Phenylephrine in Spinal Anesthesia in Preeclamptic Patients

May 9, 2022 updated by: David Walega, Northwestern University

Phenylephrine Versus Ephedrine to Treat Spinal Anesthesia-Induced Hypotension in Preeclamptic Patients During Cesarean Delivery

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study will be approved by the Northwestern University Institutional Review Board. Eligible women admitted to the Labor and Delivery Unit of Prentice Women's Hospital will be approached for study participation immediately after the routine preanesthetic evaluation. This usually occurs shortly after admission to the Labor and Delivery Unit. Women who agree to participate will give written, informed consent at this time.

Preparation and initiation of spinal anesthesia will proceed according to routine practice at our institution. A 16-gauge IV catheter will be inserted under local anesthesia in the pre-operative labor and delivery suite. An IV infusion of lactated Ringer's solution will be started at a minimal rate to maintain vein patency. Patients will be premedicated with metoclopramide 10 mg and ranitidine 50 mg IV at least 30 minutes prior to procedure for aspiration prophylaxis. Patients will be allowed to rest undisturbed for several minutes in the left lateral tilt position, during which heart rate (HR) and systolic blood pressure (SBP) will be taken every 1-2 minutes for at least 3 measurements. Baseline HR and SBP will be the mean of these three recordings.

The subjects will be randomized according to a computer-generated randomization table to one of two groups: Group 1 will receive a phenylephrine infusion and Group 2 will receive an ephedrine infusion. All study medications will be prepared by an investigator not involved in the care of the patient or collection of data. Both the anesthesiologist managing the patient's anesthetic, as well as the patient, will be blinded to the study medication.

Upon arrival to the operating room, 30 mL of 0.3 M sodium citrate will be given orally and standard monitoring will performed, including non-invasive BP, electrocardiography and pulse oximetry. Oxygen will be given at 3 liter per minute by nasal cannula. Fetal heart rate will be monitored by external cardiotocography until the time of surgical preparation. 500 mL of lactated Ringer's solution will be given as a bolus concurrently with the start of the spinal anesthesia procedure. Spinal anesthesia will be induced with patients in the sitting position. After sterile skin preparation and draping, the skin will be infiltrated with lidocaine, a 25 gauge Whitacre needle will be inserted at the L3-L4 vertebral interspace (± one vertebral interspace) and bupivacaine 0.75%, 1.6 mL (12 mg), fentanyl 15 μg and morphine 150 μg will be injected intrathecally. Patients will be immediately placed supine with left uterine displacement. SBP will be measured every 1 minute beginning 1 minute after spinal injection for 10 minutes, then every 2.5 minutes for the remainder of the procedure. Patients' hemodynamic data will be recorded throughout the procedure and printed at the end of the surgery. Five minutes after spinal injection, the sensory level of anesthesia will be assessed by loss of pinprick discrimination using von Frey hairs. If the patient fails to obtain at least a T6 sensory level of anesthesia, that patient will be withdrawn from the study. Preincision antibiotics, magnesium sulfate and uterotonic agents will be administered intraoperatively per routine practice.

An unblinded investigator will prepare solutions of phenylephrine 100 μg per mL and ephedrine 8000 μg per mL (potency phenylephrine:ephedrine 80:111). The investigator will place 20 mL of the study medication into a syringe which will be given to the managing anesthesiologist for infusion via a syringe pump. The infusion will be attached to the IV cannula at the most distal. The infusion will be initiated immediately after completion of the spinal injection at a rate of 1 mL per minute and continued for a minimum of two minutes after which the infusion will either be stopped, continued or increased based on the SBP measurement each minute. The goal will be to maintain SBP ≥ 80% baseline, but not > 160 mmHg. After each measurement of SBP, the infusion will be stopped if the SBP is greater than 80% baseline SBP, and the infusion will be continued or restarted if the SBP is approximately equal to 80% baseline SBP.12 The infusion will be increased by 1 mL per minute if the SBP measurement is less than 80% baseline. For the purpose of this study, we will define hypotension as a decrease in SBP to < 80% of baseline.13 Each time there is a SBP measurement demonstrating hypotension as defined above, the patient will receive a 1 mL IV bolus of the study solution via the infusion pump and the infusion will be increased by 1 mL per minute. The infusion and bolus protocol will be continued until delivery, after which further management will be at the discretion of the managing anesthesiologist to maintain SBP. If the baseline SBP > 160 mmHg, the infusion will not be started until the SBP decreases to 160 mmHg. Infusion management will then proceed as described above.

The total volumes of the study solutions given by infusion and bolus up to the time delivery will be recorded. Bradycardia (defined as HR < 60 bpm) associated with an SBP equal or greater to baseline SBP will be treated by stopping the study solution and bradycardia associated with SBP < 80% baseline will be treated with atropine intravenously. Hypotension unresponsive to study medication will be treated with epinephrine (10 μg/mL) intravenous boluses (1 mL) until correction of hypotension. Nausea or vomiting not associated with hypotension will be treated with ondansetron 4 mg IV.

After delivery, oxytocin 10-20 IU will be given by slow IV infusion per routine. The infant's 1 and 5 minute Apgar scores will be assessed by the nurse or pediatrician blinded to patient group. The results of routine umbilical cord blood gas analysis will be recorded.

Study Type

Interventional

Enrollment (Actual)

110

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 56 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Umbilical Artery pH
Time Frame: Immediately after delivery

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Umbilical Artery Blood Base Excess
Time Frame: Immediately after delivery

The umbilical artery blood base excess immediately after delivery. Base excess and base deficit refer to an excess or deficit, in the amount of base present in the blood.

The value (-2 to +2 normal range) is usually reported as a concentration in units of mEq/L, with positive numbers indicating an excess of base and negative a deficit
Immediately after delivery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Investigators

  • Study Chair: David Walega, M.D., Northwestern University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2006

Primary Completion (Actual)

December 1, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

April 4, 2007

First Submitted That Met QC Criteria

April 6, 2007

First Posted (Estimate)

April 9, 2007

Study Record Updates

Last Update Posted (Actual)

June 2, 2022

Last Update Submitted That Met QC Criteria

May 9, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0524-31

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe