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

Study objective: Adjuvant dexmedetomidine can be used to reduce the required concentration of ropivacaine for labor epidural analgesia. However, the potency of dexmedetomidine has not been fully studied. The purpose of this study was to determine the median effective concentration (EC50) of ropivacaine with adjuvant dexmedetomidine. Design: Prospective, double-blind, up-down sequential allocation study. Setting: Academic medical center specializing in the care of women and children. Patients: One hundred and fifty healthy, term parturients requesting labor epidural analgesia were randomly assigned to 1 of 5 different concentrations of dexmedetomidine: 0 mu g/ml, 0.3 mu g/ml, 0.4 mu g/ml, 0.5 mu g/ml, or 0.6 mu g/ml. Interventions: The study solution for the first patient in each group included the randomly assigned concentration of dexmedetomidine in 0.1% ropivacaine. Subsequent patients in each randomization group received the assigned concentration of dexmedetomidine in a new concentration of ropivacaine as determined by the updown allocation methodology. Effective analgesia was defined as pain on the visual analogue scale of<3 at30 min after administration of local anesthetic. The up-down sequential allocation method and pmbit regression were used to calculate the EC50 of epidural ropivacaine. Measurements: The primary outcome was pain 30 min after administration of local anesthetic via epidural catheter. Exploratory outcomes included side effects, neonatal outcomes, and obstetric outcomes. Main results: The EC50 values for ropivacaine in dexmedetomidine 0.4 mu g/ml, 0.5 mu g/ml, and 0.6 mu g/ml (0.044% [95% CI 0.036% to 0.045%], 0.035% [95% CI 0.031% to 0.041%], and 0.039% [95% CI 0.034% to 0.045%], respectively) were lower compared to ropivacaine in dexmedetomidine 0 mu g/ml and 0.3 mu g/ml (0.086% [95% CI 0.081% to 0.092%], and, 0.069% [95% CI 0.056% to 0.076%], respectively). Differences between EC50 values for ropivacaine in dexmedetomidine 0.4 mu g/ml, 0.5 mu g/ml, and 0.6 mu g/ml were not statistically significant. Results of our exploratory analyses did not reveal differences in side effects, neonatal outcomes, or obstetric outcomes. Conclusions: In this study, the lowest concentration of dexmedetomidine in mpivacaine with the greatest clinical effect was 0.4 mu g/ml, which is important because there may be no additional analgesic benefit of dexmedetomidine greater than 0.4 mu g/ml.

Automated summary

The purpose of this study was to determine the median effective concentration (EC50) of ropivacaine with adjuvant dexmedetomidine. The lowest concentration of dexmedetomidine with the greatest clinical effect was found to be 0.4 μg/ml. There may be no additional analgesic benefit of dexmedetomidine greater than 0.4 μg/ml.