ED90 of spinal 2-chloroprocaine 1% in ambulatory knee arthroscopy up to 45 min: a randomized biased-coin- up-and-down sequential allocation trial

Abstract

BackgroundA short acting spinal anesthetic facilitates smooth flow since quick recovery of motor function will facilitate unassisted ambulation. The aim of this study was to estimate the effective dose (ED90) of intrathecal 2-chloroprocaine 1% in outpatient knee arthroscopy.MethodsTwo cohorts were included in two different hospitals. In cohort I, a randomized biased-coin up-and-down design with 40 patients was used to find the ED90. Four dose-levels of plain 2-chloroprocaine 1% were used: 25, 30, 35 and 40 mg. The identified primary outcome, the ED90, was validated in 50 patients in cohort II with an open label design. Secondary outcomes included time to complete recovery from motor and sensory block with spinal injection as time zero, peak sensory block level, urine retention and time until hospital discharge.ResultsForty patients were included in the final analysis in cohort I. The ED90 was estimated at 27.8 mg, successful spinal anesthesia was obtained in 38 patients (95%). Fifty patients were included in the final analysis in cohort II, 49 patients had successful anesthesia with a fixed round dose of 28 mg. In this Cohort, peak sensory block was T10/T11 (range: (L4–T4)). The median time to full recovery of the motor block was 60 min (45–60) and 90 min (75–105) for the sensory block. The mean time to hospital discharge was 2.9 hours (0.7).ConclusionThe ED90 of 2-chloroprocaine 1% in knee arthroscopy was estimated to be 27.8 mg. In an external population, the ED90 resulted in successful anesthesia in 98% of the patients (95% CI 89% to 100%).Trial registration numberNetherlands Trial Registry (NL6769).

Median effective dose of ropivacaine for prophylactic cervical cerclage in Chinese women: a dose-finding study

“…The biased-coin methodology has been used to determine the ED90 or ED95 in dose-finding study26–28; however, the dose assignment needed to be randomised, which was slightly more difficult to implement than the Dixon and Massey up-and-down method. Since the Dixon and Massey up-and-down method cannot be used to accurately determine the ED95 and is associated with a broad CI, we used Centered Isotonic Regression to calculate ED50 and ED95 in our study.…”

Labor Analgesia Initiation With Dural Puncture Epidural Versus Conventional Epidural Techniques: A Randomized Biased-Coin Sequential Allocation Trial to Determine the Effective Dose for 90% of Patients of Bupivacaine

“…The biased-coin design specifically lends itself to estimating nonmedian dosage targets such as the ED90; moreover, this specific design is optimal among up-down methodologies in that the distribution of administered doses is most peaked around the target dose. 10–13…”

“…The biased-coin design specifically lends itself to estimating nonmedian dosage targets such as the ED90; moreover, this specific design is optimal among up-down methodologies in that the distribution of administered doses is most peaked around the target dose. [10][11][12][13] If a subject did not respond successfully, the dose for the next subject was increased by 2.5 mg. By contrast, if a subject responded successfully, the bupivacaine dose was decreased by 2.5 mg with a probability of 10% and maintained with a probability of 90% (ratio 1:9). This ratio of probabilities (ie, the biased coin) helps ensure that the doses administered gravitate toward levels with high success rates.…”

“…More recently, a biased-coin, versus a traditional, updown sequential allocation estimated the ED90 for local anesthetic agents with tighter CIs. [10][11][12][13] Consequently, the primary objective of this study was to use a biased-coin up-down allocation methodology to characterize the EPL dose of bupivacaine to achieve effective initial analgesia in 90% of laboring women (ED90) via the DPE or EPL technique; we hypothesized that a lower bupivacaine dose would achieve the ED90 end point with the DPE, compared to the EPL, technique.…”

“…More recently, a biased-coin, versus a traditional, up-down sequential allocation estimated the ED90 for local anesthetic agents with tighter CIs. 10–13…”