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Drug Concentration and Volume on Adequate Labor Analgesia With PIEB (CADD2)

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ClinicalTrials.gov Identifier: NCT03553576
Recruitment Status : Not yet recruiting
First Posted : June 12, 2018
Last Update Posted : August 21, 2019
Sponsor:
Information provided by (Responsible Party):
Elizabeth Lange, Northwestern University

Brief Summary:

Neuraxial labor analgesia is performed by the administration of a local anesthetic/opioid mixture in the epidural space. The delivery method is a combination of continuous infusion, provider-administered boluses and patient-administered boluses (patient controlled epidural analgesia [PCEA]) via epidural catheter. Pain during the first stage of labor is primarily due to lower uterine segment and cervical stretching. The pain signals enter the spinal cord through sensory nerves at the T10 through L1 dermatomes. Pain signals from the late first state and second stage of labor also arise from the vagina and perineum. These signals travel with the pudendal nerve and enter the spinal cord at S2-S4. Thus, the anesthetic solution administered through the lumbar epidural catheter must spread cephalad in the epidural space to reach the T10 nerve roots and spinal cord, and must spread caudad to reach the caudal nerve roots in the epidural space.

The optimal method for maintaining labor analgesia is unknown. Several studies have demonstrated that PIEB, in combination with PCEA, provide superior maintenance of labor analgesia (less need and longer time to provider intervention, lower local anesthetic consumption, less motor block, and improved patient satisfaction scores) than maintenance with a continuous infusion with PCEA.The mechanism for this difference is not known; however, one suggested mechanism is improved spread of the local anesthetic within the epidural space. Kaynar et al. injected methylene blue dye through a multi-orifice catheter using either a continuous infusion or intermittent bolus and the area of diffusion was measured on a piece of paper. The authors found that intermittent boluses were associated with a greater surface area of diffusion than continuous infusion. In a cadaver study, dye was injected into the lumbar epidural space, and cryomicrotome sections were taken.Dye flowed in rivulets through small channels in the epidural space, as opposed to moving as a unified front. The authors found dye injected at high pressures had more uniform spread through the epidural space, supporting the concept of intermittent epidural injection providing superior analgesia.

Epidural infusion pumps capable of delivering PIEB of local anesthetic with PCEA have become commercially available and many studies have attempted to assess the optimal parameter settings (including volume of programmed bolus, bolus interval, rate of bolus administration) to provide superior labor analgesia. Recently we completed a double-blinded randomized control trial evaluating two bolus delivery rates, hypothesizing that those patients randomized to receive higher bolus delivery rates would have improved labor analgesia. However, no difference was found between groups.What is more, both groups had a mean cephalad sensory level to cold of T6. This sensory level is higher than the traditional goal of T10 (upper dermatome level of uterine innervation), but despite the adequate sensory level, a large number of patients required supplemental physician-delivered boluses of local anesthetic during labor. Forty percent of the women in the high-rate group and 36% of the low-rate group required a manual re-dose during labor. This suggests that either a higher volume, or higher concentration of local anesthetic (i.e., higher dose) is needed to maintain adequate labor analgesia.

Traditionally higher concentration local anesthetic solutions have been associated with increased motor blockade leading to a higher incidence of instrumental vaginal delivery. Several local anesthetic solutions with varying drug concentrations are available for labor analgesia and are used clinically in the United States. We plan to perform a randomized, controlled, double-blind study to test the hypothesis that patients whose labor analgesia is maintained using PIEB with low-volume bolus (6.25 mL) of a higher local anesthetic concentration solution (0.1% bupivacaine with fentanyl 2.0 mcg/mL) will require less supplemental analgesia (manual provider re-doses) than patients whose PIEB is delivered with a high-volume bolus (10 mL) of lower density local anesthetic solution (0.0625% bupivacaine with fentanyl 2.0 mcg/mL).

The aim of this study is to evaluate the association between bolus volume and concentration of local anesthetic during maintenance of labor analgesia with programmed intermittent epidural bolus (PIEB) analgesia.

The hypothesis of this study is: patients whose labor analgesia is maintained using PIEB with low-volume bolus (6.25 mL) of higher local anesthetic concentration solution (0.1% bupivacaine with fentanyl 2.0 mcg/mL) will have a longer duration of adequate analgesia (time to first manual re-dose request) than patients whose PIEB is delivered with a high-volume bolus (10 mL) of lower concentration local anesthetic solution (0.0625% bupivacaine with fentanyl 2.0 mcg/mL).


Condition or disease Intervention/treatment Phase
Pain Anesthesia Labor Pain Drug: Low volume bolus Drug: High volume bolus Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Two group randomized controlled trial
Masking: Double (Participant, Outcomes Assessor)
Masking Description: The participant and outcomes assessor will be blinded to the assigned randomization.
Primary Purpose: Treatment
Official Title: The Relationship Between Local Anesthetic Concentration and Volume on Adequate Labor Analgesia With Programmed Intermittent Epidural Bolus
Estimated Study Start Date : December 1, 2019
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : January 15, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Low volume bolus
6.25 mL administration at 250 ml per hour of a greater density solution (0.1% bupivacaine with fentanyl 2.0 mcg/mL)
Drug: Low volume bolus
Administration of a low-volume bolus (6.25 mL) of greater density solution (0.1% bupivacaine with fentanyl 2.0 mcg/mL) at 250 mL per hour given by CADD pump.

Experimental: High volume bolus
10 mL administration of a lower density local anesthetic (0.0625% bupivacaine with fentanyl 2.0 mcg/mL).
Drug: High volume bolus
Administration of a high-volume bolus (10 mL) of lower density local anesthetic (0.0625% bupivacaine with fentanyl 2.0 mcg/mL) at 250 mL per hour given by CADD pump.




Primary Outcome Measures :
  1. Need for supplemental physician-delivered bolus of local anesthetic [ Time Frame: Time of delivery of baby ]
    The amount of supplemental physician delivered boluses of local anesthetic administered prior to the delivery of the baby.


Secondary Outcome Measures :
  1. Time to first request for supplemental analgesia [ Time Frame: delivery (Minutes to first request) ]
    Time elapsed in minutes from epidural set up to time to request supplemental analgesia

  2. Total hourly bupivacaine consumption [ Time Frame: Delivery of baby ]
    Total amount of bupivacaine in milligrams used by the patient from start time of epidural placement to the delivery of the baby

  3. Mode of delivery [ Time Frame: Delivery of baby ]
    Mode of delivery identified as: normal vaginal delivery, instrumental vaginal delivery, cesarean delivery or emergency cesarean delivery

  4. Motor block throughout labor (0-9 cm dilation) [ Time Frame: delivery (From 0 cm to 9 cm dilation of the cervix) ]
    The level of neuraxial blockade assessed by touch from 0-9 cm dilation.

  5. Motor block throughout labor (10cm dilation) [ Time Frame: delivery (At 10 cm dilation of the cervix) ]
    The level of neuraxial blockade assessed by touch at 10 cm cervical width.

  6. Sensory level of block throughout labor (0-9 cm) [ Time Frame: delivery (To 9 cm dilation of cervix) ]
    The level of sensory loss reported by the subject by touch 0-9 cm cervical width assessed every 2 hours

  7. Sensory level at 10 cm [ Time Frame: delivery (At 10 cm dilation of cervix) ]
    The level of sensory loss reported by the subject by touch at 10 cm cervical width.

  8. Pain burden [ Time Frame: Delivery of baby ]
    Pain burden as defined as area under the pain-time curve

  9. Patient Satisfaction [ Time Frame: delivery (After removal of epidural catheter) ]
    Overall satisfaction of labor is measured using a 100 mm unmarked line (the left end labeled "not satisfied at all (o=no satisfaction) " and the right end labeled "extremely satisfied" (100=extremely satisfied)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Pregnant female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 years and above
  • Nulliparous parturients
  • Present to the labor and delivery unit for an induction of labor or who are in spontaneous labor
  • Request neuraxial labor analgesia at ≤5 cm cervical dilation

Exclusion Criteria:

  • Patients who are not eligible to receive a combined spinal epidural (CSE) technique with 25 mcg of intrathecal fentanyl
  • Non-English speaking
  • Failed initiation of CSE analgesia (VAS pain score >10 15 minutes after intrathecal dose)
  • Need to have the epidural catheter replaced during labor
  • Who deliver within 90 minutes of initiation of labor analgesia
  • Require re-dose within 90 minutes of initiation of labor analgesia.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03553576


Contacts
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Contact: Elizabeth Lange, M.D 312-472-3585 elizabeth.lange@northwestern.edu
Contact: Paul C Fitzgerald, MS 312-695-1064 p-fitzgerald2@northwestern.edu

Locations
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United States, Illinois
Prentice Women's Hospital Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Paul Fitzgerald, RN, MS    313-695-1064    p-fitzgerald2@northwestern.edu   
Sponsors and Collaborators
Northwestern University
Investigators
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Principal Investigator: Elizabeth Lange, MD Northwestern University

Publications:
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Responsible Party: Elizabeth Lange, Principal Investigator, Northwestern University
ClinicalTrials.gov Identifier: NCT03553576     History of Changes
Other Study ID Numbers: STU00206113
First Posted: June 12, 2018    Key Record Dates
Last Update Posted: August 21, 2019
Last Verified: August 2019

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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.: No
Keywords provided by Elizabeth Lange, Northwestern University:
Labor pain
Epidural
Obstetric
Labor Analgesia
Additional relevant MeSH terms:
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Labor Pain
Pain
Neurologic Manifestations
Signs and Symptoms
Fentanyl
Bupivacaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Analgesics, Opioid
Narcotics
Analgesics
Adjuvants, Anesthesia
Anesthetics, Intravenous
Anesthetics, General