Ephedrine vs. Nor Epinephrine Infusion in Preventing Hypotension After Spinal Anesthesia for Cesarean Section

Ephedrine vs. Nor-epinephrine Infusion in Preventing Hypotension After Spinal Anesthesia for Cesarean Section

The purpose of the study is to determine if norepinephrine is more effective as a continuous intravenous (IV) infusion compared to continuous IV ephedrine associated with crystalloid loading for maintaining blood pressure during a spinal anesthetic for a cesarean delivery. Prevention of low blood pressure has been shown to decrease nausea and vomiting during and after cesarean delivery under spinal anesthesia. For elective cesarean delivery, all participants will receive spinal anesthesia with a local anesthetic and morphine. This study plans to enroll 120 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; Complications; Cesarean Section; Anesthesia; Adverse Effect, Spinal and Epidural
• Intervention / Treatment: Drug: Ephedrine; Drug: Norepinephrine

Detailed Description

This study will be a prospective, randomized, active treatment controlled trial.

After written and informed consent are obtained, the study participants are randomly assigned using a computer generated table to 1 of 2 treatment groups prior to cesarean delivery.

Group A will consist of: A continuous Ephedrine infusion 10 mcg/kg/min to maintain systolic blood pressure (SBP) within 80-120% of baseline before the spinal.

Group B will consist of: A continuous norepinephrine infusion 0.1 mcg/kg/min to maintain systolic blood pressure (SBP) within 80-120% of baseline before the spinal.

Patients will be admitted to holding area. Baseline arterial blood pressure and heart rate will be measured in supine position, with left uterine displacement. Baseline blood pressure will be calculated by taking the mean of three consecutive SBP measurements taken 5 minutes apart. 500 mL of Lactated Ringers solution will be administered immediately after induction of spinal anesthesia at the outflow rate of 100ml per hour.

The primary endpoint is the number of provider interventions needed to maintain the SBP within 100-120% of baseline for both groups. The secondary endpoint is nausea measured with each provider intervention after induction of spinal anesthesia, and immediately following delivery with 11 point verbal rating scale (0 = no nausea, 1 = nausea). Vomiting will be recorded whenever present during the surgical procedure.

Hypertensive episodes (SBP greater than 120% of baseline) will be treated with cessation of infusion. Infusion will be restarted when SBP has decreased to below the baseline SBP). If the infusion must be stopped on three occasions, it will be discontinued permanently and the blood pressure maintained with Ephedrine boluses only when needed.

Bradycardia (HR less than 50 BPM) will be treated with Atropine 0.4mg IV or ephedrine 3 mg - 12 mg IV bolus.

Study participants will receive a standard spinal anesthetic consisting of 0.5% hyperbaric bupivacaine (2 mL) plus preservative free morphine (0.1 mg) and sufentanil (5 mcg) at L3-4 or L4-5. Prior to surgical incision, the spinal sensory level will be tested to the bilateral T6-T4 dermatomal level. The patients will be positioned supine with a wedge placed under the right hip to avoid aortocaval compression. Both the patient and the researcher's assistant (who will collect data) will be blinded as to the administered Ephedrine infusion or norepinephrine infusion. The study will end when cesarean section is completed and the patient transferred to the post-operative care unit.

Measured variables will include systolic, diastolic and mean non-invasive blood pressure, the number and type of interventions for control of blood pressure, heart rate, incidedence of nausea and vomiting (NV), incidence of arrhythmia and fetal cord blood analysis (pH) at delivery.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Tunisia
  • Tunis, Tunisia, 1007
    • Tunis maternity and neonatology center, minisetry of public health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• The American Society of Anesthesiologists (ASA) Physical Status classification 1 and 2
• Pregnant women with singleton pregnancy
• Gestational age greater than 36 weeks
• Cesarean delivery under spinal anesthesia

Exclusion Criteria:

• Use of cardiac medication or medication for blood pressure control
• Cardiovascular disease
• Multiple gestation
• Gestation diabetes requiring insulin
• Refusal to be in study
• History of chronic opioid use (chronic pain syndrome)
• Emergent caesarean delivery for maternal and/or fetal distress
• Preeclampsia
• Eclampsia
• Progressive neurologic disease
• Infection at insertion site
• Allergy to local anesthetics, narcotics or other study medications

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: Ephedrine; A continuous Ephedrine infusion at 10 mcg/kg/min	Drug: Ephedrine; continuous infusion
Active Comparator: Norepinephrine; A continuous Norepinephrine infusion at 0.1 mcg/kg/min	Drug: Norepinephrine; continuous infusion; Other Names: Noradrenaline, Noraline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal Blood Pressure	Measurement of systolic, diastolic and mean, non-invasive blood pressure during cesarean section with an infusion of either Ephedrine or Norepinephrine	At time of surgery (right after spinal anesthesia untill end of surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodynamic Parameters - heart rate	mean heart rate during cesarean section with an infusion of either Ephedrine or Norepinephrine	At time of surgery (right after spinal anesthesia untill end of surgery)
Hemodynamic Parameters - arrhythmia	incidence of arrhythmic events during cesarean section with an infusion of either Ephedrine or Norepinephrine	AT TIME OF SURGERY(right after spinal anesthesia untill end of surgery)
Vomiting	incidence of Vomiting (V) during cesarean section with an infusion of either Ephedrine or Norepinephrine. Measure will be done according to a simple scale: 0= no vomiting; 1= vomiting	AT TIME OF SURGERY (right after spinal anesthesia untill end of surgery)
mean pH of the fetal cord blood in each group	fetal cord blood analysis will be done immediately after delivery in order to determine the pH value ( ie: logarithm of the blood concentration of hydrogen ions H+)in each group	At time of birth
Nausea	incidence of Nausea (N) during cesarean section with an infusion of either Ephedrine or Norepinephrine. Measure will be done according to a simple scale: 0= no nausea; 1= nausea	AT TIME OF SURGERY (right after spinal anesthesia untill end of surgery)

Collaborators and Investigators

• Sponsor: University Tunis El Manar
• Investigators: Study Director: Hayen maghrebi, professor, University Tunis El Manar

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: June 10, 2015
• First Submitted That Met QC Criteria: June 17, 2015
• First Posted (Estimate): June 22, 2015

Study Record Updates

• Last Update Posted (Actual): October 26, 2017
• Last Update Submitted That Met QC Criteria: October 25, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Spinal anesthesia; blood pressure; Norepinephrine; cesarean; Ephedrine
• 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; Central Nervous System Stimulants; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine; Ephedrine
• Other Study ID Numbers: UTEM NAD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided