Clinical trial NCT05279703: Epinephrine Infusion for Prophylaxis Against Maternal Hypotension During Cesarean Delivery
Official title: The Use of Epinephrine Infusion for Prophylaxis Against Maternal Hypotension During Cesarean Delivery: a Randomized Controlled Dose-finding Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Postspinal Hypotension
Cesarean Delivery
Epinephrine
Lead sponsor: Kasr El Aini Hospital
Sponsor class: OTHER
First posted: 2022-03-15
Enrollment: 276
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: incidence of postspinal hypotension
timeFrame: 1 minute after subarachnoid injection till 5 minutes after baby delivery
Secondary outcomes:
measure: incidence of tachycardia
timeFrame: 1 minute after subarachnoid injection till 5 minutes after baby delivery
measure: incidence of hypertension
timeFrame: 1 minute after subarachnoid injection till 5 minutes after baby delivery
measure: incidence of severe hypotension
timeFrame: 1 minute after subarachnoid injection till 5 minutes after baby delivery
measure: mean heart rate
timeFrame: 1 minute after subarachnoid injection, every 2 minutes during procedure, till 5 minutes after baby delivery
measure: mean systolic blood pressure
timeFrame: 1 minute after subarachnoid injection, every 2 minutes during procedure, till 5 minutes after baby delivery
measure: total ephedrine requirement
timeFrame: 1 minute after subarachnoid injection till 5 minutes after baby delivery
measure: total atropine requirement
timeFrame: 1 minute after subarachnoid injection till 5 minutes after baby delivery
measure: Apgar score
timeFrame: 5 minutes after delivery
measure: umbilical blood pH
timeFrame: 5 minutes after delivery
measure: umbilical blood PCO2
timeFrame: 5 minutes after delivery
measure: umbilical blood PO2
timeFrame: 5 minutes after delivery
measure: umbilical blood HCO3
timeFrame: 5 minutes after delivery
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Kasr Alaini Hospital
Study officials:
References: