Norepinephrine Versus Phenylephrine Continuous Variable Infusion in Cesarean Delivery

Norepinephrine Versus Phenylephrine Continuous Variable Infusion for Prevention of Post-spinal Hypotension During Cesarean Delivery: A Randomized Controlled Double-blinded Trial

Comparison will be conducted between continuous variable infusions of Phenylephrine with starting dose of 0.75 mcg/Kg/min and Norepinephrine Bitartrate with starting dose of 0.1 mcg/Kg/min (with norepinephrine base of 0.05 mcg/Kg/min) for prophylaxis against Post-spinal hypotension during cesarean delivery

Study Overview

• Status: Completed
• Conditions: Cesarean Section Complications; Spinal Anesthesia
• Intervention / Treatment: Drug: Phenylephrine; Drug: Bupivacaine; Drug: Norepinephrine

Detailed Description

Maternal hypotension is a common complication after spinal anesthesia for cesarean delivery (CD). Many vasopressors have been used for prevention of post-spinal hypotension (PSH) during CD; however, the optimum protocol for prophylaxis is not established yet. Phenylephrine (PE) is a popular vasopressor used in obstetric anesthesia; however, its use is limited by its marked cardiac depressant nature. Norepinephrine (NE) is a potent vasopressor characterized by both α adrenergic agonistic activity in addition to a weak β adrenergic agonistic activity; thus, NE is considered a vasopressor with minimal cardiac depressant effect; these pharmacological properties would make NE an attractive alternative to PE. In this study, the investigators will compare continuous variable infusion of both drugs (PE and NE) with doses of 0.75 mcg/Kg/min and 0.05 mcg/Kg/min respectively for prophylaxis against PSH during CD. We used Norepinephrine Bitartrate 8 mg ampules which contains norepinephrine base of 4 mg.

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Cairo University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Full term
• Pregnant women
• Scheduled for cesarean section

Exclusion Criteria:

• Pre-eclampsia
• Eclampsia
• Bleeding
• Cardiac dysfunction

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: Phenylephrine; Will receive spinal anesthesia using Bupivacaine. Then, phenylephrine infusion by a starting rate of 0.75 mcg/Kg/min. The rate will be then adjusted according to the patient blood pressure. The infusion will stop in case of reactive hypertension. The infusion will start again when blood pressure returns to normal reading. Infusion will be increased by 20% if hypotension occurred.	Drug: Phenylephrine; Phenylephrine variable infusion with a starting rate of 0.75 mcg/Kg/min.; Drug: Bupivacaine; Bupivacaine will be injected in the subarachnoid space with a dose of 10 mg.; Other Names: Marcaine
Experimental: Norepinephrine; Will receive spinal anesthesia using Bupivacaine. Then, norepinephrine bitartrate infusion by a starting rate of 0.1 mcg/Kg/min (equivalent to norepinephrine base of 0.05 mcg/Kg/min). The rate will be then adjusted according to the patient blood pressure. The infusion will stop in case of reactive hypertension. The infusion will start again when blood pressure returns to normal reading. Infusion will be increased by 20% if hypotension occurred.	Drug: Bupivacaine; Bupivacaine will be injected in the subarachnoid space with a dose of 10 mg.; Other Names: Marcaine; Drug: Norepinephrine; Norepinephrine bitartrate variable infusion with a starting rate of 0.1 mcg/Kg/min (equivalent to norepinephrine base of 0.05 mcg/Kg/min).; Other Names: Levophed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of post-spinal anesthesia hypotension.	Defined as the percentage of patients with decreased systolic blood pressure less than 80% of the baseline reading	30 minutes after spinal anesthesia

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of severe post-spinal anesthesia hypotension	Defined as the percentage of patients with decreased systolic blood pressure less than 60% of the baseline reading	30 minutes after spinal anesthesia
Incidence of severe delivery hypotension	Defined as the percentage of patients with decreased systolic blood pressure less than 80% of the baseline reading	10 minutes after delivery
Systolic blood pressure	Systolic blood pressure measured in mmHg	2 hours after subarachnoid block
Heart rate	number of heart beats per minute	2 hours after subarachnoid block
APGAR score for assessment of the general state of the fetus	APGAR score of the fetus ranging from 0 to 10. the higher the value, the better he score	10 minutes after delivery
Incidence of reactive hypertension	Defined as the percentage of patients with increased systolic blood pressure more than 80% of the baseline reading	2 hours after spinal anesthesia
Umbilical arterial potential hydrogen (PH)	PH in the blood sample obtained from umbilical artery scaled from 1 to 14	10 minutes after delivery
Umbilical arterial Partial pressure of Carbon dioxide	in the blood sample obtained from umbilical artery measured in mmHg	10 minutes after delivery
incidence of nausea	The percentage of patients with nausea	2 hours
Incidence of vomiting	The percentage of patients with nausea	2 hours
Total phenylephrine consumption	the total dose of phenylephrine consumed during the operation	2 hours
Total norepinephrine consumption	the total dose of norepinephrine consumed during the operation	2 hours
Total ephedrine consumption	the total dose of ephedrine consumed during the operation	2 hours

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Study Director: Ahmed M Mukhtar, Professor, Head of research committee section in anesthesia department

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2017
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): May 5, 2018

Study Registration Dates

• First Submitted: October 30, 2017
• First Submitted That Met QC Criteria: October 30, 2017
• First Posted (Actual): November 1, 2017

Study Record Updates

• Last Update Posted (Actual): July 17, 2018
• Last Update Submitted That Met QC Criteria: July 14, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Anesthetics, Local; Respiratory System Agents; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Bupivacaine; Norepinephrine; Phenylephrine; Oxymetazoline
• Other Study ID Numbers: N-82-2017

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