Comparison of effects of intraoperative and postoperative methadone: acute tolerance to the postoperative dose?

The effects of methadone 10 mg administered in two different clinical contexts, at induction of anaesthesia and following operation, were studied in two groups of patients undergoing elective total hip replacement. The intraoperative group received methadone 10 mg i.v. at induction of anaesthesia as part of a balanced anaesthetic technique. The postoperative group received methadone 10 mg i.v. following operation, extradural bupivacaine being used for the operative period. A demand analgesia system delivering methadone i.v. was used after operation in both groups. Arterial blood-gas tensions, cortisol and glucose concentrations, analgesic effects and plasma methadone concentrations were compared in the two groups. The only major difference between the two groups was in analgesic requirement. At the time of connection to the demand system the two groups had the same plasma methadone concentrations. Subsequently, the postoperative group had a significantly greater analgesic requirement which resulted in significantly greater plasma methadone concentrations the following morning. Thus, the administration of methadone following operation appeared to exert less analgesic effect than the same dose given during operation. The reasons for this are discussed.