Abstract: Objective · To determine the optimal intravenous norepinephrine bolus dose needed to prevent hypotension after combined spinal and epidural anesthesia in 90% of women during elective cesarean delivery. Methods · Forty women undergoing elective cesarean delivery were allocated into this double-blinded, prospective, and sequential dose-finding study using biased coin design sequential method. The primary outcome was the successful use of the norepinephrine bolus dose to maintain systolic blood pressure above 80% of the baseline until delivery. Secondary outcomes included dizziness, breathlessness, nausea, vomiting, bradycardia, secondary hypertension and supplemental use of atropine or norepinephrine of the women, as well as 1 min and 5 min Apgar scores of the newborns. The 90% effective dose (ED90) and its 95%CI were estimated using Isotonic regression methods. Results · The estimated ED90 intravenous bolus dose of norepinephrine was [10.85 (95%CI 9.20-11.67)] μg to prevent hypotension after combined spinal and epidural anesthesia during cesarean delivery. The occurrence rates of dizziness, breathlessness, and nausea were 2.5%, 7.5% and 10.0%, respectively. The occurrence rate of additional rescue norepinephrine boluses was 5.0%. No vomiting, bradycardia, secondary hypertension and supplemental use of atropine appeared. Apgar scores of all newborns at 1 min and 5 min were 10. Conclusion · An intravenous norepinephrine bolus dose of 11 μg is recommended to prevent hypotension after combined spinal and epidural anesthesia during cesarean delivery for clinical practice.

Key words: norepinephrine, 90% effective dose (ED90), hypotension, combined spinal and epidural anesthesia, cesarean delivery