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

Background: Norepinephrine 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. Methods: In a double-blind, randomised controlled trial, 80 parturients having elective Caesarean delivery received a prophylactic norepinephrine infusion at 0.025 mu g kg(-1) min(-1) (Group N1), 0.05 mu g kg(-1) min(-1) (Group N2), 0.075 mu g kg(-1) min(-1) (Group N3), or 0.10 mu g kg(-1) min(-1) (Group N4), startingimmediately after induction ofcombined spinaleepidural 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. Results: The 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) mu g 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. Conclusions: Under the conditions of this study, an infusion of norepinephrine 0.08 mu g kg(-1) min(-1) was effective for preventing hypotension in 90% of patients. This information should provide a guide for initiating norepinephrine infusions.