Outcomes were similar for comatose patients who received 36 vs 72 hours of device-based temperature control after out-of-hospital cardiac arrest, a randomized trial shows.

“Since 2005, active fever prevention in comatose patients has been advocated by the guidelines for 72 hours after an out-of-hospital cardiac arrest,” Christian Hassager, MD, of the University of Copenhagen, Copenhagen, Denmark, told theheart.org | Medscape Cardiology. “Our study is the first randomized trial ever on this subject — and it challenges the guidelines.”

At 90 days, a primary endpoint — a composite of death from any cause or hospital discharge with a high Cerebral Performance Category score — occurred in 32.4% of those in the 36-hour group and 33.6% of those in the 72-hour group; mortality was 29.5% vs 30.3%, respectively.

The study was published online November 6 in The New England Journal of Medicine. The results were also presented at the Resuscitation Science Symposium during the American Heart Association Scientific Sessions 2022.

No Significant Differences

Assessment of the two device-based fever-prevention strategies for the duration was a predefined, additional randomly assigned open-label intervention in the Blood Pressure and Oxygenation Targets in Post Resuscitation Care (BOX) trial, which involved comatose adult patients who had been resuscitated after out-of-hospital cardiac arrest at two Danish cardiac arrest centers.

The main BOX analysis compared different primary strategies in these patients in a two-by-two factorial design: higher vs lower blood pressure targets; and higher vs lower oxygenation targets. They found no difference between the various strategies in terms of death and discharge from hospital in a poor neurologic state. Those results were presented at the European Society of Cardiology Congress 2022 on August 27, and simultaneously published in separate articles in The New England Journal of Medicine.

For this current analysis, a total of 789 comatose patients (mean age, 62; 80% men) received device-based temperature control targeting 36°C for 24 hours followed by 37°C for either 12 or 48 hours (total intervention times, 36 and 72 hours, respectively) or until the patient regained consciousness.

Patients were kept sedated and were receiving mechanical ventilation during the temperature control at 36°C, the authors note. Target core body temperature was controlled using commercially available surface cooling at one of the sites in 286 patients (Criticool and Allon, Belmont Medical Technologies) and using intravenous cooling in 503 patients at the other site (Thermogard XP, and Cool Line Catheter, Zoll).

Body temperature was maintained at 37°C with the same type of device that had been used for 36°C during the initial 24 hours. If the patient awakened, cooling was terminated.

Physicians in both groups were permitted to use non-device-based fever treatment (ie, for a body temperature > 37.5°C) with drugs such as paracetamol, by uncovering the patient’s body, or both, at the discretion of the treating physician. Ice packs or pads were not used.

The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category of 3 or 4 (range, 1 to 5, with higher scores indicating more severe disability) within 90 days after randomization.

Secondary outcomes at 90 days included death from any cause and the Montreal Cognitive Assessment score (range, 0 to 30, with higher scores indicating better cognitive ability).

A primary endpoint event occurred in 32.3% of patients in the 36-hour group and in 33.6% of those in the 72-hour group (hazard ratio, 0.99). Mortality was 29.5% in the 36-hour group and 30.3% in the 72-hour group.

The median Montreal Cognitive Assessment scores were 26 and 27, respectively. No significant between-group differences in the incidence of adverse events were observed.

The authors concluded, “Active device-based fever prevention for 36 or 72 hours after cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma.”

Hassager added, “We will continue with a new trial where we will randomize to treatment as usual or immediate wakeup call and no temperature intervention at all.”

Findings ‘Very Persuasive’

Intensivist Ken Parhar, MD, clinical associate professor, Critical Care Medicine at the University of Calgary and Alberta Health Services, Calgary, Alberta, Canada, and medical director, Cardiovascular Intensive Care Unit, commented on the study for theheart.org | Medscape Cardiology.

“The findings are very clear and very persuasive,” he said. “I think this should be incorporated into future guidelines, though it would be nice to see the trial repeated in another center.”

Parhar has kept comatose patients under temperature control for less than 72 hours, but mainly because those patients started to wake up. “This study provides clarity on the safety of that process — that we don’t have to unnecessarily keep somebody sedated just for an arbitrary timeline,” he said. “Beyond 36 hours, we need to continue to use our judgment.”

The study was supported by a grant from the Novo Nordisk Foundation, as was the work of one of the coauthors. Hassager’s work was funded by a grant from the Lundbeck Foundation; he also received an individual research grant from the Novo Nordisk Foundation, as well as honoraria from ABIOMED. No other disclosures were declared.

American Heart Association Scientific Sessions 2022. Resuscitation Science Symposium 2022; Abstract #18. Presented November 6, 2022.

N Engl J Med. Published online November 6, 2022. Abstract.

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