Application of the Continual Reassessment Method to Dose-finding Studies in Regional Anesthesia-An Estimate of the ED_(95) Dose for 0.5% Bupivacaine for Ultrasound-guided Supraclavicular Block

摘要

Background: Previously reported estimates of the ED_(95) doses for local anesthetics used in brachial plexus blocks vary. The authors used the continual reassessment method, already established in oncology trials, to determine the ED_(95) dose for 0.5% bupivacaine for the ultrasound-guided supra-clavicular block. Methods: A double-blind, prospective trial was scheduled for 40 patients of American Society of Anesthesiologists class I-III presenting for upper limb surgery and supraclavicular block. The study dose to be administered was arbitrarily divided into six dose levels (12, 15, 18, 21, 24, and 27ml) with a priori probabilities of success of 0.5, 0.75, 0.90, 0.95, 0.98, and 0.99 respectively. A continual reassessment method statistical program created a dose-response curve, which would shift direction depending on the success or failure of the block. Our starting dose was 21 ml and the next allocated dose was reestimated by the program to be the dose level with the updated posterior response probability closest to 0.95. Results: After recruitment of eight patients, our initial dose levels and associated probabilities were deemed too low to determine the ED_(95)> Updated aprioris were calculated from the statistical program, and the study recommenced with a new starting dose of 30 ml. On completion, the ED_(95) dose was estimated to be 27ml (95% CI, 24-28ml). Conclusions: The continual reassessment method trial design provided a credible estimate for the ED_(95) dose for 0.5% bupivacaine for our technique of supraclavicular block and may be of value as a statistically robust method for dose-finding studies in anesthesiology.