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

First Affiliated Hospital, Sun Yat-Sen University129 enrolled

Overview

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

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

129

Conditions

Enhanced Recovery After Surgery Multimodal Analgesia Real-world Study

Interventions

hydrochloride hydromorphone + flurbiprofen axetilDRUG

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.

conventional analgesiaDRUG

When the NRS score was ≥4, flurbiprofen axetil 50 mg was administered intravenously, with intramuscular tramadol 100 mg added if analgesia was inadequate.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Perioperative numerical pain rating scale (NRS) score

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).

Time frame: From the start of the operation to 24 hours after the operation

Secondary Outcomes

Surgical Duration

Total time from puncture initiation to completion of dressing (min).

Time frame: From the start of the operation to the end of the operation

Adverse Events

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.

Time frame: From the start of the operation to 24 hours after the operation

Analgesia Satisfaction

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).

Time frame: At 24 hours postoperatively

Cost-Effectiveness Analysis

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).

Time frame: From the start of the operation to the end of perioperative period