Prevention of Hypotension During Cesarean Section

Cesarean Section Complications Clinical Trial

— NOR-PHEN  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03842046
• Other study ID #: NOR-PHEN
• Status: Completed
• Phase: N/A
• Start date: February 16, 2019
• Est. completion date: August 31, 2019

Study information

• Verified date: May 2020
• Source: Aretaieion University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: August 31, 2019
• Est. primary completion date: August 31, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 48 Years

Eligibility

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

Related Conditions & MeSH terms

• Cesarean Section Complications
• Hypotension
• Hypotension Symptomatic
• Obstetric Anesthesia Problems
• Vasoconstriction

Intervention

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

Locations

Country	Name	City	State
Greece	Alexandra General Hospital of Athens	Athens
Greece	Aretaieion University Hospital	Athens

Sponsors (2)

Lead Sponsor	Collaborator
Aretaieion University Hospital	Alexandra Hospital, Athens, Greece

Country where clinical trial is conducted

Greece, 

References & Publications (15)

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

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. — View Citation

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. — View Citation

Klöhr 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. Review. — View Citation

Laudenbach V, Mercier FJ, Rozé JC, Larroque B, Ancel PY, Kaminski M, Bréart 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Epub 2004 Feb 20. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View 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. — View 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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	incidence of bradycardia	any incidence of heart rate<60/min will be recorded	intraoperative
Secondary	need for vasoconstrictor	parturient needed or not vasoconstrictor during the operation	intraoperative
Secondary	type of vasoconstrictor administered	phenylephrine verus ephedrine	intraoperative
Secondary	number of bolus doses of vasoconstrictor administered	number of provided interventions to maintain systolic blood pressure within the set limits will be recorded	intraoperative
Secondary	total dose of vasoconstrictor administered	total dose in mg for ephedrine or µg for phenylephrine	intraoperative
Secondary	incidence of hypotension	any occurrence of hypotension throughout the operation will be recorded (systolic arterial pressure<80% of baseline throughout the operation)	intraoperative
Secondary	incidence of hypertension	any incidence of systolic blood pressure >120% of baseline will be recorded	intraoperative
Secondary	incidence of nausea/vomiting	incidence of nausea and vomiting throughout the operation	intraoperative
Secondary	neonatal Apgar score at 1 min	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
Secondary	neonatal Apgar score at 5 min	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
Secondary	neonatal blood gases	fetal cord blood analysis will be performed immediately post-delivery	1 min post delivery
Secondary	glucose in neonatal blood	glucose will be measured in the cord blood gas sample taken immediately post-delivery	1 min post delivery