Drug Concentration and Volume on Adequate Labor Analgesia With PIEB

Phase 4

Terminated

• Conditions: Pain; Anesthesia; Labor Pain
• Interventions: Drug: Low volume bolus; Drug: High volume bolus

• Registration Number: NCT03553576
• Lead Sponsor: 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).

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-05-30
• Study First Submitted QC: 2018-06-11
• Study First Posted: 2018-06-12
• Study Start: 2020-01-09
• Primary Completion: 2023-05-31
• Study Completion: 2023-06-01
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-16
• Last Update Posted: 2024-04-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 156

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low volume bolus	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)
High volume bolus	High volume bolus	10 mL administration of a lower density local anesthetic (0.0625% bupivacaine with fentanyl 2.0 mcg/mL).

Primary Outcome Measures

Name	Time	Method
Need for supplemental physician-delivered bolus of local anesthetic	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

Name	Time	Method
Total hourly bupivacaine consumption	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
Sensory level of block throughout labor (0-9 cm)	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
Patient Satisfaction	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)
Mode of delivery	Delivery of baby	Mode of delivery identified as: normal vaginal delivery, instrumental vaginal delivery, cesarean delivery or emergency cesarean delivery
Motor block throughout labor (0-9 cm dilation)	delivery (From 0 cm to 9 cm dilation of the cervix)	The level of neuraxial blockade assessed by touch from 0-9 cm dilation.
Motor block throughout labor (10cm dilation)	delivery (At 10 cm dilation of the cervix)	The level of neuraxial blockade assessed by touch at 10 cm cervical width.
Sensory level at 10 cm	delivery (At 10 cm dilation of cervix)	The level of sensory loss reported by the subject by touch at 10 cm cervical width.
Time to first request for supplemental analgesia	delivery (Minutes to first request)	Time elapsed in minutes from epidural set up to time to request supplemental analgesia
Pain burden	Delivery of baby	Pain burden as defined as area under the pain-time curve

Trial Locations

Locations (1)

Prentice Women's Hospital; 🇺🇸 Chicago, Illinois, United States