Phenylephrine in Spinal Anesthesia in Preeclamptic Patients - Full Text View

Purpose

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	Intervention
Preeclampsia Hypotension	Drug: Ephedrine Drug: Phenylephrine


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	Phenylephrine Versus Ephedrine to Treat Spinal Anesthesia-Induced Hypotension in Preeclamptic Patients During Cesarean Delivery

Resource links provided by NLM:

Genetics Home Reference related topics: preeclampsia

MedlinePlus related topics: Anesthesia Cesarean Section Low Blood Pressure

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

U.S. FDA Resources

Further study details as provided by Northwestern University:

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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: Yes ]


Estimated Enrollment:	100
Study Start Date:	July 2006
Estimated Study Completion Date:	June 2015
Estimated Primary Completion Date:	June 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Arms

Assigned Interventions

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.

Show Detailed Description

Eligibility


Ages Eligible for Study:	18 Years to 60 Years
Genders 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00458003

Contacts


Contact: Robert J McCarthy, PharmD	312-926-9015	r-mccarthy@northwestern.edu

Locations


United States, Illinois
Northwestern Memorial Hospital	Recruiting
Chicago, Illinois, United States, 60611
Contact: Robert McCarthy, PharmD 312-926-9015 r-mccarthy@northwestern.edu
Principal Investigator: Cynthia A Wong, M.D.
Northwestern University	Recruiting
Chicago, Illinois, United States, 60611
Contact: Robert J McCarthy, PharmD 312-926-9015 r-mccarthy@northwestern.edu
Principal Investigator: Cynthia A. Wong, M.D.

Sponsors and Collaborators

Northwestern University

Investigators


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.

Nelson-Piercy C, James PR. Management of hypertension before, during, and after pregnancy. Heart 2004;90:1499-1504.

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.


Responsible Party:	Cynthia Wong, Professor of Anesthesiology, Northwestern University
ClinicalTrials.gov Identifier:	NCT00458003 History of Changes
Other Study ID Numbers:	0524-31
Study First Received:	April 4, 2007
Last Updated:	October 15, 2014
Health Authority:	United States: Institutional Review Board

Keywords provided by Northwestern University:


Preeclampsia Spinal Anesthesia Hypotension	Cesarean Delivery Phenylephrine Ephedrine

Additional relevant MeSH terms:


Hypotension Cardiovascular Diseases Vascular Diseases Anesthetics Ephedrine Oxymetazoline Phenylephrine Pseudoephedrine Adrenergic Agents Adrenergic Agonists Adrenergic alpha-1 Receptor Agonists Adrenergic alpha-Agonists Anti-Asthmatic Agents Autonomic Agents Bronchodilator Agents	Cardiotonic Agents Cardiovascular Agents Central Nervous System Agents Central Nervous System Depressants Central Nervous System Stimulants Molecular Mechanisms of Pharmacological Action Mydriatics Nasal Decongestants Neurotransmitter Agents Peripheral Nervous System Agents Pharmacologic Actions Physiological Effects of Drugs Protective Agents Respiratory System Agents Sympathomimetics

ClinicalTrials.gov processed this record on March 01, 2015