EEG burst suppression is not necessary for maximum barbiturate protection in transient focal cerebral ischemia in the rat

Barbiturates have been demonstrated to reduce the cerebral metabolic rate ( CMR) in a dose-dependent manner but investigations of a dose-response relat ionship for their neuroprotective efficacy are scant. It has been suggested that barbiturates possess other mechanism of action that may be critical t o their protective effect. If so, it is conceivable that the peak effect of such mechanisms does not parallel the reduction in CMR, Thus, maximal neur oprotection may be achieved with a substantially lower dose of the drug. Th irty Sprague-Dawley rats were subjected to 2 h of middle cerebral artery oc clusion while either anesthetized with (1) halothane (control) or (2) intra venous thiopental titrated to cause mild EEG suppression or (3) thiopental titrated to maintain EEG burst suppression. Cortical blood flow was recorde d by continuous bilateral laser Doppler flowmetry (LDF). Infarct volume was assessed after 3 h of reperfusion. Low-dose thiopental decreased blood flo w to 80% of baseline and high-dose thiopental to 70% of baseline. LDF did n ot indicate improvement of blood flow by thiopental in the ischemic area. C ompared to controls, low-dose thiopental significantly decreased infarct vo lume by 28% and high-dose thiopental by 29%. The results of this study and a review of literature indicate that barbiturates provide cerebral protecti on but that the magnitude of this effect has been overestimated. Other mech anisms than CMR reduction seem to contribute to their beneficial effects, a nd high doses administered to the point of burst suppression may not be req uired to obtain maximal protection. (C) 1999 Elsevier Science B.V. All righ ts reserved.