Twenty-one patients who had undergone total hip replacement were randomly assigned to one of three groups in order to compare a single dose of 1 mg/kg of pethidine im (I) and 20 mg (II) or 60 mg of extradural pethidine (III) in a double-blind design. The degree of analgesia, the adverse effects, and the kinetics were studied for 18 h. Pain was monitored using a visual analogue scale (VAS). Supplementary doses of oxycodone if required were given no earlier than 0.75 h after pethidine. Plasma concentrations of pethidine were measured with gas chromatography mass spectrometry (GCMS). Hypoalgesia to pin prick test was evaluated. Low pain scores were observed in the extradural groups between 0.25 and 1.5 h after the dose. A significant difference in pain score compared with the im group was found after the higher extradural dose only between 0.5 and 1 h (p less than 0.05). The area under the curve (AUC) of pain score versus time (0-18 h) was not significantly different between groups. The recorded adverse effects were minor in all three groups. The terminal half-lives and plasma clearances of pethidine, and the time to peak concentration were not different between the groups. Single patients in the extradural groups showed hypoalgesia to pin prick in parallel to the effect. The present study shows that extradural pethidine produces shortlived analgesia, in contrast to the long-lasting effect of morphine found in other studies.
Low intrathecal doses of opiates produce dose-dependent long-lasting elevation of the pain threshold in rats. The effect is postulated to be mediated by a direct action on the substantia gelatinosa of the spinal cord. Eight uncontrolled and two controlled studies in man showed a long duration of analgesia for most patients in the postoperative period. The duration of effect differs widely within and between studies. Using a double-blind design, we compared the relative efficacy of epidural and parenteral pethidine to control postoperative pain after total hip replacement. Preliminary pharmacokinetic data from six patients show that epidural doses of 20 or 60 mg pethidine give a similar pattern of absorption and elimination in plasma as 1 mg pethidine/kg body weight intramuscularly. The terminal elimination half-lives of pethidine in plasma are 5-7 h for all routes of administration. The possibility cannot be excluded that the analgesic effect of epidural pethidine is partly systemically mediated.Address:
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