Pharmacodynamics study of remimazolam besylate in anxious patients undergoing gastroscopy: a biased-coin design up-and-down sequential allocation trial

瑞米唑仑苯磺酸盐在接受胃镜检查的焦虑患者中的药效学研究:一项偏倚硬币设计的上下序贯分配试验

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Abstract

BACKGROUND: This study aimed to evaluate the impact of anxiety on the pharmacodynamics of remimazolam besylate in patients undergoing gastroscopy. METHODS: Patients undergoing gastroscopy were divided into two groups: an anxiety group (Self -rating Anxiety scale, SAS ≥ 50) and a non-anxiety group (SAS < 50). All patients received intravenous administration of 5 µg/kg alfentanil combined with remimazolam besylate. The biased coin design up-and-down sequential method (BCD-UDM) was used to determine the target doses of remimazolam besylate: the initial dose was 0.1 mg/kg, with a dose gradient of 0.01 mg/kg. If coughing, swallowing, or body movement reactions occurred within the first 2 min from the start of gastroscopy, it was considered a positive reaction, and the dose was increased for the next patient. Otherwise, it was considered a negative reaction, and the dose of remimazolam besylate for the next patient was determined according to the BCD-UDM. Discharge time from the recovery room and adverse reactions were recorded. The ED(50), ED(90), and their 95% confidence intervals (CI) were calculated. RESULTS: The ED(50) and ED(90) of remimazolam besylate in the anxiety group were 0.175 mg/kg (95% CI, 0.140-0.240) and 0.251 mg/kg (95% CI, 0.173-0.250), respectively. In contrast, the ED(50) and ED(90) of remimazolam besylate in the non-anxiety group were 0.126 mg/kg (95% CI, 0.116-0.150) and 0.148 mg/kg (95% CI, 0.130-0.160), respectively. The ED(90) equivalent ratio of the non-anxiety group to the anxiety group was 0.59 (95% CI, 0.468-0.710). The discharge time from the recovery room and the incidence of adverse reactions did not differ significantly between the groups. CONCLUSIONS: When combined with 5 µg/kg alfentanil, the ED(50) and ED(90) of remimazolam besylate for inhibiting body movement response within two minutes of gastroscopy in anxious patients were 0.175 mg/kg and 0.251 mg/kg, respectively. Anxiety increased the requirement for remimazolam besylate in patients undergoing gastroscopy, but it did not increase the risk of prolonged discharge time or adverse effects. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry. (ChiCTR2400086957) on July 15, 2024.

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