Effects of Combined Transdermal Nitroglycerin and Low-dose Intrathecal Neostigmine during Gynecologic Surgery.Lauretti et al. (page 943)

Lauretti et al.  conducted a prospective, placebo-controlled, double-blind trial to assess whether transdermal nitroglycerin would enhance analgesia in patients administered single doses of intrathecal neostigmine during gynecologic surgery. Forty-eight women scheduled for vaginoplasty were randomized to one of four groups: the control group, administered spinal saline and transdermal placebo; the neostigmine group, administered spinal neostigmine and transdermal placebo; the nitroglycerin group, administered spinal saline and a transdermal nitroglycerin patch; or the neostigmine–nitroglycerin group, administered spinal neostigmine and transdermal nitroglycerin.

All patients were premedicated with 0.05–0.1 mg/kg intravenous midazolam and hydrated with 10 ml/kg Ringer’s lactate solution preoperatively and after spinal anesthesia. All drugs, both intrathecal and transdermal, were prepared by one anesthesiologist and administered by a second anesthesiologist who was blind to drug preparation. Twenty to 30 min after spinal puncture and hemodynamic stabilization, patches of 5 mg nitroglycerin or placebo were applied at the thorax (ventrally, between T2–T4). Blood pressure, heart rate, and oxyhemoglobin saturation were monitored continuously throughout surgery. Patients scored their levels of nausea with a visual analog scale N intraoperatively, and pain scores and duration of block were assessed postoperatively. Pain was also assessed at the time of first rescue analgesic and 24 h after time of spinal puncture by an anesthesiologist blind to treatment assignment. The group of patients administered neostigmine and nitroglycerin required less rescue analgesic in 24 h than did the control group. The combined treatment also resulted in a longer time to first rescue analgesic (average, 14 h) than in all other groups. Neither intrathecal neostigmine alone nor transdermal nitroglycerin alone delayed the time to first rescue analgesics. None of the patients experienced nausea or vomiting intraoperatively. Episodes of vomiting occured postoperatively in only one or two patients in three of the four treatment groups. Results from this study suggest that, at the dose studied, neostigmine and nitroglycerin may enhance the antinociceptive effects of each other.