Epinephrine Infusion for Prophylaxis Against Maternal Hypotension During Caesarean Section

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. In this study, we aim to compare three prophylactic infusion rates for epinephrine during cesarean delivery.

Study Overview

• Status: Terminated
• Conditions: Cesarean Section; Post-spinal Hypotension
• Intervention / Treatment: Drug: Epinephrin 0.03; Drug: Epinephrin 0.05; Drug: Epinephrin 0.07

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, and 50 mg ranitidine. 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.

To maintain the double-blind scheme, the total dosage of epinephrine (mcg) for patients in each group will be calculated and added to the 50 ml syringe and will be infused at rate of 50 mL/hour. The calculated epinephrine dose will be withdrawn using insulin syringe. The vasopressor infusion will be through the same line as the intravenous fluids using a three-way stopcock. the infusion will be stopped when there is tachycardia (>130% of baseline value) and/or reactive hypertension (systolic blood pressure > 120% of baseline), otherwise the infusion will be stopped 5-mins after the baby delivery.

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) will be managed by administration IV ephedrine 15 mg.

Reactive hypertension (defined as systolic blood pressure ≥120% from 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 (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 11562
    • Kasr Alaini Hospital

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 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)
• any contraindication to regional anesthesia,
• baseline systolic blood pressure (SBP) < 100 mmHg will be excluded from the study

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: epinephrine 0.03 mcg	Drug: Epinephrin 0.03; epinephrine infusion rate of 0.03 mcg/kg/min will start from subarachnoid injection of local anesthetic until 5-min after baby delivery
Active Comparator: epinephrine 0.05 mcg	Drug: Epinephrin 0.05; epinephrine infusion rate of 0.05 mcg/kg/min will start from subarachnoid injection of local anesthetic until 5-min after baby delivery
Active Comparator: epinephrine 0.07 mcg	Drug: Epinephrin 0.07; epinephrine infusion rate of 0.07 mcg/kg/min will start from subarachnoid injection of local anesthetic until 5-min after baby delivery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the incidence of post-spinal hypotension	systolic blood pressure less than 80% of baseline value	1 minutes after spinal injection until 5-minutes after the baby delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the incidence of severe post-spinal hypotension	systolic blood pressure less than 60% of baseline value	1 minutes after spinal injection until 5-minutes after the baby delivery
the incidence of reactive hypertension	systolic blood pressure more than 120% of baseline value	1 minutes after spinal injection until 5-minutes after the baby delivery
total ephedrine dose	mg	1 minutes after spinal injection until 5-minutes after the baby delivery
the incidence of tachycardia	heart rate >130% of baseline value	1 minutes after spinal injection until 5-minutes after the baby delivery
the incidence of bradycardia	heart rate < 55 bpm	1 minutes after spinal injection until 5-minutes after the baby delivery
number of physician intervention	stopping or restarting the norepinephrine infusion, or injecting ephedrine or atropine	1 minutes after spinal injection until 5-minutes after the baby delivery

Collaborators and Investigators

• Sponsor: Kasr El Aini Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: September 10, 2021
• First Submitted That Met QC Criteria: September 10, 2021
• First Posted (Actual): September 21, 2021

Study Record Updates

• Last Update Posted (Actual): March 10, 2022
• Last Update Submitted That Met QC Criteria: February 23, 2022
• Last Verified: February 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: N-31-2021

Drug and device information, study documents

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