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SummaryA clinical trial was conducted to evaluate the postoperative analgesic efficacy and the safety of intrathecal neostigmine in patients undergoing anterior and posterior vaginoplasty under spinal anaesthesia. Thirty-six patients were randomly divided into three groups to receive: normal saline (1 ml), morphine (100 mg in 1 ml of saline) or neostigmine (100 mg in 1 ml of saline) intrathecally just before a spinal injection of hyperbaric bupivacaine (0.5%, 4 ml). The mean [SD] time to the first analgesic (nonsteroidal anti-inflammatory drug) administration was significantly prolonged by intrathecal neostigmine (10.7 [4.3] h) and morphine (15.3 [3.0] h) compared with saline (4.5 [1.0] h). The three groups also differed in the number of patients requiring subcutaneous morphine to complement the analgesia provided by the intramuscular nonsteroidal anti-inflammatory drugs and the mean [SD] times for their administration: eight patients in the saline group (8.0 [3.8] h), one patient in the morphine group (18 h) and two patients in the neostigmine group (8 and 12.9 h). The morphine and neostigmine groups showed similar analgesic effectiveness. The characteristics of spinal anaesthesia were not modified by intrathecal morphine or neostigmine. Severe nausea and vomiting, sweating and distress during surgery were the most obvious adverse effects of intrathecal neostigmine. On the other hand, less hypotension was observed in the neostigmine group. The usefulness of intrathecal neostigmine as the sole postoperative analgesic may be restricted by the severity of its adverse effects.

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This study was designed to examine postoperative analgesia with intrathecal neostigmine in a randomized, blinded trial with morphine as the active control in patients undergoing anterior and posterior vaginoplasty. A secondary aim was to provide preliminary data on the interaction between these two drugs. The incidence of adverse effects was also assessed. Forty-eight patients were divided into eight groups (50 micrograms, 100 micrograms, and 200 micrograms morphine [M]; saline; 50 micrograms, 100 micrograms, and 200 micrograms neostigmine [N]; and 50 micrograms morphine + 50 micrograms neostigmine). Anesthesia was provided with a balanced technique. All patients stayed 24 h in the recovery room where adequacy of postoperative analgesia and side effects were assessed. Increasing doses of intrathecal morphine (50 micrograms, 100 micrograms, and 200 micrograms) and intrathecal neostigmine (50 micrograms, 100 micrograms, and 200 micrograms) showed a dose-dependent pattern of analgesia (P < 0.001). The M50 + N50 combination resulted in a better analgesic effect with fewer side effects than M50, N50, and control groups. These preliminary data suggest that spinal neostigmine produces analgesia for vaginoplasty surgery similar in duration to spinal morphine and that the combination of morphine and neostigmine may allow a reduction in the dose of each component for postoperative analgesia.

Two patients suffering with severe pain due to metastatic abdominal neoplasm were selected to examine whether subarachnoid neostigmine provided effective pain relief. Neostigmine was injected through a catheter introduced into the subarachnoid space at L4-L5. Patients were monitored for changes in arterial blood pressure, cardiac and respiratory rates, body temperature, level of consciousness and neurologic change. Pain was classified by the patients on a verbal four-grade scale, and analgesia was classified on a verbal three-grade scale. Complete pain relief was obtained 2 h after neostigmine (0.2 mg) in one patient and 4 h after neostigmine (0.1 mg) in the second patient. Pain of mild intensity returned 20 and 22 h after drug administration, respectively. Gastrointestinal discomfort was observed in both cases, but nausea and vomiting occurred only in the patient treated with the highest dose of neostigmine. No significant change in the monitored parameters was observed, except for a 6-h period of decreased blood pressure in the patient treated with the lower dose of neostigmine which required no specific treatment. The results obtained in these anecdotal cases indicate that subarachnoid neostigmine may provide analgesia in patients with pain arising from neoplasia, but further studies using controlled trials are needed before the drug is brought into clinical use.