Phenylephrine in Spinal Anesthesia in Preeclamptic Patients

NCT00458003 | Completed Results

• 1 other identifier: 0524-31
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 2

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.

Conditions

Preeclampsia; Hypotension

Keywords

Preeclampsia; Spinal Anesthesia; Hypotension; Cesarean Delivery; Phenylephrine; Ephedrine

Outcome Measures

Primary Outcomes (1)

• The Umbilical Artery pH

  The umbilical artery blood pH immediately after delivery. The pH scale ranges from 0 to 14. A normal pH sample from the umbilical artery ranges from pH: 7.18 - 7.38. The lower the pH the more acidic and the higher the pH the more basic.

  Immediately after delivery

Secondary Outcomes (1)

• The Umbilical Artery Blood Base Excess

  Immediately after delivery

Study Arms (2)

Phenylephrine

EXPERIMENTAL

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

Drug: Phenylephrine

Ephedrine

ACTIVE COMPARATOR

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

Drug: Ephedrine

Interventions

Ephedrine DRUG

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.

Ephedrine

Phenylephrine DRUG

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.

Phenylephrine

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (2)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Related Publications (14)

• Rout CC, Rocke DA. Prevention of hypotension following spinal anesthesia for cesarean section. Int Anesthesiol Clin. 1994 Spring;32(2):117-35. No abstract available.

  PMID: 8063445 BACKGROUND

• 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. doi: 10.1093/bja/86.3.372.

  PMID: 11573527 BACKGROUND

• 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.

  PMID: 11916798 BACKGROUND

• 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.

  PMID: 12459688 BACKGROUND

• 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.

  PMID: 14980943 BACKGROUND

• James PR, Nelson-Piercy C. Management of hypertension before, during, and after pregnancy. Heart. 2004 Dec;90(12):1499-504. doi: 10.1136/hrt.2004.035444. No abstract available.

  PMID: 15547046 BACKGROUND

• 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.

  PMID: 10920346 BACKGROUND

• 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):862-868. doi: 10.1213/01.ANE.0000160535.95678.34.

  PMID: 16116005 BACKGROUND

• Aya AGM, 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):867-872. doi: 10.1213/01.ANE.0000073610.23885.F2.

  PMID: 12933418 BACKGROUND

• Aya AGM, 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):869-875. doi: 10.1213/01.ANE.0000175229.98493.2B.

  PMID: 16116006 BACKGROUND

• 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. doi: 10.1093/bja/aei265. Epub 2005 Nov 25.

  PMID: 16311286 BACKGROUND

• 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. doi: 10.1097/00000542-200510000-00012.

  PMID: 16192766 BACKGROUND

• 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.

  PMID: 14977792 BACKGROUND

• 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.

  PMID: 28953494 DERIVED

MeSH Terms

Conditions

Pre-Eclampsia; Hypotension

Interventions

Ephedrine; Phenylephrine

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Phenethylamines; Ethylamines; Ethanolamines

Limitations and Caveats

We assumed that the potency of phenylephrine to ephedrine was 80:1 based on published works. Baseline BP on day of procedure may be elevated due to anxiousness. The definition of preeclampsia as defined by ACOG changed during study period.

Results Point of Contact

• Title: Paul Fitzgerald
• Organization: Northwestern University

p-fitzgerald2@northwestern.edu

312-6951064

Study Officials

• David Walega, M.D.

  Northwestern University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Vice Chair Anesthesiology

Study Record Dates

• First Submitted: April 4, 2007
• First Posted: April 9, 2007
• Study Start: July 1, 2006
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: June 2, 2022
• Results First Posted: June 2, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)