Neonatal outcome following norepinephrine versus phenylephrine for treatment of spinal-induced hypotension among women undergoing caesarean section: systematic review and meta-analysis of randomised controlled trials.

Abstract

Background: There are pharmacological and non-pharmacological approaches to preventing spinal induced hypotension. In obstetrics, norepinephrine may be an alternative to phenylephrine because it better maintains cardiac output and heart rate. We conducted this systematic review and meta-analysis to identify neonatal outcomes and maternal haemodynamic effects.

Methods: The systematic review of literature searched was conducted through electronic databases such as PubMed, Cochrane Library, and Google Scholar from February 1 to May 30,2025. All of the articles included in the review and meta-analysis were randomised controlled trials, and the populations of the study were normal pregnancies that underwent caesarean section under spinal anesthesia.

Results: A 19 studies of randomised controlled trials involving 2603 participants were included after screening 2446 records. Both prophylactic (MD = 0.17.95%CI: -0.06-0.4, p = 0.15) and therapeutic (MD = 0.03,95%CI: -0.18-0.23, p = 0.79) administration of norepinephrine showed no statistically significant difference in 1 min Apgar scores compared with phenylephrine. However, norepinephrine was associated with slightly higher 5 min Apgar scores during therapeutic administration compared with prophylactic administration (MD = 0.16,95% CI:0.01-0.31, p = 0.04). Norepinephrine revealed that no statistically significant difference in umbilical arterial partial carbon dioxide compared with phenylephrine when administered as bolus, infusion or combined bolus and infusion (MD = -0.98, 95%CI: -3.32-1.35, p = 0.41, MD = 0.43,95%CI: -0.54-1.4, p = 0.38 and MD = 0.25(-0.42-1.92) respectively. In contrast, norepinephrine significantly increased umbilical arterial bicarbonate level during therapeutic adminstration compared with prophylactic or combined prophylactic or therapeutic administration with phenylephrine (MD = 0.74,95%CI:0.15-1.33.p = 0.01). Regarding maternal outcomes,norepinephrine significantly reduced the risk of maternal bradycardia both in prophylactic (RR = 0.52,95%CI:0.34-0.78,p-0.02) and in therapeutic administratuin (RR = 0.46, 95%CI:0.29-0.72, p = 0.0006) compared with phenylephrine. Furthermore, pooled analysis showed that norepinephrine administration during combined of both prophylactic and therapeutic administration (RR = 0.29,95%CI:0.12-0.65, p = 0.003) was associated with lower risk of maternal reflex hypertension than during therapeutic and prophylactic alone compared with phenylephrine.

Conclusion: This systematic review and meta-analysis shows women treated with bolus or infusion, prophylactic or therapeutic administration of norepinephrine have comparable neonatal outcome and maternal haemodynamics with phenylephrine. Therefore, Norepinephrine is an alternative vasopressor for management of spinal induced hypotension and for good neonatal outcome.