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


Journal Article

Introduction: Despite routine use of fentanyl in patients after traumatic brain injury (TBI), it is unclear if it is the optimal sedative/analgesic agent. Isoflurane is commonly used in models of TBI. Recent studies in cerebral ischemia and focal cryogenic lesion suggest that isoflurane may be neuroprotective vs fentanyl.1,2 To our knowledge, fentanyl and isoflurane have not been directly compared in TBI. We hypothesized that isoflurane would be neuroprotective vs fentanyl when given early after TBI in rats. Methods: Adult rats (n=18) underwent controlled cortical impact (CCI) with physiologic monitoring and then received 4h of N2O2 (2:1) and either fentanyl (10 meg/kg bolus, 50 mcg/kg/h infusion) or isoflurane (1% inhalation). Shams (n=8) underwent identical preparation and anesthesia but no CCI. Functional outcome (beam balance, beam walking, Morris water maze [MWM] tasks) was assessed over 20d in injured and sham rats. Lesion volume was quantified on d21. Additional rats (n=14) underwent CCI and anesthesia as described above with intracranial pressure (ICP) monitoring (Codman intraparenchymal transducer) for 4h. Brain water (wet-dry weight method) was assessed at the end of the anesthetic period. Results: After injury, motor and MWM performances were better in isoflurane vs fentanyl treated rats (p<0.05, ANOVA) but did not differ between shams. Lesion volumes were similar between groups. There was increased frequency of ICP>20 mm Hg and higher brain water in rats treated with isoflurane vs fentanyl (p<0.05, ANOVA). Conclusions: Rats treated with isoflurane had improved long-term functional outcome after CCI compared to those treated with fentanyl, despite increases in ICP and brain water. We speculate that isoflurane may mediate improved long-term functional outcome after CCI in rats through promotion of cerebral blood flow, suppression of metabolism, and/or modulation of excitotoxicity. Fentanyl may not be the optimal sedative/analgesic agent early after TBI in humans.

Duke Authors

Cited Authors

  • Statler, KD; Kochanek, PM; Dixon, CE; Alexander, HL; Warner, DS; Clark, RSB; Wisniewski, SR; Jenkins, LW; Marion, DW; Safar, PJ

Published Date

  • December 1, 1999

Published In

Volume / Issue

  • 27 / 12 SUPPL.

International Standard Serial Number (ISSN)

  • 0090-3493

Citation Source

  • Scopus