Analgesics, sedatives, anticonvulsant drugs, and the cooled brain.

Multiple randomized controlled trials have shown that prolonged, moderate cerebral hypothermia initiated within a few hours after severe hypoxia-ischemia and continued until resolution of the acute phase of delayed cell death reduces mortality and improves neurodevelopmental outcome in term infants. The challenge is now to find ways to further improve outcomes. In the present review, we critically examine the evidence that conventional analgesic, sedative, or anticonvulsant agents might improve outcomes, in relation to the known window of opportunity for effective protection with hypothermia. This review strongly indicates that there is insufficient evidence to recommend routine use of these agents during therapeutic hypothermia. Further systematic research into the effects of pain and stress on the injured brain, and their treatment during hypothermia, is essential to guide the rational development of clinical treatment protocols.