Comparison of Epidural Fentanyl and Clonidine for Breakthrough Pain

Study Overview
=================
Brief Summary
-----------------
Epidural analgesia has proven to be an effective method for severe pain relief associated with labor and delivery. During labor, a low dose continuous infusion of local anesthetic and narcotic will be administered through an epidural catheter. As labor progresses and the baby's head makes it way through the pelvis, breakthrough pain may emerge and often needs further treatment. The investigators provide pain relief by administering analgesics through the epidural catheter. The patients will be randomly assigned to receive one of two medication mixtures believed to be successful in treating this type of pain associated with advanced labor. After this initial treatment, if pain relief is not attained, the patient may receive the other medication as well. The medications used in this study have been used at this institution for some time and have been found to be safe for mother and baby. The opioid (fentanyl) dose is small and only a small fraction will be transmitted to the baby. The other medication (clonidine) better known as a blood pressure medication has also been used for pain relief. Studies and clinical experience have shown that clonidine when given epidurally in the doses used in this study has minimal, if any effect, on the blood pressure of the mother or of the baby. The investigators will record medical and obstetric history and labor progress relevant to the patient. The patient will be asked questions regarding labor pain and side effects before and after the analgesic is administered. The primary objective is to determine which treatment regimen is more successful in abolishing breakthrough pain in advanced labor.

Detailed Description
-----------------
Epidural analgesia is a popular choice among patients for relief of severe pain associated with labor and delivery. Currently, at the investigators' institution the investigators use a continuous infusion of low dose local anesthetic and narcotic (12 ml/hr of 0.0625% bupivacaine with 2 micrograms/ml fentanyl) after the initial spinal or epidural dose to maintain patient comfort until delivery. This dose of the infusion is chosen because it often provides adequate comfort without interfering with the mobility of the patient and her ability to effectively push during delivery. However, this low-dose epidural infusion strategy often results in recurrence of pain after an initial pain-free period. This recurring pain is known as breakthrough pain and is alleviated by administering small boluses of analgesics via the epidural catheter. The pain occurring in labor is initially of visceral origin and is mediated by pain fibers originating from the low thoracic and upper lumbar segments of the spinal cord. As labor progresses to the late first phase (also known as transitional stage), pain sensations originating from the distension of the pelvic floor, vagina and perineum adds a somatic component to labor pain. This type of breakthrough pain, mediated by nerve fibers originating from the sacral nerves at dermatomes S2-S4, is often difficult to treat. Patients may experience inadequate analgesia even after boluses of analgesics are administered. Inadequate analgesia is deleterious due to subjective discomfort with its associated neurohumoral and physiological changes, and can be an initiator of the urge to bear down (push). Pushing before complete dilation of the cervix may lead to swelling, cervical injury and premature exhaustion of the mother. Adequate pain control will allow the cervix to fully dilate and motivate the mother to push effectively at the appropriate time. Although requests from patients to alleviate late stage breakthrough pain are common, there are no established data in the literature regarding the most effective strategy for pain management in this stage of labor. This study is designed to compare the efficacy of two treatments for controlling late first stage breakthrough pain during labor: clonidine-bupivacaine versus fentanyl-bupivacaine. Both strategies are used at Columbia University Medical Center (CUMC) in this clinical situation, and there is no clear evidence whether one is superior.

Official Title
-----------------
Comparison of Fentanyl-bupivacaine and Clonidine-bupivacaine for Breakthrough Pain in Advanced Labor in Patients With Continuous Epidural Analgesia

Conditions
-----------------
Labor Pain

Intervention / Treatment
-----------------
* Drug: Clonidine
* Drug: Fentanyl


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: women in labor at term pregnancy healthy epidural analgesia in place breakthrough pain in advanced labor Exclusion Criteria: chronic pain syndrome receiving systemic opioids within 4 hours receiving chronic antidepressants, clonidine, opioids

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will randomly receive either a mixture of 100 mcg of clonidine and 12.5 mg of bupivacaine for a total volume of 10 ml (CLON group) and the other group will receive 100 mcg of fentanyl and 12.5 mg of bupivacaine for a total volume of 10 ml (FENT group). If the treatment is declared a failure, the patient will receive the alternative of the initial treatment.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clonidine<br>Participants randomized to this arm of the study receive 100 micrograms clonidine with the bupivacaine in their epidural when requesting pain relief in advanced labor | Drug: Clonidine<br>* Subjects randomized to clonidine will receive a mixture of 100 micrograms clonidine and 12.5 mg bupivacaine 10 ml of volume.<br>* Other names: DuraClon;|
| Experimental: Fentanyl<br>Participants randomized to this arm of study will receive 100 mcg fentanyl with the bupivacaine in their epidural when requesting pain relief in advanced labor | Drug: Fentanyl<br>* Subjects randomized to fentanyl will receive 100 mcg fentanyl and 12.5 mg bupivacaine in 10 ml of volume.<br>* Other names: Sublimaze;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Success Rate at 15 Minutes Post-epidural Bolus Injection | Pain Visual Analogue Scale (VAS) was evaluated every 5 min for 15 min. 'Success' is defined as at least a 4-point reduction in VAS at 15 min. (0=no pain, 10= worst pain) | Baseline, 15 Minutes post epidural administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal Systolic Blood Pressure | Blood pressure will be measured at different timepoints. | Baseline, 30 Minutes post epidural administration | 
| Maternal Heart Rate | Heart rate will be measured at different timepoints. | Baseline, 30 Minutes post epidural administration | 
| Neonatal Apgar Score | The Apgar score is based on a total score of 1 to 10. The higher the score, the better the baby is doing after birth. A score of 7, 8, or 9 is normal and is a sign that the newborn is in good health. | 1 minute and 5 minutes post delivery | 
| Number of Spontaneous Vaginal Deliveries | Mode of delivery: spontaneous vaginal or instrumental vaginal versus cesarean. | Upon delivery (approximately up to 8 hours from baseline) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Analgesia, Epidural, Pregnancy, Labor, Clonidine, Fentanyl, Bupivacaine, Childbirth