Programmed Intermittent Epidural Bolus Versus Continuous Epidural Infusion for Postoperative Analgesia After Total Knee Arthroplasty

May 24, 2026 updated by: Ayça Taş Tuna, Sakarya University

Effect of Programmed Intermittent Epidural Bolus Versus Continuous Epidural Infusion on Postoperative Analgesia and Quality of Recovery After Total Knee Arthroplasty: A Prospective Randomized Double-Blind Controlled Trial

The goal of this clinical trial is to compare two different epidural analgesia delivery methods for pain control after total knee arthroplasty in adults undergoing elective surgery. The study will evaluate whether programmed intermittent epidural bolus (PIEB) provides better postoperative analgesia and recovery outcomes than continuous epidural infusion (CEI).

The main questions it aims to answer are:

Does PIEB reduce total epidural local anesthetic consumption during the first 24 postoperative hours compared with CEI? Does PIEB improve postoperative pain control and quality of recovery? Are there differences between the two methods regarding motor block, rescue analgesic requirement, patient-controlled epidural analgesia use, and adverse effects?

Researchers will compare PIEB plus patient-controlled epidural analgesia (PCEA) with CEI plus PCEA in patients undergoing total knee arthroplasty.

Participants will:

Receive combined spinal-epidural anesthesia during surgery Receive postoperative epidural analgesia using either PIEB or CEI Be evaluated for pain scores, motor block, recovery quality, epidural local anesthetic consumption, rescue analgesic requirement, and adverse events during the first 24 postoperative hours

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Total knee arthroplasty (TKA) is one of the most commonly performed orthopedic procedures and is associated with significant postoperative pain. Inadequate pain control after TKA may delay mobilization, prolong hospitalization, impair rehabilitation, and negatively affect patient satisfaction and recovery quality. Therefore, optimizing postoperative analgesia while minimizing opioid consumption and preserving motor function is an important component of enhanced recovery after surgery (ERAS) protocols.

Epidural analgesia has been widely used for postoperative pain management for decades. Conventional continuous epidural infusion (CEI) provides stable delivery of local anesthetic but may be associated with uneven epidural spread, higher local anesthetic consumption, and increased motor blockade in some patients.

Programmed intermittent epidural bolus (PIEB) is an alternative epidural drug delivery technique in which local anesthetic is administered automatically at predefined intervals as intermittent boluses rather than as a continuous infusion. Due to the higher injection pressure and intermittent delivery pattern, PIEB may improve epidural spread and analgesic quality while reducing total local anesthetic requirements and motor block. Although PIEB has been extensively investigated in obstetric analgesia, evidence regarding its use in major orthopedic surgery remains limited.

This prospective, randomized, double-blind, parallel-group clinical trial aims to compare PIEB plus patient-controlled epidural analgesia (PCEA) with CEI plus PCEA in patients undergoing elective primary total knee arthroplasty under combined spinal-epidural anesthesia.

A total of 90 participants will be enrolled and randomized in a 1:1 ratio into two groups:

  • PIEB + PCEA group
  • CEI + PCEA group

Randomization will be performed using a computer-generated randomization sequence with allocation concealment through sequentially numbered opaque sealed envelopes.

All participants will receive standardized combined spinal-epidural anesthesia. Epidural catheter placement will be performed at the L2-L3 interspace using the needle-through-needle technique. Spinal anesthesia will be achieved with 12.5 mg hyperbaric bupivacaine administered intrathecally.

Postoperatively, all participants will receive epidural analgesia using the same epidural solution consisting of 0.1% bupivacaine diluted in normal saline.

In the PIEB group, epidural analgesia will be delivered as programmed intermittent epidural boluses of 6 mL every 60 minutes combined with patient-controlled epidural boluses of 6 mL with a 30-minute lockout interval.

In the CEI group, epidural analgesia will be delivered as continuous epidural infusion at 6 mL/hour combined with patient-controlled epidural boluses of 6 mL with a 30-minute lockout interval.

All participants will additionally receive standardized multimodal analgesia with scheduled paracetamol administration. Intravenous tramadol will be used as rescue analgesia when the visual analog scale (VAS) pain score is 4 or greater.

The primary outcome measure is total epidural local anesthetic consumption during the first 24 postoperative hours.

Secondary outcome measures include:

  • Quality of recovery assessed using the QoR-15 questionnaire
  • Motor block assessed with the modified Bromage scale
  • Number of patient-controlled epidural bolus demands and delivered boluses
  • Rescue analgesic consumption
  • Resting and movement-related VAS pain scores

Pain scores will be assessed at postoperative 2, 4, 8, 12, and 24 hours. QoR-15 will be evaluated preoperatively and at postoperative 24 hours.

The study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent will be obtained from all participants before enrollment.

Study Type

Interventional

Enrollment (Estimated)

90

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Turkey (Türkiye)
    • Adapazari
      • Sakarya, Adapazari, Turkey (Türkiye), 54000
        • Sakarya University Training and Research Hospital, Department of Anesthesiology and Reanimation
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults aged 18 to 80 years
  • American Society of Anesthesiologists (ASA) physical status I-III
  • Scheduled for elective primary total knee arthroplasty
  • Eligible for combined spinal-epidural anesthesia and postoperative epidural analgesia
  • Able to understand and use patient-controlled epidural analgesia
  • Provided written informed consent

Exclusion Criteria:

  • Refusal to participate in the study
  • Known allergy or hypersensitivity to study medications
  • Body mass index (BMI) ≥ 40 kg/m²
  • Body weight < 40 kg
  • Severe cardiac disease, including symptomatic arrhythmia or advanced conduction abnormalities
  • Coagulopathy (INR > 1.5 or platelet count < 100,000/mm³)
  • Pregnancy or breastfeeding
  • Revision total knee arthroplasty or emergency surgery
  • Active infection at the site of regional anesthesia
  • Chronic opioid use or opioid dependence
  • Neurological disease or preexisting motor/sensory deficit in the lower extremities
  • ASA physical status IV or V
  • Requirement for intraoperative epidural local anesthetic supplementation due to inadequate spinal anesthesia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PIEB
Participants will receive postoperative epidural analgesia using programmed intermittent epidural bolus (PIEB) combined with patient-controlled epidural analgesia (PCEA). The epidural solution will consist of 0.1% bupivacaine. Automatic epidural boluses of 6 mL will be delivered every 60 minutes. Patient-controlled epidural boluses of 6 mL with a 30-minute lockout interval will also be available.
Procedure: Programmed intermittent epidural bolus 6 ml
Postoperative epidural analgesia delivered as programmed intermittent epidural boluses using 0.1% bupivacaine. Automatic boluses of 6 mL will be administered every 60 minutes in combination with patient-controlled epidural analgesia boluses of 6 mL with a 30-minute lockout interval.
Other Names:
  • PIEB
Active Comparator: CEI
Participants will receive postoperative epidural analgesia using continuous epidural infusion (CEI) combined with patient-controlled epidural analgesia (PCEA). The epidural solution will consist of 0.1% bupivacaine. Continuous epidural infusion will be administered at a rate of 6 mL/hour. Patient-controlled epidural boluses of 6 mL with a 30-minute lockout interval will also be available.
Procedure: continuous epidural infusion
Postoperative epidural analgesia delivered as continuous epidural infusion using 0.1% bupivacaine at a rate of 6 mL/hour in combination with patient-controlled epidural analgesia boluses of 6 mL with a 30-minute lockout interval.
Other Names:
  • CEI

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total epidural local anesthetic consumption during the first 24 postoperative hours
Time Frame: From initiation of postoperative epidural analgesia in the post-anesthesia care unit (PACU) to postoperative 24 hours
Total epidural local anesthetic consumption will be calculated as the sum of automatic epidural boluses and patient-controlled epidural analgesia boluses delivered during the first 24 postoperative hours. Total consumption will be recorded in milliliters (mL) using epidural pump records.
From initiation of postoperative epidural analgesia in the post-anesthesia care unit (PACU) to postoperative 24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of recovery assessed with QoR-15
Time Frame: Preoperative baseline and postoperative 24 hours
Postoperative recovery quality will be evaluated using the Quality of Recovery-15 (QoR-15) questionnaire. The QoR-15 is a validated 15-item patient-reported outcome measure with total scores ranging from 0 to 150, where higher scores indicate better recovery.
Preoperative baseline and postoperative 24 hours
Number of patient-controlled epidural analgesia bolus demands and delivered boluses
Time Frame: During the first 24 postoperative hours
The total number of patient-controlled epidural analgesia (PCEA) bolus demands and successfully delivered boluses will be recorded using epidural pump data.
During the first 24 postoperative hours
Rescue analgesic consumption
Time Frame: During the first 24 postoperative hours
Rescue analgesic consumption will be assessed as the total amount of intravenous tramadol administered for breakthrough pain requiring rescue analgesia.
During the first 24 postoperative hours
Resting and movement-related pain scores assessed with VAS
Time Frame: Postoperative 2, 4, 8, 12, and 24 hours
Postoperative pain intensity at rest and during movement will be assessed using a 10-point visual analog scale (VAS), where 0 indicates no pain and 10 indicates the worst imaginable pain.
Postoperative 2, 4, 8, 12, and 24 hours
Motor block assessed with the modified Bromage scale
Time Frame: Postoperative 2 and 4 hours
Motor block severity will be evaluated using the modified Bromage scale, ranging from 0 to 3, where 0 indicates no motor block and 3 indicates complete motor block. Higher scores indicate greater motor blockade. Motor block presence will additionally be defined as a Bromage score of 1 or greater.
Postoperative 2 and 4 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sakarya University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

May 18, 2026

First Submitted That Met QC Criteria

May 18, 2026

First Posted (Actual)

May 22, 2026

Study Record Updates

Last Update Posted (Actual)

May 28, 2026

Last Update Submitted That Met QC Criteria

May 24, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • SEAH-OTOBOLUS-2026

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Individual participant data (IPD) sharing has not yet been determined. De-identified data may be shared upon reasonable request following publication of the study results, subject to institutional and ethical considerations.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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