Norepinephrine and Phenylephrine for Spinal Anesthesia-induced Hypotension.

Prophylactic vs Rescue Norepinephrine and Phenylephrine for Spinal Anesthesia-induced Hypotension on Neonatal Outcomes During Cesarean Section: A Multicenter, Single-blind, Crossover, Factorial Cluster Trial

This study aims to explore the effects of different application modes (prophylactic and rescue strategy) of norepinephrine and norepinephrine on neonate umbilical artery pH undergoing cesarean section.

Study Overview

• Status: Completed
• Conditions: Outcome
• Intervention / Treatment: Drug: Norepinephrine; Drug: Phenylephrine

Detailed Description

Spinal anesthesia-induced hypotension is a frequent complication during spinal anesthesia for cesarean section. The incidence of spinal anesthesia-induced hypotension is as high as 62.1-89.7% if prophylactic measures are not taken. The 2016 ASA guidelines for obstetric anesthesia suggest avoiding hypotension following spinal anesthesia in women and emphasize the use of vasopressors, specifically alpha-receptor agonists, as the preferred strategy to prevent and manage spinal anesthesia-induced hypotension. The prophylactic vasopressor strategy is more effective in enhancing hemodynamic stability and reducing adverse events such as nausea and vomiting during cesarean section, compared to rescue strategy. However, it does not demonstrate significant advantages in neonatal outcomes such as umbilical artery pH and Apgar score. The impact of various vasopressor application patterns on neonatal outcomes after cesarean section lacks further supporting evidence. Therefore, this study aims to explore the effects of different application modes (prophylactic and rescue strategy) of norepinephrine and norepinephrine on neonate umbilical artery pH undergoing cesarean section through a multicenter, single-blind, 2*2 crossover and cluster randomized trial.

• Study Type: Interventional
• Enrollment (Actual): 700
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • General Hospital of Ningxia Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18-45 years
• Primipara or multipara
• Singleton pregnancy ≥37 weeks
• American Society of Anesthesiologists physical status classification II
• Scheduled for cesarean section under spinal anesthesia

Exclusion Criteria:

• Body height < 150 cm
• Body weight > 100 kg or body mass index (BMI) ≥ 40 kg/m2
• Eclampsia or chronic hypertension or baseline blood pressure ≥140 mmHg
• Hemoglobin < 7g/dl
• Fetal distress, or known fetal developmental anomaly

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prophylactic norepinephrine group; A maintenance dose of norepinephrine (0.05 ug/kg/min) infusion simultaneous with spinal anesthesia. The maternal systolic blood pressure was consistently maintained above 80% of the preoperative baseline value from the initiation of spinal anesthesia until fetal delivery.	Drug: Norepinephrine; Prophylactic or rescue norepinephrine for spinal anesthesia-induced hypotension; Other Names: Vasopressor
Experimental: Prophylactic phenylephrine group; A maintenance dose of phenylephrine (0.625 ug/kg/min) infusion simultaneous with spinal anesthesia. The maternal systolic blood pressure was consistently maintained above 80% of the preoperative baseline value from the initiation of spinal anesthesia until fetal delivery.	Drug: Phenylephrine; Prophylactic or rescue phenylephrine for spinal anesthesia-induced hypotension; Other Names: Vasopressor
Active Comparator: Rescue norepinephrine group; The maternal systolic blood pressure was consistently maintained above 80% of the preoperative baseline value from the initiation of spinal anesthesia until fetal delivery. Spinal anesthesia-induced hypotension is managed by administering a 6 μg intravenous bolus of norepinephrine.	Drug: Norepinephrine; Prophylactic or rescue norepinephrine for spinal anesthesia-induced hypotension; Other Names: Vasopressor
Active Comparator: Rescue phenylephrine group; The maternal systolic blood pressure was consistently maintained above 80% of the preoperative baseline value from the initiation of spinal anesthesia until fetal delivery. Spinal anesthesia-induced hypotension is managed by administering a 75 μg intravenous bolus of phenylephrine.	Drug: Phenylephrine; Prophylactic or rescue phenylephrine for spinal anesthesia-induced hypotension; Other Names: Vasopressor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pH	From umbilical arterial blood gases.	Immediately after delivery
Base excess (BE)	From umbilical arterial blood gases.	Immediately after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of post-spinal anesthesia hypotension	Systolic blood pressure (SBP) < 80% of the baseline	1-15 minutes after spinal anesthesia
The incidence of severe post-spinal anesthesia hypotension	Systolic blood pressure (SBP) < 60% of the baseline	1-15 minutes after spinal anesthesia
The incidence of nausea and vomiting	Presence of nausea and vomiting in patients after spinal anesthesia	1-15 minutes after spinal anesthesia
The incidence of bradycardia	Heart rate < 60 beats/min	1-15 minutes after spinal anesthesia
APGAR score	A= Appearance P=Pulse G=Grimace A=Attitude R=Respiration	1 min after delivery
APGAR score	A= Appearance P=Pulse G=Grimace A=Attitude R=Respiration	5 min after delivery
Partial pressure of oxygen (PO2)	From umbilical arterial blood gases.	Immediately after delivery
The incidence of hypertension	Systolic blood pressure (SBP) >120% of the baseline.	1-15 minutes after spinal anesthesia

Collaborators and Investigators

• Sponsor: General Hospital of Ningxia Medical University
• Investigators: Study Chair: Yi Chen, M.D., General Hospital of Ningxia Medical University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2025
• Primary Completion (Actual): April 21, 2026
• Study Completion (Actual): April 21, 2026

Study Registration Dates

• First Submitted: July 14, 2024
• First Submitted That Met QC Criteria: July 14, 2024
• First Posted (Actual): July 18, 2024

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Cesarean section; Norepinephrine; Phenylephrine; Neonatal outcomes; Spinal anesthesia-induced hypotension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypotension; Organic Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amines; Catechols; Phenols; Benzene Derivatives; Alcohols; Amino Alcohols; Ethanolamines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Cardiovascular Agents; Norepinephrine; Phenylephrine; Vasoconstrictor Agents
• Other Study ID Numbers: Yi Chen-2025-1

Drug and device information, study documents

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