Isoflurane improves long-term neurologic outcome versus fentanyl after traumatic brain injury in rats

Despite routine nse of fentanyl in patients after traumatic brain injury (T BI), it is unclear if it is the optimal sedative/analgesic agent. Isofluran e is commonly used in experimental TBI. We hypothesized that isoflurane wou ld be neuroprotective versus fentanyl after TBI. Rats underwent controlled cortical impact (CCI) and received 4 h of N2O/O-2 (2:1) and either fentanyl (10 mug/kg i.v. bolus, 50 mug/kg/h infusion) or isoflurane (1% by inhalati on) with controlled ventilation. Shams underwent identical preparation, wit hout CCI. Functional outcome (beam balance, beam walking, Morris water maze [MWM] tasks) was assessed over 20 days. Lesion volume and hippocampal neur on survival were quantified on day 21. Additional rats underwent identical CCI and anesthesia with intracranial pressure (ICP) monitoring, and brain w ater content was assessed. Motor and MWM performances were better in injure d rats treated with isoflurane versus fentanyl (p < 0.05). CA1 hippocampal damage was attenuated in isoflurane-treated rats (p < 0.05). Fentanyl-treat ed rats had higher mean arterial blood pressure after injury (p < 0.05); ho wever, ICP and brain water were similar between groups. Isoflurane improved functional outcome and attenuated damage to CA1 versus fentanyl in rats su bjected to CCI. Isoflurane may be neuroprotective by augmenting cerebral bl ood flow and/or reducing excitotoxicity, not by reducing ICP or brain water content. Alternatively, fentanyl may be detrimental. Isoflurane may mask b eneficial effects of novel agents tested in TBI models. Additionally, fenta nyl may not be optimal early after TBI in humans.