Neuroaxial hydromorphone for control of postsurgical, obstetric, and chronic pain

Abstract

H YDROMORPHONE (dihydromorphinone) is a semisynthetic, /x-selective opioid agonist developed more than 80 years ago and used for control of moderate to severe pain. Except for a 6-ketone substitution, hydromorphone's chemical structure and molecular weight are similar to that of morphine (Fig 1). Similarities also exist regarding lipid solubility and polarity; however, hydromorphone exhibits higher analgesic potency. On a milligram basis, the analgesic potency of oral and intravenous (IV) hydromorphone has been reported to be five times greater than morphine after a single dose L2 and three times greater with continuous exposure) After IV administration, analgesic onset and time to peak effect are more rapid than morphine, although the duration of activity is slightly shorter (3.5 v 4 h). 1'4'5 Peak analgesic effect is noted 10 to 20 minutes after IV injection, and minimum effective plasma concentration is 4 ng/mL. 1'4'5 Hydromorphone's elimination half-life is approximately 2.5 hour s , and the parent compound is primarily metabolized in liver by Ndemethylation and glucuronidation. 4'6'7 Free drug, as well as the glucuronidated metabolite, are excreted in urine, v's Drug accumulation, leading to exaggerated effect/toxicity, can be expected in patients with hepatic and renal failure) Hydromorphone is associated with dose-dependent reductions in respiratory rate and minute ventilation, however, it is less sedating than morphine 7'9 and less likely to release histamine. 1'7 When compared with equivalent IV doses of morphine, patients treated with hydromorphone expe-