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

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

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. 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.

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.

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).

Study Overview

• Status: Terminated
• Conditions: Pain; Labor Pain; Anesthesia
• Intervention / Treatment: Drug: Low volume bolus; Drug: High volume bolus

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Prentice Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anesthesia Provider Administered Bolus	Anesthesia provider (MD) administered boluses of additional anesthetic administered prior to the delivery of the baby.	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VAS at 10 Centimeters Dilation of Cervix	VAS (visual analogue scale) at 10 centimeters dilation of cervix on a scale of 0 (no pain,good) to 100 (worst pain imaginable,bad)	24 hours
VAS Score After Delivery	VAS score (Visual Analogue Scale) on a score of 0 (no pain,good) to 100 (worst pain imaginable,bad) immediately after delivery of baby	24 hours
Intrascapular Pain	Number of participants who experienced intrascapular pain (pain in your shoulder blade) during the study period.	72 hours
Provider Administered Bolus	Number of participants requiring anesthesia provider administration of additional bolus doses of pain medication.	72 hours
Number of Participants Who Required Additional Provider Redoses	Additional number of participants who required additional anesthesia care provider redoses of pain medication.	72 hours
Time to First Anesthesiology Provider Bolus	Time elapsed in minutes from epidural set up to time to request supplemental analgesia provided by the anesthesiology care provider.	72 hours
VAS Score Prior to First Provider Bolus Dose	Patient reported visual analogue scale score (0 no pain,good-100 worst pain imaginable, bad) prior to the first anesthesiology care provider bolus dose of anesthetic (pain medication).	72 hours
VAS Score 30 Minutes After Anesthetic Care Provider Dose	Patient reported visual analogue scale score (0 no pain, good -100 worst pain imaginable, bad) 30 minutes after the first anesthesiology care provider bolus dose of anesthetic was administered to the participant for pain relief.	72 hours
Bupivacaine Consumption Per Hour	Average consumption of bupivacaine in milligrams per hour.	72 hours
Maximum Oxytocin Dose	Maximum oxytocin dose administered intravenously in international units.	72 hours
Time of Intrathecal Administration to Delivery	Elapsed time in minutes from the intrathecal administration of anesthetic by anesthesiology provider to time of delivery of baby.	72 hours
Number of Participants Categorized by Mode of Delivery	Mode of delivery identified as: normal vaginal delivery, instrumental vaginal delivery, cesarean delivery or emergency cesarean delivery	72 hours
PCA Boluses	Number of Patient-Controlled Epidural Analgesia (PCEA) boluses of pain medication requested and number of PCEA medication boluses administered.	72 hours
PCA Boluses Ratio	The ratio of the number of Patient-Controlled Epidural Analgesia (PCEA) pain medication boluses requested and number of PCEA pain medication boluses administered by the PCEA pump.	72 hours

Collaborators and Investigators

• Sponsor: Northwestern University
• Investigators: Principal Investigator: Feyce Peralta, MD, Northwestern University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2020
• Primary Completion (Actual): May 31, 2023
• Study Completion (Actual): June 1, 2023

Study Registration Dates

• First Submitted: May 30, 2018
• First Submitted That Met QC Criteria: June 11, 2018
• First Posted (Actual): June 12, 2018

Study Record Updates

• Last Update Posted (Actual): May 21, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Labor pain; Epidural; Labor Analgesia; Obstetric
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Labor Pain
• Other Study ID Numbers: STU00206113

Drug and device information, study documents

• 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