Determination of the maximum tolerated dose of intranasal sufentanil and midazolam in Chinese: a pilot study

作者：Zou, Y.; Shao, L.; Tian, M.; Zhang, Y.^*; Liu, F.^*

来源：Acta Anaesthesiologica Scandinavica, 2018, 62(6): 773-779.

DOI：10.1111/aas.13081

• CONTINUAL REASSESSMENT METHOD
• CLINICAL-TRIALS
• STOPPING RULES
• PHASE-I
• SEDATION
• CHILDREN
• SPRAY
• PHARMACOKINETICS
• DESIGN
• ADULTS

BackgroundThe purpose of this study was to determine the maximum tolerated dose (MTD, the dose of causing 10% respiratory depression) of intranasal sufentanil (SUF) and midazolam (MID) for sedation during gastroscopy by continual reassessment method (CRM). @@@ MethodsPatients (18-65years old) scheduled for gastroscopy were recruited in this study. Subjects received intranasal SUF and MID for sedation. The dose of MID (5mg) was fixed, while the dose of SUF was increased progressively (six incremental doses ranging from 0-0.60g/kg, n=3 for each dose). The first cohort received a conservative, predetermined dose of 5mg MID and 0g/kg SUF, subsequent cohorts received doses of SUF that were determined by the responses of all previous patients using Bayesian-based software. The dose allocated to the next cohort is the one with an updated posterior response probability closest to 10%. @@@ ResultsThirty Chinese patients scheduled for gastroscopy were included. Probability of respiratory depression at each dose was as follows: 5mg MID + 0g/kg SUF, 0.4%; 5mg MID + 0.1g/kg SUF, 0.8%; 5mg MID + 0.2g/kg SUF, 1.8%; 5mg MID + 0.3g/kg SUF, 3.7%; 5mg MID + 0.4g/kg SUF, 9.9%; 5mg MID + 0.5g/kg SUF, 17.8%; 5mg MID + 0.6g/kg SUF, 36.0%. @@@ ConclusionThe MTD of intranasal MID and SUF for sedation during gastroscopy causing 10% respiratory depression is 5mg MID + 0.4g/kg SUF, based on CRM.

• 出版日期2018-7
• 单位首都医科大学