Paracetamol Metabolism Research in Postoperative Hepatic Surgery

Not Applicable

• Conditions: Paracetamol Causing Adverse Effects in Therapeutic Use; Hepatic Disease
• Interventions: Drug: paracetamol; Procedure: hepatic surgery

• Registration Number: NCT03297073
• Lead Sponsor: University Hospital, Lille

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-12-20
• Study First Submitted: 2017-09-25
• Study First Submitted QC: 2017-09-25
• Study First Posted: 2017-09-29
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-10
• Last Update Posted: 2019-10-11
• Primary Completion: 2020-01
• Study Completion: 2020-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
hepatic surgery	hepatic surgery	resection less than three hepatic segments
hepatic surgery recovery	hepatic surgery	-
major hepatic surgery	hepatic surgery	resection greater than or equal to three hepatic segments
major hepatic surgery	paracetamol	resection greater than or equal to three hepatic segments
hepatic surgery	paracetamol	resection less than three hepatic segments
hepatic surgery recovery	paracetamol	-

Primary Outcome Measures

Name	Time	Method
Dosing and kinetics of paracetamolemia	during the 5 post-operative days	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)

Secondary Outcome Measures

Name	Time	Method
Dosage of urinary metabolites of paracetamol (paracetamol sulphate, paracetamol glucuronide)	At Day 1, day 3, day 5 post operative
Percentage of patients with paracetamolemia greater than 60 mg / mL	during the 5 post-operative days	60mj/ml = paracetamol toxicity threshold according to Prescott diagram to 6 hours
Rate of postoperative hepatocellular insufficiency	at day 5	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).
Plasma Disappearance Rate of indocyanine green (TDP-ICG) by LiMon®	At Day 1, day 3, day 5 post operative
Duration of hospitalization in perioperative intensive care	at 30 days
Composite characteristics of surgery.	at 30 days	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.
Dosage of N-acetyl-cysteinyl paracetamol ( NAPQI)	At Day 1, day 3, day 5 post operative
Occurrence of complications related to hepatic failure	at day 5	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.
Duration of total hospitalization.	at 30 days
Mortality	at 30 days

Trial Locations

Locations (1)

Hôpital Huriez, CHRU; 🇫🇷 Lille, France