Ephedrine Versus Phenylephrine for Spinal Block - Related Hypotension in Cesarean Delivery

The Effect of Prophylactic Phenylephrine Infusion and Interventional Ephedrine Boluses on Umbilical Blood pH in Women Undergoing Cesarean Delivery Under Spinal Anesthesia: a Retrospective Case - Control Study

The study is designed to compare two strategies used in the management of hypotension caused by spinal anesthesia for cesarean section: intravenous phenylephrine given as prophylactic infusion and interventional boluses of intravenous ephedrine. Phenylephrine is currently recommended for battling spinal anesthesia - related sympathectomy, due to some scientific data on possible negative effects of ephedrine on fetal wellbeing. Therefore this study will retrospectively compare both clinical and laboratory data of the newborns delivered by cesarean section where either large dose of ephedrine or continuous infusion of phenylephrine was used for management of hypotension

Study Overview

• Status: Completed
• Conditions: Spinal Anesthesia; Cesarean Delivery; Neonatal Acidosis
• Intervention / Treatment: Drug: Ephedrine; Drug: Phenylephrine

Detailed Description

Single - shot spinal block is a gold standard of anesthesia for cesarean delivery. It has been proven to decrease maternal morbidity and improve neonatal outcomes. Despite being most frequently used type of anesthesia in obstetrics, spinal block - related complications remain frequent in term parturients, of which hypotension is of utmost importance. Two widely accepted medications used in its prevention and treatment are phenylephrine and ephedrine, of which continuous, preventive phenylephrine infusion is considered superior in terms of neonatal safety.

Although there is some scientific evidence towards ephedrine having negative effect on neonatal acid - base status, it is still the most popular vasoconstrictor used for management of perioperative hypotension in Poland. It is an indirect adrenergic agonist, acting through release of noradrenaline from peripheral nerve endings. Beta - receptors mediated adrenergic stimulation of neonatal tissues is thought to be responsible for endocrine abnormalities, acid - base disturbances and possibly worse Apgar scores. Phenylephrine on the other hand is a direct and selective alpha-1 agonist and is regarded to exert very little or even no neonatal effects. Maternal complications related to phenylephrine infusion is hypertension and reflex bradycardia.

As convincing evidence is still lacking, this study is designed to retrospectively compare neonatal outcomes and perioperative hemodynamic data of mothers where either infusion of phenylephrine or boluses of ephedrine were used to control spinal -related hypotension during cesarean section.

• Study Type: Observational
• Enrollment (Actual): 94

Contacts and Locations

Study Locations

• Poland
  • Warsaw, Poland, 01-813
    • Centre of Postgraduate Medical Education,Department of Anesthesia and Intensive Care

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Initial cohort of patients will consist of selected cases of cesarean deliveries from Orlowski Hospital in years 2020 - 2022, Department of Obstetrics and Gynaecology, Warsaw, Poland.

Intention is to include 40 cases in each group.

Description

Inclusion Criteria:

• Cesarean delivery at term under spinal anesthesia
• American Society of Anesthesiologists (ASA) physical status <3
• BMI <40
• Preemptive phenylephrine infusion or ephedrine boluses used during surgical procedure

Exclusion Criteria:

• No vasoconstrictor (phenylephrine nor ephedrine) used throughout the procedure
• Total dose of ephedrine less than 15mg
• poor quality of anesthetic record - data required for analysis not available

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ephedrine; Cesarean delivery cases where spinal block was administered and hypotension was managed with intravenous ephedrine. Hospital electronic database will be searched to identify cases of cesarean delivery in years 2020 - 2022. After that, manual review of the medical notes will follow in order to extract cases where spinal block was administered and ephedrine was used to treat spinal - related hypotension. Further chart analysis will yield demographic and hemodynamic data of the parturient, as well as clinical data of the neonate (weight, gender, Apgar score). Further laboratory data on neonatal acid - base status will be acquired from hospital's laboratory electronic database. Attention will be paid to assure that identification of the patients would not be possible using data acquired for the study. All data will be anonymized and accessible only for investigators.	Drug: Ephedrine; Intravenous boluses of ephedrine
Phenylephrine; Cesarean delivery cases where spinal block was administered and hypotension was managed with intravenous phenylephrine infusion Hospital electronic database will be searched to identify cases of cesarean delivery in years 2020 - 2022. After that, manual review of the medical notes will follow in order to extract cases where spinal block was administered and infusion of phenylephrine was used to treat spinal - related hypotension. Further chart analysis will yield demographic and hemodynamic data of the parturient, as well as clinical data of the neonate (weight, gender, Apgar score). Further laboratory data on neonatal acid - base status will be acquired from hospital's laboratory electronic database. Attention will be paid to assure that identification of the patients would not be possible using data acquired for the study. All data will be anonymized and accessible only for investigators.	Drug: Phenylephrine; Intravenous continuous infusion of phenylephrine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Umbilical blood pH	Sets of data will be tested for normality and standard statistical tests (Student's t - test or Mann - Whitney U - test) will be used to detect the differences in umbilical blood pH between the groups.	During delivery (from spinal injection to umbilical clamping and cutting)
Umbilical blood Base Excess (BE)	Sets of data will be tested for normality and standard statistical tests (Student's t - test or Mann - Whitney U - test) will be used to detect the differences in umbilical blood Base Excess (BE) between the groups.	During delivery (from spinal injection to umbilical clamping and cutting)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamic stability	Number of episodes of hypotension recorded in anesthetic sheet after spinal injection will be compared using chi-square or Fisher's exact test.	During delivery (from spinal injection to umbilical clamping and cutting)

Collaborators and Investigators

• Sponsor: Centre of Postgraduate Medical Education
• Investigators: Study Chair: Małgorzata Malec-Milewska, MD, Prof., Department of Anesthesia and Intensive Care, Orlowski Hospital, Warsaw

Publications and helpful links

General Publications

• Ngan Kee WD, Khaw KS, Tan PE, Ng FF, Karmakar MK. Placental transfer and fetal metabolic effects of phenylephrine and ephedrine during spinal anesthesia for cesarean delivery. Anesthesiology. 2009 Sep;111(3):506-12. doi: 10.1097/ALN.0b013e3181b160a3.
• Mohta M, Aggarwal M, Sethi AK, Harisinghani P, Guleria K. Randomized double-blind comparison of ephedrine and phenylephrine for management of post-spinal hypotension in potential fetal compromise. Int J Obstet Anesth. 2016 Aug;27:32-40. doi: 10.1016/j.ijoa.2016.02.004. Epub 2016 Feb 21.
• Higgins N, Fitzgerald PC, van Dyk D, Dyer RA, Rodriguez N, McCarthy RJ, Wong CA. The Effect of Prophylactic Phenylephrine and Ephedrine Infusions on Umbilical Artery Blood pH in Women With Preeclampsia Undergoing Cesarean Delivery With Spinal Anesthesia: A Randomized, Double-Blind Trial. Anesth Analg. 2018 Jun;126(6):1999-2006. doi: 10.1213/ANE.0000000000002524.

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2024
• Primary Completion (Actual): September 16, 2025
• Study Completion (Actual): September 16, 2025

Study Registration Dates

• First Submitted: December 11, 2024
• First Submitted That Met QC Criteria: December 14, 2024
• First Posted (Actual): December 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 19, 2025
• Last Update Submitted That Met QC Criteria: September 18, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: ephedrine; spinal anesthesia; hypotension; phenylephrine; cesarean delivery
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypotension; Organic Chemicals; Amines; Alcohols; Propanolamines; Amino Alcohols; Propanols; Ethanolamines; Phenethylamines; Ethylamines; Ephedrine; Phenylephrine
• Other Study ID Numbers: 96/2024

Drug and device information, study documents

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