Bolus Norepinephrine and Phenylephrine for Maternal Hypotension During Elective Cesarean Section with Spinal Anesthesia: A Randomized, Double-Blinded Study
Maternal hypotension is a common complication during cesarean section with spinal anesthesia, resulting from reduced venous return, decreased cardiac output (CO), or reduced peripheral vascular resistance. This condition can lead to adverse maternal outcomes such as nausea, vomiting, and dizziness, as well as compromised placental perfusion, which raises concerns about fetal acidosis, hypoxia, and even postnatal neurological injury. Effective prevention or treatment of maternal hypotension is therefore of great clinical significance. Phenylephrine, a pure α-adrenergic receptor agonist, is the current gold-standard vasopressor in obstetric anesthesia. However, it is associated with dose-dependent depression of heart rate (HR) and a decrease in CO. Norepinephrine, on the other hand, has both α- and weak β-adrenergic receptor agonistic properties, making it a promising alternative for managing maternal hypotension.
This randomized, double-blinded study aimed to compare the efficacy and safety of equivalent bolus doses of norepinephrine and phenylephrine for rescuing maternal post-spinal hypotension during elective cesarean section. The study was conducted at a tertiary women’s hospital in Nanjing, China, and included 102 women who were randomly allocated to receive either 8 µg norepinephrine (group N, n = 52) or 100 µg phenylephrine (group P, n = 50) immediately after spinal anesthesia. Additional boluses of the same dosage were administered whenever maternal systolic blood pressure (SBP) fell below 80% of the baseline until delivery. The primary outcome was standardized maternal CO from spinal anesthesia until delivery, analyzed using a two-step method. Secondary outcomes included other hemodynamic parameters, maternal side effects, and neonatal outcomes.
The results showed that women in group N had a higher CO (5.8 ± 0.9 vs. 5.3 ± 1.0 L/min, P = 0.02) and stroke volume (SV, 73.6 ± 17.2 vs. 60.0 ± 13.3 mL, P < 0.001), and a lower total peripheral resistance (TPR, 875 ± 174 vs. 996 ± 182 dyne·s/cm5, P < 0.001) compared to group P. Additionally, the incidence of bradycardia was lower in group N (2% vs. 14%, P = 0.023), and the standardized HR was higher (78.8 ± 11.6 vs. 75.0 ± 7.3 beats/min, P = 0.049). Other hemodynamic parameters, maternal side effects, and neonatal outcomes were similar between the two groups. The study concluded that intermittent bolus norepinephrine provides a greater CO for managing maternal hypotension during elective cesarean section with spinal anesthesia compared to phenylephrine, but no obvious maternal or neonatal clinical advantages were observed.
Introduction
Maternal hypotension during cesarean section with spinal anesthesia is a significant concern due to its potential adverse effects on both the mother and the fetus. Phenylephrine, a pure α-adrenergic receptor agonist, is widely used to manage this condition. However, its dose-dependent negative chronotropic effect can lead to decreased HR and CO, which may compromise fetal well-being. Norepinephrine, with its weak β-adrenergic receptor activity, has been proposed as an alternative vasopressor that may offer better hemodynamic stability.
Previous studies have compared the efficacy of norepinephrine and phenylephrine in maintaining maternal SBP and CO. Ngan Kee et al. (2015) found that norepinephrine provided a higher CO compared to phenylephrine, primarily due to better HR maintenance. Vallejo et al. (2017) compared fixed infusion rates of norepinephrine and phenylephrine but found no significant differences in CO, HR, SV, or systemic vascular resistance. This study aimed to further explore the hemodynamic effects of intermittent bolus norepinephrine and phenylephrine in the context of obstetric spinal anesthesia.
Methods
The study was approved by the Clinical Research Ethics Committee of Women’s Hospital of Nanjing Medical University and conducted between June and July 2018. A total of 160 parturients were initially enrolled, and after exclusions, 102 were randomized to receive either 8 µg norepinephrine or 100 µg phenylephrine immediately after spinal anesthesia. Additional boluses were administered if SBP fell below 80% of the baseline until delivery. Hemodynamic parameters, including CO, SV, TPR, SBP, and HR, were monitored using a Cheetah transthoracic impedance NICOM monitor. Maternal side effects and neonatal outcomes, including Apgar scores and umbilical cord blood gas analysis, were also recorded.
Results
The study found that women in group N had a higher CO (5.8 ± 0.9 vs. 5.3 ± 1.0 L/min, P = 0.02) and SV (73.6 ± 17.2 vs. 60.0 ± 13.3 mL, P < 0.001), and a lower TPR (875 ± 174 vs. 996 ± 182 dyne·s/cm5, P < 0.001) compared to group P. The incidence of bradycardia was significantly lower in group N (2% vs. 14%, P = 0.023), and the standardized HR was higher (78.8 ± 11.6 vs. 75.0 ± 7.3 beats/min, P = 0.049). Other hemodynamic parameters, maternal side effects, and neonatal outcomes were similar between the two groups.
Discussion
The findings of this study suggest that intermittent bolus norepinephrine provides a greater CO and lower incidence of bradycardia compared to phenylephrine for managing maternal hypotension during elective cesarean section with spinal anesthesia. The higher CO observed with norepinephrine may be attributed to its weak β-adrenergic receptor activity, which helps maintain HR and SV. However, the clinical significance of this CO advantage remains unclear, as no obvious maternal or neonatal clinical benefits were observed.
The study also found that norepinephrine restored TPR less effectively than phenylephrine, which may contribute to the higher SV observed with norepinephrine. This lower TPR could be due to norepinephrine’s weaker α-adrenergic mediated vasoconstriction action compared to phenylephrine. Despite these differences, both vasopressors were equally effective in maintaining maternal SBP, and the incidence of maternal side effects was similar between the two groups.
Neonatal outcomes, including Apgar scores and umbilical cord blood gas analysis, were comparable between the two groups. Although a higher umbilical artery and venous glucose content was observed in group N, this was not associated with differences in pH, base excess, or lactate levels, suggesting that it may be due to maternal glucose content differences rather than the effects of the vasopressors.
Conclusion
In summary, this study demonstrates that intermittent bolus norepinephrine provides a greater CO and lower incidence of bradycardia compared to phenylephrine for managing maternal hypotension during elective cesarean section with spinal anesthesia. However, the clinical significance of these hemodynamic advantages remains uncertain, as no obvious maternal or neonatal clinical benefits were observed. Further research is needed to determine the role of norepinephrine in conditions where uteroplacental perfusion is restricted, such as in fetal compromise or preeclampsia.
doi.org/10.1097/CM9.0000000000000621
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