Antinociceptive Effect of Low-Dose Intrathecal Neostigmine Combined with Intrathecal Morphine following Gynecologic Surgery

Background: The purpose of this study was to determine whether combination of 1-5 mu]g intrathecal neostigmine would enhance analgesia from a fixed intrathecal dose of morphine.

Methods: A total of 60 patients undergoing gynecologic surgery were randomized to one of five groups. Patients received 15 mg bupivacaine plus 2 ml of the test drug intrathecally (saline, 100 mu]g morphine, or 1-5 mu]g neostigmine). The control group received spinal saline as the test drug. The morphine group received spinal morphine as test drug. The morphine + 1 mu]g neostigmine group received spinal morphine and 1 mu]g neostigmine. The morphine + 2.5 mu]g neostigmine group received spinal morphine and 2.5 mu]g neostigmine. Finally, the morphine + 5 mu]g neostigmine group received spinal morphine and 5 mu]g neostigmine.

Results: The groups were demographically similar. The time to first rescue analgesic (minutes) was longer for all patients who received intrathecal morphine combined with 1-5 mu]g neostigmine (median, 6 h) compared with the control group (median, 3 h) (P < 0.02). The morphine group (P < 0.05) and the groups that received the combination of 100 mu]g intrathecal morphine combined with neostigmine (P < 0.005) required less rescue analgesics in 24 h compared with the control group. The incidence of perioperative adverse effects was similar among groups (P > 0.05).