Opioid neurotoxicity: fentanyl-induced exacerbation of cerebral ischemia in rats

We tested the hypothesis that fentanyl would worsen ischemia-induced brain damage. In two sequential protocols forty rats were physiologically monitor ed and controlled. In protocol 1, rats were randomized (n = 10/group) to 30 min of control (N2O plus 0.4% halothane), low dose fentanyl (loading dose [LD] 50 mu g kg(-1), maintenance dose [MD] 2 mu g kg(-1) min(-1)), or high- dose fentanyl (LD 800 mu g kg(-1), MD 32 mu g kg(-1) min(-1)). After 15 min of fentanyl or sham infusion trimethaphan 0.5 mg was given i.v. and 3 min later bilateral carotid artery occlusion and blood withdrawal-induced hypot ension were maintained for 12 min. At 18 h postischemia rats underwent cere bral perfusion fixation. Brain areas were graded from 0 (normal) to 5. In a ddition to analysis of specific regions, neuropathologic scores were also s ummated over all brain regions and analyzed to compute a summed neuropathol ogic score. In protocol 2, five control and five high-dose fentanyl rats we re treated identically except that post-ischemic oxygenation was maintained for 6 h and cerebral perfusion-fixation was performed 6 h post-ischemia. O nly the caudate/putamen was examined in protocol 2. Fentanyl worsened lesio ns in both fentanyl groups' summed neuropathologic scores (P = 0.002) in pr otocol 1 and specifically, in the caudate/putamen (P < 0.01) in both protoc ols. Fentanyl in both high and low doses can exacerbate incomplete forebrai n ischemia in rats. (C) 1999 Elsevier Science B.V. All rights reserved.