A Randomized, Double-Blind, Graded Dose-Response Study of Norepinephrine Administration for Prevention of Post-Spinal Hypotension during Elective Cesarean Delivery

Abstract

Norepinephrine has been recently introduced for prophylaxis against post-spinal hypotension during cesarean delivery; however, no data are available regarding its optimum dosing scheme. The primary objective of this study is to compare three different infusion and bolus dose combinations of norepinephrine for prophylaxis against post-spinal hypotension during cesarean delivery. This randomized, double-blind study was performed between February 2021 and May 2022. The study protocol was registered at Clinicaltrials.gov with the identification number NCT04701190. A total of 192 parturients were enrolled into this study. Patients were assigned to three groups—Zero-Bolus High-Infusion (Group ZBHI, 0 µg/0.1 µg kg−1 min−1, n = 61), Moderate-Bolus Moderate-Infusion (Group MBMI, 5 µg/0.075 µg kg−1 min−1, n = 61) and High-Bolus Low-Infusion (Group HBLI, 10 µg/0.05 µg kg−1 min−1, n = 61)—according to different combinations of norepinephrine infusion and bolus doses. All patients received spinal anesthesia with 10 mg hyperbaric bupivacaine plus 12.5 µg fentanyl. Immediately after cerebrospinal fluid was obtained, patients underwent a norepinephrine protocol corresponding to the randomized group. The primary outcome was the incidence of post-spinal hypotension. Secondary outcomes were post-delivery hypotension, frequency of post-spinal hypertension and bradycardia, and neonatal outcomes. The incidence of post-spinal hypotension was 11.7% in Group HBLI, 6.7% in Group ZBHI and 1.7% in Group MBMI (p = 0.1). The overall incidence of post-delivery hypotension in parturients was 41.1% (p = 0.797). The lowest frequency of post-spinal bradycardia (8.3%) and hypertension (11.7%) was seen in Group HBLI. The neonatal APGAR scores at 1st minute were higher in Group MBMI than in Group ZBHI (8.58 vs. 8.23, p = 0.001). All three infusion and bolus dose combinations of norepinephrine effectively reduced the incidence of post-spinal hypotension. However, high-dose bolus (10 µg) followed by low-dose infusion (0.05 µg kg−1 min−1) of norepinephrine can be preferred due to the reduced frequency of bradycardia and hypertension during cesarean delivery under spinal anesthesia.