A randomised double-blind dose–response study of weight-adjusted infusions of norepinephrine for preventing hypotension during combined spinal–epidural anaesthesia for Caesarean delivery

Abstract

BackgroundNorepinephrine infusion has been suggested as an effective method for preventing hypotension during spinal anaesthesia for Caesarean delivery. However, optimal dosing regimens for norepinephrine have not been well established. This study aimed to determine the dose–response characteristics of a weight-adjusted fixed-rate infusion of norepinephrine to prevent hypotension during neuraxial anaesthesia for Caesarean delivery. MethodsIn a double-blind, randomised controlled trial, 80 parturients having elective Caesarean delivery received a prophylactic norepinephrine infusion at 0.025 μg kg−1 min−1 (Group N1), 0.05 μg kg−1 min−1 (Group N2), 0.075 μg kg−1 min−1 (Group N3), or 0.10 μg kg−1 min−1 (Group N4), starting immediately after induction of combined spinal–epidural anaesthesia. The primary outcome was non-occurrence of hypotension, defined as a decrease in systolic arterial pressure ≥20% below baseline value or to ≤90 mm Hg, before delivery. Values for 50% effective dose (ED50) and ED90 were calculated using probit regression. ResultsThe incidence of hypotension was 11/20 (55%), 6/20 (30%), 2/20 (10%), and 1/20 (5%) in Groups N1, N2, N3, and N4, respectively (P<0.0001). The ED50 and ED90 (95% confidence interval) of norepinephrine infusions for preventing hypotension were 0.029 (–0.002 to 0.043) and 0.080 (0.065–0.116) μg kg−1 min−1, respectively. The incidence of reactive hypertension increased with increasing norepinephrine dose (P=0.002). Other adverse effects were similar among groups. ConclusionsUnder the conditions of this study, an infusion of norepinephrine 0.08 μg kg−1 min−1 was effective for preventing hypotension in 90% of patients. This information should provide a guide for initiating norepinephrine infusions. Clinical trial registrationChiCTR1900022322 at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/enindex.aspx).