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Optimal dose range of epidural naloxone to reduce nausea in patients receiving epidural morphine

Seoul, Korea

To the Editor:

Epidural co-administration of morphine and naloxone reduces morphine-induced side effects without reversal of the analgesic effect in patients undergoing gynecological surgery.¹ Naloxone in low doses has been shown to release endorphins, or perhaps displaces endorphins from receptor sites not relevant to analgesia, whereas at higher doses it blocks the action of the released or displaced endorphin at the postsynaptic receptor for analgesia.² However, little is known regarding the dose response relationship of epidural naloxone. We initiated research to determine the optimal dose range of epidural naloxone.

Seventy-four patients scheduled for hysterectomy received epidural analgesia with 0.33% bupivacaine 18 mL at the L3 to L4 level and then underwent general anesthesia. Patients then received between 1/2 and 1/3 of the initial dosage of bupivacaine through an epidural catheter at one-hour intervals until the end of surgery. As the surgeons started to close the abdominal cavity, each patient was given 2 mg of morphine via the epidural catheter. Patients were randomly allocated into three groups, each of which received a different medication mixture via the 100 mL two-day infusors (Accufuser PLUS®, Wooyoung, Korea). Group I received 4 mg morphine in 25 mL bupivacaine 0.5% in 75 mL normal saline (2 mL per hour). Groups II and III received the same mixture, but with the addition of 0.167 µg•kg^–1•hr^–1 and 0.412 µg•kg^–1•hr^–1 of naloxone, respectively. A 10-cm visual analogue scale (VAS) and a five-point scale were employed for pain assessment and nausea, respectively, during the postoperative period at two, eight, 16, 24 and 48 hr. The effects of the treatments were evaluated at each point using the Kruskal Wallis statistic to determine whether significant differences existed among groups and specific inter-group differences were identified using the Mann-Whitney U test.

Group III had lower VAS pain scores than Group I but the difference was significant only at 16 hr. Group II had the lowest VAS scores at eight, 16 and 24 hr postoperatively compared to Group I (P < 0.05). Groups II and III showed lower nausea scores than Group I at 16 and 24 hr postoperatively (P < 0.05; Table). Thus, increasing the dose of epidural naloxone did not reduce nausea any further.

References

1 Choi JH, Lee J, Choi JH, Bishop MJ. Epidural naloxone reduces pruritus and nausea without affecting analgesia by epidural morphine in bupivacaine. Can J Anesth 2000; 47: 33–7.[Abstract/Free Full Text]

2 Gan TJ, Ginsberg B, Glass PS, Fortney J, Jhaveri R, Perno R. Opioid-sparing effects of a low-dose infusion of naloxone in patient-administered morphine sulfate. Anesthesiology 1997; 87: 1075–81.[Medline]

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