Ephedrine Versus Norepinephrine and Fetal Acid-Base Status During Cesarean Delivery Under Spinal Anesthesia (NEO-FET)

Comparative Effects of Ephedrine and Norepinephrine on Fetal Acid-Base Status During Cesarean Delivery Under Spinal Anesthesia: A Randomized Double-Blind Study

This study compares ephedrine and norepinephrine for the treatment of low blood pressure (hypotension) that may occur during cesarean delivery under spinal anesthesia. Maternal hypotension can reduce uteroplacental blood flow and may affect fetal well-being. Both medications are commonly used to restore blood pressure. The primary aim of this study is to compare their effects on neonatal acid-base status, assessed by umbilical arterial pH measured immediately after birth. Secondary outcomes include other umbilical arterial blood gas parameters, maternal blood pressure and heart rate, vasopressor requirements, maternal adverse events, and neonatal Apgar scores.

Study Overview

• Status: Completed
• Conditions: Acidosis; Cesarean Delivery Affecting Newborn; Maternal Hypotension; Spinal Aneshtesia
• Intervention / Treatment: Drug: Ephedrine; Drug: Norepinephrine

Detailed Description

This is a prospective, randomized, double-blind, controlled clinical trial designed to compare the effects of ephedrine and norepinephrine on fetal acid-base status during elective cesarean delivery under spinal anesthesia. Maternal hypotension is a common complication of spinal anesthesia and may reduce uteroplacental perfusion. Ephedrine and norepinephrine are both used to restore maternal blood pressure, but their comparative effects on fetal acid-base balance and maternal hemodynamics remain incompletely defined.

The primary aim of the study is to compare umbilical arterial pH between patients treated with ephedrine and those treated with norepinephrine for postspinal hypotension. Secondary outcomes include other umbilical arterial blood gas parameters, including pCO₂, bicarbonate, base excess, and lactate; the incidence of neonatal acidosis defined as umbilical arterial pH <7.20; Apgar scores at 1 and 5 minutes; maternal systolic blood pressure and heart rate; vasopressor requirements; and maternal adverse events.

A total of 155 parturients were randomized in a 1:1 ratio before spinal anesthesia. Because the study drugs were administered only when postspinal hypotension occurred, the analysis population consisted of randomized participants who developed hypotension and received the allocated vasopressor. This resulted in 102 participants in the final analysis population, including 50 in the ephedrine group and 52 in the norepinephrine group.

All randomized participants underwent a standardized spinal anesthesia protocol. Postspinal hypotension was treated with repeated intravenous boluses of either ephedrine 5 mg or norepinephrine 5 µg according to the allocated treatment arm. The study was designed to compare fetal acid-base effects and maternal hemodynamic responses associated with these two vasopressor strategies.

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Phase 4

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Diyarbakır, Turkey (Türkiye), 21070
    • SBÜ Gazi Yaşargil Eğitim ve Araştırma Hastanesi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

nclusion Criteria:

• Women aged 18-45 years
• Singleton term pregnancy (≥37 weeks of gestation)
• American Society of Anesthesiologists (ASA) physical status I-II
• Scheduled for elective cesarean delivery under spinal anesthesia

Exclusion Criteria:

• Hypertensive disorders of pregnancy
• Known systemic disease
• Multiple gestation
• Emergency cesarean delivery
• Contraindication to spinal anesthesia
• Known allergy to the study medications
• Pre-diagnosed fetal growth restriction identified using standardized growth curves and pathological Doppler findings
• Suspected fetal distress
• Oligohydramnios
• Known congenital fetal anomalies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ephedrine Group; Participants allocated to this group received intravenous ephedrine 5 mg boluses for the treatment of postspinal hypotension. Additional 5 mg boluses were administered at 1-minute intervals as needed until the predefined blood pressure target was achieved.	Drug: Ephedrine; Intravenous ephedrine 5 mg bolus administered for the treatment of postspinal hypotension during elective cesarean delivery. Additional 5 mg boluses were administered at 1-minute intervals as needed until the predefined blood pressure target was achieved.; Other Names: Ephedrine hydrochloride
Experimental: Norepinephrine Group; Participants allocated to this group received intravenous norepinephrine 5 µg boluses for the treatment of postspinal hypotension. Additional 5 µg boluses were administered at 1-minute intervals as needed until the predefined blood pressure target was achieved.	Drug: Norepinephrine; Intravenous norepinephrine 5 µg bolus administered for the treatment of postspinal hypotension during elective cesarean delivery. Additional 5 µg boluses were administered at 1-minute intervals as needed until the predefined blood pressure target was achieved.; Other Names: Steradin®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Umbilical arterial pH	Umbilical arterial pH measured immediately after delivery from an arterial blood sample obtained from a double-clamped segment of the umbilical cord and analyzed within 5 minutes using a blood gas analyzer.	Immediately after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal hypotension	Postspinal hypotension was defined as a decrease in systolic blood pressure to less than 80% of the baseline value. The number and duration of hypotensive episodes were recorded.	From spinal anesthesia until delivery
Incidence of neonatal acidosis (UA pH <7.20)	Incidence of neonatal acidosis, defined as an umbilical arterial pH <7.20, determined from an umbilical arterial blood sample obtained immediately after delivery and analyzed using a point-of-care blood gas analyzer.	Immediately after delivery
Maternal heart rate response	Maternal heart rate was recorded after spinal anesthesia and during periods requiring vasopressor administration. Temporal heart rate changes and the occurrence of tachycardia were recorded.	From spinal anesthesia until delivery / during surger

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apgar score at 1 minute	Apgar Score (Appearance, Pulse, Grimace, Activity, Respiration) will be assessed by the attending neonatologist. The score ranges from 0 to 10, where higher scores indicate better neonatal condition. The outcome is the distribution of Apgar scores at 1 minute after birth.	At 1 minute after delivery
Apgar score at 5 minutes	Apgar Score (Appearance, Pulse, Grimace, Activity, Respiration) will be assessed by the attending neonatologist. The score ranges from 0 to 10, where higher scores indicate better neonatal condition. The outcome is the distribution of Apgar scores at 5 minutes after birth.	At 5 minutes after delivery
Requirement for additional vasopressor doses	The number of vasopressor boluses and the total amount of ephedrine (mg) or norepinephrine (µg) administered for treatment of postspinal hypotension were recorded.	During surgery
Neonatal heart rate after delivery	Neonatal heart rate measured after delivery and compared between the ephedrine and norepinephrine groups.	Immediately after delivery

Collaborators and Investigators

• Sponsor: mehmet özkılıç
• Investigators: Principal Investigator: Mehmet ÖZKILIÇ, Anesthesiology and Intensive Care Specialist, MD, Gazi Yaşargil Training and Research Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2025
• Primary Completion (Actual): December 1, 2025
• Study Completion (Actual): December 1, 2025

Study Registration Dates

• First Submitted: April 1, 2025
• First Submitted That Met QC Criteria: April 8, 2025
• First Posted (Actual): April 10, 2025

Study Record Updates

• Last Update Posted (Actual): October 8, 2026
• Last Update Submitted That Met QC Criteria: October 4, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Keywords: Norepinephrine; Cesarean Delivery; Ephedrine; Postspinal Hypotension; Umbilical Arterial pH; Fetal Acid-Base Status
• Additional Relevant MeSH Terms: Metabolic Diseases; Acid-Base Imbalance; Nutritional and Metabolic Diseases; Acidosis; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amines; Catechols; Phenols; Benzene Derivatives; Alcohols; Propanolamines; Amino Alcohols; Propanols; Ethanolamines; Phenethylamines; Ethylamines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Norepinephrine; Ephedrine
• Other Study ID Numbers: GYEAH-OB-NE-EF-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

IPD will not be shared because data sharing was not included in the approved study protocol.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No