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    Effects of age on minimum effective volume of local anesthetic for ultrasound-guided supraclavicular brachial plexus block. Pavičić Šarić Jadranka,Vidjak Vinko,Tomulić Katarina,Zenko Jelena Acta anaesthesiologica Scandinavica BACKGROUND:Involutional changes of peripheral nervous system occur with aging. The aim of the study was to determine the minimum effective volume of local anesthetic required to offer an effective ultrasound-guided supraclavicular brachial plexus block in 50% of middle-aged (< 50 years) and elderly (> 65 years) patients. We hypothesized reduced minimum effective volume of local anesthetic in elderly patients. METHODS:Middle-aged (n = 22) and elderly (n = 22) patients undergoing upper limb surgery received an ultrasound-guided supraclavicular brachial plexus block. Structural analysis of the brachial plexus in supraclavicular region was obtained by measuring the cross-sectional area. The prospective, observer-blinded study method is a previously validated step-up/step-down sequence model where the local anesthetic volume for the next patient is determined by the outcome of the previous block. The starting volume was 30 ml (50 : 50 mixture, 0.5%wt/vol levobupivacaine, 2%wt/vol lidocaine). The minimum effective volume of local anesthetic was determined using Dixon and Masey method. RESULTS:The minimum effective local anesthetic volume significantly differed between middle-aged and elderly [23.0 ml, 95% confidence interval (CI) 13.7-32.3 vs. 11.9 ml, 95% CI 9.3-14.6; 95% CI of the difference 1.6-20.6, P = 0.027]. The cross-sectional area of brachial plexus was 0.95 ± 0.15 in middle-aged and 0.51 ± 0.06 cm(2) in elderly patients (P < 0.001). CONCLUSIONS:Within the present study, we report a reduced minimum effective anesthetic volume for ultrasound-guided supraclavicular block in elderly patients. Additionally, smaller cross-sectional surface area of brachial plexus in the supraclavicular region was observed. 10.1111/aas.12109
    Dose-finding methodology for peripheral nerve blocks. Saranteas Theodosios,Finlayson Roderick J,Tran De Q H Regional anesthesia and pain medicine Dose-finding studies enable the successful conduct of peripheral nerve blocks by ensuring the administration of appropriate doses of local anesthetic. However, the optimal dose-finding methodology remains ambiguous. In this research methodology article, we set out to review the basic aspects pertaining to dose-response curves (graded vs quantal), the pharmacodynamic indices required by dose-finding studies, the properties of different dose-finding methods (sigmoidal dose-response curve analysis, Dixon-Mood method, Biased Coin Design, and Bayesian analysis), as well as strategies and recommendations for future research. 10.1097/AAP.0000000000000157
    EC50 of Epidural Ropivacaine Combined With Dexmedetomidine for Labor Analgesia. Zhang Wp,Li Cuiling The Clinical journal of pain BACKGROUND:It has been reported that the optimal concentration of epidural dexmedetomidine for labor analgesia is 0.5 μg/mL when combined with 0.1% ropivacaine. This study investigated the median effective concentration (EC50) of epidural ropivacaine for labor analgesia when combined with 0.5 μg/mL dexmedetomidine. MATERIALS AND METHODS:Sixty full-term primiparas were enrolled and divided into 2 groups in this prospective study. Group D received 10 mL solution (ropivacaine+0.5 μg/mL dexmedetomidine) in the induction of epidural anesthesia, and group C (control group) received 10 mL of ropivacaine alone. The dose of epidural ropivacaine was decided by using the up-and-down sequential allocation method with an initial concentration of 0.1%×0.01% gradient. Effective analgesia was defined as the visual analogue scale for pain as ≤3 within 30 minutes after epidural injection when cervical dilation is about 2 cm. The EC50 of ropivacaine was calculated by the Massey formula. Hemodynamic parameters, the stages of labor, and fetal heart rate were recorded. Neonatal Apgar scores and umbilical artery pH were also recorded. The side effects, if any, were noted. RESULTS:The EC50 of ropivacaine was 0.062% (95% confidence interval [CI], 0.058%-0.066%) in the group D, and 0.083% (95% CI, 0.077%-0.089%) in the group C, there was a significant difference between the groups (P<0.05). CONCLUSIONS:The EC50 of epidural ropivacaine for labor analgesia was 0.083% (95% CI, 0.077%-0.089%) and decreased to 0.062% (95% CI, 0.058%-0.066%) when combined with 0.5 μg/mL dexmedetomidine (http://www.chictr.org.cn, registration number: ChiCTR-OPC-16008548). 10.1097/AJP.0000000000000613
    The minimum effective concentration (MEC90 ) of ropivacaine for ultrasound-guided supraclavicular brachial plexus block. Fang G,Wan L,Mei W,Yu H H,Luo A L Anaesthesia The aim of this study was to determine the minimum effective concentration of ropivacaine for ultrasound-guided supraclavicular brachial plexus block. Fifty-one patients undergoing arm surgery received double-injection ultrasound-guided supraclavicular block using ropivacaine 40 ml. The concentration of ropivacaine administered to each patient started at 0.225% and then depended on the response of the previous one, based on a biased coin design up-and-down sequential method. In case of failure, the ropivacaine concentration was increased by 0.025% w/v in the next subject. In the case of a successful block, the next patient was randomised to the same concentration or a concentration 0.025% w/v less. Success was defined as complete sensory blockade of the brachial plexus 30 min after the block together with pain-free surgery. The minimum effective ropivacaine concentration in 90% of subjects was 0.257% w/v (95% CI 0.241-0.280%). 10.1111/anae.13445
    Quantile estimation following non-parametric phase I clinical trials with ordinal response. Paul Ranjan K,Rosenberger William F,Flournoy Nancy Statistics in medicine A non-parametric multi-dimensional isotonic regression estimator is developed for use in estimating a set of target quantiles from an ordinal toxicity scale. We compare this estimator to the standard parametric maximum likelihood estimator from a proportional odds model for extremely small data sets. A motivating example is from phase I oncology clinical trials, where various non-parametric designs have been proposed that lead to very small data sets, often with ordinal toxicity response data. Our comparison of estimators is performed in conjunction with three of these non-parametric sequential designs for ordinal response data, two from the literature and a new design based on a random walk rule. We also compare with a non-parametric design for binary response trials, by keeping track of ordinal data for estimation purposes, but dichotomizing the data in the design phase. We find that a multidimensional isotonic regression-based estimator far exceeds the others in terms of accuracy and efficiency. A rule by Simon et al. (J. Natl. Cancer Inst. 1997; 89:1138-1147) yields particularly efficient estimators, more so than the random walk rule, but has higher numbers of dose-limiting toxicity. A small data set from a leukemia clinical trial is analysed using our multidimensional isotonic regression-based estimator. 10.1002/sim.1834
    I appreciate the dialog between Drs. Anderson and Schonfeld and Murphy et al. Shafer Steven L Anesthesia and analgesia 10.1213/ane.0b013e318190a6c5