Longer Temperature Management No Better After Cardiac Arrest

Comatose out-of-hospital cardiac arrest (OHCA) survivors had similar mortality and disability outcomes with active device-based fever prevention whether for 36 or 72 hours after cardiac arrest, a randomized clinical trial found.

At 90 days, there was no significant difference in the incidence of all-cause death or severe cerebral disability or coma, which occurred in 32.3% of those randomized to 36 hours of temperature control and 33.6% of those assigned to the 72-hour group (HR 0.99, 95% CI 0.77-1.26, P=0.70), reported Christian Hassager, MD, DMSc, of Copenhagen University Hospital in Denmark, and colleagues.

"This finding was consistent across subgroups, including older patients and patients with coexisting conditions," the group noted in the New England Journal of Medicine.

Mortality rates at 90 days were also similar, at 29.5% in the 36-hour group and 30.3% in the 72-hour group.

While important in attempting to shore up the "less-than-optimal evidence base" behind international guidelines that call for temperature control for the first 72 hours after OHCA, the trial didn't really settle anything, suggested an accompanying editorial by Stephen Bernard, MD, and Janet Bray, PhD, both of Monash University in Melbourne, Australia.

The idea has been that fever may harm cardiac arrest patients through increasing oxygen demand, as observational studies have suggested that fever after cessation of temperature control by physical cooling is associated with worse neurologic outcomes.

However, "there is limited evidence that the onset of early fever after an out-of-hospital cardiac arrest is actually harmful," Bernard and Bray noted. They cited a large retrospective analysis that found that body temperatures greater than 38°C were not associated with adverse outcomes.

They reiterated study authors' caveat that these results are from "a subordinate study within the BOX trial, without a separate statistical analysis plan or formal sample-size calculation for evaluating the duration of fever prevention" and thus had limited power to detect small differences.

"The findings should reassure researchers that future studies to evaluate whether early fever prevention is helpful or harmful are needed to clarify the care pathway for this group of patients," they concluded.

For Hassager's study, patients were kept sedated and received 24-hours of temperature control at 36°C as soon as possible. Then, their core temperature was gradually increased by 0.5°C per hour to 37°C. Thereafter, they were randomly assigned to an additional 12 hours or 48 hours of device-based fever prevention.

As per the guidelines, temperature control was terminated after awakening in patients who were able to obey verbal commands and were potentially eligible for extubation, they said.

Median time from OHCA to randomization was 146 minutes. At randomization, median body temperature was 35.6°C in the 36-hour group and 35.4°C in the 72-hour group. By 72 hours, body temperatures above 37.7°C were noted in 50.1% of the patients in the 36-hour group and 38.1% of those in the 72-hour group.

Still, within 90 days, the primary endpoint of death or a Cerebral Performance Category (CPC) of 3 or 4 at hospital discharge was similar between groups across prespecified subgroups and with no evidence of interaction with the trial's main oxygen target or blood pressure interventions.

Three-month secondary outcomes were also similar with the two durations of temperature control. Median Montreal Cognitive Assessment scores were 26 in the 36-hour and 27 in the 72-hour group. Both treatment groups had a median CPC of 1 and a median modified Rankin scale score of 1.

Incidence of adverse events did not differ significantly between the groups. The most frequent adverse events were infection (RR 0.96, 95% CI 0.82-1.11), bleeding (RR 0.96, 95% CI 0.82-1.13), and seizure (RR 1.04, 95% CI 0.87-1.24).

Hassager and coauthors noted that adapted guidelines in 2022 "allow for two different temperature-control strategies for the initial 24 hours: one strategy involves maintaining the body temperature in the range of 32° to 36°C, and the other involves active fever prevention with a target body temperature of less than 37.7°C; after the initial 24 hours, active fever prevention continues until 72 hours in patients who remain comatose."

Authors acknowledged potentially limited generalizability of their findings, which were based on a patient cohort in which "almost 85% of the patients had a shockable primary rhythm, and almost 90% had received bystander cardiopulmonary resuscitation."

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