Morphine과 Naloxone의 경막외 동반 투여가 Morphine의 제통효과와 부작용에 미치는 효과

Does Epidural Naloxone Reduce Side Effects of Epidural Morphine without Reversing Analgesia?

Background: Epidural coadministration of opioids and local anesthetics has provided excellent analgesia during postoperative period. However, it is usually associated with the occurance of many side effects which were induced by epidural morphine. Low dose of intravenous naloxone has been known to reduce morphine-induced side effects without reversing analgesia, but the effect of epidural naloxone has not been defined in human study. Therefore we evaluated side effects and analgesia when naloxone was administered via epidural route. Methods: Eighty patients having epiduro-general anesthesia for hysterectomy were randomly assigned to one of four study groups. As a mean of postoperative pain control, all received 2 mg of epidural morphine bolusly at 1 hr before the end of surgery and continuous epidural infusion was started by Two-day Infusor containing morphine 4 mg in 0.125% bupivacaine 100 ml with either none of naloxone(Group 1, n=20), 2 ug/kg/day of naloxone(Group 2, n=20), 3 ug/kg/day of naloxone(Group 3, n=20) or 4 ug/kg/day of naloxone(Group 4, n=20). Study endpoints included visual analog scales(VAS) for pain, severity of nausea, itching, somnolence and respiratory depression. They were assessed at 2, 4, 8, 16, 32, and 48 hr postoperatively. Results: VAS for pain showed significant difference in Group 4 compared with Group 1 at all of the evaluation time. Itching score decreased significantly in Group 3 and 4 after 8 hr postoperatively and nausea score decreased significantly in Group 3 after 4 hr postoperatively. Alertness score decreased significantly in Group 3 and 4 especially in early postoperative period. Conclusion: This study suggests that epidural naloxone reduce morphine-induced side effects in dose-dependent fashion without reversal of the analgesic effect of epidural morphine.