Hypothermia after Cardiac Arrest in Large Animals (HACA-LA): a randomized controlled experimental study.

BACKGROUND

Induced hypothermia after cardiac arrest is neuroprotective in several animal models of cardiac arrest, but few high-quality studies have been conducted in larger animals. Recent clinical trials have questioned the beneficial effects of post-ischemic hypothermia. This study investigated whether immediate cooling or a 2-h delay in cooling to 33 °C after cardiac arrest was neuroprotective compared to controlled normothermia in large animals.

METHODS

Young adult female swine were anesthetized and kept at normothermia (38 °C). All animals were subject to 10 min of cardiac arrest by ventricular fibrillation, followed by 4 min of cardiopulmonary resuscitation, before the first countershock. At 10 min of return of spontaneous circulation (ROSC), animals were included and randomized to receive immediate hypothermia (33 °C), 2-h delayed hypothermia (33 °C), or normothermia for 30 h, including both cooling and rewarming time. Animals were extubated and assessed for 7 days. The primary outcome was brain histopathology using a modified Histology Damage Score. Secondary outcomes were neurocognitive testing, neurologic deficit score, and biomarkers of brain injury.

RESULTS

Among 42 animals, 33 were included; 11 in each arm, 23 survived until day 7. The modified Histology Damage Score was not significantly different between groups (p = 0.29). Neither neurocognitive testing nor neurologic deficit scores showed significant differences between the groups (p = 0.11 and p = 0.67, respectively). Neurofilament light chain (NfL) levels were significantly lower in the immediate hypothermia group at 48 h and on day 7 compared to the normothermia group (p = 0.0087, p = 0.012), but not in the delayed hypothermia group (p = 0.075, p = 0.33).

CONCLUSION

Our experimental model in large swine showed no neuropathological or functional protective effect of induced hypothermia after cardiac arrest, but NfL levels were lower in animals receiving immediately induced hypothermia, suggesting mitigation of neuronal injury.

TRIAL REGISTRY: Preclinicaltrials.eu (PCTE0000272), published 2021-11-03.