Abstract
Targeted temperature management with mild hypothermia (TTM-hypothermia; 32-34 °C) is a treatment strategy for adult patients who are comatose after cardiac arrest. Robust preclinical data support the beneficial effects of hypothermia beginning within 4 hours of reperfusion and maintained during the several days of postreperfusion brain dysregulation. TTM-hypothermia increased survival and functional recovery after adult cardiac arrest in several trials and in realworld implementation studies. TTM-hypothermia also benefits neonates with hypoxic-ischemic brain injury. However, larger and methodologically more rigorous adult trials do not detect benefit. Reasons for inconsistency of adult trials include the difficulty delivering differential treatment between randomized groups within 4 hours and the use of shorter durations of treatment. Furthermore, adult trials enrolled populations that vary in illness severity and brain injury, with individual trials enriched for higher or lower illness severity. There are interactions between illness severity and treatment effect. Current data indicate that TTM-hypothermia implemented quickly for adult patients after cardiac arrest, may benefit select patients at risk of severe brain injury but not benefit other patients. More data are needed on how to identify treatment-responsive patients and on how to titrate the timing and duration of TTM-hypothermia.