Paracetamol Metabolism Research in Postoperative Hepatic Surgery

Study Overview
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Brief Summary
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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.

Official Title
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Paracetamol Metabolism Research in Postoperative Hepatic Surgery

Conditions
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Paracetamol Causing Adverse Effects in Therapeutic Use, Hepatic Disease

Intervention / Treatment
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* Drug: paracetamol
* Procedure: hepatic surgery


Participation Criteria
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Eligibility Criteria
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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,

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: major hepatic surgery<br>resection greater than or equal to three hepatic segments | Drug: paracetamol<br>* 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<br>Procedure: hepatic surgery<br> <br> |
| Experimental: hepatic surgery<br>resection less than three hepatic segments | Drug: paracetamol<br>* 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<br>Procedure: hepatic surgery<br> <br> |
| Experimental: hepatic surgery recovery<br> | Drug: paracetamol<br>* 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<br>Procedure: hepatic surgery<br> <br> |

What is the study measuring?
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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 |