Phenylephrine in Spinal Anesthesia in Preeclamptic Patients

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ClinicalTrials.gov Identifier: NCT00458003

Recruitment Status : Completed

First Posted : April 9, 2007

Last Update Posted : February 2, 2017

Sponsor:

Information provided by (Responsible Party):

Cynthia Wong, Northwestern University

Study Description

Brief Summary:

Hypotension remains a common clinical problem after induction of spinal anesthesia for cesarean delivery. Maternal hypotension has been associated with considerable morbidity (maternal nausea and vomiting and fetal/neonatal acidemia). Traditionally, ephedrine has been the vasopressor of choice because of concerns about phenylephrine's potential adverse effect on uterine blood flow. This practice was based on animal studies which showed that ephedrine maintained cardiac output and uterine blood flow, while direct acting vasoconstrictors, e.g., phenylephrine, decreased uteroplacental perfusion. However, several recent studies have demonstrated that phenylephrine has similar efficacy to ephedrine for preventing and treating hypotension and may be associated with a lower incidence of fetal acidosis. All of these studies have been performed in healthy patients undergoing elective cesarean delivery.

Preeclampsia complicates 5-6% of all pregnancies and is a significant contributor to maternal and fetal morbidity and mortality. Many preeclamptic patients require cesarean delivery of the infant. These patients often have uteroplacental insufficiency. Given the potential for significant hypotension after spinal anesthesia and its effect on an already compromised fetus, prevention of (relative) hypotension in preeclamptic patients is important. Spinal anesthesia in preeclamptic patients has been shown to have no adverse neonatal outcomes as compared to epidural anesthesia when hypotension is treated adequately. Due to problems related to management of the difficult airway and coagulopathy, both of which are more common in preeclamptic women, spinal anesthesia may be the preferred regional anesthesia technique. Recent studies have demonstrated that preeclamptic patients may experience less hypotension after spinal anesthesia than their healthy counterparts. To our knowledge, phenylephrine for the treatment of spinal anesthesia-induced hypotension has not been studied in women with preeclampsia. The aim of our study is to compare intravenous infusion regimens of phenylephrine versus ephedrine for the treatment of spinal anesthesia induced hypotension in preeclamptic patients undergoing cesarean delivery. The primary outcome variable is umbilical artery pH.

Condition or disease	Intervention/treatment	Phase
Preeclampsia Hypotension	Drug: Ephedrine Drug: Phenylephrine	Not Applicable

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Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	110 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	Phenylephrine Versus Ephedrine to Treat Spinal Anesthesia-Induced Hypotension in Preeclamptic Patients During Cesarean Delivery
Study Start Date :	July 2006
Actual Primary Completion Date :	December 2016
Actual Study Completion Date :	December 2016

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Preeclampsia

MedlinePlus related topics: Low Blood Pressure

Drug Information available for: Ephedrine Hydrochloride Phenylephrine Phenylephrine hydrochloride Pseudoephedrine Ephedrine sulfate Ephedrine Pseudoephedrine hydrochloride Oxymetazoline Oxymetazoline hydrochloride Pseudoephedrine sulfate

Genetic and Rare Diseases Information Center resources: Eclampsia

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Phenylephrine Subject will receive a phenylephrine infusion to prevent and to treat hypotension associated with spinal anesthesia	Drug: Phenylephrine Phenylephrine concentration: 100 mcg/mL. The infusion will be initiated immediately after completion of the spinal injection at a rate of 1 mL/min and continued for a minimum of 2 min after which the infusion will be stopped, continued or increased based on the SBP each minute. After each SBP measurement the infusion will be stopped if SBP > 80% baseline, and the infusion will be continued or restarted if the SBP is approximately equal to 80% baseline. The infusion will be increased by 1 mL/min if the SBP < 80% baseline. Each time there is hypotension the patient will receive a 1 mL IV bolus of the study solution and the infusion will be increased by 1 mL/min until delivery.
Active Comparator: Ephedrine Subject will receive an ephedrine infusion to prevent and to treat hypotension associated with spinal anesthesia	Drug: Ephedrine Ephedrine concentration: 8 mg/mL. The infusion will be initiated immediately after completion of the spinal injection at a rate of 1 mL/min and continued for a minimum of 2 min after which the infusion will be stopped, continued or increased based on the SBP each minute. After each SBP measurement the infusion will be stopped if SBP > 80% baseline, and the infusion will be continued or restarted if the SBP is approximately equal to 80% baseline. The infusion will be increased by 1 mL/min if the SBP < 80% baseline. Each time there is hypotension the patient will receive a 1 mL IV bolus of the study solution and the infusion will be increased by 1 mL/min until delivery.

Arm

Intervention/treatment

Experimental: Phenylephrine

Subject will receive a phenylephrine infusion to prevent and to treat hypotension associated with spinal anesthesia

Drug: Phenylephrine

Phenylephrine concentration: 100 mcg/mL. The infusion will be initiated immediately after completion of the spinal injection at a rate of 1 mL/min and continued for a minimum of 2 min after which the infusion will be stopped, continued or increased based on the SBP each minute. After each SBP measurement the infusion will be stopped if SBP > 80% baseline, and the infusion will be continued or restarted if the SBP is approximately equal to 80% baseline. The infusion will be increased by 1 mL/min if the SBP < 80% baseline. Each time there is hypotension the patient will receive a 1 mL IV bolus of the study solution and the infusion will be increased by 1 mL/min until delivery.

Active Comparator: Ephedrine

Subject will receive an ephedrine infusion to prevent and to treat hypotension associated with spinal anesthesia

Drug: Ephedrine

Ephedrine concentration: 8 mg/mL. The infusion will be initiated immediately after completion of the spinal injection at a rate of 1 mL/min and continued for a minimum of 2 min after which the infusion will be stopped, continued or increased based on the SBP each minute. After each SBP measurement the infusion will be stopped if SBP > 80% baseline, and the infusion will be continued or restarted if the SBP is approximately equal to 80% baseline. The infusion will be increased by 1 mL/min if the SBP < 80% baseline. Each time there is hypotension the patient will receive a 1 mL IV bolus of the study solution and the infusion will be increased by 1 mL/min until delivery.

Outcome Measures

Primary Outcome Measures :

The umbilical artery pH in the phenylephrine group will be higher than in the ephedrine group, although the overall incidence of absolute fetal acidosis is not anticipated to be different between groups. [ Time Frame: Immediately after delivery ]

Secondary Outcome Measures :

Efficacy of study drug in preventing and treating hypotension associated with spinal anesthesia in women with preeclampsia [ Time Frame: During and immediately after study drug infusion ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 60 Years (Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

ASA PS II - III women
18 years old and older
scheduled for cesarean delivery (no trial of labor)
eligible for spinal anesthesia
diagnosis of preeclampsia

Exclusion Criteria:

patients with failed trial of labor
preexisting hypertension
body mass index (BMI) ≥ 40 kg/m2
resting heart rate < 60 bpm
progression to eclampsia, > twin gestation
known fetal anomalies
contraindications to spinal anesthesia
emergency procedure or refusal of consent
failure to achieve a T6 level of anesthesia
conversion to general anesthesia

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00458003

Locations

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United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
Northwestern University
Chicago, Illinois, United States, 60611

Sponsors and Collaborators

Northwestern University

Investigators

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Principal Investigator:	Cynthia A. Wong, M.D.	Northwestern University

More Information

Publications:

Rout CC, Rocke DA. Prevention of hypotension following spinal anesthesia for cesarean section. Int Anesthesiol Clin. 1994 Spring;32(2):117-35. Review.

Ayorinde BT, Buczkowski P, Brown J, Shah J, Buggy DJ. Evaluation of pre-emptive intramuscular phenylephrine and ephedrine for reduction of spinal anaesthesia-induced hypotension during Caesarean section. Br J Anaesth. 2001 Mar;86(3):372-6.

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.

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.

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.

James PR, Nelson-Piercy C. Management of hypertension before, during, and after pregnancy. Heart. 2004 Dec;90(12):1499-504. Review.

Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. 2000 Jul;183(1):S1-S22.

Visalyaputra S, Rodanant O, Somboonviboon W, Tantivitayatan K, Thienthong S, Saengchote W. Spinal versus epidural anesthesia for cesarean delivery in severe preeclampsia: a prospective randomized, multicenter study. Anesth Analg. 2005 Sep;101(3):862-8, table of contents.

Aya AG, Mangin R, Vialles N, Ferrer JM, Robert C, Ripart J, de La Coussaye JE. Patients with severe preeclampsia experience less hypotension during spinal anesthesia for elective cesarean delivery than healthy parturients: a prospective cohort comparison. Anesth Analg. 2003 Sep;97(3):867-72.

Aya AG, Vialles N, Tanoubi I, Mangin R, Ferrer JM, Robert C, Ripart J, de La Coussaye JE. Spinal anesthesia-induced hypotension: a risk comparison between patients with severe preeclampsia and healthy women undergoing preterm cesarean delivery. Anesth Analg. 2005 Sep;101(3):869-75, table of contents.

Saravanan S, Kocarev M, Wilson RC, Watkins E, Columb MO, Lyons G. Equivalent dose of ephedrine and phenylephrine in the prevention of post-spinal hypotension in Caesarean section. Br J Anaesth. 2006 Jan;96(1):95-9. Epub 2005 Nov 25.

Ngan Kee WD, Khaw KS, Ng FF. Prevention of hypotension during spinal anesthesia for cesarean delivery: an effective technique using combination phenylephrine infusion and crystalloid cohydration. Anesthesiology. 2005 Oct;103(4):744-50.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Higgins N, Fitzgerald PC, van Dyk D, Dyer RA, Rodriguez N, McCarthy RJ, Wong CA. The Effect of Prophylactic Phenylephrine and Ephedrine Infusions on Umbilical Artery Blood pH in Women With Preeclampsia Undergoing Cesarean Delivery With Spinal Anesthesia: A Randomized, Double-Blind Trial. Anesth Analg. 2018 Jun;126(6):1999-2006. doi: 10.1213/ANE.0000000000002524.

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Responsible Party:	Cynthia Wong, Professor of Anesthesiology, Northwestern University
ClinicalTrials.gov Identifier:	NCT00458003 History of Changes
Other Study ID Numbers:	0524-31
First Posted:	April 9, 2007 Key Record Dates
Last Update Posted:	February 2, 2017
Last Verified:	January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Cynthia Wong, Northwestern University:


Preeclampsia Spinal Anesthesia Hypotension	Cesarean Delivery Phenylephrine Ephedrine

Additional relevant MeSH terms:

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Pre-Eclampsia Hypotension Vascular Diseases Cardiovascular Diseases Hypertension, Pregnancy-Induced Pregnancy Complications Phenylephrine Oxymetazoline Ephedrine Pseudoephedrine Anesthetics Central Nervous System Depressants Physiological Effects of Drugs Cardiotonic Agents Mydriatics	Autonomic Agents Peripheral Nervous System Agents Sympathomimetics Vasoconstrictor Agents Nasal Decongestants Respiratory System Agents Adrenergic alpha-1 Receptor Agonists Adrenergic alpha-Agonists Adrenergic Agonists Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Protective Agents Central Nervous System Stimulants Bronchodilator Agents

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