Temperature management in studies of barbiturate protection from focal cerebral ischemia: systematic review and speculative synthesis

Abstract

Our goal was to test the hypothesis that-given the barbiturates' novel ability to reduce brain temperature-the high prevalence of reports describing cerebral protection by barbiturates in animal models are, in part, the result of inadvertent cerebral hypothermia. We reviewed all published reports evaluating barbiturate protection in animal models of focal cerebral ischemia where functional or anatomic endpoints were assessed. Presence or absence of protection, and additionally the year of publication, were tabulated. Temperature monitoring was categorized as: (a) not monitored, (b) inadequately monitored (ie, temperature monitored, but not at appropriate sites or times), or (c) adequately monitored (brain or cranial temperature monitored at appropriate times, with or without core temperature). Twenty eight references published between 1974 and 2008 described 57 separate protocols. Cerebral protection by barbiturates was reported in 35 of 57 (61%) protocols. Temperature was not monitored in 10 protocols (18%), inadequately monitored in 32 (56%), and adequately monitored in 15 (26%). Although the majority (32 of 57; 56%) of the protocols were published before December 1987, none of these properly monitored temperature. In the protocols published in 1988 or later, 15 of 25 (60%) had proper temperature monitoring and 9 of the 15 (60%) reported protection by the barbiturates. Very few (ie, 15 of 57; 26%) protocols were capable of distinguishing between direct cerebral protection by the barbiturates and an artifactual, hypothermia-related, effect. However, among those protocols having proper temperature monitoring, there remained considerable evidence of barbiturate protection.