Dissecting Vasopressor Efficacy in the Management of Maternal Hypotension in Preeclamptic Cesarean Delivery: A Systematic Review of Randomized Controlled Trials

Abstract Objective: To evaluate the safety and effectiveness of intermittent bolus administration of ephedrine, norepinephrine, and phenylephrine in the treatment of maternal hypotension during spinal anesthesia for cesarean sections in preeclamptic women. Methods: This PRISMA-based systematic review included English RCTs of women with singleton preeclampsia (ACOG criteria) undergoing cesarean delivery with spinal anesthesia, excluding chronic hypertension or systemic disease. Interventions were intermittent bolus phenylephrine, norepinephrine, or ephedrine, with outcomes on maternal hemodynamics, neonatal status, and adverse events. Searches of PubMed, ScienceDirect, Google Scholar, and Cochrane (to December 2024) plus reference screening identified eligible studies. Two reviewers independently selected studies, extracted data, and assessed risk of bias (Cochrane RoB 2.0). Due to heterogeneity in vasopressor regimens and outcome measures, results were synthesized narratively. Results: Of 2333 records screened, six RCTs (sample sizes 20-166) were included, all in preeclamptic women undergoing cesarean delivery. Overall risk of bias was low. Norepinephrine better preserved maternal hemodynamics than phenylephrine or ephedrine, with higher cardiac output (6.31 ± 1.08 vs . 5.45 ± 1.21 L/min; P = 0.009) and lower uteroplacental resistance (0.04 ± 0.02 vs . 0.06 ± 0.03; P = 0.002). Ephedrine caused higher heart rates (84.9 ± 7.1 vs . 76.6 ± 6.9 bpm; P < 0.05) and more nausea/vomiting. Neonatal umbilical artery pH was higher with norepinephrine or phenylephrine than ephedrine (7.32 ± 0.02 vs . 7.31 ± 0.03; P < 0.05), while Apgar scores did not differ. Adverse events favored norepinephrine, which reduced bradycardia versus phenylephrine (5.1% vs . 20.5%; RR = 0.25; P = 0.042) and tachycardia versus ephedrine (16.1% vs . 36.4%; RR = 0.54; P = 0.02). Conclusion: Intermittent bolus administration of norepinephrine offers superior maternal cardiac output and neonatal safety, making it optimal for preeclamptic cesarean deliveries. Phenylephrine is effective for blood pressure control but may induce bradycardia, while the use of ephedrine is limited by its association with neonatal acidosis. Tailored vasopressor selection is thus essential for optimal outcomes. Registration: PROSPERO; CRD42024565007