Dose dependent reduction in median effective concentration (EC50) of ropivacaine with adjuvant dexmedetomidine in labor epidural analgesia: An up-down sequential allocation study

We investigate the procedure of checking for overlap between confidence intervals or standard error intervals to draw conclusions regarding hypotheses about differences between population parameters. Mathematical expressions and algebraic manipulations are given, and computer simulations are performed to assess the usefulness of confidence and standard error intervals in this manner. We make recommendations for their use in situations in which standard tests of hypotheses do not exist. An example is given that tests this methodology for comparing effective dose levels in independent probit regressions, an application that is also pertinent to derivations of LC50s for insect pathogens and of detectability half-lives for prey proteins or DNA sequences in predator gut analysis.

Sequential design methods for binary response variables exist for determination of the concentration or dose associated with the 50% point along the dose-response curve; the up-and-down method of Dixon and Mood is now commonly used in anesthesia research. There have been important developments in statistical methods that (1) allow the design of experiments for the measurement of the response at any point (quantile) along the dose-response curve, (2) demonstrate the risk of certain statistical methods commonly used in literature reports, (3) allow the estimation of the concentration or dose-the target dose-associated with the chosen quantile without the assumption of the symmetry of the tolerance distribution, and (4) set bounds on the probability of response at this target dose. This article details these developments, briefly surveys current use of the up-and-down method in anesthesia research, reanalyzes published reports using the up-and-down method for the study of the epidural relief of pain during labor, and discusses appropriate inferences from up-and-down method studies.

Nerve blocks improve postoperative analgesia, but their benefits may be short-lived. This quantitative review examines whether perineural dexmedetomidine as a local anaesthetic (LA) adjuvant for neuraxial and peripheral nerve blocks can prolong the duration of analgesia compared with LA alone. All randomized controlled trials (RCTs) comparing the effect of dexmedetomidine as an LA adjuvant to LA alone on neuraxial and peripheral nerve blocks were reviewed. Sensory block duration, motor block duration, block onset times, analgesic consumption, time to first analgesic request, and side-effects were analysed. were combined using random-effects modelling. A total of 516 patients were analysed from nine RCTs. Five trials investigated dexmedetomidine as part of spinal anaesthesia and four as part of a brachial plexus (BP) block. Sensory block duration was prolonged by 150 min [95% confidence interval (CI): 96, 205, P<0.00001] with intrathecal dexmedetomidine. Perineural dexmedetomidine used in BP block may prolong the mean duration of sensory block by 284 min (95% CI: 1, 566, P=0.05), but this difference did not reach statistical significance. Motor block duration and time to first analgesic request were prolonged for both intrathecal and BP block. Dexmedetomidine produced reversible bradycardia in 7% of BP block patients, but no effect on the incidence of hypotension. No patients experienced respiratory depression. Dexmedetomidine is a potential LA adjuvant that can exhibit a facilitatory effect when administered intrathecally as part of spinal anaesthesia or peripherally as part of a BP block. However, there are presently insufficient safety data to support perineural dexmedetomidine use in the clinical setting.