Application of the Continual Reassessment Method for Dose Finding Studies in Regional Anaesthesia

I conducted five dose-finding studies as three different treatment arms of one clinical trial. The primary objective of this prospective randomised, double-blind trial was to estimate the ED95 of: (1) 1% and 2% lidocaine with adrenaline for axillary plexus blocks, (2) 1% prilocaine and 1% lidocaine with adrenaline for supraclavicular plexus blocks and (3) 0.25% levobupivacaine for interscalene plexus blocks. Based on data from 41 and 40 patients receiving axillary blocks, the estimated ED95 of 1% lidocaine with adrenaline was 40 mL (95% credible interval: 89.5–99.2%), and 2%lidocaine with adrenaline was 15 mL (95% credible interval: 87.4–97.5%), respectively. This indicates that a lower mass of a more concentrated local anaesthetic is likely to be required to achieve a 95% success rate. For supraclavicular blocks, the ED95 of 1% prilocaine and 1% lidocaine with adrenaline fell outside the dose range studied (31 and 42 patients, respectively), suggesting more than 40 mL of these drugs may be required to achieve 95% success rates. Based on data from 46 patients, the ED95 of 0.25% levobupivacaine is 24 mL (95% credible interval: 93.2% - 99.6%) for interscalene blocks for an operation under general anaesthesia. Also, early success at the radial and ulnar nerves increases the odds of successful axillary and supraclavicular blocks. All blocks were performed under ultrasound guidance.
The results of these studies provide high-quality information for clinical practice and training, enhance the safety of local anaesthetic use and minimise the risk of their toxicity. They consolidate the position of the modified Continual Reassessment Method as a reliable and robust methodology for future dose-finding studies in regional anaesthesia.