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.