Paracetamol Metabolism Research in Postoperative Hepatic Surgery (PARAFOI)

The main objective of this study was to evaluate the 5-day kinetics of plasma paracetamol levels in postoperative major hepatic surgery (resection greater than or equal to three hepatic segments) compared with less extensive liver resection and hepatic re-intervention. The clearance of indocyanine green is a marker of hepatic perfusion but also of the proper hepatocyte functioning, if hemodynamic conditions are stable.

Some patients may be operated on up to four or five times in the liver. Moreover, these patients probably present an increased risk of postoperative hepatocellular insufficiency due to a quantitative and qualitative decrease in their hepatic parenchyma. It is therefore interesting to evaluate the use of paracetamol in this situation.

Study Overview

• Status: Completed
• Conditions: Hepatic Disease; Paracetamol Causing Adverse Effects in Therapeutic Use
• Intervention / Treatment: Drug: paracetamol; Procedure: hepatic surgery

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Lille, France
    • Hôpital Huriez, CHRU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients requiring surgery for hepatic resection by initiation under chest or laparoscopic without hepatocellular insufficiency,
• ASA score 1 to 3 (American Society of Anesthesiologists score ranging from 1 to 5 evaluating the preoperative health status of a patient),
• Verification of the understanding of the protocol,

Exclusion Criteria:

• Patients classified ASA 4 or 5,
• Allergy or intolerance to indocyanine green
• Allergy or intolerance to paracetamol,
• Taking of paracetamol the week before the intervention,
• Patient less than 60 Kgs (because decrease of doses of paracetamol),
• Emergency surgery, palliative surgery and surgical recovery,
• Psychic disorder,
• Contra-indication to a treatment used during the study,
• incapable major,
• Intellectual incapacity preventing proper understanding of the protocol,
• Pregnant or nursing woman,

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: major hepatic surgery; resection greater than or equal to three hepatic segments	Drug: paracetamol; Paracetamol 1000 mg will be administered 30 minutes before the end of the procedure and then every 6 hours systematically at the following times: 6h / 12h / 18h / 00h. The analgesic treatment after hepatectomy with paracetamol will be maintained for at least 5 days in all patients in parenteral form; Procedure: hepatic surgery
Experimental: hepatic surgery; resection less than three hepatic segments	Drug: paracetamol; Paracetamol 1000 mg will be administered 30 minutes before the end of the procedure and then every 6 hours systematically at the following times: 6h / 12h / 18h / 00h. The analgesic treatment after hepatectomy with paracetamol will be maintained for at least 5 days in all patients in parenteral form; Procedure: hepatic surgery
Experimental: hepatic surgery recovery	Drug: paracetamol; Paracetamol 1000 mg will be administered 30 minutes before the end of the procedure and then every 6 hours systematically at the following times: 6h / 12h / 18h / 00h. The analgesic treatment after hepatectomy with paracetamol will be maintained for at least 5 days in all patients in parenteral form; Procedure: hepatic surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dosing and kinetics of paracetamolemia	this determination of the plasma paracetamol dosage on D0 (H6: 6 hours after the end of the procedure) and D1 D2 D3 D4 D5 (samples taken at 6 am each day just before the injection of paracetamol whose administration hours will be 6h 12h 18h and midnight)	during the 5 post-operative days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dosage of urinary metabolites of paracetamol (paracetamol sulphate, paracetamol glucuronide)		At Day 1, day 3, day 5 post operative
Dosage of N-acetyl-cysteinyl paracetamol ( NAPQI)		At Day 1, day 3, day 5 post operative
Percentage of patients with paracetamolemia greater than 60 mg / mL	60mj/ml = paracetamol toxicity threshold according to Prescott diagram to 6 hours	during the 5 post-operative days
Plasma Disappearance Rate of indocyanine green (TDP-ICG) by LiMon®		At Day 1, day 3, day 5 post operative
Rate of postoperative hepatocellular insufficiency	The postoperative hepatocellular insufficiency according to the 50/50 criteria (TP <50% and bilirubinemia> 50 μmol / L on the 5th day) according to the type of hepatic resection (with or without clamping, continuous or discontinuous, duration intervention).	at day 5
Occurrence of complications related to hepatic failure	the complications related to hepatic failure not falling within the "50/50" criteria: jaundice, hepatic encephalopathy, coagulation disorders, ascites, cytolysis, cholestasis. Other medical and surgical. Duration of hospitalization in perioperative intensive care and duration of total hospitalization. Mortality at 30 days.	at day 5
Duration of hospitalization in perioperative intensive care		at 30 days
Duration of total hospitalization.		at 30 days
Mortality		at 30 days
Composite characteristics of surgery.	Characteristics of surgery: duration of intervention, numbers, duration and types of vascular clamping, detailed description of the type of liver resection performed, quantification of bleeding.	at 30 days

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Investigators: Principal Investigator: Gilles Lebuffe, MD,PhD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2016
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): November 1, 2019

Study Registration Dates

• First Submitted: September 25, 2017
• First Submitted That Met QC Criteria: September 25, 2017
• First Posted (Actual): September 29, 2017

Study Record Updates

• Last Update Posted (Estimated): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Digestive System Diseases; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Acetaminophen
• Other Study ID Numbers: 2015_61; 2016-002632-32 (Other Identifier: ID-RCB number)

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