Targeted temperature management with hypothermia for comatose patients after cardiac arrest

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.

Keywords: Brain; Coma; Heart arrest; Hypothermia; Resuscitation.

Fig. 1.

Targeted temperature management with mild hypothermia can benefit ischemic brain injury in different ways, depending on when it is delivered. Specifically, hypothermia can protect from brain injury, reduce reperfusion injury, or treat secondary brain injury. CPR, cardiopulmonary resuscitation; ROSC, return of spontaneous circulation.

Fig. 2.

Preclinical data [19,23] illustrate that a 4-hour delay allows for treating ischemic brain injury with prolonged postischemia targeted temperature management with mild hypothermia but this benefit declines with 6- to 8-hour delay. (A) Histological protection of striatum (lower percentage of necrotic neurons) is present when hypothermia starts within 2 hours, but not after 6 hours. Protection of the medial CA1 region of the hippocampus decreases at 6 hours and is not detected at 12 hours [19]. (B) Survival after cardiac arrest increases when hypothermia starts 0 to 4 hours after cardiac arrest but declines with 8-hour delay. Behavioral recovery vanishes with 8-hour delay. [23]. NS, not significant; NDS, neurological deficit score (higher NDS is more favorable).