Epinephrine Infusion for Prophylaxis Against Maternal Hypotension During Cesarean Delivery

The Use of Epinephrine Infusion for Prophylaxis Against Maternal Hypotension During Cesarean Delivery: a Randomized Controlled Dose-finding Trial

Maternal hypotension after spinal block is a common complication after subarachnoid block in this population. The incidence of maternal hypotension is nearly 60% when prophylactic vasopressors are not used. Therefore, it is highly recommended to use vasopressors, preferably as continuous infusion, for prophylaxis rather than delaying their use until hypotension occurs.

Phenylephrine (PE) is the recommended drug for prophylaxis against hypotension during cesarean delivery; however, the use of PE is commonly associated with decreased heart rate and probably cardiac output because PE is a pure alpha adrenoreceptor agonist. Introduction of NE in obstetric practice had shown favorable maternal and neonatal outcomes and was associated with higher heart rate and cardiac output compared to PE. However, there is still some mothers who develop bradycardia and diminished cardiac output with the use of NE. The most desired scenario during hemodynamic management of mothers during cesarean delivery would achieve the least possible incidences of maternal hypotension, bradycardia and reactive hypertension. Therefore, it is warranted to reach a vasopressor regimen with the most stable hemodynamic profile.

In the last year, epinephrine was reported for the first time in obstetric practice with acceptable safety on the mother and the fetus. However, there is still lack of data about the most appropriate dose for infusion during cesarean delivery. This study aims to compare three prophylactic infusion rates for epinephrine during cesarean delivery.

Study Overview

• Status: Recruiting
• Conditions: Cesarean Delivery; Epinephrine; Postspinal Hypotension
• Intervention / Treatment: Drug: Epinephrine 0.03; Drug: Epinephrin 0.02; Drug: Epinephrin 0.01

Detailed Description

Upon arrival to the operating room, the patient will be in supine position with left uterine displacement using a wedge below the right buttock. Routine monitoring will be applied (electrocardiography, pulse oximetry, and non-invasive blood pressure monitor). An 18G-cannula will be inserted, and the patients will receive 10 mg metoclopramide. Baseline heart rate and systolic blood pressure will be recorded as the average of three consecutive readings with 2-minutes interval.

Lactated Ringer's solution will be infused at rate of 15 mL/Kg over 10 minutes as a co-load; spinal anesthesia will be achieved by injecting 10 mg of hyperbaric bupivacaine and 20 mcg fentanyl into the subarachnoid space at L3-L4 or L4-L5 interspace using 25G spinal needle.

After subarachnoid block, mothers will be placed in supine position with left-lateral tilt and the vasopressor infusion will be started.

• 0.01 mcg group
• 0.02 mcg group
• 0.03 mcg group The vasopressor infusion will be through the same line as the fluid a three-way stopcock. The vasopressor infusion will be stopped if heart rate became ≥130% of baseline or systolic blood pressure ≥120% of baseline, otherwise the infusion will be stopped 5 minutes after delivery of the baby.

Block success will be assessed after 5 minutes from intrathecal injection of local anesthetic; and will be confirmed if sensory block level is at T4.

Post-spinal hypotension (defined as systolic blood pressure ≤80% of the baseline reading during the period from intrathecal injection to delivery of the fetus) will be managed by administration of 9 mg of ephedrine Severe post-spinal hypotension (defined as systolic blood pressure ≤60% of the baseline reading during the period from intrathecal injection to delivery of the fetus) will be managed by administration IV ephedrine 15 mg.

Reactive hypertension (defined as systolic blood pressure ≥120% of the baseline reading) will be managed by stoppage of the infusion till the next systolic blood pressure reading. The infusion will be then re-started at the half of the initial rate, when systolic blood pressure decreases to be within 20% of the baseline reading.

Intraoperative bradycardia (defined as heart rate less than 55 bpm) will be managed by IV atropine bolus (0.5 mg) will be administered.

Fluid administration will be continued up to a maximum of 1.5 liters. An oxytocin bolus (0.5 IU) will be delivered over five seconds after delivery the infused at a rate of 2.5 IU/hour.

• Study Type: Interventional
• Enrollment (Anticipated): 276
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ahmed Hasanin; Phone Number: 01095076954; Email: ahmedmohamedhasanin@gmail.com

Study Locations

• Egypt
  • Cairo, Egypt, 11562
    • Recruiting
    • Kasr Alaini hospital
    • Contact: Anesthesia, Pain Management and Surgical ICU Department; Phone Number: 00201222224057; Email: Anesthesia.kasralainy@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• full-term singleton pregnant women
• American society of anesthesiologist-physical status I or II,
• scheduled for elective cesarean delivery

Exclusion Criteria:

• Patients with uncontrolled cardiac morbidities (patients with tight valvular lesion, impaired contractility with ejection fraction < 50%, heart block, and arrhythmias),
• hypertensive disorders of pregnancy,
• peripartum bleeding,
• coagulation disorders (patients with INR >1.4 and or platelet count < 80000 /dL) or
• any contraindication to regional anesthesia,
• and baseline systolic blood pressure (SBP) < 100 mmHg

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 0.03 mcg group; epinephrine infusion will be started after subarachnoid block until 5 minutes after delivery of the baby	Drug: Epinephrine 0.03; epinephrine infusion rate of 0.03 mcg/kg/min; Other Names: adrenaline
Active Comparator: 0.02 mcg group; epinephrine infusion will be started after subarachnoid block until 5 minutes after delivery of the baby	Drug: Epinephrin 0.02; epinephrine infusion rate of 0.02 mcg/kg/min; Other Names: adrenaline
Active Comparator: 0.01 mcg group; epinephrine infusion will be started after subarachnoid block until 5 minutes after delivery of the baby	Drug: Epinephrin 0.01; epinephrine infusion rate of 0.01 mcg/kg/min; Other Names: adrenaline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of postspinal hypotension	systolic blood pressure ≤80% of the baseline reading	1 minute after subarachnoid injection till 5 minutes after baby delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of tachycardia	heart rate > 130% of baseline	1 minute after subarachnoid injection till 5 minutes after baby delivery
incidence of hypertension	systolic blood pressure >120% of baseline	1 minute after subarachnoid injection till 5 minutes after baby delivery
incidence of severe hypotension	systolic blood pressure ≤60% of the baseline reading	1 minute after subarachnoid injection till 5 minutes after baby delivery
mean heart rate	beat per minute	1 minute after subarachnoid injection, every 2 minutes during procedure, till 5 minutes after baby delivery
mean systolic blood pressure	mmHg	1 minute after subarachnoid injection, every 2 minutes during procedure, till 5 minutes after baby delivery
total ephedrine requirement	mg	1 minute after subarachnoid injection till 5 minutes after baby delivery
total atropine requirement	mg	1 minute after subarachnoid injection till 5 minutes after baby delivery
Apgar score	Breathing effort Heart rate Muscle tone Reflexes Skin color Each category is scored with 0, 1, or 2, depending on the observed condition	5 minutes after delivery
umbilical blood pH	pH	5 minutes after delivery
umbilical blood PCO2	mmHg	5 minutes after delivery
umbilical blood PO2	mmHg	5 minutes after delivery
umbilical blood HCO3	mmol/L	5 minutes after delivery

Collaborators and Investigators

• Sponsor: Kasr El Aini Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2022
• Primary Completion (Anticipated): August 1, 2022
• Study Completion (Anticipated): August 1, 2022

Study Registration Dates

• First Submitted: February 23, 2022
• First Submitted That Met QC Criteria: March 4, 2022
• First Posted (Actual): March 15, 2022

Study Record Updates

• Last Update Posted (Actual): August 26, 2022
• Last Update Submitted That Met QC Criteria: August 25, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypotension; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Epinephrine; Racepinephrine; Epinephryl borate
• Other Study ID Numbers: MD-399-2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Available from PI upon reasonable request

Drug and device information, study documents

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