Analgesic and adverse effects of a low dose of intrathecally administered hyperbaric neostigmine alone or combined with morphine in patients submitted to spinal anaesthesia: pilot studies

We report the analgesic and adverse effects of intrathecally administered hyperbaric neostigmine, alone or combined with morphine, in two patients suffering from severe lower limb ischaemic pain (group 1), five patients undergoing Caesarean section (group 2) and 19 patients scheduled for orthopaedic surgery (group 3) under spinal anaesthesia. These patients were enrolled in three pilot studies undertaken before the initiation of the planned controlled studies. Hyperbaric neostigmine (50 mu g in glucose 8%) produced analgesia lasting more than 6 h in patients of group 1, but the effect was accompanied by episodes of vomiting. A lower dose of hyperbaric neostigmine (25 mu g), alone (two patients) or combined with morphine (50 mu g) tone patient) produced no discernible analgesic effect but was followed by severe nausea and vomiting within 15 min of intrathecal injection in patients of group 2. Two patients who received hyperbaric morphine (100 mu g) had analgesia for more than 24 h and exhibited mild pruritus. In patients of group 3, hyperbaric neostigmine alone (25 mu g) produced analgesia of shorter duration than neostigmine (25 mu g) plus morphine (50 mu g) or morphine (100 mu g). Neostigmine alone or combined with morphine was associated with adverse events, mainly nausea and vomiting that lasted up to 9-12 h in some patients. Other adverse events observed included anxiety, somnolence and involuntary defaecation. Most patients who received the combination of neostigmine and morphine exhibited more severe nausea, vomiting and somnolence. The low clinical efficacy of intrathecally administered neostigmine alone or in combination with morphine impairs the design of a double-blind protocol and might restrict the clinical usefulness of the drug combination.