Prevention of Hypotension During Cesarean Section (NOR-PHEN)

May 21, 2020 updated by: Dr Kassiani Theodoraki, Aretaieion University Hospital

Comparison of Continuous Infusion of Noradrenaline Versus Phenylephrine During Cesarean Section Under Spinal Anesthesia. A Randomized Controlled Trial

The aim of this double-blind randomized study will be to compare a fixed-rate prophylactic noradrenaline infusion to a fixed-rate prophylactic phenylephrine infusion during elective cesarean section under combined spinal-epidural anesthesia

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

  • Spinal anesthesia is the anesthetic technique of choice for elective cesarean section.
  • Spinal anesthesia can be complicated by hypotension, with incidence exceeding 80% occasionally. Hypotension can lead to nausea, emesis and a subjective feeling of discomfort due to cerebral hypoperfusion. If left untreated, severe or sustained hypotension can lead to decreased uteroplacental flow and fetal distress of premature or compromised fetuses while severe complications to the parturient might ensue, such as loss of consciousness, aspiration, apnea or cardiac arrest
  • One of the standard techniques to avoid maternal hypotension is the administration of a continuous phenylephrine infusion while studies have demonstrated its superiority as compared to rescue bolus phenylephrine administration. Additionally, as compared to ephedrine, phenylephrine is associated with less neonatal acidosis and better maintenance of uteroplacental blood flow. However, phenylephrine can lead to baroreceptor-mediated reflex bradycardia, with untoward consequences for maternal cardiac output.
  • Recently, noradrenaline has been shown to be effective in maintaining blood pressure in obstetric patients. Noradrenaline is a strong-alpha agonist with weak beta-action, too. Therefore, it might prove superior in maintaining cardiac output as compared to phenylephrine. There have been a few studies examining the use of noradrenaline as a continuous infusion in this context but the optimal dose and safety and efficacy profile of noradrenaline continuous infusion in obstetrics is yet to be determined
  • In all parturients, standard hemodynamic monitoring will be applied. Baseline systolic arterial pressure will be considered the average of three consecutive measurements that will not differ more than 10% among them. All parturients will have a peripheral intravenous catheter placed in the upper extremity after baseline hemodynamic measurements are recorded and will be infused 5 mL/kg of hydroxyethylstarch (pre-loading) before the regional procedure.
  • Study group allocation will taker place according to a computer-generated sequence of random numbers. A standard spinal anesthetic consisting of ropivacaine 0.75% 1.8 mL plus fentanyl 10 μg will be administered in the left lateraL position at the L3-4 or L4-5 vertebral interspace. The study infusion medication (either phenylephrine or norepinephrine, depending on group allocation) will be started at the same time cerebrospinal fluid is obtained, immediately before injection of spinal medications. After the intrathecal injection, patients will placed in the supine position with a left lateral tilt of the table to provide left uterine displacement and to prevent aortocaval compression. The spinal sensory level will be tested bilaterally by pinprick to ensure a T4 dermatomal level before surgical incision.
  • Hemodynamic parameters (systolic arterial blood pressure, diastolic arterial blood pressure, mean arterial blood pressure and heart rate) will be measured and recorded at discrete timepoints throughout the operation (baseline, start of vasoactive agent administration, parturient at supine position, sympathetic block at T4, knife-to-skin, neonatal delivery, start of oxytocin administration, start of skin closure, end of operation.
  • During the operation, a rescue dose of phenylephrine 50 μg will be administered when systolic arterial pressure drops below 80% of baseline in combination with heart rate>80 bpm. Ephedrine 5 mg will be administered when there is hypotension (systolic arterial pressure <80% of baseline) in combination with heart rate less than 80 bpm. Hypertensive episodes (systolic blood pressure >120% of baseline) will be treated with halving the infusion while when systolic arterial pressure increases above 130% of baseline the infusion will be discontinued and will be restarted when systolic blood pressure decreases below the upper limit of the target range (120% of baseline value).

Study Type

Interventional

Enrollment (Actual)

82

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Greece
      • Athens, Greece, 11528
        • Alexandra General Hospital of Athens
      • Athens, Greece, 115 28
        • ARETAIEION University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 48 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • adult parturients, American Society of Anesthesiologists (ASA) I-II, singleton gestation>37 weeks
  • elective cesarean section

Exclusion Criteria:

  • Body Mass Index (BMI) >40 kg/m2
  • Body weight <50 kg
  • Body weight>100 kg
  • height<150 cm
  • height>180 cm
  • multiple gestation
  • fetal abnormality
  • fetal distress
  • active labor
  • cardiac disease
  • pregnancy-induced hypertension
  • thrombocytopenia
  • coagulation abnormalities
  • use of antihypertensive medication during pregnancy
  • communication or language barriers
  • lack of informed consent
  • contraindication for regional anesthesia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: phenylephrine infusion
phenylephrine infusion (30 mL/h corresponding to 50 μg/min)
Procedure: phenylephrine infusion
In parturients allocated to the phenylephrine group, a phenylephrine infusion will be initiated as soon as spinal anesthesia is established
Active Comparator: norepinephrine infusion
norepinephrine infusion (30 mL/h corresponding to 4 μg/min)
Procedure: norepinephrine infusion
In parturients allocated to the norepinephrine group group, a phenylephrine infusion will be initiated as soon as spinal anesthesia is established

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
incidence of bradycardia
Time Frame: intraoperative
any incidence of heart rate<60/min will be recorded
intraoperative

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
neonatal blood gases
Time Frame: 1 min post delivery
fetal cord blood analysis will be performed immediately post-delivery
1 min post delivery
glucose in neonatal blood
Time Frame: 1 min post delivery
glucose will be measured in the cord blood gas sample taken immediately post-delivery
1 min post delivery
need for vasoconstrictor
Time Frame: intraoperative
parturient needed or not vasoconstrictor during the operation
intraoperative
type of vasoconstrictor administered
Time Frame: intraoperative
phenylephrine verus ephedrine
intraoperative
number of bolus doses of vasoconstrictor administered
Time Frame: intraoperative
number of provided interventions to maintain systolic blood pressure within the set limits will be recorded
intraoperative
total dose of vasoconstrictor administered
Time Frame: intraoperative
total dose in mg for ephedrine or μg for phenylephrine
intraoperative
incidence of hypotension
Time Frame: intraoperative
any occurrence of hypotension throughout the operation will be recorded (systolic arterial pressure<80% of baseline throughout the operation)
intraoperative
incidence of hypertension
Time Frame: intraoperative
any incidence of systolic blood pressure >120% of baseline will be recorded
intraoperative
incidence of nausea/vomiting
Time Frame: intraoperative
incidence of nausea and vomiting throughout the operation
intraoperative
neonatal Apgar score at 1 min
Time Frame: 1 min post delivery
neonatal Apgar score will be recorded at 1 min after delivery. The Apgar score is determined by evaluating the newborn baby on five simple criteria on a scale from zero to two, then summing up the five values thus obtained. The resulting Apgar score ranges from zero to 10. Scores 7 and above are generally normal; 4 to 6, fairly low; and 3 and below are generally regarded as critically low and cause for immediate resuscitative efforts.
1 min post delivery
neonatal Apgar score at 5 min
Time Frame: 5 min post delivery
neonatal Apgar score will be recorded at 5 min after delivery. The Apgar score is determined by evaluating the newborn baby on five simple criteria on a scale from zero to two, then summing up the five values thus obtained. The resulting Apgar score ranges from zero to 10. Scores 7 and above are generally normal; 4 to 6, fairly low; and 3 and below are generally regarded as critically low and cause for immediate resuscitative efforts.
5 min post delivery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aretaieion University Hospital

Collaborators

Alexandra Hospital, Athens, Greece

Investigators

  • Principal Investigator: Emmanouil Stamatakis, PhD, Alexandra General Hospital of Athens
  • Principal Investigator: Dimitrios Valsamidis, PhD, Alexandra General Hospital of Athens
  • Principal Investigator: Sofia Chatzilia, PhD, Alexandra General Hospital of Athens

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 16, 2019

Primary Completion (Actual)

August 31, 2019

Study Completion (Actual)

August 31, 2019

Study Registration Dates

First Submitted

February 13, 2019

First Submitted That Met QC Criteria

February 13, 2019

First Posted (Actual)

February 15, 2019

Study Record Updates

Last Update Posted (Actual)

May 26, 2020

Last Update Submitted That Met QC Criteria

May 21, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NOR-PHEN

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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