Phenylephrine in Spinal Anesthesia in Preeclamptic Patients - Full Text View

Sponsored by:	Northwestern University
Information provided by:	Northwestern University
ClinicalTrials.gov Identifier:	NCT00458003

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 vasocontrictors, 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 Spinal Anesthesia Hypotension Cesarean Section	Drug: Ephedrine Drug: Phenylephrine

MedlinePlus related topics: Anesthesia Cesarean Section Low Blood Pressure

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

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Phenylephrine Versus Ephedrine to Treat Spinal Anesthesia-Induced Hypotension in Preeclamptic Patients During Cesarean Delivery

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:	December 2010
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Phenylephrine: Experimental Subject will receive a phenylephrine infusion to prevent and treatment spinal anesthesia-associated hypotension	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. The goal will be to maintain SBP ≥ 80% baseline, but < 160 mmHg. 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. Hypotension is defined as a decrease in SBP to < 80% of baseline. Each time there hypotension the patient will receive a 1 mL IV bolus of the study solution and the infusion will be increased by 1 mL/min. The infusion and bolus protocol will be continued until delivery. If the baseline SBP > 160 mmHg, the infusion will not be started until the SBP decreases to 160 mmHg.
Ephedrine: Active Comparator Subject will receive an ephedrine infusion to prevent and treatment spinal anesthesia-associated hypotension	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. The goal will be to maintain SBP ≥ 80% baseline, but < 160 mmHg. 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. Hypotension is defined as a decrease in SBP to < 80% of baseline. Each time there hypotension the patient will receive a 1 mL IV bolus of the study solution and the infusion will be increased by 1 mL/min. The infusion and bolus protocol will be continued until delivery. If the baseline SBP > 160 mmHg, the infusion will not be started until the SBP decreases to 160 mmHg.

Arms

Assigned Interventions

Phenylephrine: Experimental

Subject will receive a phenylephrine infusion to prevent and treatment spinal anesthesia-associated hypotension

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. The goal will be to maintain SBP ≥ 80% baseline, but < 160 mmHg. 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.

Hypotension is defined as a decrease in SBP to < 80% of baseline. Each time there hypotension the patient will receive a 1 mL IV bolus of the study solution and the infusion will be increased by 1 mL/min. The infusion and bolus protocol will be continued until delivery. If the baseline SBP > 160 mmHg, the infusion will not be started until the SBP decreases to 160 mmHg.

Ephedrine: Active Comparator

Subject will receive an ephedrine infusion to prevent and treatment spinal anesthesia-associated hypotension

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. The goal will be to maintain SBP ≥ 80% baseline, but < 160 mmHg. 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.

Hypotension is defined as a decrease in SBP to < 80% of baseline. Each time there hypotension the patient will receive a 1 mL IV bolus of the study solution and the infusion will be increased by 1 mL/min. The infusion and bolus protocol will be continued until delivery. If the baseline SBP > 160 mmHg, the infusion will not be started until the SBP decreases to 160 mmHg.

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

ASA PS II - III women 18 years old and older with singleton pregnancies scheduled for cesarean delivery (no trial of labor) under spinal anesthesia with a diagnosis of preeclampsia (see criteria above) will be eligible for inclusion in the study.

Exclusion Criteria:

Patients with failed trial of labor, with preexisting hypertension, body mass index ≥ 40 kg/m2, resting heart rate < 60 bpm, progression to eclampsia, multiple gestation pregnancy, known fetal anomalies, contraindications to spinal anesthesia, participation in another investigational study, emergency procedure or refusal of consent will be excluded.
Patients that fail to achieve a T6 level of anesthesia to pinprick sensation or require conversion to general anesthesia will be withdrawn from the investigation.

Contacts and Locations

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

Locations

United States, Illinois
Northwestern University	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 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.

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. No abstract available.

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.

[No authors listed] 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.

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:	Northwestern University ( Cynthia A. Wong, MD )
Study ID Numbers:	0524-31
Study First Received:	April 4, 2007
Last Updated:	November 25, 2008
ClinicalTrials.gov Identifier:	NCT00458003 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Northwestern University:

Preeclampsia
Spinal Anesthesia
Hypotension

Cesarean Delivery
Phenylephrine
Ephedrine

Study placed in the following topic categories:

Hypotension
Neurotransmitter Agents
Pregnancy Complications
Adrenergic Agents
Benzocaine
Anesthetics
Pre-Eclampsia
Preeclampsia
Adrenergic Agonists
Nasal Decongestants
Hypertension, Pregnancy-Induced
Phenylephrine
Vasoconstrictor Agents
Pseudoephedrine

Adrenergic alpha-Agonists
Eclampsia
Vascular Diseases
Central Nervous System Depressants
Anti-Asthmatic Agents
Central Nervous System Stimulants
Cardiovascular Agents
Oxymetazoline
Mydriatics
Ephedrine
Peripheral Nervous System Agents
Bronchodilator Agents
Hypertension

Additional relevant MeSH terms:

Hypotension
Respiratory System Agents
Neurotransmitter Agents
Pregnancy Complications
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Cardiotonic Agents
Physiological Effects of Drugs
Anesthetics
Pre-Eclampsia
Adrenergic Agonists
Nasal Decongestants
Hypertension, Pregnancy-Induced
Phenylephrine
Therapeutic Uses

Vasoconstrictor Agents
Cardiovascular Diseases
Pseudoephedrine
Adrenergic alpha-Agonists
Sympathomimetics
Vascular Diseases
Anti-Asthmatic Agents
Central Nervous System Depressants
Central Nervous System Stimulants
Cardiovascular Agents
Protective Agents
Pharmacologic Actions
Oxymetazoline
Mydriatics
Autonomic Agents

ClinicalTrials.gov processed this record on May 07, 2009