Prevention of Hypotension During Cesarean Section

NCT ID: NCT03842046

Last Updated: 2020-05-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

82 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-16

Study Completion Date

2019-08-31

Brief Summary

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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

Detailed Description

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* 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).

Conditions

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Hypotension Symptomatic Obstetric Anesthesia Problems Cesarean Section Complications Vasoconstriction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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phenylephrine infusion

phenylephrine infusion (30 mL/h corresponding to 50 μg/min)

Group Type ACTIVE_COMPARATOR

phenylephrine infusion

Intervention Type PROCEDURE

In parturients allocated to the phenylephrine group, a phenylephrine infusion will be initiated as soon as spinal anesthesia is established

norepinephrine infusion

norepinephrine infusion (30 mL/h corresponding to 4 μg/min)

Group Type ACTIVE_COMPARATOR

norepinephrine infusion

Intervention Type PROCEDURE

In parturients allocated to the norepinephrine group group, a phenylephrine infusion will be initiated as soon as spinal anesthesia is established

Interventions

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phenylephrine infusion

In parturients allocated to the phenylephrine group, a phenylephrine infusion will be initiated as soon as spinal anesthesia is established

Intervention Type PROCEDURE

norepinephrine infusion

In parturients allocated to the norepinephrine group group, a phenylephrine infusion will be initiated as soon as spinal anesthesia is established

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

48 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Alexandra Hospital, Athens, Greece

OTHER

Sponsor Role collaborator

Aretaieion University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Dr Kassiani Theodoraki

Associate Professor of Anesthesiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Kassiani Theodoraki, PhD

Role: PRINCIPAL_INVESTIGATOR

Aretaieion University Hospital

Emmanouil Stamatakis, PhD

Role: PRINCIPAL_INVESTIGATOR

Alexandra General Hospital of Athens

Dimitrios Valsamidis, PhD

Role: PRINCIPAL_INVESTIGATOR

Alexandra General Hospital of Athens

Sofia Chatzilia, PhD

Role: PRINCIPAL_INVESTIGATOR

Alexandra General Hospital of Athens

Locations

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Aretaieion University Hospital

Athens, , Greece

Site Status

Alexandra General Hospital of Athens

Athens, , Greece

Site Status

Countries

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Greece

References

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Afolabi BB, Lesi FE. Regional versus general anaesthesia for caesarean section. Cochrane Database Syst Rev. 2012 Oct 17;10(10):CD004350. doi: 10.1002/14651858.CD004350.pub3.

Reference Type BACKGROUND
PMID: 23076903 (View on PubMed)

Klohr S, Roth R, Hofmann T, Rossaint R, Heesen M. Definitions of hypotension after spinal anaesthesia for caesarean section: literature search and application to parturients. Acta Anaesthesiol Scand. 2010 Sep;54(8):909-21. doi: 10.1111/j.1399-6576.2010.02239.x. Epub 2010 Apr 23.

Reference Type BACKGROUND
PMID: 20455872 (View on PubMed)

Maayan-Metzger A, Schushan-Eisen I, Todris L, Etchin A, Kuint J. Maternal hypotension during elective cesarean section and short-term neonatal outcome. Am J Obstet Gynecol. 2010 Jan;202(1):56.e1-5. doi: 10.1016/j.ajog.2009.07.012. Epub 2009 Aug 28.

Reference Type BACKGROUND
PMID: 19716536 (View on PubMed)

Ngan Kee WD. Prevention of maternal hypotension after regional anaesthesia for caesarean section. Curr Opin Anaesthesiol. 2010 Jun;23(3):304-9. doi: 10.1097/ACO.0b013e328337ffc6.

Reference Type BACKGROUND
PMID: 20173633 (View on PubMed)

Laudenbach V, Mercier FJ, Roze JC, Larroque B, Ancel PY, Kaminski M, Breart G, Diemunsch P, Subtil D, Lejus C, Fresson J, Arnaud C, Rachet B, Burguet A, Cambonie G; Epipage Study Group. Anaesthesia mode for caesarean section and mortality in very preterm infants: an epidemiologic study in the EPIPAGE cohort. Int J Obstet Anesth. 2009 Apr;18(2):142-9. doi: 10.1016/j.ijoa.2008.11.005. Epub 2009 Feb 4.

Reference Type BACKGROUND
PMID: 19195873 (View on PubMed)

Ngan Kee WD, Khaw KS, Ng FF, Lee BB. Prophylactic phenylephrine infusion for preventing hypotension during spinal anesthesia for cesarean delivery. Anesth Analg. 2004 Mar;98(3):815-21, table of contents. doi: 10.1213/01.ane.0000099782.78002.30.

Reference Type BACKGROUND
PMID: 14980943 (View on PubMed)

Ngan Kee WD, Khaw KS, Ng FF. Comparison of phenylephrine infusion regimens for maintaining maternal blood pressure during spinal anaesthesia for Caesarean section. Br J Anaesth. 2004 Apr;92(4):469-74. doi: 10.1093/bja/aeh088. Epub 2004 Feb 20.

Reference Type BACKGROUND
PMID: 14977792 (View on PubMed)

Siddik-Sayyid SM, Taha SK, Kanazi GE, Aouad MT. A randomized controlled trial of variable rate phenylephrine infusion with rescue phenylephrine boluses versus rescue boluses alone on physician interventions during spinal anesthesia for elective cesarean delivery. Anesth Analg. 2014 Mar;118(3):611-8. doi: 10.1213/01.ane.0000437731.60260.ce.

Reference Type BACKGROUND
PMID: 24299932 (View on PubMed)

Lee A, Ngan Kee WD, Gin T. A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean delivery. Anesth Analg. 2002 Apr;94(4):920-6, table of contents. doi: 10.1097/00000539-200204000-00028.

Reference Type BACKGROUND
PMID: 11916798 (View on PubMed)

Ngan Kee WD, Khaw KS, Lau TK, Ng FF, Chui K, Ng KL. Randomised double-blinded comparison of phenylephrine vs ephedrine for maintaining blood pressure during spinal anaesthesia for non-elective Caesarean section*. Anaesthesia. 2008 Dec;63(12):1319-26. doi: 10.1111/j.1365-2044.2008.05635.x.

Reference Type BACKGROUND
PMID: 19032300 (View on PubMed)

Cooper DW, Carpenter M, Mowbray P, Desira WR, Ryall DM, Kokri MS. Fetal and maternal effects of phenylephrine and ephedrine during spinal anesthesia for cesarean delivery. Anesthesiology. 2002 Dec;97(6):1582-90. doi: 10.1097/00000542-200212000-00034.

Reference Type BACKGROUND
PMID: 12459688 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20841418 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25635593 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27720613 (View on PubMed)

Carvalho B, Dyer RA. Norepinephrine for Spinal Hypotension during Cesarean Delivery: Another Paradigm Shift? Anesthesiology. 2015 Apr;122(4):728-30. doi: 10.1097/ALN.0000000000000602. No abstract available.

Reference Type BACKGROUND
PMID: 25654435 (View on PubMed)

Other Identifiers

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NOR-PHEN

Identifier Type: -

Identifier Source: org_study_id

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