Effect of Adding a Low-Dose Epinephrine Bolus Prior to Infusion on Maternal Hemodynamic Stability During Cesarean Section

Effect of Adding a Low-Dose Epinephrine Bolus Prior to Infusion on Maternal Hemodynamic Stability During Cesarean Section Under Spinal Anesthesia: A Randomized Clinical Trial

In North America, norepinephrine, ephedrine, and epinephrine have been recommended as first-choice vasopressors for the treatment of spinal hypotension during cesarean delivery. However, in international consensus guidelines, epinephrine was recommended for circulatory collapse only. Phenylephrine infusion is an important therapeutic strategy for preventing spinal-induced hypotension (SIH) in cesarean delivery, as it decreases the incidence of hypotension, nausea, and vomiting. However, high doses may reduce maternal heart rate and cardiac output in a dose-dependent manner.

Ephedrine, previously considered the first-choice drug, has both α and β receptor agonistic activity and causes norepinephrine release from sympathetic neurons. Its β1 effect increases heart rate and contractility, but may cause undesirable tachycardia. Tachyphylaxis can develop with repeated doses. Norepinephrine, the biosynthetic precursor of epinephrine, has both potent α and weak β agonist effects, tending to cause bradycardia.

Despite a lower incidence of hypotension with prophylactic norepinephrine, PSH still occurs in up to 30% of parturients undergoing cesarean section. The administration of a bolus dose of epinephrine prior to continuous infusion is an unusual practice in obstetric anesthesia, but has been reported to be safe in other contexts and in pregnant women when used for hemodynamic support.

Epinephrine has both potent α- and β-adrenoceptor agonist activity. Its β effects could offset reflex decreases in maternal HR and CO during spinal anesthesia for cesarean delivery. Although some studies compared epinephrine infusion with phenylephrine, it remains unclear whether adding an initial bolus of epinephrine before infusion offers superior maternal hemodynamic stability compared to infusion alone.

Study Overview

• Status: Recruiting
• Conditions: Hemodynamic (MAP) Stability
• Intervention / Treatment: Drug: Epinephrine (Adrenaline) bolus then infusion; Drug: Epinephrine (Adrenaline) infusion

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Recruiting
    • Kasr Alaini hospital
    • Contact: abdelkhalek m Samy; Phone Number: 01025854248; Email: dr.abdo86@gmail.com
    • Principal Investigator: Dina A Turki, MD of anesthesia

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age: 18 to 35 years.
2. American Society of Anesthesiologists (ASA) physical status II.
3. Undergoing Elective Lower Segment Cesarean Section under Spinal Anesthesia.

Exclusion Criteria:

1. Uncontrolled cardiac morbidities as reduction of ejection fraction< 60%, History (within 3months) of myocardial infarction, cerebrovascular accident, transient ischemic attacks or coronary artery disease/stents
2. Poorly controlled Hypertensive disorders of pregnancy
3. Peripartum bleeding
4. Multiple pregnancies (e.g., twin gestations)
5. Coagulation disorders defined as platelet count <100,000/μL, INR >1.4, or known inherited clotting factor deficiency.
6. Baseline systolic blood pressure (SBP) < 100 mmHg or >130 mmHg
7. Refusal of patients.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Infusion group	Drug: Epinephrine (Adrenaline) infusion; Patients will receive the epinephrine infusion dose of 0.03 mcg/Kg/min (6) immediately without the bolus.
Active Comparator: Bolus plus infusion group	Drug: Epinephrine (Adrenaline) bolus then infusion; A bolus of 4 mcg epinephrine will be given just after spinal anaesthesia followed by 0.03 mcg/kg/min infusion which is equivalent to 1.8 mcg/kg/hr. Epinephrine dose of 3000 mcg will be diluting in 500 mL saline (6 mcg/mL), and the infusion rate will be set on 0.3 mL/kg/hr.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of post-spinal hypotension	defined as systolic blood pressure drop >20% from baseline, measured from block onset until 5 minutes after delivery	up to 2 hours after spinal anesthesia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of severe post-spinal hypotension	systolic blood pressure drop >30% from baseline or systolic blood pressure<80 mmHg	up to 2 hours after spinal anaesthesia
Number of hypotensive and severe hypotensive episodes per patient		up to 2 hours after spinal anaesthesia
Incidence of reactive hypertension (systolic blood pressure ≥ 120% of baseline)		up to 2 hours after spinal anaesthesia
Number of reactive hypertension episodes per patient		up to 2 hours after spinal anaesthesia
Incidence of tachycardia (heart rate >130% baseline, not related to hypotension)		up to 2 hours after spinal anaesthesia
Incidence of intraoperative nausea and vomiting		up to 2 hours after spinal anesthesia
Total intraoperative norepinephrine consumption		up to 2 hours after spinal anaesthesia
Fetal outcomes: umbilical artery blood gases	Umbilical artery blood gases obtained after delivery at 1 and 5 minutes	up to 5 minutes after fetal delivery
• Fetal outcomes: Apgar scores	Apgar scores at 1 and 5 minutes after delivery Appearance (Skin color: 0=Blue/Pale, 1=Pink body/blue limbs, 2=All pink) Pulse (Heart rate: 0=None, 1=<100 bpm, 2=>100 bpm) Grimace (Reflex irritability: 0=None, 1=Grimace, 2=Cry/vigorous reaction) Activity (Muscle tone: 0=Limp, 1=Some flexion, 2=Active motion) Respiration (Breathing: 0=None, 1=Weak/irregular, 2=Strong cry) Interpretation: 7-10: Normal (reassuring). 4-6: Fair/Abnormal (may require stimulations or oxygen). 0-3: Low/Critically low (indicates need for intensive resuscitation).	up to 5 minutes after delivery

Collaborators and Investigators

• Sponsor: Cairo University

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2026
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: March 14, 2026
• First Submitted That Met QC Criteria: March 14, 2026
• First Posted (Actual): March 18, 2026

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amines; Catechols; Phenols; Benzene Derivatives; Alcohols; Amino Alcohols; Ethanolamines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Epinephrine
• Other Study ID Numbers: MS-572-2025

Drug and device information, study documents

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