Effect of Remimazolam Supplementation on Propofol Requirements During Hysteroscopy: A Double-Blind, Dose-Response Study

BACKGROUND: Propofol is commonly used for procedural sedation but may increase side effects in a dose-dependent manner. Remimazolam, an ultrashort-acting benzodiazepine, has been approved for procedural sedation but may delay awakening. This study tested the hypothesis that remimazolam as a supplement reduces effect-site propofol concentration (Ce prop ) required to suppress response to cervical dilation in patients undergoing hysteroscopy. METHODS: One hundred and fifty patients who were scheduled for hysteroscopy were randomized to receive 0, 0.05, 0.1, 0.15, or 0.2 mg·kg –1 intravenous remimazolam, followed by a bolus of sufentanil 0.15 μg⋅kg –1 , and a target-controlled propofol infusion. The initial target Ce prop was 3.5 μg·mL –1 and was increased or decreased in subsequent patients by steps of 0.5 μg·mL –1 according to whether there was loss of response to cervical dilation in the previous patient. We used up-down sequential analysis to determine values of Ce prop that suppressed response to cervical dilation in 50% of patients (EC 50 ). RESULTS: The EC 50 of propofol for suppressing response to cervical dilation was lower in patients given 0.1 mg·kg –1 (2.08 [95% confidence interval, CI, 1.88–2.28] μg·mL –1 ), 0.15 mg⋅kg –1 (1.83 [1.56–2.10] μg·mL –1 ), and 0.2 mg⋅kg –1 (1.43 [1.27–1.58] μg·mL –1 ) remimazolam than those given 0 mg⋅kg –1 (3.67 [3.49–3.86] μg·mL –1 ) or 0.05 mg⋅kg –1 (3.47 [3.28–3.67] μg·mL –1 ) remimazolam (all were P < .005). Remimazolam at doses of 0.1, 0.15, and 0.2 mg·kg –1 decreased EC 50 of propofol by 43.3% (95% CI, 41.3%–45.5%), 50.3% (48.0%–52.8%), and 61.2% (58.7%–63.8%), respectively, from baseline (remimazolam 0 mg⋅kg –1 ). Propofol consumption was lower in patients given 0.1 mg⋅kg –1 (4.15 [3.51–5.44] mg·kg –1 ), 0.15 mg⋅kg –1 (3.54 [3.16–4.46] mg·kg –1 ), and 0.2 mg⋅kg –1 (2.74 [1.73–4.01] mg·kg –1 ) remimazolam than those given 0 mg⋅kg –1 (6.09 [4.99–7.35] mg·kg –1 ) remimazolam (all were P < .005). Time to anesthesia emergence did not differ significantly among the 5 groups. CONCLUSIONS: For women undergoing hysteroscopic procedures, remimazolam at doses from 0.1 to 0.2 mg·kg –1 reduced the EC 50 of propofol inhibiting response to cervical dilation and the total propofol requirement. Whether the combination could improve perioperative outcomes deserves further investigation.