Opioid Neurotoxicity

We tested the hypotheses that convulsant doses of opioids would produce limbic system damage exacerbated by hexamethonium.Ventilated paralyzed rats received intravenous (IV) isovolumic infusion of fentanyl loading dose (LD) 1000 micro gram/kg, maintenance dose (MD) 40 micro gram centered dot kg-1 centered dot min-1 (n = 10), sufentanil LD 400 micro gram/kg, MD 13.3 micro gram centered dot kg-1 centered dot min-1 (n = 10), alfentanil LD 1500 micro gram/kg, MD 150 micro gram centered dot kg-1 centered dot min-1 (n = 10), or 0.9% saline control LD 4 mL/kg, MD 4 mL centered dot kg-1 centered dot h-1 (n = 10), with O2/N2 30%/70% during opioid infusion and O2/N2 O in controls during saline infusion. Hexamethonium (LD 20 mg/kg, MD 40-120 mg centered dot kg-1 centered dot h-1) was given IV during opioid infusion to half of the rats. Cerebral perfusion-fixation with formalin was performed 24 h later, followed by histopathologic assessment. None of the control rats showed any histologic abnormalities. Overall summed neuropathologic severity was worse in opioid treated groups (P = 0.01). Lesions occurred primarily in cortical regions and limbic system structures. When arterial blood pressure was controlled to a lower level with hexamethonium (147 vs 100 mm Hg), rats had less severe lesions (P = 0.02). These data indicate that fentanyl, sufentanil, and alfentanil all can produce histopathologic evidence of brain injury in rats mitigated by hexamethonium. (Anesth Analg 1996;83:141-6)