Bolus norepinephrine and phenylephrine for maternal hypotension during elective cesarean section with spinal anesthesia: a randomized, double-blinded study

Abstract

Background: In recent years, norepinephrine has attracted increasing attention for the management of maternal hypotension during elective cesarean section with spinal anesthesia. Intermittent bolus is a widely used administration paradigm for vasopressors in obstetric anesthesia in China. Thus, in this randomized, double-blinded study, we compared the efficacy and safety of equivalent bolus norepinephrine and phenylephrine for rescuing maternal post-spinal hypotension.

Methods: In a tertiary women's hospital in Nanjing, China, 102 women were allocated with computer derived randomized number to receive prophylactic 8 μg norepinephrine (group N; n = 52) or 100 μg phenylephrine (group P; n = 50) immediately post-spinal anesthesia, followed by an extra bolus of the same dosage until delivery whenever maternal systolic blood pressure became lower than 80% of the baseline. Our primary outcome was standardized maternal cardiac output (CO) reading from spinal anesthesia until delivery analyzed by a two-step method. Other hemodynamic parameters related to vasopressor efficacy and safety were considered as secondary outcomes. Maternal side effects and neonatal outcomes were collected as well.

Results: Compared to group P, women in group N had a higher CO (standardized CO 5.8 ± 0.9 vs. 5.3 ± 1.0 L/min, t = 2.37, P = 0.02) and stroke volume (SV, standardized SV 73.6 ± 17.2 vs. 60.0 ± 13.3 mL, t = 4.52, P < 0.001), and a lower total peripheral resistance (875 ± 174 vs. 996 ± 182 dyne·s/cm, t = 3.44, P < 0.001). Furthermore, the incidence of bradycardia was lower in group N than in group P (2% vs. 14%, P = 0.023), along with an overall higher standardized heart rate (78.8 ± 11.6 vs. 75.0 ± 7.3 beats/min, P = 0.049). Other hemodynamics, as well as maternal side effects and neonatal outcomes, were similar in two groups (P > 0.05).

Conclusions: Compared to equivalent phenylephrine, intermittent bolus norepinephrine provides a greater CO for management of maternal hypotension during elective cesarean section with spinal anesthesia; however, no obvious maternal or neonatal clinical advantages were observed for norepinephrine.

Figure 1

Flow chart of parturient enrollment, allocation, follow-up, and analysis.

Figure 2

Hemodynamic trends including CO (A), SV (B), and TPR (C) during the observational period are depicted in parturients receiving norepinephrine and phenylephrine in the first 10 min post-anesthesia. Norepinephrine treatment is associated with a higher CO, SV, and lower TPR compared to phenylephrine. Horizontal coordinates in A–C mean minutes post-spinal anesthesia. CO: Cardiac output; SV: Stroke volume; TPR: Total peripheral resistance.

Figure 3

Hemodynamic variables including HR, CO, SV, and TPR at baseline and post-analgesia are presented in parturients receiving norepinephrine (gray) and phenylephrine (black). Norepinephrine treatment is associated with an increase of CO and SV, reduced decrease of HR, and a greater decrease of TPR compared to phenylephrine. Data are shown as mean ± standard error, and intergroup comparison is performed with non-paired t test. ^∗P < 0.05. CO: Cardiac output; HR: Heart rate; SV: Stroke volume; TPR: Total peripheral resistance.