NOR-PHEN: Prevention of Hypotension During Cesarean Section

Sponsor

Aretaieion University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT03842046

Collaborator

Alexandra Hospital, Athens, Greece (Other)

Enrollment

Locations

Arms

6.4

Actual Duration (Months)

Patients Per Site

6.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Hypotension Symptomatic Obstetric Anesthesia Problems Cesarean Section Complications Vasoconstriction	Procedure: phenylephrine infusion Procedure: norepinephrine infusion	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

82 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Feb 16, 2019

Actual Primary Completion Date :

Aug 31, 2019

Actual Study Completion Date :

Aug 31, 2019

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

incidence of bradycardia [intraoperative]
any incidence of heart rate<60/min will be recorded

Secondary Outcome Measures

need for vasoconstrictor [intraoperative]
parturient needed or not vasoconstrictor during the operation
type of vasoconstrictor administered [intraoperative]
phenylephrine verus ephedrine
number of bolus doses of vasoconstrictor administered [intraoperative]
number of provided interventions to maintain systolic blood pressure within the set limits will be recorded
total dose of vasoconstrictor administered [intraoperative]
total dose in mg for ephedrine or μg for phenylephrine
incidence of hypotension [intraoperative]
any occurrence of hypotension throughout the operation will be recorded (systolic arterial pressure<80% of baseline throughout the operation)
incidence of hypertension [intraoperative]
any incidence of systolic blood pressure >120% of baseline will be recorded
incidence of nausea/vomiting [intraoperative]
incidence of nausea and vomiting throughout the operation
neonatal Apgar score at 1 min [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.
neonatal Apgar score at 5 min [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.
neonatal blood gases [1 min post delivery]
fetal cord blood analysis will be performed immediately post-delivery
glucose in neonatal blood [1 min post delivery]
glucose will be measured in the cord blood gas sample taken immediately post-delivery

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 48 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aretaieion University Hospital	Athens		Greece	115 28
2	Alexandra General Hospital of Athens	Athens		Greece	11528

Sponsors and Collaborators

Aretaieion University Hospital
Alexandra Hospital, Athens, Greece

Investigators

Principal Investigator: Kassiani Theodoraki, PhD, Aretaieion University Hospital
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