Effects of Bupivacaine Induced Motor Blockade During the Second Stage of Labor

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to measure the effects of bupivacaine administered via epidural catheters on indices of motor blockade ascertained during the second stage of labor. This is a randomized, double-blind, controlled trial designed to address the primary research question: Does bupivacaine lengthen the second stage of labor? The secondary research question is: Is there other evidence of motor blockade attributable to bupivacaine during the second stage of labor? The investigators know from prior studies that the length of the second stage in nulliparous women delivered at Parkland Hospital without epidural analgesia is 28 minutes. The investigators hypothesize in this now proposed study that epidural analgesia with bupivacaine will significantly increase this baseline from 28 minutes to 37 minutes or more (a 33% increase) thus implicating motor blockade. Baseline data for the Bromage and Breen scores during the second stage as well as the uterine contractility data are not available as these indices of motor blockade have not here-to-fore been studied in this context. Currently at Parkland Hospital, 82% of nulliparous women undergoing induction of labor at term receive continuous epidural infusions with bupivacaine during the first and second stages of labor. Such women will be identified when admitted for scheduled inductions at Parkland. After informed consent is obtained standard management of labor induction will be provided. Those consented women reaching 8 cm cervical dilation will be randomized. Group I will receive bupivacaine plus fentanyl via epidural catheter during the second stage (i.e. 10 cm dilation) and Group II will receive only fentanyl infusion via epidural catheter (see study procedure below). Both the patient and the caregiver will be blinded as to whether the patient is in the bupivacaine plus fentanyl arm or the fentanyl only arm. To detect a 33% increase (from 28 minutes to 37 minutes) in the primary outcome the investigators need a total of 310 women enrolled in the study (or 155 per arm). Assuming a 30% consent rate and given that approximately 1000 women meet the inclusion criteria each year at Parkland, the investigators project that this study could be completed in 12 months.

Detailed Description
-----------------
Nulliparous women scheduled for labor inductions on Monday through Friday and who have consented to this study will be randomized to one of two arms: bupivacaine plus fentanyl epidural analgesia throughout labor and delivery (including the second stage) or epidural bupivacaine plus fentanyl until 8 cm cervical dilation and only fentanyl thereafter. From activation of epidural analgesia to 8 cm cervical dilation the prevailing standard epidural technique in use at Parkland Hospital will be used. Briefly, 19-ga multi-orifice epidural catheter is placed using 17-ga 3 ½cm Tuohy needle into the L3-L4 lumbar interspace. Lactated Ringers solution, 500-1000mL will be infused during placement of the epidural catheter to mitigate hypotension. A test dose using 1.5% lidocaine with 1:200,000 epinephrine, 3mL, will be given via the epidural catheter. If the test dose is negative, then an initial bolus of 0.25% bupivacaine, 4-8mL, with fentanyl 100mcg is given via the catheter. After securing the epidural catheter the patient will be placed in the supine position and the anesthetic sensory level measured with the desired level of T6-T8. Once a T6-T8 sensory block is secured the epidural infusion using 0.125% bupivacaine with 2mcg/mL fentanyl at 10mL/hr will be started. At any time during epidural infusion the epidural catheter may be replaced at the discretion of the anesthesia provider for inadequate analgesia. Ephedrine or phenylephrine will be given intravenously for maternal hypotension defined as systolic blood pressure ≤ 90 mmHg or a decrease of 20% systolic blood pressure from patient's baseline. Randomization will occur when the woman reaches 8 cm cervical dilation. Envelopes containing cassettes will be sequentially randomized by Dr. McIntire and given to the attending obstetrical anesthesiologist containing one of two medications. Group I will receive a 100mL epidural cassette of 0.125% bupivacaine with fentanyl 2mcg/mL to be infused at 10mL/hr. Group II will receive a 100mL cassette of fentanyl 10mcg/mL (to be infused at 10mL/hr. Both groups will have the same rate of epidural infusion such that the patient, nurse, obstetrician, and anesthesia providers will be blinded to the randomized treatment group. The Parkland Investigational Drug Service (IDS) will provide the study drugs. The patient may request a 5mL bolus from the epidural infusion every 30 minutes if pain relief is inadequate. The obstetrician can also give patients in either study group 25mg of intravenous meperidine every hour for up to two doses if pain relief is unsatisfactory. The study regimen will continue until spontaneous delivery of the infant or until which time operative vaginal delivery or cesarean delivery is planned. At this point the study will be over and routine anesthesia care resumed. The standard of care for management of labor induction at Parkland requires continuous electronic fetal heart rate monitoring (EFM) as well as uterine contraction monitoring. The standard is to apply EFM internal transducers when the membranes are ruptured. Standard fetal monitors equipped with laptop computers will be used to electronically store the fetal heart rate and uterine contraction data during this study. This will permit qualification of uterine contractility during the second stage of labor. The Bromage and Breen scores for motor blockade will be assessed at complete cervical dilation and at 30, 60, and 90 minutes thereafter. The scoring system is as follows: Score Criteria Unable to move feet or knees (complete block) Able to move feet only Just able to move knees Detectable weakness of hip flexion while supine No weakness of hip flexion Able to perform partial knee bend Visual analog pain (VAS) scores for the adequacy of epidural analgesia from 1-10 will also be assessed at each time point used for the Bromage and Breen scores. Data collection will include maternal demographic characteristics as well as antepartum and intrapartum obstetrical features. Condition of the infant at birth based on Apgar scores and umbilical artery blood pH, as well as neonatal outcomes will be ascertained.

Official Title
-----------------
A Randomized Double-blinded Trial of the Effects of Bupivacaine Induced Motor Blockade on the Second Stage of Labor

Conditions
-----------------
Pregnancy

Intervention / Treatment
-----------------
* Drug: Epidural Bupivacaine plus fentanyl
* Drug: Epidural fentanyl


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Nulliparous women at 37 weeks gestation or greater. Scheduled for induction of labor for any indication, to include hypertensive disorders, diabetes, decreased fetal motion, or prolonged pregnancy. Single without known malformations. Maternal age > or equal to 16 years. ASA classification 1 or 2. Exclusion Criteria: Women who refuse epidural analgesia. Women with contraindications to epidural analgesia, i.e., severe thrombocytopenia. Any renal disease with serum creatinine > 1.0 mg/dL. Allergy to bupivacaine or fentanyl. Known liver disease such as hepatitis. Known contraindications to internal electronic fetal monitoring i.e., active herpes, maternal HIV seropositivity.

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 44 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: double-blinded 2 arm
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Epidural fentanyl<br>A continuous epidural infusion of fentanyl 10 mcg/cc at a basal infusion rate of 10 ml/hr with a patient-controlled epidural analgesia (PCEA) demand dose of 5 mL/hr for pain. Meperidine 25 mg intravenously every 1 hour for breakthrough pain as needed. | Drug: Epidural fentanyl<br>* The subjects will receive epidural fentanyl 10 mcg/mL with the rate of 10mL/hr.<br>* Other names: Epidural continous infusion of fentanyl;|
| Placebo Comparator: Epidural bupivacaine plus fentanyl<br>A continuous epidural infusion of bupivacaine plus fentanyl during the second stage (i.e. 10 cm dilation) of labor. Epidural infusion are 10 ml/hr basal infusion plus 5 ml/hr demand dose via patient-controlled epidural analgesia (PCEA). Meperidine 25 mg intravenously every 1 hour for breakthrough pain as needed . | Drug: Epidural Bupivacaine plus fentanyl<br>* The subjects will receive 0.125% bupivacaine with fentanyl 2 mcg/mL at a rate of 10 mL/hr.<br>* Other names: Epidural continous infusion of bupivacaine and fentanyl;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Duration of the Second Stage of Labor | The length of the second stage of labor (measured as minutes a parturient spends in Stage II) in nulliparous women received a epidural bupivacaine plus fentanyl or fentanyl alone. | Duration of second stage of labor approximately 30 minutes to 150 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Anesthetic Motor Blockade Indices During Stage II of Labor | Motor blockade will be estimated using Bromage and Breen scores (measured on a 6-point standardized scale, 1= Unable to more feet, 6= Able to perform partial knee bend) that estimate motor blockade. This scoring system is based upon the laboring womans' ability to move her lower extremities. | Duration of second stage of labor approximately 30 minutes to 150 minutes | 
| Mode of Delivery in Women Randomized to Bupivacaine vs. No Bupivacaine During the Second Stage of Labor |  | At the time of Delivery | 
| Number of Participants Whose Newborns Received an APGAR Score of <=3 at 1 Min | Number of participants whose newborns received an APGAR score of <=3 at 1 min. A lower APGAR score represents poor health or a worsening in the Outcome, | At the time of Delivery, up to 3 hours | 
| Number of Participants Whose Newborns Received an APGAR Score of <=3 at 5 Min | Number of participants whose newborns received an APGAR score of <=3 at 5 minutes. A lower APGAR score represents poor health or a worsening in the Outcome | At the time of Delivery, up to 3 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bupivacaine, Fentanyl, Epidural, Second Stage of Labor, Randomized Controlled Trial