Serum Levels Following Epidural Administration of Morphine and Correlation with Relief of Postsurgical Pain

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Abstract
The serum levels of free morphine base due to the epidural administration of morphine were studied and correlated with analgesic effect. Results from 21 patients are presented. Following major surgery with bupivicaine or lidocaine continuous epidural block as the primary anesthetic, 5 or 10 mg/70 kg body weight of preservative-free morphine sulfate was administered through the epidural catheter when the patient noted the onset of postsurgical pain. Serum morphine levels were determined at intervals between 5 and 240 min postinjection using a liquid chromatography technique with electrochemical detection, and analgesic effectiveness was assessed using a linear pain analog scale and the subjective response of the patient. The mean peak serum level in the patients receiving 5 mg/70 kg was 28.0 .+-. 20.6 ng/ml with mean serum levels declining to 2.1 .+-. 1.6 ng/ml over the 4 h postinjection period. The patients receiving 10 mg/70 kg had a mean peak serum level of 49.7 .+-. 35.6 ng/ml with mean serum levels declining to 5.4 .+-. 4.8 ng/ml over the 4 h postinjection period. Average onset of significant analgesin was 15 min postinjection. Duration of adequate analgesia varied from 4 h to several days, the mean being 37.9 h for those receiving 5 mg/70 kg and 51.6 h for those receiving 10 mg/70 kg. Side effects included pruritis, ameliorated with diphenhydramine, and urinary retention. Somnolence and slowing of respiratory rate which developed in 1 patient were reversed with naloxone without notable effect on the duration or intensity of the analgesic response to the epidural morphine. This study demonstrates the analgesic effectiveness of and the serum morphine levels consequent to the epidural administration of morphine, and supports the concept of a selective spinal analgesic action.