Enhanced Recovery After Surgery-Based Multimodal Preemptive Analgesia for Perioperative Management in Transarterial Chemoembolization of Intermediate-to-Advanced Hepatocellular Carcinoma

December 31, 2025 updated by: Jiaping Li, First Affiliated Hospital, Sun Yat-Sen University

Enhanced Recovery After Surgery-Based Multimodal Preemptive Analgesia for Perioperative Management in Transarterial Chemoembolization of Intermediate-to-Advanced Hepatocellular Carcinoma: a Multicenter Retrospective Cohort Study

To evaluate the effectiveness of the combination of hydrochloride hydromorphone and flurbiprofen ester for post-TACE intravenous patient-controlled intravenous analgesia (PCIA).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This multicenter retrospective study analyzed clinical data from 129 patients with intermediate or advanced HCC who underwent TACE at three centers. Patients were divided into perioperative analgesia protocol groups: Group A (n=85) received patient-controlled intravenous analgesia-based multimodal preemptive analgesia (hydromorphone hydrochloride 6 mg, flurbiprofen axetil 50 mg) with background infusion. Group B (n=44) received conventional on-demand analgesia (intraoperative intravenous flurbiprofen axetil 50 mg, intramuscular tramadol 100 mg as needed for pain). Outcome measures included numerical rating pain scale scores, perioperative adverse events, inflammatory markers, hepatic function indicators, analgesia satisfaction, and cost-effectiveness.

Study Type

Interventional

Enrollment (Actual)

129

Phase

  • Phase 4

Contacts and Locations

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

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510000
        • The First Affiliated Hospital, Sun Yat-sen University

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:

  1. Pathologically or clinically diagnosed with hepatocellular carcinoma according to the "Guidelines for Diagnosis and Treatment of Primary Liver Cancer" issued by the National Health Commission of China in 2024;
  2. staged as China Liver Cancer Stage II-III1 or 2022 Barcelona Clinic Liver Cancer stage B-C14;
  3. liver function classified as Child-Pugh grade A or B;
  4. ECOG PS score 0-215;
  5. meeting the following hematological criteria: white blood cell count ≥3×10⁹/L, platelet count ≥50×10⁹/L, hemoglobin ≥80 g/L, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤twice the upper limit of normal (ULN), serum creatinine ≤1.5×ULN, INR <1.5 or prothrombin time <ULN + 4 s, albumin (ALB) ≥30 g/L, total bilirubin <34 mmol/L.

Exclusion Criteria:

  1. History of iodine contrast allergy;
  2. severe psychological or psychiatric disorders;
  3. history of long-term analgesic medication use;
  4. severe cardiopulmonary disease;
  5. severe uncontrolled infection;
  6. incomplete medical records.

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: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A:hydromorphone + flurbiprofen axetil
Group A received hydromorphone hydrochloride combined with flurbiprofen axetil via PCIA. Hydromorphone hydrochloride 6 mg (2 mL:2 mg, Hubei Yichang Humanwell Pharmaceutical) + flurbiprofen axetil 50 mg (5 mL:50 mg, Beijing Tide Pharmaceutical) were diluted with normal saline to 100 ml and loaded into a PCIA pump (48-h cycle). The pump was initiated 15 min before surgery, with settings of background infusion 2 ml/h, bolus dose 2 ml, and lockout interval 15 min. Patients could self-administer boluses when the numerical pain rating scale (NRS) score was ≥4, with repeated presses during lockout having no effect. For patients with an NRS score ≥4 after two effective boluses, hydromorphone 1 mg diluted in normal saline to 10 ml was administered as a slow push over 2-3 min.
Drug: hydrochloride hydromorphone + flurbiprofen axetil
Group A received hydromorphone hydrochloride combined with flurbiprofen axetil via PCIA. The pump was initiated 15 min before surgery, with settings of background infusion 2 ml/h, bolus dose 2 ml, and lockout interval 15 min.
Active Comparator: conventional analgesia
Group B received on-demand analgesia. When the NRS score was ≥4, flurbiprofen axetil 50 mg was administered intravenously, with intramuscular tramadol 100 mg added if analgesia was inadequate.
Drug: conventional analgesia
When the NRS score was ≥4, flurbiprofen axetil 50 mg was administered intravenously, with intramuscular tramadol 100 mg added if analgesia was inadequate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Perioperative numerical pain rating scale (NRS) score
Time Frame: From the start of the operation to 24 hours after the operation
The NRS was used to assess pain intensity intraoperatively, immediately postoperatively, and at 1 h, 4 h, 8 h, 12 h, and 24 h postoperatively, with scores ranging 0-10 (0=no pain, 1-3=mild pain, 4-6=moderate pain, 7-10=severe pain).
From the start of the operation to 24 hours after the operation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Surgical Duration
Time Frame: From the start of the operation to the end of the operation
Total time from puncture initiation to completion of dressing (min).
From the start of the operation to the end of the operation
Adverse Events
Time Frame: From the start of the operation to 24 hours after the operation
Adverse events within 24 h postoperatively were recorded, including elevated ALBI scores, ALT and AST >2×ULN, nausea and vomiting, drowsiness and dizziness, pruritus, and urinary difficulty, with related indicator changes and incidence documented.
From the start of the operation to 24 hours after the operation
Analgesia Satisfaction
Time Frame: At 24 hours postoperatively
At 24 h postoperatively, patients' subjective experiences were assessed using a 5-point Likert scale (5=very satisfied, 4=satisfied, 3=neutral, 2=dissatisfied, 1=very dissatisfied).
At 24 hours postoperatively
Cost-Effectiveness Analysis
Time Frame: From the start of the operation to the end of perioperative period
TACE perioperative analgesia costs plus postoperative hospitalization costs were used as the cost indicator (C), with analgesia satisfaction ≥4 as the effectiveness indicator (E). The average cost approach was used for incremental cost-effectiveness analysis (ΔC/ΔE).
From the start of the operation to the end of perioperative period

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum Inflammatory Markers
Time Frame: preoperatively and on the second postoperative morning
Fasting venous blood was collected preoperatively and on the second postoperative morning to measure procalcitonin (PCT)(ng/ml) and interleukin-6 (IL-6)(pg/ml) levels.
preoperatively and on the second postoperative morning
Hepatic Function Indicators
Time Frame: preoperatively and on the second postoperative morning
Fasting venous blood was collected preoperatively and on the second postoperative morning to measure serum alanine aminotransferase (ALT)(U/L), aspartate aminotransferase (AST)(U/L), albumin (ALB)(g/L), total bilirubin levels(μmol/L), and ALB-bilirubin (ALBI) scores.
preoperatively and on the second postoperative morning

Collaborators and Investigators

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

Sponsor

First Affiliated Hospital, Sun Yat-Sen University

Collaborators

Jinshazhou Hospital of Guangzhou University of Chinese Medicine
Guangzhou Institute of Cancer Reasearch, the Affiliated Cancer Hospital, Guangzhou Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

August 1, 2024

Primary Completion (Actual)

August 30, 2025

Study Completion (Actual)

August 30, 2025

Study Registration Dates

First Submitted

December 5, 2025

First Submitted That Met QC Criteria

December 31, 2025

First Posted (Estimated)

January 2, 2026

Study Record Updates

Last Update Posted (Estimated)

January 2, 2026

Last Update Submitted That Met QC Criteria

December 31, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EMAT2025

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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