Aim and Objective: To compare the analgesic effectiveness of the patient-controlled inhaled nitrous oxide (Entonox®) with intravenous opioids (pethidine/midazolam) in reducing pain during minor gynecological operative procedures, including manual vacuum aspiration (MVA), fractional curettage and dilatation and curettage. Materials and Methods: Patients undergoing minor gynecological procedures from August 2021 to December 2022 were randomized to receive nitrous oxide or intravenous pethidine (50–75 micrograms) plus midazolam (2 mg). Pain scores during and post-procedure, satisfaction level, and side effects were assessed and compared. Results: A total of 106 patients met the inclusion criteria, including 53 in the pethidine/midazolam group and 53 in the nitrous oxide group. Baseline characteristics were comparable (p-value > 0.05). Pain scores during, immediately and 30 min after procedures were not significantly different in two groups (4.94 ± 3.15, 2.74 ± 2.57, 1.58 ± 2.13 vs. 5.47 ± 2.80, 2.98 ± 2.70, 1.64 ± 2.70; p-value: 0.174, 0.634, 0.889, for pethidine/midazolam vs. nitrous oxide group, respectively. Satisfaction scores were comparable in both groups (p-value > 0.05). However, the rate of side effects was significantly lower in the nitrous oxide group (3.8% vs. 28.3%; p-value 0.001). Additionally, the discharge scores showed a significantly faster recovery time in the nitrous oxide group at 60 and 90 min after the procedure; median (IQR): 10 (9–10) vs. 9 (8–10) and 10 (10–10) vs. 10 (8.5–10); p-value 0.002 and 0.029, respectively). Conclusions: Nitrous oxide is as effective as pethidine/midazolam for pain relief in minor gynecological operative procedures but associated with significantly lower side effects and significantly faster recovery time.
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