Acta Anaesthesiologica Belgica, Journal Year: 2024, Volume and Issue: 75(Supplement 1), P. 63 - 74

Published: Dec. 1, 2024

Background: Obese patients may need higher doses of acetaminophen (APAP) for adequate analgesia, due to increased total clearance and distribution volume. APAP-induced hepatotoxicity is mainly caused through CYP2E1 pathway. Its activity induced by obesity, potentially endangering the safety profile APAP. Metabolic-dysfunction associated liver disease (MASLD) an important risk factor APAP induced-hepatotoxicity. Objectives: This pilot study aimed at observing analyzing related protein adducts (APAP-cysteine APAP-mercapturate) in obese compared non-obese during therapeutic dosing Study design setting: Interim analysis ongoing prospective observational gender-stratified cohort PK study, conducted Ghent University Hospital. Methods: 35 (BMI>35kg/m²) 18 (18,5kg/m²<BMI< 30kg/m²) undergoing laparoscopy were included. All received intravenously 2g 1g q6h. Plasma concentrations measured predefined timepoints after first fifth dose. Main outcome measures: was indirectly assessed measuring adducts. Linear mixed model used assess correlations between repeated measurements plasma and: age, gender, body weight, lean mass metabolic syndrome. Hepatotoxicity evaluated assessing function markers 1.0 µmol/L threshold Results: No statistically significant interaction observed obesity APAP- cysteine or APAP-mercapturate. noted syndrome these Significant found APAP-Cysteine with sex, mass. Statistically differences bilirubin, prothrombin time (PT), international normalized ratio (INR) 30 hours, though without clinical relevance. Conclusions: Obesity did not have a impact on activity. Liver significantly different patients,

Language: Английский