Cardiac Index Changes With Ephedrine, Phenylephrine, Ondansetron and Norepinephrine During Spinal Anesthesia (EPhON)

Cardiac Index Changes With Ephedrine, Phenylephrine, Ondansetron and Norepinephrine During Spinal Anesthesia for Cesarian Section

The purpose of the study is to evaluate the cardiac output changes after an intravenous bolus of ephedrine, phenylephrine, ondansetron or norepinephrine during a spinal anesthetic for a cesarean delivery.

For elective cesarean delivery, all participants will receive spinal anesthesia with a local anesthetic and sufentanil. This study includes 120 pregnant women. Patients will be randomly assigned according to a computer generated system to be in one of four groups.

Study Overview

• Status: Completed
• Conditions: Cardiac Output, Low
• Intervention / Treatment: Drug: cardiac output changes with "ephedrine"; Drug: cardiac output changes with "phenylephrine"; Drug: cardiac output changes with "ondansetron"; Drug: cardiac output changes with "nor-epinephrine"

Detailed Description

This study will be a prospective, randomized, double-blind controlled trial. After written and informed consent are obtained, the study participants are randomly assigned using a computer generated table to 1 of 4 treatment groups prior to cesarean delivery.

Group A: 9 mg of ephedrine Group B: 100 mcg of phenylephrine Group C: 8 mg of ondansetron Group D: 0,25 mcg/kg of norepinephrine Baseline arterial blood pressure and heart rate will be measured in the left lateral tilt position, before anesthesia and then every minute.The cardiac output is calculated on the apical cut 5 cavities, before anesthesia and then every 5 miutes. No fluid preloading will be administered till delivery.

The primary endpoint is cardiac output changes in each groups. The secondary endpoint is the number of provider interventions needed to maintain the SBP within 80-120% of baseline for each groups.

Bradycardia (HR less than 50 BPM) will be treated with 1 mg of Atropine. Hypotension ( decrease of more than 20% of the baseline value or a PAS <90 mm Hg) will be treated with 6 mg of ephedrine, without any fluid loading.

The spinal anesthesia will be carried out in a seated position, level L3-L4 or L4-L5 with a slow injection over 30 seconds of a mixture of 10 mg of 0.5% Bupivacaine with 5 mcg of Sufentanil. The hot / cold test to determine the block level is required. A spinal anesthesia is validated if the cold test reaches the T4 level. The 10 ml syringe will be administered immediately after spinal anesthesia. The patient will be placed in the left lateral tilt position of 15¤, then put back into strict DD immediately after the delivery. Cardiovascular parameters (PAS, PAM, PAD, HR) will be recorded every minute until delivery. Echocardiographic measurement of cardiac output will be recorded every five minutes until delivery.

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, cardiac output, incidence 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: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• ASA I / II
• Caesarean section, non-twinned

Exclusion Criteria:

• heart disease
• HTA
• non-gestational diabetes
• pre-eclampsia
• sepsis
• BMI greater than 40
• contraindication to spinal anesthesia: patient refusal, medicinal allergy, long QT syndrome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: ephedrine; will receive ephedrine :a bolus of 9 mg after SA once intervention: will receive complementary doses of ephedrine 6 mgto maintain systolic blood pressure above 80 % of baseline	Drug: cardiac output changes with "ephedrine"; measure cardiac output after giving a bolus of ephedrine intervention: will receive complementary doses of ephedrine to maintain systolic blood pressure above 80 % of baseline; Other Names: cardiac output: CO (cm3 / min) = ITV * S * HR . ITV (cm) = integral time velocity is measured by pulsed doppler at the level of the ascending aorta, on apical cut.
ACTIVE_COMPARATOR: phenylephrine; will receive Phenylephrine : a bolus of 100 mcg once intervention: will receive complementary doses of ephedrine 6 mg to maintain systolic blood pressure above 80 % of baseline	Drug: cardiac output changes with "phenylephrine"; measure cardiac output after giving a bolus of phenylephrine intervention: will receive complementary doses of ephedrine to maintain systolic blood pressure above 80 % of baseline; Other Names: cardiac output: CO (cm3 / min) = ITV * S * HR. ITV (cm) = integral time velocity is measured by pulsed doppler at the level of the ascending aorta, on apical cut.
ACTIVE_COMPARATOR: ondansetron; will receive ondansetron: a bolus of 8 mg once intervention: will receive complementary doses of ephedrine 6 mg to maintain systolic blood pressure above 80 % of baseline	Drug: cardiac output changes with "ondansetron"; measure cardiac output after giving a bolus of ondansetron intervention: will receive complementary doses of ephedrine to maintain systolic blood pressure above 80 % of baseline; Other Names: cardiac output: CO (cm3 / min) = ITV * S * HR. ITV (cm) = integral time velocity is measured by pulsed doppler at the level of the ascending aorta, on apical cut.
ACTIVE_COMPARATOR: norepinephrine; will receive noradrenaline (norepinephrine) a bolus of 0,25 mcg/kg once intervention: will receive complementary doses of ephedrine 6 mg to maintain systolic blood pressure above 80 % of baseline	Drug: cardiac output changes with "nor-epinephrine"; measure cardiac output after giving a bolus of nor-epinephrine intervention: will receive complementary doses of ephedrine to maintain systolic blood pressure above 80 % of baseline; Other Names: cardiac output: CO (cm3 / min) = ITV * S * HR. ITV (cm) = integral time velocity is measured by pulsed doppler at the level of the ascending aorta, on apical cut.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cardiac output changes for 120 patients	In left lateral tilt position, cardiac output is calculated on the echocardiographic apical cut 5 cavities, every 5 minutes till delivery, with an infusion of either Ephedrine, Phenylephrine, Ondansetron or Norepinephrine. The cardiac output is calculated on the apical cut 5 cavities: Dc (cm3 / min) = ITV * S * HR Dc = cardiac output ITV (cm) = integral time velocity is measured by pulsed doppler at the level of the ascending aorta, on apical cut. Only the closing click (B2) is visible. If B2 is not visible, the sample is placed too much in the hunting chamber, which underestimates the ITV. If B1 and B2 are visible, the sample is too close to the aortic ring, which overestimates the ITV measurement. S = surface area of the aortic ring = (aorta diameter) ₂ * π / 4 The diameter of the aorta is the average of three measurements at the beginning of systole, on the major axis.	at time of delivery (right after spinal anesthesia until delivery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal Blood Pressure	Measurement of systolic, diastolic and mean, non-invasive blood pressure during cesarean delivery with an infusion of either Ephedrine, Phenylephrine, Ondansetron or Norepinephrine	at time of delivery (right after spinal anesthesia until delivery)
heart rate	mean heart rate during cesarean delivery with an infusion of either Ephedrine, Phenylephrine, Ondansetron or Norepinephrine	at time of delivery (right after spinal anesthesia until delivery)
Vomiting	incidence of Vomiting during cesarean section with an infusion of either Ephedrine, Phenylephrine, Ondansetron or Norepinephrine	at time of delivery (right after spinal anesthesia until delivery)
mean pH of the fetal cord blood	fetal cord blood analysis will be done immediately after delivery in order to determine the pH value in each group	at time of delivery (right after spinal anesthesia until delivery)
Nausea	incidence of nausea during cesarean section with an infusion of either Ephedrine, Phenylephrine, Ondansetron or Norepinephrine	at time of delivery (right after spinal anesthesia until delivery)

Collaborators and Investigators

• Sponsor: University Tunis El Manar

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 23, 2017
• Primary Completion (ACTUAL): February 23, 2018
• Study Completion (ACTUAL): March 30, 2018

Study Registration Dates

• First Submitted: August 4, 2017
• First Submitted That Met QC Criteria: February 1, 2018
• First Posted (ACTUAL): February 5, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 29, 2018
• Last Update Submitted That Met QC Criteria: August 27, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Spinal anesthesia; cardiac output; vasopressor
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Cardiac Output, Low; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Dermatologic Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin Antagonists; Anti-Anxiety Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antipruritics; Central Nervous System Stimulants; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Norepinephrine; Epinephrine; Ephedrine; Ondansetron; Phenylephrine; Oxymetazoline
• Other Study ID Numbers: bich-fel

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No