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

BACKGROUND: The 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).

METHODS: Patients (18-65 years old) scheduled for gastroscopy were recruited in this study. Subjects received intranasal SUF and MID for sedation. The dose of MID (5 mg) was fixed, while the dose of SUF was increased progressively (six incremental doses ranging from 0-0.60 μg/kg, n = 3 for each dose). The first cohort received a conservative, predetermined dose of 5 mg MID and 0 μg/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%.

RESULTS: Thirty Chinese patients scheduled for gastroscopy were included. Probability of respiratory depression at each dose was as follows: 5 mg MID + 0 μg/kg SUF, 0.4%; 5 mg MID + 0.1 μg/kg SUF, 0.8%; 5 mg MID + 0.2 μg/kg SUF, 1.8%; 5 mg MID + 0.3 μg/kg SUF, 3.7%; 5 mg MID + 0.4 μg/kg SUF, 9.9%; 5 mg MID + 0.5 μg/kg SUF, 17.8%; 5 mg MID + 0.6 μg/kg SUF, 36.0%.

CONCLUSION: The MTD of intranasal MID and SUF for sedation during gastroscopy causing 10% respiratory depression is 5 mg MID + 0.4 μg/kg SUF, based on CRM.