Comparative spinal neuropathology of hydromorphone and morphine after 9- and 30-day epidural administration in sheep

Despite extensive clinical use of epidural morphine and to a lesser extent hydromorphone, the neurotoxicologic effects of large-dose epidural administration have not been reported. We compared the impact on behavior, blood and cerebrospinal fluid (CSF) chemistry and hematology, and neuropathology of both epidural morphine (M) and hydromorphone (H) versus preservative-free normal saline (S) given to control animals. Silicone lumbar epidural catheters were implanted in adult sheep and attached to either a subcutaneous port (acute 9-day study) or continuous flow type implantable drug pump (chronic 30-day study) through which the ewes were repeatedly exposed to either the epidural test drug or to similar volumes of saline. The 9-day groups received 5 mL of epidural injections twice daily with the dose incrementally increased as follows: M (n = 6) 40 mg/d, 4 mg/mL; H (n = 6), 16 mg/d, 1.6 mg/mL; S (n = 3), preservative-free normal saline. The 30-day M and H groups were continuously infused epidurally with increasing concentrations eventually augmented with daily epidural boluses: M group (n = 3), 100 mg maximum daily dose, 25 mg/mL maximum concentration; H group (n = 3), 30 mg maximum daily dose, 10 mg/mL maximum concentration; S group (n = 3).(ABSTRACT TRUNCATED AT 250 WORDS)