Abstract
Postspinal hypotension is a frequent complication during cesarean delivery, particularly in high-risk pregnancies. Although vasopressors are routinely used for its management, their relative efficacy and safety after the onset of hypotension remain uncertain. Following PROSPERO registration (CRD420251050321) and in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, this systematic review and meta-analysis evaluated the efficacy and safety of norepinephrine, phenylephrine, and ephedrine administered for treatment, rather than prophylaxis, of postspinal hypotension during cesarean delivery. A comprehensive search of PubMed, Embase, CENTRAL, and Scopus through April 2025 was performed using a combination of MeSH and free-text terms related to cesarean section, spinal anesthesia, hypotension, and vasopressors. Randomized controlled trials (RCTs) comparing intravenous bolus or infusion administration of these agents in parturients undergoing high-risk cesarean delivery were included, while prophylactic trials were excluded. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2.0 tool. Quantitative synthesis was performed using a random-effects model, and subgroup and sensitivity analyses explored potential sources of heterogeneity, with publication bias evaluated via funnel plot asymmetry. Nineteen randomized trials, including 1,715 parturients, met the inclusion criteria. Most studies involved high-risk pregnancies, including preeclampsia, fetal compromise, or emergency cesarean delivery, and were generally rated as low risk of bias. The primary outcome was successful correction of intraoperative postspinal hypotension, and secondary outcomes included maternal bradycardia, nausea, vomiting, requirement for additional vasopressors, and neonatal parameters such as Apgar score <7 at one and five minutes, umbilical artery pH <7.2, and NICU admission. Vasopressors produced non-significant relief of hypotension (relative risk (RR) = 1.18, 95% confidence interval (CI): 0.90-1.55) with minimal heterogeneity (I² = 6.03%). Subgroup analysis favored norepinephrine over phenylephrine (RR = 1.43, 95% CI: 1.01-1.79) and phenylephrine over ephedrine (RR = 1.63, 95% CI: 1.11-2.09). Overall, vasopressors demonstrated comparable efficacy in resolving postspinal hypotension, with a modest advantage for norepinephrine. Differences likely reflect variations in dosing and administration protocols. Standardized treatment algorithms and head-to-head comparative trials are needed to identify the optimal vasopressor for managing intraoperative hypotension in high-risk cesarean delivery.