Sepsis and hepatotoxic drugs contribute to liver test disturbances in criticaly ill patients receiving parenteral nutrition for more than three days. The cumulative volume of parenteral nutrition does not.

Rationale
Parenteral Nutrition (PN) use is in clinical setting often associated with liver dysfunction (PNALD) although PN is not the only contributing factor. Sepsis, acute heart failure (AHF) and hepatotoxic drugs can also induce liver parameters deterioration. Clinical research in this field is of great value to steer decision making related to nutrition.

Methods
In a retrospective single center cohort study in a tertiary intensive care department, adult patients who were admitted at the ICU for at least 3 days between 01/01/2017 and 31/12/2019 and treated with PN ≥3 consecutive days were analyzed. The presence of AHF sepsis or septic shock, use of paracetamol, amoxicillin/clavulanic acid, flucloxacillin, valproic acid and sulfamethoxazol/trimethoprim was recorded. Volume of PN (mL/day), amount of calories, proteins, lipids and carbohydrates and duration of therapy was analyzed. A linear mixed-effect model using SPSS version 28, was used to find possible correlations between PN, acute heart failure, sepsis, hepatotoxic drugs and AST, ALT, AP, GGT, TB and INR (set as dependent variables).

Results
In 224 ICU patients (mean age 63 +/- 17 years, 38% female) treated with PN, sepsis, paracetamol, amoxicillin/clavulanic acid, valproic acid, flucloxacillin (cumulative dose), APACHE II score and to a lesser extend AHF, contributed significantly to deterioration of liver function tests. Sulfamethoxazol/trimethoprim, volume PN and treatment lenght of PN did not contribute significantly. Neither proteins, nor carbohydrates nor lipids had an impact.

Conclusions
In ICU patients treated with PN for at least three days, hepatotoxic drugs affect liver parameters as well as the presence of AHF and sepsis/septic shock. Volume and treatment lenght of PN has no impact.