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

Sun Yat-sen University

Status and phase: Completed; Phase 4

Conditions: Multimodal Analgesia; Transarterial Chemoembolization; Real-world Study; Enhanced Recovery After Surgery

Treatments: Drug: hydrochloride hydromorphone + flurbiprofen axetil; Drug: conventional analgesia

Study type: Interventional

Funder types: Other

Identifiers

NCT07315022

EMAT2025

Details and patient eligibility

About

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

Full 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.

Enrollment: 129 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

129 participants in 2 patient groups

A:hydromorphone + flurbiprofen axetil

Experimental group

Description:

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.

Treatment:

Drug: hydrochloride hydromorphone + flurbiprofen axetil

conventional analgesia

Active Comparator group

Description:

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.

Treatment:

Drug: conventional analgesia