A MULTICENTER STUDY OF INTRATHECAL NEOSTIGMINE FOR ANALGESIA FOLLOWING VAGINAL HYSTERECTOMY

Background: Intrathecal neostigmine injection produces analgesia in vo lunteers and reduces hypotension from intrathecal bupivacaine in anima ls. Initial clinical trials with neostigmine studied doses of more tha n 100 mu g, but animal studies suggest that smaller doses may be effec tive. In addition, all controlled clinical trials of neostigmine have come from one Brazilian university. This multicenter, placebo-controll ed trial investigated the effects of 25-75 mu g intrathecal neostigmin e on analgesia and blood pressure in women undergoing vaginal hysterec tomy. Methods: After institutional review board approval was obtained at the three university centers, and after patients gave informed cons ent, 92 women scheduled for vaginal hysterectomy were randomized to re ceive an intrathecal injection of 2 mi bupivacaine, 0.75%, in dextrose plus either 1 ml saline or 25, 50, or 75 mu g neostigmine. Blood pres sure, heart rate, pain and nausea (both assessed by visual analog scal e), and intravenous morphine use were recorded during surgery and at s pecified intervals afterward. Results: Morphine use was reduced simila rly by all doses of neostigmine. Only the 75-mu g dose of neostigmine increased the nausea score in the recovery room. The incidence of trea tment for nausea was greater in patients receiving neostigmine (61%) t han in those receiving saline placebo (29%) and was unaffected by neos tigmine dose. Neostigmine did not reduce the incidence of hypotension from bupivacaine. Conclusion: These data in patients after vaginal hys terectomy suggest that analgesia from intrathecal neostigmine may occu r at doses less than 50 mu g. In these doses, neostigmine does not red uce spinal bupivacaine-induced hypotension but may increase the need f or treatment of nausea.