Drug Concentration and Volume on Adequate Labor Analgesia With PIEB

Pain Clinical Trial

— CADD2  

Official title:

The Relationship Between Local Anesthetic Concentration and Volume on Adequate Labor Analgesia With Programmed Intermittent Epidural Bolus

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03553576
• Other study ID #: STU00206113
• Status: Terminated
• Phase: Phase 4
• Start date: January 9, 2020
• Est. completion date: June 1, 2023

Study information

• Verified date: April 2024
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 156
• Est. completion date: June 1, 2023
• Est. primary completion date: May 31, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anesthesia
• Labor Pain
• Pain

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Prentice Women's Hospital	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Northwestern University

Country where clinical trial is conducted

United States, 

References & Publications (6)

Chua SM, Sia AT. Automated intermittent epidural boluses improve analgesia induced by intrathecal fentanyl during labour. Can J Anaesth. 2004 Jun-Jul;51(6):581-5. doi: 10.1007/BF03018402. — View Citation

Comparative Obstetric Mobile Epidural Trial (COMET) Study Group UK. Effect of low-dose mobile versus traditional epidural techniques on mode of delivery: a randomised controlled trial. Lancet. 2001 Jul 7;358(9275):19-23. doi: 10.1016/S0140-6736(00)05251-X. — View Citation

Hogan Q. Distribution of solution in the epidural space: examination by cryomicrotome section. Reg Anesth Pain Med. 2002 Mar-Apr;27(2):150-6. doi: 10.1053/rapm.2002.29748. — View Citation

Kaynar AM, Shankar KB. Epidural infusion: continuous or bolus? Anesth Analg. 1999 Aug;89(2):534. doi: 10.1097/00000539-199908000-00063. No abstract available. — View Citation

Lim Y, Sia AT, Ocampo C. Automated regular boluses for epidural analgesia: a comparison with continuous infusion. Int J Obstet Anesth. 2005 Oct;14(4):305-9. doi: 10.1016/j.ijoa.2005.05.004. — View Citation

Wong CA, Ratliff JT, Sullivan JT, Scavone BM, Toledo P, McCarthy RJ. A randomized comparison of programmed intermittent epidural bolus with continuous epidural infusion for labor analgesia. Anesth Analg. 2006 Mar;102(3):904-9. doi: 10.1213/01.ane.0000197778.57615.1a. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Need for supplemental physician-delivered bolus of local anesthetic	The amount of supplemental physician delivered boluses of local anesthetic administered prior to the delivery of the baby.	Time of delivery of baby
Secondary	Time to first request for supplemental analgesia	Time elapsed in minutes from epidural set up to time to request supplemental analgesia	delivery (Minutes to first request)
Secondary	Total hourly bupivacaine consumption	Total amount of bupivacaine in milligrams used by the patient from start time of epidural placement to the delivery of the baby	Delivery of baby
Secondary	Mode of delivery	Mode of delivery identified as: normal vaginal delivery, instrumental vaginal delivery, cesarean delivery or emergency cesarean delivery	Delivery of baby
Secondary	Motor block throughout labor (0-9 cm dilation)	The level of neuraxial blockade assessed by touch from 0-9 cm dilation.	delivery (From 0 cm to 9 cm dilation of the cervix)
Secondary	Motor block throughout labor (10cm dilation)	The level of neuraxial blockade assessed by touch at 10 cm cervical width.	delivery (At 10 cm dilation of the cervix)
Secondary	Sensory level of block throughout labor (0-9 cm)	The level of sensory loss reported by the subject by touch 0-9 cm cervical width assessed every 2 hours	delivery (To 9 cm dilation of cervix)
Secondary	Sensory level at 10 cm	The level of sensory loss reported by the subject by touch at 10 cm cervical width.	delivery (At 10 cm dilation of cervix)
Secondary	Pain burden	Pain burden as defined as area under the pain-time curve	Delivery of baby
Secondary	Patient Satisfaction	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)	delivery (After removal of epidural catheter)