Comparison of Intrathecal Versus Epidural Fentanyl on Fetal Bradycardia in Labor Combined Spinal Epidural Analgesia

Comparison of Intrathecal Versus Epidural Fentanyl: Effect of Neuraxial Route of Administration on Fetal Bradycardia in Labor Combined Spinal Epidural Analgesia

There have been studies reporting that combined spinal-epidural (CSE) with fentanyl and bupivacaine produce fetal bradycardia, (M.Kuczkowski, 2004) (Abrão K, 2009 ). It is unknown whether any differences in risk exist between fentanyl and bupivacaine when used as a part of the CSE procedure. Some authors have reported cases of parturients who developed uterine hyperactivity and fetal bradycardia after subarachnoid administration of fentanyl during labor. (D'Angelo & Eisenach, 1997) (Friedlander JD, 1997). It has been suggested that uterine hypertonus, leading to non-reassuring fetal heart rate tracings, might be an etiologic factor in these situations. (Landau, 2002).

We propose this study to test the hypothesis that administration of epidural fentanyl is associated with a lower incidence of fetal bradycardia compared to intrathecal fentanyl.

Study Overview

• Status: Recruiting
• Conditions: Labor Pain; Obstetric Pain
• Intervention / Treatment: Drug: Spinal fentanyl; Drug: Spinal bupivacaine; Drug: Spinal Fentanyl and Bupivacaine; Drug: Epidural fentanyl /spinal bupivacaine

Detailed Description

After approval by the Institutional Review Board and written informed consent, we plan to prospectively study pregnant patients who undergo neuraxial labor analgesia. All patients will receive combined-spinal-epidural analgesia. Patients will be randomly assigned to one of four groups by means of sealed envelope technique. Group A will receive a spinal dose of preservative-free fentanyl 25 mcg. Group B will receive one dose of spinal preservative-free 0.25% bupivacaine. Group C will receive a spinal combination of preservative-free 0.25% bupivacaine and fentanyl 25 mcg. Group D will receive spinal preservative-free 0.25% bupivacaine and epidural fentanyl 100 mcg. After the procedure, we will monitor the fetal heart rate and tocometry tracings for 20 min. Thereafter, an epidural infusion with a solution containing 0.125% bupivacaine and 2mcg/mL of fentanyl will be started. We will record demographic variables (age, and BMI), obstetric variables (parity, gestational age, cervical dilation, oxytocin infusion) and anesthetic variables (level of insertion of epidural catheter).

Primary outcomes:

Fetal heart rate (baseline, minimal and abnormal patterns)

Secondary outcomes:

• Blood pressure (systolic, diastolic and mean) measured at baseline and every 5 minutes after administration of medication.
• Dermatomal level measured after 20 minutes of medication administration.
• Pain level (visual analogue scale) after 20 minutes of medication administration.
• Patient satisfaction level (1-10 scale) after 20 minutes of medication administration.
• Uterine tone measured with tocometer at baseline and during 20 minutes after medication administration.

• Study Type: Interventional
• Enrollment (Anticipated): 558
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Efrain Riveros Perez, MD; Phone Number: 7067217361; Email: eriverosperez@augusta.edu
• Study Contact Backup: Name: Alexander R Rocuts Martinez, MD; Phone Number: 3304074681; Email: krocutsmartinez@augusta.edu

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Recruiting
      • Augusta University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Older than 18 years
• Term pregnancy (> 37 weeks)
• Absence of obstetric morbidities
• Active labor
• Request of neuraxial analgesia per patient and/or obstetrician
• Combined spinal-epidural technique

Exclusion Criteria:

• Abnormal fetal heart rate tracing.
• Uterine tachysystole before neuraxial analgesia.
• Baseline blood pressure <90/60 mmHg.
• Allergies to local anesthetics or fentanyl.
• Maternal fever.
• Pruritus before performance of neuraxial analgesia.
• Contraindications for neuraxial technique.
• Unwillingness to participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Spinal Fentanyl; Spinal dose of preservative-free fentanyl 25 mcg (Volume 0.5 mL)	Drug: Spinal fentanyl; 25 mcg of fentanyl (0.5 mL) will be administered by intrathecal route.; Other Names: Fentora
ACTIVE_COMPARATOR: Spinal Bupivacaine; Spinal dose of preservative-free 0.25% bupivacaine (Volume 0.5 mL)	Drug: Spinal bupivacaine; 1.25 mg of preservative-free bupivacaine 0.25% (0.5 mL) will be administered by intrathecal route.; Other Names: Marcaine
ACTIVE_COMPARATOR: Spinal Fentanyl and Bupivacaine; Spinal combination of preservative-free 0.25% bupivacaine (0.5 mL) and fentanyl 25 mcg (0.5 mL). (Total Volume 1 mL).	Drug: Spinal Fentanyl and Bupivacaine; 1.25 mg of preservative-free bupivacaine 0.25% (0.5 mL), and 25 mcg of fentanyl (0.5 mL) will be administered by intrathecal route.; Other Names: Marcaine and Fentora
EXPERIMENTAL: Epidural fentanyl /spinal bupivacaine; Spinal preservative-free 0.25% bupivacaine (Volume 0.5 mL) and epidural fentanyl 100 mcg (Volume 2 mL).	Drug: Epidural fentanyl /spinal bupivacaine; 1.25 mg of preservative-free bupivacaine 0.25% (0.5 mL) will be administered by intrathecal route, and 100 mcg of fentanyl (2 mL) will be administered by epidural route.; Other Names: Marcaine and Fentora

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fetal heart rate	Fetal bradycardia and abnormal fetal heart rate tracing	20 minutes (Starting from placement of labor neuraxial block)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure	Maternal systolic, diastolic and mean arterial pressure measured at baseline and every 5 minutes after administration of medication	20 minutes (Starting from placement of labor neuraxial block)
Dermatomal level	Analgesic level measured by sensitivity to temperature stimulus	20 minutes (Starting from placement of labor neuraxial block)
Maternal Pain level: visual analogue scale	Pain evaluated by visual analogue scale (0, no pain; 10, worst pain)	20 minutes (Starting from placement of labor neuraxial block)
Patient satisfaction level: Likert Scale	Satisfaction level measured by Likert Scale (5: fully satisfied, 4: satisfied, 3: neutral, 2: dissatisfied, 1: fully dissatisfied)	20 minutes (Starting from placement of labor neuraxial block)
Uterine tone	Measured with tocometer (In milimeters above baseline) at baseline and during 20 minutes after medication administration.	20 minutes (Starting from placement of labor neuraxial block)

Collaborators and Investigators

• Sponsor: Augusta University
• Investigators: Principal Investigator: Efrain Riveros Perez, MD, Augusta University

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 28, 2019
• Primary Completion (ANTICIPATED): October 1, 2023
• Study Completion (ANTICIPATED): October 31, 2023

Study Registration Dates

• First Submitted: August 6, 2018
• First Submitted That Met QC Criteria: August 8, 2018
• First Posted (ACTUAL): August 9, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 22, 2021
• Last Update Submitted That Met QC Criteria: July 21, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Pain; Neurologic Manifestations; Arrhythmias, Cardiac; Bradycardia; Labor Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Anesthetics, Local; Fentanyl; Bupivacaine
• Other Study ID Numbers: 1238162

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The study team will decide about sharing information upon request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes