An optimal dose of ropivacaine for ultrasound-guided supraclavicular brachial plexus block

Editor, Dose, concentration and volume of local anaesthetics have been described as a 'triangulated circular argument'.1 It is then necessary to fix one variable to evaluate the others for dose-finding studies in regional anaesthesia. We previously used a fixed volume of 40 ml and found that 0.257 and 0.273%wt vol−1 were the minimum effective concentrations (MECs) in 90 and 99% of patients, respectively, of ropivacaine for ultrasound-guided supraclavicular block (SCB).2 In this follow-on study, we use 0.275%wt vol−1 as the MEC99 with the aim of estimating the minimum effective volume in 90% of patients (MEV90) using an up-down sequential allocation biased coin design (BCD). After obtaining local clinical trial ethics committee approval and written informed consent, we prospectively enrolled a minimum of 45 patients aged 41 to 65 years undergoing elective unilateral upper limb surgery from May to October 2015 at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (NCT02512471). All participants received double-injection ultrasound-guided SCB using 0.275%wt vol−1 ropivacaine (Naropin; AstraZeneca AB, Sodertalje, Sweden) with a protocol similar to our previous study.2 Half the volume was deposited in the 'corner pocket' after repeated aspiration, and the remainder was injected at the centre of the main neural cluster formed by the brachial plexus, using the compressed air injection technique.3 The starting volume and testing interval were 24 and 2 ml, respectively. The volumes were determined by the responses of previous patients with a failed block being followed by an increment for the next participant. After a successful block, the next patient was randomised to the same volume or a decrement with probabilities of 0.89 or 0.11, respectively. Success was defined as complete sensory blockade of the brachial plexus at 30 min and pain-free surgery. MEV90 was estimated using isotonic regression and the 95% confidence interval (95% CI) with 2000 bootstrap replicates using R version 3.6.1 (2019 The R Foundation for Statistical Computing, Vienna, Austria; ISBN 3-900051-07-0, http://www.r-project.org).4 The results for the 53 patients are shown in Fig. 1. MEV90 was 30.2 ml (95% CI 28.1 to 33.8). MEV95 was 31.1 ml (95% CI 29.6 to 33.6) and MEV99 was 31.8 ml (95% CI 30.7 to 33.6). Successful blocks (n = 45) resulted in satisfactory surgical anaesthesia. All failed blocks (n = 8) responded to local infiltration or rescue blocks without conversion to general anaesthesia. There were no pneumothoraces or vascular punctures.Fig. 1: Up-down biased coin design sequence of blocks with different ropivacaine volumes. The horizontal line is the calculated minimum effective volume of ropivacaine providing successful supraclavicular block in 90% of patients (MEV90); error bars represent 95% CI.We believe that this is the first study investigating the MEV90 of ropivacaine for SCB. This study completes a two-step strategy to find the best combination of concentration and volume that may be applicable to different clinical settings. We found that 32 ml was the lowest volume for a 100% success of ultrasound-guided SCB, fitting well in the range of 30 to 40 ml, which is generally believed to obtain dependable surgical anaesthesia. Thus, an optimal dose of ropivacaine is 0.275%wt vol−1 × 32 ml = 88.0 mg. Gupta and Hopkins5 used a Dixon small sample method to find the median effective volumes of three different concentrations of bupivacaine for ultrasound-guided SCB. They found that the ED50 of bupivacaine was independent of concentration. However, we did not find this at ED90. For 0.257%wt vol−1 ropivacaine, the ED90 is 0.257%wt vol−1 × 40 ml = 102.8 mg (95% CI 96.4 to 112),2 while for 0.275%wt vol−1 ropivacaine, the ED90 is 0.275%wt vol−1 × 30.2 ml = 83.05 mg (95% CI 77.3 to 93.0). The lack of overlap in the 95% CIs indicates a significant difference between the two ED90 results. Thus ED90, unlike ED50, is clearly dependent on the concentration of local anaesthetics. This disagreement may be explained by the inaccurate estimation of high quantiles far from the midpoint by the Dixon-Mood method.6 A single experienced anaesthetist performed all the blocks, which may limit the generalisability of our results. Also, caution should be exercised when studies with different criteria of block success are compared. In conclusion, an optimal dose of ropivacaine for double-injection ultrasound-guided SCB in middle-aged adults is 0.275%wt vol−1 × 32.0 ml = 88.0 mg.