Application of the continual reassessment method to dose-finding studies in regional anesthesia: an estimate of the ED95 dose for 0.5% bupivacaine for ultrasound-guided supraclavicular block

Anesthesiology. 2013 Jul;119(1):29-35. doi: 10.1097/ALN.0b013e31829764cf.


Background: Previously reported estimates of the ED95 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 ED95 dose for 0.5% bupivacaine for the ultrasound-guided supraclavicular 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 27 ml) 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 ED95. Updated a prioris were calculated from the statistical program, and the study recommenced with a new starting dose of 30 ml. On completion, the ED95 dose was estimated to be 27 ml (95% CI, 24-28 ml).

Conclusions: The continual reassessment method trial design provided a credible estimate for the ED95 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Algorithms
  • Anesthesia, Conduction / methods*
  • Anesthetics, Local / administration & dosage*
  • Anesthetics, Local / blood
  • Brachial Plexus*
  • Bupivacaine / administration & dosage*
  • Bupivacaine / blood
  • Cohort Studies
  • Data Interpretation, Statistical
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nerve Block*
  • Orthopedic Procedures
  • Ultrasonography, Interventional
  • Upper Extremity / surgery


  • Anesthetics, Local
  • Bupivacaine