Therapeutic Vasopressor Use for Postspinal Hypotension in Low-Risk Elective Cesarean Deliveries: A Systematic Review, Network Meta-Analysis, and Trial Sequential Analysis

Abstract

Spinal anesthesia-induced hypotension (SAIH) is a common complication of cesarean delivery (CD), potentially leading to maternal discomfort and fetal compromise. Vasopressors such as norepinephrine (NE), phenylephrine (PE), and ephedrine (EP) are frequently used for treatment, yet their comparative efficacy and safety remain uncertain. This study aimed to assess and compare the effectiveness and tolerability of NE, PE, and EP for managing postspinal hypotension (PSH) in low-risk elective CD. Systematic searches were conducted in PubMed, Embase, Cochrane CENTRAL, ScienceDirect, and ClinicalTrials.gov through June 2025. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD420251074831). We included randomized controlled trials (RCTs) involving parturients undergoing low-risk elective cesarean section who received NE, PE, or EP for the management of PSH. A systematic review, network meta-analysis (NMA), and trial sequential analysis (TSA) were performed. The primary outcome was the successful correction of PSH. Secondary outcomes included maternal bradycardia, nausea, vomiting, neonatal Apgar scores, and umbilical artery pH. Risk of bias was assessed using the Cochrane RoB 2 tool, and the certainty of evidence was graded with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. A total of 16 RCTs encompassing 2,102 parturients were included. NE demonstrated superior efficacy in reversing PSH (odds ratio (OR): 0.23; 95% confidence interval (CI): 0.09-0.58) and was associated with fewer adverse maternal events, including bradycardia (OR: 0.28) and nausea/vomiting (OR: 0.36), compared to PE and EP. Neonatal outcomes were generally comparable across groups, though NE showed a favorable trend in reducing the risk of neonatal acidosis (umbilical artery pH OR: 1.25; 95% CI: 1.06-1.54). Surface under the cumulative ranking curve (SUCRA) rankings and TSA supported the robustness of these findings. NE appears to be the most effective and best-tolerated vasopressor for treating SAIH during elective CD, without compromising neonatal safety. These results support the preferential use of NE over PE and EP in this clinical setting.

Keywords: low-risk elective cesarean delivery; network meta-analysis; norepinephrine; spinal anesthesia; vasopressors.

Figure 1. PRISMA flow diagram

PRISMA: Preferred Reporting Items for Systematic reviews and Meta-Analyses

Figure 2. Risk of bias assessment of included studies using the QUADAS-2 tool

Risk of bias was evaluated across four domains: patient selection, index test, reference standard, and flow & timing. An overall risk of bias judgment is also presented for each study Green circle with “+”: low risk of bias; yellow circle with “–”: unclear risk of bias; red circle with “×”: high risk of bias

Figure 3. Forest plot: pairwise comparison of vasopressors for PSH resolution

PSH: postspinal hypotension; PE: phenylephrine; NE: norepinephrine; EP: ephedrine; CI: confidence interval

Figure 4. Network plots of treatment comparisons among norepinephrine, phenylephrine, and ephedrine for maternal hypotension management

(a) Overall network geometry depicting all available direct comparisons across studies. (b) Network plot for studies using norepinephrine vs. phenylephrine. (c) Network plot for studies using phenylephrine vs. ephedrine The size of each node is proportional to the total number of participants receiving that intervention across included studies. The thickness of the connecting lines reflects the number of direct comparisons between the treatments, with the numbers on each edge indicating the total number of studies for that comparison

Figure 5. Forest plot: bradycardia and N/V outcomes

(a) Bradycardia incidence: NE significantly reduced risk compared to PE/EP (pooled OR 0.28 (0.10–0.43)). (b) N/V incidence: intervention VPs, especially NE, associated with lower odds (pooled OR 0.36 (0.21–0.69)) N: nausea; V: vomiting; NE: norepinephrine; PE: phenylephrine; EP: ephedrine; OR: odds ratio; VP: vasopressor; CI: confidence interval

Figure 6. Forest plot: neonatal outcomes

(a) Apgar scores at 1 and 5 minutes: no significant difference between VPs; pooled effect size 1.12 (95% CI: 0.98–1.36). (b) UA pH/neonatal acidosis: slightly favors intervention VPs; pooled effect size 1.25 (95% CI: 1.06–1.54) CI: confidence interval; VP: vasopressor; UA pH: umbilical artery pH; NE: norepinephrine; PE: phenylephrine; EP: ephedrine

Figure 7. Contour-enhanced funnel plots for publication bias assessment

(a) Primary outcome: PSH resolution; (b) neonatal outcome: UA pH/neonatal acidosis; (c) maternal outcome: bradycardia incidence; (d) maternal outcome: N/V incidence. No major asymmetry observed; contour shading indicates statistical significance thresholds (p < 0.1, p < 0.05, and p < 0.01). The red dashed line represents the pooled effect size UA pH: umbilical artery pH; PSH: postspinal hypotension; N: nausea; V: vomiting

Figure 8. Trial sequential analysis plot: PSH resolution

PSH: postspinal hypotension