Hypothermia Boosts 90-Day Function for Nonshockable Cardiac Arrest

Patients who experience out-of-hospital cardiac arrest and are in a coma stand to gain better neurologic function by 90 days if they receive moderate therapeutic hypothermia, even if they present with nonshockable rhythm, data from the HYPERION randomized trial suggest. The researchers also found no signs of adverse effects from targeted temperature management (TTM).

Clinical guidelines from the International Liaison Committee on Resuscitation released in 2015 advise a target of 32°C to 36°C for cardiac arrest patients with shockable rhythm who remain in a coma after being successfully resuscitated (“strong recommendation, low-quality evidence”). But TTM is merely suggested in those with nonshockable rhythm (“weak recommendation, very-low-quality evidence”).

This is because evidence on whether therapeutic hypothermia works in the setting of nonshockable rhythm has been mixed, with a 2015 substudy of the TTM randomized trial showing no benefit and various case series showing everything from benefit to no effect to harm.

“This uncertainty requires resolution, because nonshockable rhythms now predominate among patients with cardiac arrest and are associated with a poor prognosis, with only 2% to 15% of patients having good neurologic outcomes, as compared with nearly 65% of patients who have cardiac arrest with a shockable rhythm,” Jean-Baptiste Lascarrou, MD (CHU de Nantes, France), and colleagues write in their paper published in the December 12, 2019, issue of the New England Journal of Medicine.

Speaking with TCTMD, Lascarrou said that clinical use of TTM in nonshockable rhythm is currently heterogeneous, since there have been no trials dedicated to this population. The protocols employed in the HYPERION trial are flexible, without mandating use of a specific device, and thus could be applied widely, he said. “It’s a pragmatic trial. It reflects real life.”

HYPERION

HYPERION, an open-label, randomized controlled trial conducted across 25 intensive care units (ICUs) in France, enrolled 584 adults who had persistent coma after being resuscitated from cardiac arrest with nonshockable rhythm (asystole or pulseless electrical activity). Patients were randomized to moderate therapeutic hypothermia (33°C during the first 24 hours; n = 284) or targeted normothermia (37°C; n = 297). Each center followed its own standard protocol for cooling, and decisions to withdraw life support were based on current guidelines.

Survival at 90 days with favorable neurological outcomes, defined as a Cerebral Performance Category (CPC) score of 1 to 2, served as the primary outcome. The rate of this combined endpoint was higher for the hypothermia patients than for the normothermia patients (10.2% vs 5.7%; P = 0.04). However, this difference was not driven by mortality (81.3% and 83.2%, respectively). The cause of death was withdrawal of life support for 61.9% of the hypothermia patients and 65.2% of the normothermia patients.

By 90 days, 7.7% of patients in the hypothermia group had a CPC score of 3 and 0.4% had a score of 4. In the normothermia group, 10.4% had a score of 3 and none had a CPC score of 4.

There were no differences between the study arms regarding the duration of mechanical ventilation, length of stay in the ICU, survival to hospital discharge, infections, or hematologic adverse events.

To TCTMD, Lascarrou explained the quality of life captured by the 5-point CPC scale, which has more recently been superseded by the modified Rankin Scale. CPC 1 represents good neurological function “without any sequelae of the cardiac arrest,” he said, whereas with a score of 2, consequences are “very small” and patients can return to work and activities of daily living. At CPC 3, patients require assistance from a caregiver to eat or use the toilet. At CPC 4, patients cannot communicate and are in a long-term coma. Finally, a score of 5 indicates brain death.

The researchers acknowledge limitations to their study; in particular, Lascarrou pointed out that an outcome change of just one patient would render the difference in primary endpoint nonsignificant.

Still, Lascarrou remains enthusiastic about TTM. “It’s not very expensive. You can cool patients with just ice and a ventilator,” he said, adding that with no increase in adverse events, “the improvement in prognosis at day 90 is very huge.”