Abstract
PURPOSE: There is evidence that labor pain and the doses of drugs used to treat it exhibit circadian variation. Previously, we reported that during the night, the effective dose (ED(50)) of epidural ropivacaine for labor analgesia in 50% of patients was approximately 15% greater than that during the day. However, the influence of time of day on dose requirement at points higher on the dose-response curve is unknown. This double-blinded randomized trial aimed to determine and compare the full dose-response relationship for epidural ropivacaine administered to initiate labor analgesia during the day versus at night. PATIENTS AND METHODS: We recruited 150 nulliparous parturients requesting epidural labor analgesia during the day (day group, 07:01-19:00 h) and 150 during the night (night group, 19:01-07:00 h). Within each group, we randomly allocated patients to receive one of six doses of ropivacaine (7.5, 15, 22.5, 30, 37.5, or 45 mg) diluted to 20 mL to initiate epidural analgesia. Effective analgesia was defined as a visual analogue scale pain score of ≤ 3 cm (scale: 0--10 cm) within 30 min. We generated dose-response curves for ropivacaine using probit regression and estimated the values for ED(50) and ED(95). RESULTS: The estimated ED(50) value of ropivacaine was greater during the night (22.4 [95% CI 19.9 to 24.8] mg) than during the day (17.9 [95% CI 15.7 to 20.0] mg), and the estimated ED(95) value was greater during the night (41.3 [95% CI 36.4 to 48.7] mg) than during the day (32.9 [95% CI 28.9 to 39.0] mg). CONCLUSION: The time of day is an important factor that should be considered when selecting the dose of ropivacaine to initiate epidural labor analgesia. TRIAL NUMBER AND REGISTRY URL: ChiCTR1900025381; https://www.chictr.org.cn/bin/project/edit?pid=42363.