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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Labor Pain, Obstetric Pain

Intervention / Treatment
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* Drug: Spinal fentanyl
* Drug: Spinal bupivacaine
* Drug: Spinal Fentanyl and Bupivacaine
* Drug: Epidural fentanyl /spinal bupivacaine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomly assigned to one of four groups: Group A: Spinal dose of preservative-free fentanyl 25 mcg. Group B: Spinal preservative-free 0.25% bupivacaine. Group C: Spinal combination of preservative-free 0.25% bupivacaine and fentanyl 25 mcg. Group D: 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 30 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). We will also record level of insertion, blood pressure every 5 minutes, dermatomal level, pain level, patient satisfaction level and pruritus.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Spinal Fentanyl<br>Spinal dose of preservative-free fentanyl 25 mcg (Volume 0.5 mL) | Drug: Spinal fentanyl<br>* 25 mcg of fentanyl (0.5 mL) will be administered by intrathecal route.<br>* Other names: Fentora;|
| Active Comparator: Spinal Bupivacaine<br>Spinal dose of preservative-free 0.25% bupivacaine (Volume 0.5 mL) | Drug: Spinal bupivacaine<br>* 1.25 mg of preservative-free bupivacaine 0.25% (0.5 mL) will be administered by intrathecal route.<br>* Other names: Marcaine;|
| Active Comparator: Spinal Fentanyl and Bupivacaine<br>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<br>* 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.<br>* Other names: Marcaine and Fentora;|
| Experimental: Epidural fentanyl /spinal bupivacaine<br>Spinal preservative-free 0.25% bupivacaine (Volume 0.5 mL) and epidural fentanyl 100 mcg (Volume 2 mL). | Drug: Epidural fentanyl /spinal bupivacaine<br>* 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.<br>* Other names: Marcaine and Fentora;|

What is the study measuring?
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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) |