European Journal of Cardiovascular Medicine

Maternal hypotension is one of the most common complications encountered during cesarean delivery performed under spinal anesthesia. Spinal anesthesia is widely preferred in obstetric practice because of its rapid onset, dense neural blockade, minimal drug exposure to the fetus, and high maternal satisfaction. However, the sympathetic blockade it induces can lead to a significant reduction in systemic vascular resistance and venous return, thereby resulting in maternal hypotension. The incidence of hypotension after spinal anesthesia in cesarean sections has been reported to range from 60% to 80%, depending on the anesthetic dose, maternal physiology, and intraoperative factors. Maternal hypotension is not a trivial event; it can lead to maternal nausea, vomiting, dizziness, and in severe cases, loss of consciousness. More importantly, it compromises uteroplacental perfusion, potentially resulting in fetal hypoxia, acidosis, and adverse neonatal outcomes.^[1]

To counteract this hemodynamic challenge, vasopressors have become the cornerstone of preventive and therapeutic strategies. Among the various vasopressors, ephedrine and phenylephrine are the most commonly used agents in obstetric anesthesia. Ephedrine, a mixed-acting sympathomimetic amine, increases blood pressure primarily by stimulating β-adrenergic and, to a lesser degree, α-adrenergic receptors, thereby enhancing cardiac output and systemic vascular resistance. Historically, it has been considered the vasopressor of choice in obstetrics due to its ability to preserve uteroplacental blood flow. However, emerging evidence suggests that ephedrine crosses the placenta in significant amounts and is associated with a higher incidence of fetal acidosis.^[2]

Phenylephrine, on the other hand, is a selective α-1 adrenergic agonist that increases systemic vascular resistance through vasoconstriction, thereby restoring maternal blood pressure. Unlike ephedrine, phenylephrine has minimal effect on heart rate and cardiac output, though reflex bradycardia is common. Recent studies have demonstrated that phenylephrine is associated with superior neonatal acid-base status compared to ephedrine, making it a preferred choice in many obstetric anesthesia guidelines. Nonetheless, the concern with phenylephrine lies in its tendency to reduce maternal cardiac output due to increased afterload and bradycardia, which may indirectly affect uteroplacental perfusion.^[3]

Given these pharmacological differences, the choice of vasopressor in managing maternal hypotension during cesarean delivery continues to be a topic of debate. While ephedrine has been favored historically, modern evidence leans towards phenylephrine for better neonatal outcomes. However, the context of practice varies by region, availability of drugs, patient populations, and institutional protocols, warranting comparative clinical studies in diverse settings. A direct head-to-head comparison between phenylephrine and ephedrine in Indian patients undergoing cesarean section under spinal anesthesia is essential to clarify their relative efficacy and safety.^[4]

Aim

To compare the efficacy and safety of phenylephrine versus ephedrine in managing maternal hypotension during cesarean section under spinal anesthesia.

Objectives

1. To assess the effectiveness of phenylephrine and ephedrine in maintaining maternal blood pressure during spinal anesthesia for cesarean section.
2. To compare maternal side effects such as nausea, vomiting, and bradycardia between phenylephrine and ephedrine groups.
3. To evaluate neonatal outcomes using Apgar scores and umbilical cord blood pH in both groups.

Source of Data

The study population comprised pregnant women undergoing elective or emergency cesarean section under spinal anesthesia at the Department of Anesthesiology, BAVMC Pune, during the study period.

Study Design

The study was designed as a prospective, randomized, comparative clinical study.

Study Location

The study was conducted at the Department of Anesthesiology and Obstetrics, BAVMC, Pune, a tertiary care teaching hospital.

Study Duration

The study was carried out over a period of 12 months, from January 2024 to December 2024.

Sample Size

A total of 200 parturients scheduled for cesarean delivery under spinal anesthesia were included in the study. The sample was divided equally into two groups:

• Group P (n=100): Received phenylephrine
• Group E (n=100): Received ephedrine

Inclusion Criteria

• Pregnant women aged 18-40 years.
• American Society of Anesthesiologists (ASA) physical status I or II.
• Term pregnancy (≥37 weeks gestation).
• Elective or emergency cesarean section under spinal anesthesia.

Exclusion Criteria

• Known hypersensitivity to phenylephrine or ephedrine.
• Pre-existing hypertension, preeclampsia, or eclampsia.
• Cardiovascular disease, arrhythmias, or severe anemia.
• Contraindications to spinal anesthesia.
• Multiple gestation or intrauterine fetal demise.

Procedure and Methodology

All eligible patients were counseled and written informed consent was obtained. Routine preoperative assessments including history, physical examination, and baseline investigations were performed.

In the operating room, standard monitors were applied: electrocardiogram, non-invasive blood pressure, and pulse oximetry. Baseline heart rate and blood pressure were recorded. Intravenous access was secured with an 18G cannula and preload with 500 ml of crystalloid was given.

Spinal anesthesia was performed at the L3-L4 or L4-L5 interspace using a 25G Quincke spinal needle. Injection of 2 ml of 0.5% hyperbaric bupivacaine was administered. Following confirmation of adequate block height, surgery was commenced.

Maternal blood pressure and heart rate were monitored every 2 minutes for the first 20 minutes and every 5 minutes thereafter. Hypotension was defined as a fall in systolic blood pressure >20% from baseline or <90 mmHg.

• Group P patients received phenylephrine 100 µg IV bolus.
• Group E patients received ephedrine 6 mg IV bolus.

Repeat doses were given as needed to maintain systolic blood pressure within 20% of baseline.

Side effects such as nausea, vomiting, and bradycardia (HR <60 bpm) were noted. Bradycardia was treated with atropine 0.6 mg IV.

At delivery, neonatal outcome was assessed by Apgar scores at 1 and 5 minutes. Umbilical cord blood samples were collected for pH analysis.

Sample Processing

Umbilical cord blood samples were collected in heparinized syringes immediately after delivery and analyzed within 30 minutes using a blood gas analyzer to determine pH and base excess.

Statistical Methods

Data were entered into Microsoft Excel and analyzed using SPSS (version 27.0). Continuous variables were expressed as mean ± standard deviation and compared using the Student’s t-test. Categorical variables were analyzed using the Chi-square test or Fisher’s exact test as appropriate. A p-value of <0.05 was considered statistically significant.

Data Collection

All data regarding demographic details, intraoperative hemodynamic parameters, vasopressor requirement, maternal side effects, and neonatal outcomes were systematically recorded in predesigned case record forms

Table 1. Efficacy & safety overview

Notes: AE = adverse event. Effect size for categorical outcomes = risk ratio (RR) with Pearson χ² (no continuity correction).

Table 1 highlights the primary efficacy and safety outcomes between the phenylephrine and ephedrine groups. The incidence of the composite adverse events or neonatal acidosis was significantly lower in the phenylephrine group (21.0%) compared with the ephedrine group (38.0%), with a relative risk (RR) of 0.55 (95% CI: 0.35-0.87; p = 0.0084), indicating that phenylephrine reduced overall adverse outcomes by nearly half. Similarly, intraoperative nausea and vomiting were observed less frequently in the phenylephrine group (12.0%) than in the ephedrine group (27.0%), again demonstrating a significant protective effect (RR = 0.44; 95% CI: 0.24-0.83; p = 0.0074). However, the incidence of bradycardia (<60 bpm) was higher in the phenylephrine group (16.0%) compared with the ephedrine group (6.0%), with a statistically significant RR of 2.67 (95% CI: 1.09-6.54; p = 0.0238). Tachycardia (>110 bpm) occurred more frequently in the ephedrine group (15.0%) compared with phenylephrine (8.0%), though this difference was not statistically significant (p = 0.1208). Reactive hypertension (>140 mmHg) was slightly higher with phenylephrine (7.0% vs. 4.0%), but this difference was also not significant (p = 0.3521).

Figure 1

Table 2: Blood pressure maintenance effectiveness

Notes: Continuous outcomes analyzed with Welch’s t-test; effect size = mean difference (Phenyl - Ephed). Proportion analyzed with χ².

Table 2 compares maternal blood pressure stability between the two vasopressors. Patients in the phenylephrine group spent a significantly greater proportion of intraoperative time within the target systolic blood pressure (SBP) range (mean 86.7% ± 8.4) compared with the ephedrine group (74.9% ± 10.6), with a mean difference of 11.80% (95% CI: 9.13-14.47; p < 0.0001). The number of hypotensive episodes per patient was markedly lower in the phenylephrine group (1.1 ± 0.9) compared with the ephedrine group (2.3 ± 1.2), mean difference = -1.20 (95% CI: -1.50 to -0.90; p < 0.0001). The minimum intraoperative SBP was also significantly higher with phenylephrine (102.4 ± 9.7 mmHg) versus ephedrine (92.1 ± 11.2 mmHg), with a mean difference of 10.30 mmHg (95% CI: 7.38-13.22; p < 0.0001). The requirement for total vasopressor boluses was slightly lower in the phenylephrine group (2.0 ± 1.1) compared with ephedrine (2.5 ± 1.3), which reached statistical significance (p = 0.0037). Importantly, the need for rescue vasopressor infusion was substantially lower in the phenylephrine group (9.0%) than in the ephedrine group (23.0%), with an RR of 0.39 (95% CI: 0.19-0.80; p = 0.0069).

Figure 2

Table 3. Maternal side-effects

Notes: RR < 1 favors phenylephrine (lower risk); RR > 1 indicates higher risk with phenylephrine.

Table 3 presents maternal side effects observed with the two vasopressors. Nausea occurred in 11.0% of phenylephrine-treated patients compared with 22.0% of those receiving ephedrine, and this difference was statistically significant (RR = 0.50; 95% CI: 0.26-0.98; p = 0.0361). Vomiting was less frequent in the phenylephrine group (7.0%) than in the ephedrine group (13.0%), but this did not reach statistical significance (p = 0.1573). Bradycardia was significantly more frequent with phenylephrine (16.0%) compared to ephedrine (6.0%), with RR = 2.67 (95% CI: 1.09-6.54; p = 0.0238). Other side effects such as shivering, dizziness, and headache were observed at comparable rates between groups and were not statistically significant (p > 0.05 for all comparisons).

Figure 3

Table 4: Neonatal outcomes

Table 4 summarizes neonatal outcomes following maternal vasopressor use. Apgar scores at 1 minute were significantly higher in the phenylephrine group (mean 8.1 ± 0.7) compared to the ephedrine group (7.6 ± 0.9), with a mean difference of 0.50 (95% CI: 0.28-0.72; p < 0.0001). Similarly, Apgar scores at 5 minutes were superior with phenylephrine (9.1 ± 0.5 vs. 8.8 ± 0.6), mean difference 0.30 (95% CI: 0.15-0.45; p = 0.0002). The umbilical arterial pH was also significantly higher in neonates from the phenylephrine group (7.29 ± 0.05) compared with the ephedrine group (7.25 ± 0.06), mean difference 0.04 (95% CI: 0.02-0.06; p < 0.0001), suggesting reduced risk of neonatal acidosis. Neonatal acidosis (defined as pH <7.20) was less frequent in the phenylephrine group (3.0%) than in the ephedrine group (9.0%), though this difference did not reach statistical significance (p = 0.0740). NICU admission rates were also lower in the phenylephrine group (6.0%) compared with ephedrine (12.0%), but again not statistically significant (p = 0.1382).

Overall efficacy & safety (Table 1). Primary composite (maternal AE or neonatal acidosis) was significantly lower with phenylephrine (21.0%) than ephedrine (38.0%) (RR 0.55, 95% CI 0.35-0.87), mirroring the long-standing signal from randomized trials and meta-analyses that phenylephrine reduces fetal acidaemia and maternal emesis relative to ephedrine. Oparanozie EI et al.(2024)^[5] showed higher umbilical arterial pH and base excess with phenylephrine despite similar blood pressure control, attributing benefit to reduced placental transfer and fetal metabolic stimulation seen with ephedrine (which is β-agonist predominant). Sirait RH.(2025)^[6] quantitative review likewise favored phenylephrine for neonatal acid-base status and maternal nausea/vomiting without excess severe hypertension.² Markedly lower intraoperative nausea/vomiting (12% vs 27%; RR 0.44) closely matches these reports. By contrast, the higher bradycardia with phenylephrine in cohort (16% vs 6%; RR 2.67) is expected given its pure α-agonism and baroreflex-mediated vagal response-an effect consistently reported by Badran AS et al.(2025)^[7] when bolus or infusion phenylephrine is used to maintain SBP. The small, non-significant differences in tachycardia and reactive hypertension align with trials where both agents were titrated to pressure targets, resulting in similar extremes but different heart-rate profiles.

Blood-pressure maintenance (Table 2). It is found superior hemodynamic stability with phenylephrine: greater time within SBP target (+11.8%), fewer hypotension episodes (-1.20 per patient), higher minimum SBP (+10.3 mmHg), fewer boluses, and less need for rescue infusion (RR 0.39). These results are concordant with infusion-based RCTs where fixed or variable-rate phenylephrine achieved tighter blood pressure control than ephedrine while improving fetal acid-base outcomes. Ganeshnavar AS et al.(2024)[8] demonstrated that α-dominant vasoconstriction more reliably restores SVR and SBP after sympathetic block, whereas ephedrine’s β-chronotropy can be less predictable in the denervated, vasoplegic state of spinal anesthesia. Contemporary guidance therefore endorses phenylephrine (often via prophylactic infusion with rescue boluses) as first-line for spinal-induced hypotension during cesarean delivery. Effect sizes are also compatible with Sun L et al.(2024)[9] estimates showing fewer hypotensive episodes and less rescue therapy when phenylephrine protocols are used.

Maternal side-effects (Table 3). The halving of nausea risk with phenylephrine (11% vs 22%; RR 0.50) is clinically important and repeatedly documented. Nausea under neuraxial anesthesia is tightly linked to hypotension and reduced cerebral/mesenteric perfusion; thus, the better SBP control in phenylephrine arm plausibly mediates this benefit. Mao J et al.(2025)^[10] The trade-off remains bradycardia (16% vs 6%), a known and manageable phenomenon; trials typically treat with atropine when symptomatic or when coexisting hypotension persists. Rates of shivering, dizziness, and headache being similar is consistent with prior RCTs where these symptoms were not vasopressor-specific once blood pressure was controlled. Sathyaseelan R et al.(2025)^[11]

Neonatal outcomes (Table 4). Neonates exposed to phenylephrine had higher Apgar scores at 1 and 5 minutes and a higher umbilical arterial pH (+0.04), with trends to less acidosis and fewer NICU admissions. This pattern is strongly aligned with Cooper et al. and subsequent work showing that ephedrine, due to placental transfer and fetal β-stimulation, is associated with lower pH and base excess despite adequate maternal blood pressure. Garg H et al.(2024)[12] & Marni MS et al.(2024)^[13] The non-significant differences in hard neonatal endpoints (acidosis <7.20; NICU admission) could reflect sample size and relatively low event rates-an observation made in meta-analyses where acid-base improvements do not always translate into large differences in NICU metrics in trials powered primarily for maternal hypotension. Notably, modern comparisons introducing norepinephrine (α with mild β) suggest one can preserve cardiac output with similar fetal acid-base advantages as phenylephrine; however, current consensus still places phenylephrine as standard first-line therapy, with norepinephrine an emerging alternative. Kang H et al.(2024)^[14] & Thejane F et al.(2024)^[15]

The present study demonstrated that phenylephrine was more effective than ephedrine in maintaining maternal blood pressure during cesarean section under spinal anesthesia. Phenylephrine provided tighter control of systolic blood pressure, reduced the incidence of intraoperative hypotension and maternal nausea/vomiting, and resulted in improved neonatal Apgar scores and umbilical cord arterial pH. However, its use was associated with a higher incidence of maternal bradycardia, which was clinically manageable. In contrast, ephedrine was linked to a higher frequency of hypotension episodes and less favorable neonatal acid-base outcomes. Overall, phenylephrine appears to be a safer and more efficacious vasopressor than ephedrine in this setting, reinforcing its role as the preferred first-line agent for managing maternal hypotension during cesarean delivery under spinal anesthesia.

LIMITATIONS OF THE STUDY

1. The study was conducted at a single tertiary care hospital, which may limit the generalizability of results to different healthcare settings.
2. Only healthy parturients (ASA I and II) were included; therefore, findings may not apply to high-risk populations such as women with preeclampsia, cardiac disease, or multiple gestations.
3. The study was limited to bolus dosing of vasopressors; continuous infusion regimens, which are increasingly recommended, were not evaluated.
4. Neonatal outcomes were assessed primarily by Apgar scores and cord blood pH; long-term neonatal follow-up was not performed.
5. Observer bias could not be completely excluded, as blinding of vasopressor preparation and administration was not possible in all cases.

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