Intrathecal methadone and morphine for postoperative analgesia: a comparison of the efficacy, duration, and side effects.

A double-blind study of patients selected at random compared the analgesic and adverse effects of intrathecal methadone (1 mg) with those of intrathecal morphine (0.5 and 1 mg). The study was conducted on 30 patients who underwent major orthopedic or urologic surgery. The intrathecal opioid was administered at the end of surgery, and assessments began 1 h thereafter and continued for 20 h. Pain measurements, supplementary analgesia requirements, and adverse effects were recorded. Intrathecal morphine (0.5 and 1 mg) provided effective and prolonged analgesia. Methadone, however, was unable to ensure the same degree of analgesia; consequently, the median pain scores were consistently higher following methadone than morphine (0.5 and 1 mg) (P less than 0.05). The time to the onset of discomfort severe enough to require supplemental morphine was longer after intrathecal morphine than that following methadone (24 and 29 h with morphine 0.5 and 1 mg; 6.5 h with methadone; P less than 0.05). Respiratory depression (increases PaCO2) was not associated with methadone and morphine 0.5 mg but was common following morphine 1 mg (P less than 0.05). Facial pruritus was unique to intrathecal morphine. Urinary retention requiring bladder catheterization was more frequent following morphine than methadone, although this was not statistically significant. Nausea and vomiting were common to all groups. Intrathecal morphine (0.5 and 1 mg) provides superior postoperative analgesia to 1 mg methadone. Various explanations for the observed differences between the drugs are discussed, including the possibility that the dose of methadone used in the subarachnoid space was inadequate and that a larger dose might have produced an effect equal to that of morphine.

A dose-response study of intrathecal morphine: efficacy, duration, optimal dose, and side effects.

We performed a double-blind study of the dose-response relationship of intrathecal morphine (0, 0.3, 1, and 2.5 mg) for postoperative pain relief in 33 subjects who underwent total knee or hip replacement surgery. Assessments commenced 1 hour after the opioid injection, which was given at the end of surgery, and continued for 24 hours. Pain measurements, supplementary analgesia requirements, and adverse effects were recorded. Intrathecal morphine provided effective, long-lasting pain relief. All doses delayed the initial perception of discomfort (T-Pain) and also postponed the onset of severe pain requiring analgetic supplementation (T-Morphine) (1.25 hours control with placebo injections; greater than 20 hours with intrathecal morphine 0.3, 1, and 2.5 mg: P less than 0.05). Although 0.3 mg usually provided good analgesia it was unsatisfactory in three of 10 patients (30%), whereas 1 and 2.5 mg were absolutely reliable. Respiratory depression (increased PaCO2), common after the administration of 1 or 2.5 mg intrathecal morphine, was slow in onset and prolonged. The respiratory depression after 2.5 mg was more profound than after 1 mg, and produced apnea necessitating large-dose naloxone therapy. Pruritus was unique to intrathecal morphine administration, but nausea, vomiting, and urinary retention were common in all the groups. We conclude that no ideal dose of intrathecal morphine exists because, even with small quantities, minor adverse effects are evident. Doses between 0.3 and 1 mg, however, should provide good analgesia free from the major complication, respiratory depression.