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Phenylephrine Versus Norepinephrine for Maintenance of Hemodynamic During Cesarean Section Under Spinal Anesthesia

Phase 4
Completed
Conditions
Spinal Anesthesia
Cesarean Section Complications
Interventions
Registration Number
NCT03849508
Lead Sponsor
Centre Hospitalier Régional d'Orléans
Brief Summary

Comparison between prophylactic continuous variable infusion of phenylephrine (starting dose 0,5mcg/kg/min) and norepinephrine tartrate (starting dose 0,1mcg/kg/min) to prevent hypotension and maintain cardiac output under spinal anesthesia during cesarean delivery.

Detailed Description

Maternal hypotension is a frequent complication after spinal anesthesia for cesarean delivery. Many vasopressors have been studied and used, but the perfect vasopressor is yet to be found. Phenylephrine is the most common used in obstetric anesthesia but its cardiac depressant activity, being an only alpha-adrenergic agonistic, is linked to frequent side effects such as bradycardia and decreased cardiac output.

Norepinephrine is a vasopressor characterized by both alpha and minor beta-adrenergic agonistic activity, it has then a minimal cardiac depressant activity. Hence it would provide a better stability of hemodynamic and cardiac output, and appears as a better alternative to phenylephrine.

In this study, the investigators will compare prophylactic continuous variable infusion of both vasopressors. Phenylephrine started at the dose of 0,5mcg/kg/min and Norepinephrine tartrate started at the dose of 0,1mcg/kg/min. The doses will be adjusted according to maternal systolic blood pressure in order to prevent hypotension (defined by a systolic blood pressure under 80% of baseline).

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
124
Inclusion Criteria
  • Pregnancy higher than 36 weeks of amenorrhea
  • Scheduled or semi-urgent (interval between decision and delivery by cesarean section higher than 12hours) cesarean section under spinal anesthesia
Exclusion Criteria
  • Extreme height (less than 140cm; higher than 180cm)
  • Weight less than 50kg
  • Weight higher than 120kg
  • Cardiovascular disease with use of cardiac medication (including antihypertensive drug)
  • Active neurological disease
  • Anti-hypertension treatment.
  • High blood pressure or severe pre-eclampsia
  • American Society of Anesthesiologists physical status class higher than 3
  • Placenta accrete/percreta
  • Cesarean section scheduled under general anesthesia
  • Contraindications to spinal anesthesia
  • Minor (age less than 18 years old)
  • Guardianship/ curatorship
  • Anemia less than or equal to 8 g/dl
  • Allergy to any study medication
  • Simultaneous participation in another study

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
NorepinephrineNorepinephrineSpinal anesthesia with bupivacaine, sufentanil and morphine will be performed and prophylactic infusion of norepinephrine tartrate started at an initial rate of 0,1mcg/kg/min. The rate will be adjusted according to maternal systolic blood pressure.
phenylephrinePhenylephrineSpinal anesthesia with bupivacaine, sufentanil and morphine will be performed and prophylactic infusion of phenylephrine started at an initial rate of 0,5mcg/kg/ min. The rate will be adjusted according to maternal systolic blood pressure.
Primary Outcome Measures
NameTimeMethod
Cardiac output maintenance (measured in L/min by bioreactance).5 minutes before the induction of spinal anesthesia until umbilical cord clamping.

Cardiac output values were analyses at eight points

* Baseline measurement: patient placed in the supine position with the table tilted 10° left, before spinal anesthesia

* Seven measurements at regular intervals: first measurement just after administration of spinal anesthesia in supine position with the table tilted 10° left and last measurement at umbilical cord clamping.

Secondary Outcome Measures
NameTimeMethod
Systolic blood pressureFrom induction of spinal anesthesia until weaning of vasopressor

Systolic blood pressure measured in mmHg

Mean blood pressureFrom induction of spinal anesthesia until weaning of vasopressor

Mean blood pressure measured in mmHg

Cardiac Outputafter applying spinal anesthesia until weaning of vasopressor

Measured in L/min

Fetal lactatesAt time of birth

from umbilical artery blood sample, measured in mmol/l

Heart rateFrom induction of spinal anesthesia until weaning of vasopressor

number of heart beats per minute

Duration of bradycardiaFrom induction of spinal anesthesia until weaning of vasopressor]

Cumulative time in minutes with heart rate less than 60 beats/min

Duration of hypotension with Mean blood pressure less than 65mmHgafter applying spinal anesthesia until weaning of vasopressor

Cumulative time in minutes

Total dose of study drug consumedafter applying spinal anesthesia until weaning of vasopressor

Total dose of study drug given from induction of spinal anesthesia to delivery of the fetus

Incidence of nausea or vomitingafter applying spinal anesthesia until weaning of vasopressor

The percentage of patients with nausea or vomiting (at least one episode)

APGAR score10 minutes after delivery

APGAR score of the fetus ranging from 0 to 10

Umbilical arterial partial pressure of oxygenAt time of birth

in the blood sample obtained from umbilical artery measured in mmHg

Duration of hypotension with Systolic Blood Pressure less than 80mmHgafter applying spinal anesthesia until weaning of vasopressor

Cumulative time in minutes

Duration of hypertensionafter applying spinal anesthesia until weaning of vasopressor

Cumulative time in minutes with Systolic Blood Pressure more than 140mmHg

Stroke Volumeafter applying spinal anesthesia until weaning of vasopressor

Measured in ml/beat

Total Peripheral Resistanceafter applying spinal anesthesia until weaning of vasopressor

Measured in dynes.sec.cm-5

Total Rescue Bolus Dose of atropine to maintain Systolic Blood Pressureafter applying spinal anesthesia until weaning of vasopressor

Total dose of atropine administered (mg)

Umbilical arterial base excessAt time of birth

in the blood sample obtained from umbilical artery measured in mmol/L

Maximum flow rate of study drug givenafter applying spinal anesthesia until weaning of vasopressor

Measured in mcg/hour

Total Rescue Bolus Dose of ephedrine or other vasopressor to maintain Systolic Blood Pressureafter applying spinal anesthesia until weaning of vasopressor

Total dose of ephedrine or other vasopressor administered (mg)

Maternal blood glucose concentrationat umbilical cord clamping

concentration measured in mmol/l

Umbilical arterial partial pressure of carbon dioxideAt time of birth

in the blood sample obtained from umbilical artery measured in mmHg

Fetal blood glucose concentration at birthAt time of birth

from umbilical artery blood sample, measured in mmol/l

Neonatal blood glucose concentrationat 1 hour after birth

Capillary blood glucose is measured in mmol/l

Uterine and umbilical arteries Doppler with measurement of the pulsatility5 minutes after induction of spinal anesthesia

pulsatility index of Gosling (peak systolic velocity - end diastolic velocity /mean velocity)

Incidence of dizziness or malaiseafter applying spinal anesthesia until weaning of vasopressor

The percentage of patients with dizziness or malaise (at least one episode)

Umbilical arterial potential hydrogenAt time of birth

potential hydrogen in the blood sample obtained from umbilical artery scaled from 1 to 14

Trial Locations

Locations (1)

Regional Hospital Center of ORLEANS

🇫🇷

Orléans, France

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