Clinical trial NCT05051150: Epinephrine Infusion for Prophylaxis Against Maternal Hypotension During Caesarean Section
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: TERMINATED
Phase: PHASE4
Conditions: Post-spinal Hypotension
Cesarean Section
Lead sponsor: Kasr El Aini Hospital
Sponsor class: OTHER
First posted: 2021-09-21
Enrollment: 18
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. In this study, we aim 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, 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.

Eligibility criteria: 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

Primary outcomes:
measure: the incidence of post-spinal hypotension
timeFrame: 1 minutes after spinal injection until 5-minutes after the baby delivery
Secondary outcomes:
measure: the incidence of severe post-spinal hypotension
timeFrame: 1 minutes after spinal injection until 5-minutes after the baby delivery
measure: the incidence of reactive hypertension
timeFrame: 1 minutes after spinal injection until 5-minutes after the baby delivery
measure: total ephedrine dose
timeFrame: 1 minutes after spinal injection until 5-minutes after the baby delivery
measure: the incidence of tachycardia
timeFrame: 1 minutes after spinal injection until 5-minutes after the baby delivery
measure: the incidence of bradycardia
timeFrame: 1 minutes after spinal injection until 5-minutes after the baby delivery
measure: number of physician intervention
timeFrame: 1 minutes after spinal injection until 5-minutes after the baby delivery
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Kasr Alaini Hospital
Study officials:
References: