Manging Post Spinal Hypotension During Elective Cesarean Section (EpiEph)

Managing Post Spinal Hypotension During Elective Cesarean Section: Epinephrine Versus Ephedrine, a Randomized Double-blinded Controlled Trial

Spinal anesthesia is the gold standard technique for elective cesarean section. It helps to avoid risks regarding airway management and provides effective neuraxial postoperative analgesia, enabling quicker maternal recovery. Cesarean section normally require an anesthetic block at T4 level. So that maternal hypotension is reported to occur in up to 80%. This can result in significant morbidity for both the mother and fetus.The purpose of this study is to determine if epinephrine is as effective and safe compared to ephedrine for maintaining arterial blood pressure during elective cesarean section under spinal anesthesia. All participants will receive spinal anesthesia with a local anesthetic and sufentanil. This study plans to enroll 140 healthy pregnant women. Patients will be randomly assigned according to a computer generated system to be in one of two groups.

Study Overview

• Status: Completed
• Conditions: Hypotension
• Intervention / Treatment: Drug: Adrenaline; Drug: Ephedrine

Detailed Description

Its a prospective double-blinded controlled trial. All participants gave a written informed consent. One hundred and twenty healthy women, ASA II, with singleton pregnancies at term scheduled for elective cesarean section under spinal anesthesia are targeted for the study. They are randomized to receive either epinephrine or ephedrine. Upon arrival in the operating room, parturient was placed in the supine position with 15° left lateral tilt with routine monitoring (HR, non-invasive BP, pulse oximetry, electrocardiography). Baseline BP and HR were computed as the mean of three consecutive BP and HR readings respectively at 1-minute intervals. Study participants will receive a standard spinal anesthetic consisting of 0.5% hyperbaric bupivacaine (2 mL) plus sufentanil (5 µg) at L3-4 vertebral interspace.

Group A (for adrenaline group): received a prophylactic intravenous (i.v) bolus of Epinephrine 0.15µg/Kg at time of SA. In this group, rescue boluses of Epinephrine 0.15µg/Kg, were given if maternal BP decreased more than 20% from the baseline value.

Group E (for ephedrine group): received a prophylactic i.v bolus of Ephedrine 0.1mg/Kg at time of SA. In this group, rescue boluses of Ephedrine 0.1mg/Kg, were given if maternal BP decreased more than 20% from the baseline value. Once the spinal injection was performed a rapid intravenous (i.v.) coload with 15mL/Kg of isotonic saline solution was started through a 16 G i.v. cannula (by turning the i.v. infusion to maximum and using a pressure bag inflated to 150 mmHg). A prophylactic bolus of vasopressor was administered at the end of spinal injection. After performing anesthesia, the parturient was immediately replaced in the supine position with a 15° left lateral table tilt until delivery of the infant. Prior to surgical incision, the spinal sensory level will be tested to the bilateral T6-T4 dermatomal level. Sensory block level was checked by cold-hot test and the Modified Bromage Scale was used for the assessment of motor block. The surgery was allowed when the sensory block level reached D4. Both the patient and the researcher's assistant (who will collect data) will be blinded as to the administered Epinephrine or Ephedrine bolus. Supplemental oxygen will be given only when the pulse oximeter reading decreased below 95%. After delivery, 5 IU of oxytocin diluted in 20 ml of isotonic saline solution were slowly injected over 1 minute. Then an i.v infusion was given (10 IU/500ml of isotonic saline solution at a flow rate of 28 drops/min).

Heart rate (beats/min), systolic, mean and diastolic blood pressure (mmHg) will be recorded every 1 min after spinal injection until the end of surgery. The incidence of hypotension (defined as a reduction in SBP of >20% from baseline determined just before the administration of spinal anesthesia) will be recorded. Reactive hypertension (defined as a rise of SBP >20% of baseline) will also be recorded. Bradycardia (defined as HR <50 beats/min) will be recorded. Tachycardia (defined as a HR >140 beats/min) will also be recorded. Umbilical blood samples will be obtained by clamping it on both sides and a gas analysis will be performed to determine fetal pH, HCO3-, base excess and lactates. Furthermore, Apgar scores at 1 and 5 minutes after delivery will be recorded by the attending pediatrician, who will be unaware of the vasopressor used. The study will end when cesarean section is completed and the patient is transferred to the post-operative care unit.

• Study Type: Interventional
• Enrollment (Actual): 143
• Phase: Phase 4

Contacts and Locations

Study Locations

• Tunisia
  • Tunis, Tunisia, 1007
    • Tunis maternity and neonatology center,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• ASA II
• BMI>18 and <35 Kg/m2
• full term parturients with singleton pregnancy
• scheduled of elective cesarean section under spinal anesthesia

Non-inclusion criteria:

• Patient refusal.
• ASA > II
• Preexisting or pregnancy-induced hypertension
• The use of cardiac medication or medication for BP control.
• Cardiovascular or cerebrovascular disease.
• Multiple pregnancy.
• Suspicion of abnormal placentation.
• Known fetal abnormalities or fetal distress.
• CS under general anesthesia.
• Active labor.
• Emergency.
• Allergy to any of the medications used in the study.

Exclusion Criteria:

• Hemodynamic instability that is not in relationship with SA (occurrence of a surgical per-operative complication e.g. bleeding by placental insertion abnormality or a uterine atony).
• An abnormal extension of the anesthetic block defined as a sensory block level > D4.
• SA failure.
• The need to convert to general anesthesia.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group Adrenaline: Group A; All parturients received a prophylactic i.v bolus of Epinephrine 0.15µg/Kg at time of SA. In this group, rescue boluses of Epinephrine 0.15µg/Kg, will be given if maternal BP decreased more than 20% from the baseline value.	Drug: Adrenaline; i.v bolus of adrenaline 0.15µg/Kg rescue boluses of adrenaline 0.15µg/Kg; Other Names: epinehrine
Active Comparator: Group Ephedrine: Group E; All parturients received a prophylactic i.v bolus of Ephedrine 0.1mg/Kg at time of SA. In this group, rescue boluses of Ephedrine 0.1mg/Kg, will be given if maternal BP decreased more than 20% from the baseline value.E	Drug: Ephedrine; i.v bolus of Ephedrine 0.1mg/Kg rescue boluses of Ephedrine 0.1mg/Kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
delta SBP (D)	difference between baseline and the lowest systolic blood pressure.	at the end of intrathecal injection until delivery
delta MBP (D)	difference between baseline and the lowest mean blood pressure.	at the end of intrathecal injection until delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
delta SBP (S)	difference between baseline and the lowest systolic blood pressure.	at the end of intrathecal injection until the end of surgery
delta MBP (S)	difference between baseline and the lowest mean blood pressure.	at the end of intrathecal injection until the end of surgery
time to onset of first post spinal hypotension episode	first episode of hypotension after spinal anesthesia induction	At time of surgery (right after spinal anesthesia until end of surgery)
Incidence of post spinal hypotension	a decrease of SBP >20% of baseline	At time of surgery (right after spinal anesthesia until end of surgery)
Vasopressor consumption	cumulative dose of vasopressor consumption	from the end of intrathecal injection until delivery.
Vasopressor consumption	cumulative dose of vasopressor consumption	from the end of intrathecal injection until the end of surgery.
number of rescue boluses	number of rescue boluses before and after delivery	At time of surgery (right after spinal anesthesia until end of surgery)
incidence of hypertension	a rise of SBP >20% of baseline	At time of surgery (right after spinal anesthesia until end of surgery)
tachycardia	heart rate>140 beats/min	At time of surgery (right after spinal anesthesia until end of surgery)
incidence of arrythmia	incidence of arrhythmic events	At time of surgery (right after spinal anesthesia until end of surgery)
incidence of bradycardia	heart rate (HR) < 50 beats/min	At time of surgery (right after spinal anesthesia until end of surgery)
use of atropine	cumulative dose, if needed	At time of surgery (right after spinal anesthesia until end of surgery)
incidence of nausea and vomiting	Measure will be done according to a simple scale: 0= no nausea and vomiting; 1= nausea or vomiting	At time of surgery (right after spinal anesthesia until end of surgery)
foetal gas analysis: pH, Lactates, HCO3-, BE	fetal cord blood analysis will be done immediately after delivery	At time of birth
APGAR score	range from 0 to 10,incorporates five elements: respiratory effort, heart rate, reflex irritability, muscle tone, and color A score of 0 to 3 indicates a severely depressed neonate, whereas a score of 7 to 10 is considered normal.	at 1 and 5 minutes after birth

Collaborators and Investigators

• Sponsor: Ben marzouk Sofiene
• Investigators: Study Chair: HAYEN MAGHREBIG, PROFESSOR, UNIVERSITY OF TUNIS EL MANAR

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: October 10, 2018
• First Submitted That Met QC Criteria: October 10, 2018
• First Posted (Actual): October 15, 2018

Study Record Updates

• Last Update Posted (Actual): March 13, 2019
• Last Update Submitted That Met QC Criteria: March 11, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Epinephrine, Ephedrine, cesarean section, spinal anesthesia
• 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; Central Nervous System Stimulants; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Epinephrine; Racepinephrine; Epinephryl borate; Ephedrine
• Other Study ID Numbers: Adrenaline

Drug and device information, study documents

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