Programmed Intermittent Epidural Bolus Compared With Continuous Infusion in Multiparous Women

Impact of Programmed Intermittent Epidural Bolus Compared With Continuous Epidural Infusion on Breakthrough Pain Among Laboring Multiparous Women. A Randomized Controlled Trial

The goal of this randomized controlled trial is to examine the impact of programmed intermittent bolus epidural analgesia technique on the incidence of breakthrough pain during labor in multiparous women compared to continuous epidural infusion.

multiparous women will randomly be divided during labor into two groups; study group will receive mix of Bupivacaine and fentanyl once (bolus) every 60 minutes; the control group will receive continuously the same dose during an hour, until delivery.

Study Overview

• Status: Recruiting
• Conditions: Breakthrough Pain
• Intervention / Treatment: Drug: programmed intermittent Bolus epidural analgesia; Drug: continuous epidural infusion

Detailed Description

There are several pharmacological and non-pharmacological techniques for pain relief during labor. Epidural analgesia is considered the most effective modality for intrapartum pain relief.

Maintenance of epidural analgesia is achieved by different techniques; continuous epidural infusion (CEI), intermittent epidural analgesia (IEA), patient control epidural analgesia (PCEA) and combination between the techniques.

Another technique, the Programmed Intermittent Bolus Epidural Analgesia (PIBEA). The advantage of this technique is that boluses are given all the time at planned intervals, so laboring women do not depend on the medical staff to receive the bolus when there is a breakthrough pain.

This method has been reported to be associated with less motor block, lower incidence of instrumental vaginal deliveries, and less consumption of anesthetic agents when compared to CEI. There are no conclusive data regarding the use of PIBEA in combination with PCEA compared to CEI and PCEA on the effect of pain relief during labor and birth outcomes. The hypothesis of the current trial is that PIBEA and PCEA will decrease the incidence of breakthrough pain, and probably shorten the second stage of labor, lead to fewer instrumental deliveries and higher women's satisfaction compared to CEI and PCEA.

• Study Type: Interventional
• Enrollment (Estimated): 186
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Asmaa Masri Esmail, MD; Email: Asmaa.Masri94@gmail.com
• Study Contact Backup: Name: Raed Salim, MD; Phone Number: +972 0544986960; Email: r.salim@hfhosp.org

Study Locations

• Israel
  • Nazareth, Israel, 1641100
    • Recruiting
    • Holy Family Hospital
    • Contact: Raed Salim, MD; Phone Number: 0544986960; Email: r.salim@hfhosp.org
    • Principal Investigator: Asmaa Masri Esmail, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. multiparous women
2. Term pregnancy
3. Singleton
4. Vertex presentation
5. Latent phase (cervical dilatation less than 6 cm)
6. Epidural analgesia request
7. Visual Analogue Scale score greater than 40

Exclusion Criteria:

1. Estimated fetal weight greater than 4.0 kg
2. Intra uterine fetal death
3. Drug sensitivity

5. Anomalous fetus 6. Contraindication for epidural analgesia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: study group; Epidural analgesia will be maintained by receiving programmed intermittent 10ml bolus of 0.1% Bupivacaine and 2microgram\ml Fentanyl every one hour, until the delivery is completed, and lacerations are sutured.	Drug: programmed intermittent Bolus epidural analgesia; About 30 minutes after the end of the epidural and administration of the loading dose, the woman will be asked to report her pain level. If the VAS score <30, the woman will receive the study group protocol for pain maintenance, i.e., a programmed intermittent bolus of 10 ml of 0.1% bupivacaine and 2 μg/ml fentanyl every hour until the completion of labor and suturing of the incision. The participant can add to herself 5 ml of the same solution of Bupivacaine and Fentanyl every 30 minutes. The maximum dose that the parturient is allowed to receive is 20 ml for one hour. If a breakthrough pain appears during labor, a bolus of 10 ml of anesthetic solution with the same concentration will be added. Participants with a VAS score >30 after 30 minutes of the loading dose will be asked to perform a new epidural (if it was decided that the epidural failed) otherwise her data will not be collected for the final analysis of the study.; Other Names: Bupivacaine + Fentanyl
Active Comparator: control group; Epidural analgesia will be maintained by receiving 10ml\h continuous infusion of 0.1% Bupivacaine and 2microgram\ml Fentanyl until the delivery is completed, and lacerations are sutured.	Drug: continuous epidural infusion; About 30 minutes after the end of the epidural and administration of the loading dose, the woman will be asked to report her pain level. If the VAS score <30, the woman will receive the control group protocol for pain maintenance, i.e., 0.1% Bupivacaine and 2 μg/ml fentanyl as a continuous infusion per one hour, until the delivery is completed, and laceration is sutured. The participant can add to herself 5 ml of the same solution of Bupivacaine and Fentanyl every 30 minutes. The maximum dose that the parturient is allowed to receive is 20 ml for one hour. If a breakthrough pain appears during labor, a bolus of 10 ml of anesthetic solution with the same concentration will be added. Participants with a VAS score >30 after 30 minutes of the loading dose will be asked to perform a new epidural (if it was decided that the epidural failed) otherwise her data will not be collected for the final analysis of the study.; Other Names: Bupivacaine + Fentanyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
breakthrough pain	Incidence of breakthrough pain, defined as Visual Analogue Scale (VAS) score > 30. The VAS consists of a 100cm line, with two end points representing 0 ('no pain') and 100 (severe pain).	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mode of delivery	Whether the birth was a normal spontaneous birth, operative vaginal birth or a cesarean section.	48 hours
Intrapartum fever	Number of patients that will have intrapartum fever ≥ 38 °C	48 hours
Number of patients that will require use of intrapartum use of antibiotic treatment	Number of patients that will require use of intrapartum use of antibiotic treatment due to intrapartum infection.	48 hours
manual bolus (top up)	Number of participants who will require top up of Bupivacaine and Fentanyl due to breakthrough pain.	48 hours
Time to delivery	Time from epidural analgesia to delivery.	48 hours
Oxytocin augmentation	Incidence of women who will require Oxytocin for labor augmentation	48 hours
Duration of second stage	The time from complete cervical dilatation until delivery of the fetus (minutes)	48 hours
Indications for cesarean or operative vaginal deliveries	Was the reason for operative vaginal delivery or cesarean delivery due to non-progressive labor, fetal status, or a combination of both?	48 hours
duration of third stage	time from delivery of the fetus the delivery of the placenta (minutes)	48 hours
Early postpartum hemorrhage (PPH)	Number of Participants with develop PPH	48 hours
Hemoglobin level	The lowest postpartum Hemoglobin level	96 hours
Blood transfusion	Number of Participants that will need blood transfusion.	72 hours
Obstetric anal sphincter injury	Number of Participants with that will develop 3rd and 4th degrees perineal lacerations.	48 hours
Motor block of any leg	Incidence of motor block will be assessed according to Bromage score: Bromage 0 = No motor block. Bromage 1 = the participant is unable to flex her hip Bromage 2 = the participant is able to flex her ankle but unable to flex her hip and knee Bromage 3 = the participant is unable to flex her hip, knee and ankle	48 hours
Urinary retention	Participant will not be able to urinate spontaneously 6 hours after delivery	48 hours
Dural puncture	Incidence of dural puncture during performing epidural analgesia	48 hours
Side effects related epidural analgesia use	nausea, vomiting, and pruritis	48 hours
mean arterial blood pressure	mean arterial blood pressure (mmHg) of the participant during labor	48 hours
systolic blood pressure < 90mmHg	incidence of systolic blood pressure < 90 during labor	48 hours
Bupivacaine consumption	total Bupivacaine consumption during labor (ml)	48 hours
maternal satisfaction	participant satisfaction from labor experience from 1 to 10. 1= very dissatisfied 10 = very satisfied	48 hours
fetal cord artery pH	Cord artery pH <7.1	48 hours
meconium staining	Incidence of meconium-stained amniotic fluid before delivery of the fetus	48 hours
Neonatal sepsis	Incidence of early neonatal sepsis	72 hours
Hourly visual analogue scale	Hourly pain according to visual analogue scale (VAS) score. The VAS consists of a 100cm line, with two end points representing score 0 (no pain) and score 100 (severe pain).	48 hours
Apgar score (0 to 10)	APGAR score < 7 after 1 and 5 minutes where lower scores mean a worse outcome.	48 hours

Collaborators and Investigators

• Sponsor: Holy Family Hospital, Nazareth, Israel
• Investigators: Study Chair: Raed Salim, MD, Holy Family Hospital, Nazareth, Israel

Publications and helpful links

General Publications

• 1. American College of Obstetricians and Gynecologists. Obstetric analgesia and anesthesia. ACOG Practice Bulletin No. 209. Obstet Gynecol. 2019;133:e208-25. 2. Anim-Somuah M, Smyth RM, Cyna AM, Cuthbert A. Epidural versus non-epidural or no analgesia for pain management in labour. Cochrane Database of Systematic Reviews 2018:5;CD000331. 3. Jones L, Othman M, Dowswell T, Alfirevic Z, Gates S, Newburn M, et al. Pain management for women in labour: an overview of systematic reviews. Cochrane Database of Systematic Reviews 2012:3;CD009234. 4. George RB, Allen TK, Habib AS. Intermittent epidural bolus compared with continuous epidural infusions for labor analgesia: a systematic review and meta-analysis. Anesth Analg 2013;116:133-44. 5. Sng BL, Zeng Y, de Souza NNA, Leong WL, Oh TT, Siddiqui FJ, Assam PN, Han NR, Chan ES, Sia AT. Automated mandatory bolus versus basal infusion for maintenance of epidural analgesia in labour. Cochrane Database Syst Rev. 2018;5:CD011344. 6. Ferrer LE, Romero DJ, Vasquez OI, Matute EC, Van de Velde M. Effect of programmed intermittent epidural boluses and continuous epidural infusion on labor analgesia and obstetric outcomes: a randomized controlled trial. Arch Gynecol Obstet. 2017;296:915-22. 7. Ojo OA, Mehdiratta JE, Gamez BH, Hunting J, Habib AS. Comparison of programmed intermittent epidural boluses with continuous epidural infusion for the maintenance of labor analgesia: a randomized, controlled, double-blind study. Anesth Analg. 2020;130:426-35. 8. Haidl F, Arne Rosseland L, Rorvik AM, Dahl V. Programmed intermittent boluses vs continuous epidural infusion in labor using an adrenaline containing solution: A randomized trial. Acta Anaesthesiol Scand. 2020;64:1505-12. 9. Riazanova OV, Alexandrovich YS, Guseva YV, Ioscovich AM. A randomized comparison of low dose ropivacaine programmed intermittent epidural bolus with continuous epidural infusion for labour analgesia. Rom J Anaesth Intensive Care. 2019;26:25-30. 10. Fan Y, Hou W, Feng S, Mao P, Wang X, Jiang J, Yuan H, Shen X, Feng S, Li P. Programmed intermittent epidural bolus decreases the incidence of intra-partum fever for labor analgesia in primiparous women: a randomized controlled study. Arch Gynecol Obstet. 2019;300:1551-7 11. Xu J, Zhou J, Xiao H, Pan S, Liu J, Shang Y, Yao S. A systematic review and meta-analysis comparing programmed intermittent bolus and continuous infusion as the background infusion for parturient-controlled epidural analgesia. Sci Rep. 2019;9:2583. 12. Wang XX, Zhang XL, Zhang ZX, Xin ZQ, Guo HJ, Liu HY, Xiao J, Zhang YL, Yuan SZ. Programmed intermittent epidural bolus in parturients: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2022;101: e28742. 13. Bullingham A, Liang S, Edmonds E, Mathur S, Sharma S. Continuous epidural infusion vs programmed intermittent epidural bolus for labour analgesia: a prospective, controlled, before-and-after cohort study of labour outcomes. Br J Anaesth. 2018;121:432-7. 14. Lin Y, Li Q, Liu J, Yang R, Liu J. Comparison of continuous epidural infusion and programmed intermittent epidural bolus in labor analgesia. Ther Clin Risk Manag. 2016;12:1107-12. 15. Lim Y, Sia AT, Ocampo C. Automated regular boluses for epidural analgesia: a comparison with continuous infusion. Int J Obstet Anesth. 2005;14:305-9. 16. Salim R, Nachum Z, Moscovici R, Lavee M, Shalev E. Continuous compared with intermittent epidural infusion on progress of labor and patient satisfaction. Obstet Gynecol 2005;106:301-6. 17. Lim Y, Ocampo CE, Supandji M, Teoh WH, Sia AT. A randomized controlled trial of three patient-controlled epidural analgesia regimens for labor. Anesth Analg 2008;107:1968-72. 18. Capogna G, Camorcia M, Stirparo S, Farcomeni A. Programmed intermittent epidural bolus versus continuous epidural infusion for labor analgesia: the effects on maternal motor function and labor outcome. A randomized double-blind study in nulliparous women. Anesth Analg 2011;113:826-31. 19. Carvalho B, George RB, Cobb B, McKenzie C, Riley ET. Implementation of Programmed Intermittent Epidural Bolus for the Maintenance of Labor Analgesia. Anesth Analg 2016;123:965-71 20. Diez-Picazo LD, Guasch E, Brogly N, Gilsanz F. Is breakthrough pain better managed by adding programmed intermittent epidural bolus to a background infusion during labor epidural analgesia? A randomized controlled trial. Minerva Anestesiol. 2019;85:1097-104. 21. 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;102:904-9.

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: August 26, 2024
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Term pregnancy; Singleton; Vertex presentation; Latent phase; Maternal request for epidural; Visual analogue scale > 4; multipara
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Breakthrough Pain; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Anilides; Amides; Aniline Compounds; Amines; Piperidines; Bupivacaine; Fentanyl
• Other Study ID Numbers: 298\2024 HFH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD that underlie results in a publication
• IPD Sharing Time Frame: starting 6 months after publication

IPD Sharing Access Criteria

Access to IPD can be requested by qualified researchers and will be granted after review and approval of a research proposal and statistical analysis plan and execution of a data sharing agreement.

For more information or to apply, please contact the Principal Investigator

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No