Comparison of Two Doses of Norepinephrine in Preventing Hypotension After Spinal Anesthesia

Comparison of Two Doses of Norepinephrine in Preventing Hypotension After Spinal Anesthesia for Cesarean Section

The purpose of the study is to determine the more effective intravenous bolus of norepinephrine for maintaining blood pressure during a spinal anesthesia for a cesarean delivery with the fewer side effects. Low blood pressure has been shown to decrease uterine perfusion and foetal outcomes during cesarean delivery under spinal anesthesia. For elective or semi-urgent cesarean delivery, all participants will receive spinal anesthesia with a local anesthetic and either sufentanil or fentanyl. This study plans to enroll 124 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: Cesarean Section Complications; Hypotension; Anesthesia; Adverse Effect; Vasopressor
• Intervention / Treatment: Drug: Norepinephrine: 1mcg/kg; Drug: Norepinephrine 0,5mcg/kg

Detailed Description

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

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

Group A will receive an intravenous bolus of 1mcg/Kg of norepinephrine bitartrate to maintain systolic blood pressure (SBP) within 80-120% of baseline before the spinal anesthesia.

Group B will receive an intravenous bolus of 0.5mcg/kg of norepinephrine bitartrate to maintain systolic blood pressure (SBP) within 80-120% of baseline before the spinal anesthesia.

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 as the mean of three consecutive SBP measurements taken 3 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 endpoints are:

the timing of the first maternal hypotension before delivery (defined as a decrease of SBP >20% of baseline and/or PAS<100mmHg) the delta PAS and delta PAM before delivery ( difference between basline and the lowest systolic and mean blood pressure respectively)

The secondary endpoints are:

Incidence of hypotension,norepinephrine consumption (mean dose of Norepinephrine to maintain blood pressure between 80 and 100 % of baseline values after the primary preventive bolus), nausea and vomiting will be recorded whenever present during the surgical procedure as well as reactive hypertension (defined as a rise of SBP >20% of baseline or SBP>140mmHg) and arrhythmia. Bradycardia (HR less than 50 BPM) will be treated with Atropine 0.5mg IV. 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

Study participants will receive a standard spinal anesthetic consisting of 0.5% hyperbaric bupivacaine (2 mL) with either sufentanil (5 mcg) or fentanyl (50 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 Norepinephrine bolus A or B.

When PAS<80% of baseline or < 100 mmHg a bolus of Norepinephrine will be administrated(half dose A or B).

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, heart rate, number of rescue boluses , incidence of nausea and vomiting (NV), incidence of arrhythmia, Apgar score and fetal cord blood analysis (pH) at delivery.

• Study Type: Interventional
• Enrollment (Actual): 124
• 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:

• Elective or semi-urgent CD under spinal anesthesia
• Age over 18 years
• Healthy singleton pregnancy beyond 36 weeks' gestation
• American Society of Anesthesiologists (ASA) physical status classification 2
• Weight 50 to 100 kg, and height 150 to 180 cm

Exclusion Criteria:

• Emergency CD red code
• Allergy or hypersensitivity to norepinephrine or sulfite
• Preexisting or pregnancy-induced hypertension, preeclampsia, eclampsia, the use of cardiac medication or medication for blood pressure control
• multiple gestation
• Cardiovascular or cerebrovascular disease
• Fetal abnormalities
• Suspicion of abnormal placentation
• History of diabetes mellitus (excluding gestational diabetes)
• Use of monoamine oxidase inhibitors, triptyline or imipramine antidepressants
• documented history of postoperative nausea and vomiting, previous gastric bypass surgery, history of chronic opioid use (chronic pain syndrome)
• Patient refusal

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: A; group A: will receive 1 mcg/Kg of Norepinephrine intravenously	Drug: Norepinephrine: 1mcg/kg; intervention:Parturients will receive Norepinephrine: a bolus of 1 mcg/Kg immediately after SA (preventive bolus) then they will receive complementary doses of Norepinephrine (half dose: 0.5 mcg/Kg) to maintain systolic blood pressure above 80 % of baseline; Other Names: Noradrenaline; Noraline
Active Comparator: B; group B: will receive 0.5 mcg/Kg of Norepinephrine intravenously	Drug: Norepinephrine 0,5mcg/kg; intervention: Parturients will receive Norepinephrine: a bolus of 0.5 mcg/Kg immediately after SA (preventive bolus) then they will receive complementary doses of Norepinephrine (half dose: 0.25 mcg/Kg) to maintain systolic blood pressure above 80 % of baseline; Other Names: Noradrenaline; Noraline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to administartion of the first rescue bolus	timing of the first hypotension(defined as a decrease of SBP >20% of baseline and/or PAS<100mmHg) recsue bolus will be given at that moment	time from immediately after spinal anesthesia until delivery
systolic blood pressure variation	difference between the baseline systolic blood pressure (PAS0) and the lowest systolic blood pressure (PASmin) registred before delivery and computed as (PAS min -PAS0)/PAS0	time from immediately after spinal anesthesia until delivery
mean blood pressure variation	difference between the baseline mean blood pressure(PAM0) and the lowest mean blood pressure (PAMmin) registred before delivery and computed as (PAM min -PAM0)/PAM0	time from immediately after spinal anesthesia until delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of hypotension	incidence of hypotension after the primary preventive bolus	tile from right after spinal anesthesia until delivery
Norepinephrine consumption	Mean dose of Norepinephrine ( micrograms) given to maintain blood pressure between 80 and 100 % of baseline values after the primary preventive bolus	time fro right after spinal anesthesia until the end of surgery
Nausea	Incidence of nausea. Measure will be done according to a simple scale: 0= no nausea; 1= nausea [Time	time of surgery (right after spinal anesthesia until end of surgery)
Vomiting	incidence of Vomiting (V) during cesarean section with an infusion of a bolus Norepinephrine. Measure will be done according to a simple scale: 0= no vomiting; 1= vomiting	time of surgery (right after spinal anesthesia until end of surgery)
arrhythmia	incidence of arrhythmic events during cesarean section with an infusion of a bolus of Norepinephrine	time of surgery (right after spinal anesthesia until end of surgery)
Hypertension	a rise of systolic blood pressure (SBP)>20% of baseline or SBP>140mmHg	right after spinal anesthesia until end of surgery)]
mean pH of the fetal cord blood	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	time of birth
Apgar score	apgar at 1 and 5 minutes Apgar at 1 and 5 minutes	at time of birth

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2018
• Primary Completion (Actual): September 2, 2018
• Study Completion (Actual): October 1, 2018

Study Registration Dates

• First Submitted: October 11, 2018
• First Submitted That Met QC Criteria: October 11, 2018
• First Posted (Actual): October 16, 2018

Study Record Updates

• Last Update Posted (Actual): October 16, 2018
• Last Update Submitted That Met QC Criteria: October 11, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: blood pressure; norepinephrine; spinal anesthesia; Cesarean Section
• 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; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine
• Other Study ID Numbers: Norepinephrine

Drug and device information, study documents

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