Norepinephrine or Phenylephrine in Bolus for Hypotension in Cesarean Delivery

Randomized Double-blinded Comparison of Norepinephrine and Phenylephrine in Bolus for Maintenance of Blood Pressure During Spinal Anesthesia for Cesarean Delivery

This study evaluate the ability of phenylephrine and of noradrenaline to maintain normal systemic arterial blood pressure and heart rate in healthy pregnant women submitted to cesarean section with spinal anesthesia. Half of participants will receive bolus of phenylephrine while the other half will receive bolus of noradrenaline.

Study Overview

• Status: Completed
• Conditions: Hypotension; Spinal Anesthesia
• Intervention / Treatment: Drug: Phenylephrine 100 mcg; Drug: Norepinephrine 5 mcg

Detailed Description

This is a prospective, randomized, double-blind, comparative two-group clinical study to observe two vasopressor drugs, phenylephrine and noradrenaline, in the ability to maintain systemic arterial pressure in pregnant women after spinal anesthesia for cesarean section; based on the hypothesis that, since noradrenaline has a predominant alpha-adrenergic action and a weak 1- beta-adrenergic beta action, it could be as capable of maintaining blood pressure effectively as phenylephrine, but with a lower frequency of bradycardia; patients who meet the inclusion criteria will be randomly assigned to one of the groups to be studied: group F - phenylephrine at a dose of 100mcg bolus and N - noradrenaline at the dose of 5mcg. One of these drugs will be used whenever systolic blood pressure drops below 10% of the baseline, additional doses will be allowed whenever necessary, aiming at maintaining the systolic blood pressure at baseline values; the blood pressure will be measured non-invasively and the heart rate by pulse oximeter and electrocardiogram.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • RJ
    • Rio De Janeiro, RJ, Brazil, 22451-030
      • Hospital Federal dos Servidores do Estado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Pregnant women, with single gestation, with cesarean programming to be performed under spinal anesthesia;
• Age above 18 years;
• Physical State American Society of Anesthesiologists (ASA) II and III;
• Weight between 50kg and 120kg;
• Height between 140cm and 180cm.

Exclusion Criteria:

• Refusal to participate in the study;
• Pregnant women with fetus with known abnormalities;
• Pregnant women with cardiovascular disease;
• Pregnant women with pregnancy-specific hypertensive disease;
• Allergy to any medication to be used in the study;
• Users of monoamine oxidase inhibitors;
• Users of tricyclic antidepressants;
• Emergency caesarean section due to acute fetal distress;
• Situations in which the sensory level after single intrathecal injection of the local anesthetic does not reach at least T6 within 5 minutes after spinal anesthesia.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Phenylephrine 100 mcg; Phenylephrine will be used at a dose of 100 mcg bolus at a dilution containing 20 mcg / mL of the drug to be used whenever systolic blood pressure falls below 10% of baseline.	Drug: Phenylephrine 100 mcg; Phenylephrine at a dose of 100 mcg bolus at a dilution containing 20 mcg / mL of the drug, 5 mL each bolus; Other Names: Fenilefrin
Experimental: Norepinephrine 5 mcg; Norepinephrine will be used at a dose of 5 mcg at a dilution containing 1 mcg / mL to be used whenever systolic blood pressure falls below 10% of baseline.	Drug: Norepinephrine 5 mcg; Norepinephrine at a dose of 5 mcg at dilution containing 1 mcg / mL, 5 mL each bolus; Other Names: Hemitartarato de norepinefrina

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of bolus required	Number of bolus doses of phenylephrine and noradrenaline to maintain systemic arterial pressure at 90% of baseline in pregnant women undergoing spinal anesthesia for cesarean	during the procedure
Heart rate	Number of episodes of heart rate under 60 bpm while using phenylephrine and noradrenaline in pregnant women undergoing spinal anesthesia for cesarean	during the procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neonatal gasometric outcome	To evaluate the neonatal outcome through the analysis of venous and arterial blood gases collected in the cord umbilical after birth.	during the procedure
Neonatal Apgar outcome	To evaluate the neonatal outcome through the classification given by the neonatologist responsible for the care to the newborn in the delivery room with the use of the Apgar Scale (0-10), 10 the better classification.	during the procedure
Nausea and vomiting	To evaluate the incidence of nausea and vomiting of the parturient during cesarean section	during the procedure

Collaborators and Investigators

• Sponsor: Hospital dos Servidores do Estado do Rio de Janeiro
• Investigators: Principal Investigator: DANIEL V DE QUEIROZ, Hospital Federal dos Servidores do Estado

Publications and helpful links

General Publications

• Vallejo MC, Attaallah AF, Elzamzamy OM, Cifarelli DT, Phelps AL, Hobbs GR, Shapiro RE, Ranganathan P. An open-label randomized controlled clinical trial for comparison of continuous phenylephrine versus norepinephrine infusion in prevention of spinal hypotension during cesarean delivery. Int J Obstet Anesth. 2017 Feb;29:18-25. doi: 10.1016/j.ijoa.2016.08.005. Epub 2016 Aug 28.
• Ngan Kee WD, Lee SW, Ng FF, Tan PE, Khaw KS. Randomized double-blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery. Anesthesiology. 2015 Apr;122(4):736-45. doi: 10.1097/ALN.0000000000000601.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Actual): June 1, 2020
• Study Completion (Actual): October 1, 2020

Study Registration Dates

• First Submitted: October 6, 2018
• First Submitted That Met QC Criteria: October 8, 2018
• First Posted (Actual): October 11, 2018

Study Record Updates

• Last Update Posted (Actual): April 13, 2021
• Last Update Submitted That Met QC Criteria: April 8, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: norepinephrine; phenylephrine; cesarean delivery under 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; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Respiratory System Agents; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Norepinephrine; Phenylephrine; Oxymetazoline
• Other Study ID Numbers: 000.603

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