Clinical trial NCT03849508: Phenylephrine Versus Norepinephrine for Maintenance of Hemodynamic During Cesarean Section Under Spinal Anesthesia
Official title: Randomized, Double-blind, Controlled Clinical Trial for Comparison of Continuous Phenylephrine Versus Norepinephrine Infusion for Maintenance of Hemodynamic Stability During Cesarean Section Under Spinal Anesthesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cesarean Section Complications
Spinal Anesthesia
Keywords: cesarean section complications
spinal anesthesia
norepinephrine
maternal hemodynamic and cardiac output
Lead sponsor: Centre Hospitalier Régional d'Orléans
Sponsor class: OTHER
First posted: 2019-02-21
Enrollment: 124
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

Eligibility criteria: 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

Primary outcomes:
measure: Cardiac output maintenance (measured in L/min by bioreactance).
timeFrame: 5 minutes before the induction of spinal anesthesia until umbilical cord clamping.
Secondary outcomes:
measure: Heart rate
timeFrame: From induction of spinal anesthesia until weaning of vasopressor
measure: Systolic blood pressure
timeFrame: From induction of spinal anesthesia until weaning of vasopressor
measure: Mean blood pressure
timeFrame: From induction of spinal anesthesia until weaning of vasopressor
measure: Duration of bradycardia
timeFrame: From induction of spinal anesthesia until weaning of vasopressor]
measure: Duration of hypotension with Mean blood pressure less than 65mmHg
timeFrame: after applying spinal anesthesia until weaning of vasopressor
measure: Duration of hypotension with Systolic Blood Pressure less than 80mmHg
timeFrame: after applying spinal anesthesia until weaning of vasopressor
measure: Duration of hypertension
timeFrame: after applying spinal anesthesia until weaning of vasopressor
measure: Cardiac Output
timeFrame: after applying spinal anesthesia until weaning of vasopressor
measure: Stroke Volume
timeFrame: after applying spinal anesthesia until weaning of vasopressor
measure: Total Peripheral Resistance
timeFrame: after applying spinal anesthesia until weaning of vasopressor
measure: Maximum flow rate of study drug given
timeFrame: after applying spinal anesthesia until weaning of vasopressor
measure: Total dose of study drug consumed
timeFrame: after applying spinal anesthesia until weaning of vasopressor
measure: Total Rescue Bolus Dose of atropine to maintain Systolic Blood Pressure
timeFrame: after applying spinal anesthesia until weaning of vasopressor
measure: Total Rescue Bolus Dose of ephedrine or other vasopressor to maintain Systolic Blood Pressure
timeFrame: after applying spinal anesthesia until weaning of vasopressor
measure: Incidence of nausea or vomiting
timeFrame: after applying spinal anesthesia until weaning of vasopressor
measure: Incidence of dizziness or malaise
timeFrame: after applying spinal anesthesia until weaning of vasopressor
measure: Maternal blood glucose concentration
timeFrame: at peripheral intravenous line placement
measure: Maternal blood glucose concentration
timeFrame: at umbilical cord clamping
measure: APGAR score
timeFrame: 1 minute after delivery
measure: APGAR score
timeFrame: 3 minutes after delivery
measure: APGAR score
timeFrame: 5 minutes after delivery
measure: APGAR score
timeFrame: 10 minutes after delivery
measure: Umbilical arterial potential hydrogen
timeFrame: At time of birth
measure: Fetal lactates
timeFrame: At time of birth
measure: Umbilical arterial partial pressure of carbon dioxide
timeFrame: At time of birth
measure: Umbilical arterial partial pressure of oxygen
timeFrame: At time of birth
measure: Umbilical arterial base excess
timeFrame: At time of birth
measure: Fetal blood glucose concentration at birth
timeFrame: At time of birth
measure: Neonatal blood glucose concentration
timeFrame: at 1 hour after birth
measure: Uterine and umbilical arteries Doppler with measurement of the pulsatility
timeFrame: 5 minutes before realization of spinal anesthesia
measure: Uterine and umbilical arteries Doppler with measurement of the pulsatility
timeFrame: 5 minutes after induction of spinal anesthesia
Other outcomes:
Locations:
city: Orléans
country: France
facility: Regional Hospital Center of ORLEANS
Study officials:
affiliation: CHR d'Orléans
name: Olivier BELIN, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mercier FJ, Auge M, Hoffmann C, Fischer C, Le Gouez A. Maternal hypotension during spinal anesthesia for caesarean delivery. Minerva Anestesiol. 2013 Jan;79(1):62-73. Epub 2012 Nov 18.
citation: Langesaeter E, Dyer RA. Maternal haemodynamic changes during spinal anaesthesia for caesarean section. Curr Opin Anaesthesiol. 2011 Jun;24(3):242-8. doi: 10.1097/ACO.0b013e32834588c5.
citation: Kinsella SM, Carvalho B, Dyer RA, Fernando R, McDonnell N, Mercier FJ, Palanisamy A, Sia ATH, Van de Velde M, Vercueil A; Consensus Statement Collaborators. International consensus statement on the management of hypotension with vasopressors during caesarean section under spinal anaesthesia. Anaesthesia. 2018 Jan;73(1):71-92. doi: 10.1111/anae.14080. Epub 2017 Nov 1. No abstract available.
citation: Chooi C, Cox JJ, Lumb RS, Middleton P, Chemali M, Emmett RS, Simmons SW, Cyna AM. Techniques for preventing hypotension during spinal anaesthesia for caesarean section. Cochrane Database Syst Rev. 2017 Aug 4;8(8):CD002251. doi: 10.1002/14651858.CD002251.pub3.
citation: Stewart A, Fernando R, McDonald S, Hignett R, Jones T, Columb M. The dose-dependent effects of phenylephrine for elective cesarean delivery under spinal anesthesia. Anesth Analg. 2010 Nov;111(5):1230-7. doi: 10.1213/ANE.0b013e3181f2eae1. Epub 2010 Sep 14.
citation: Ngan Kee WD. The use of vasopressors during spinal anaesthesia for caesarean section. Curr Opin Anaesthesiol. 2017 Jun;30(3):319-325. doi: 10.1097/ACO.0000000000000453.
citation: 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.
citation: Ngan Kee WD, Lee SWY, Ng FF, Khaw KS. Prophylactic Norepinephrine Infusion for Preventing Hypotension During Spinal Anesthesia for Cesarean Delivery. Anesth Analg. 2018 Jun;126(6):1989-1994. doi: 10.1213/ANE.0000000000002243.
citation: McLaughlin K, Wright SP, Kingdom JCP, Parker JD. Clinical Validation of Non-Invasive Cardiac Output Monitoring in Healthy Pregnant Women. J Obstet Gynaecol Can. 2017 Nov;39(11):1008-1014. doi: 10.1016/j.jogc.2017.02.015. Epub 2017 Jul 18.
citation: Belin O, Casteres C, Alouini S, Le Pape M, Dupont A, Boulain T. Manually Controlled, Continuous Infusion of Phenylephrine or Norepinephrine for Maintenance of Blood Pressure and Cardiac Output During Spinal Anesthesia for Cesarean Delivery: A Double-Blinded Randomized Study. Anesth Analg. 2023 Mar 1;136(3):540-550. doi: 10.1213/ANE.0000000000006244. Epub 2022 Oct 24.