Phenylephrine in Spinal Anesthesia in Preeclamptic Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Northwestern University
Sponsor:
Information provided by (Responsible Party):
Cynthia Wong, Northwestern University
ClinicalTrials.gov Identifier:
NCT00458003
First received: April 4, 2007
Last updated: October 15, 2014
Last verified: October 2014

April 4, 2007
October 15, 2014
July 2006
June 2015   (final data collection date for primary outcome measure)
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 ]
  • 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.
  • We expect to demonstrate that phenylephrine for the treatment of spinal anesthesia induced hypotension in women with preeclampsia is safe, and may be associated with improved neonatal acid-base status.
Complete list of historical versions of study NCT00458003 on ClinicalTrials.gov Archive Site
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 ]
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Phenylephrine in Spinal Anesthesia in Preeclamptic Patients
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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Preeclampsia
  • 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. 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.
  • 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.
  • Experimental: Phenylephrine
    Subject will receive a phenylephrine infusion to prevent and to treat hypotension associated with spinal anesthesia
    Intervention: Drug: Phenylephrine
  • Active Comparator: Ephedrine
    Subject will receive an ephedrine infusion to prevent and to treat hypotension associated with spinal anesthesia
    Intervention: Drug: Ephedrine

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
June 2015
June 2015   (final data collection date for primary outcome measure)

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
Female
18 Years to 60 Years
Yes
Contact: Robert J McCarthy, PharmD 312-926-9015 r-mccarthy@northwestern.edu
United States
 
NCT00458003
0524-31
No
Cynthia Wong, Northwestern University
Northwestern University
Not Provided
Principal Investigator: Cynthia A. Wong, M.D. Northwestern University
Northwestern University
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP