgroup, they say.
For now, however, the CAPITAL CHILL results provide no support for a lower target temperature of 31°C to improve outcomes in OHCA patients, Le May and colleagues conclude.
JAMA. Published online October 19, 2021. Abstract
CAPITAL CHILL was an investigator-initiated study and funding was provided by the University of Ottawa Heart Institute Cardiac Arrest Program. Le May has disclosed no relevant financial relationships.