Prophylactic phenylephrine and norepinephrine infusions during caesarean delivery for non-reassuring fetal heart rate: A randomised noninferiority trial to assess neonatal outcome.

Background: Phenylephrine is recommended for the management of hypotension after spinal anaesthesia for women undergoing caesarean delivery. Norepinephrine, an adrenergic agonist with weak β-adrenergic activity, has been reported to have a more favourable haemodynamic profile than phenylephrine. However, there are concerns that norepinephrine may be associated with higher risk of fetal acidosis which can be serious in an already compromised foetus.

Objective: This study aimed to test the hypothesis that in terms of the umbilical artery base excess norepinephrine is not inferior to phenylephrine when it is used to prevent spinal hypotension during caesarean delivery.

Design: A prospective, randomised, double-blind trial.

Setting: Operating room of Tertiary Care Hospital in Northern India from January 2022 to November 2022.

Patients: Parturients with non-reassuring fetal heart rate undergoing nonelective caesarean delivery under spinal anaesthesia.

Intervention: Equipotent prophylactic infusions of either phenylephrine 80 μg min-1 or norepinephrine 6 μg min-1 were administered to maintain maternal systolic BP between 90 and 110% of baseline using a predefined algorithm.

Main Outcome Measures: The primary outcome was umbilical arterial base excess comparing the limits of the 95% confidence interval with a predefined noninferiority margin of -0.05 mmol l-1. The incidence of fetal acidosis was also evaluated for norepinephrine and phenylephrine group.

Results: Data were analysed from 104 patients. The mean ± SD umbilical arterial base excess was higher in norepinephrine group than the phenylephrine group: -6.85 ± 2.20 mmol l-1vs. -7.95 ± 2.99 mmol l-1, respectively (P  = 0.034). Norepinephrine was found to be noninferior as the lower limit of 95% CI of mean difference between base excess of two groups was 1.10 (95% CI, 0.084 to 2.123) mmol l-1, P  = 0.034) which did not cross our predefined noninferiority margin of -0.05 mmol l-1. No significant difference in the incidence of fetal acidosis was observed between norepinephrine and phenylephrine groups: 62% vs. 75% (P  = 0.140).

Conclusion: Prophylactic norepinephrine infusion (6 μg min-1) was found to be noninferior to phenylephrine infusion (80 μg min-1) in terms of umbilical arterial base excess values. A similar incidence of fetal acidosis was observed in both groups.

Trial Registration: CTRI/2022/01/039343; dated - 12 January 2022.