Enteral nutrition and dynamics of citrulline and intestinal fatty acid-binding protein in adult ICU patients.

Background and Aims: Plasma citrulline and intestinal fatty acid binding protein (I-FABP) are biomarkers reflecting enterocyte function and intestinal mucosal injury. The aim was to describe daily dynamics of citrulline and I-FABP concentrations in association with enteral nutrition (EN) in adult ICU patients. We hypothesized that success or failure of EN is reflected by differences in citrulline and I-FABP levels at admission, as well as in daily dynamics over the first week.
Methods: The present study was a planned sub-study of the iSOFA study (ClinicalTrials.gov Identifier: NCT02613000). With delayed informed consent we included adult (18 years or older) patients admitted for unlimited care to 5 ICUs in Europe. Citrulline and I-FABP were assessed and nutritional data recorded daily during the first week of the patients' ICU stay.
Results: The study included 224 patients with 693 plasma samples analyzed for citrulline and 695 for I-FABP. The median ICU stay was 2 (IQR 1-4) days and 35 patients (15.6 %) stayed in the ICU for ≥ 7 days. The majority of patients (184/224; 82.1 %) received EN or oral nutrition (ON) during their ICU stay, in 164 patients (73.2 %) nutrition was started within 48 h of admission (early enteral or oral nutrition, EEN/ON). Median biomarker concentrations on admission were: citrulline 24.5 (IQR 18.1-31.7) μmol/L and I-FABP 2763 (1326-4805) pg/mL. Reference range for citrulline was 17-46 μmol/L and for I-FABP 377-2049 pg/mL. Patients with EEN/ON demonstrated an increase in citrulline concentrations over the first week in ICU unlike those not receiving EEN/ON (P = 0.049 for the mean log-citrulline values over time between groups) as well as higher average citrulline concentrations. Success of EEN/ON (80 % of caloric target achieved by day 4) was associated with citrulline values increasing from day 4, whereas a slight decrease was observed with unsuccessful EEN/ON. However, these dynamics over time were not statistically significantly different (P = 0.654). Patients with EEN/ON unexpectedly had I-FABP values higher than those without (average values for all days P = 0.004). Median I-FABP values on day 3 were higher with successful EEN/ON (646 (IQR 313-1116) vs 278 (IQR 190-701) pg/mL, P = 0.022).
Conclusions: EEN/ON was associated with higher values and different dynamics of citrulline over the first week in ICU. No clear difference of measured biomarkers was seen when patients were compared according to success of EEN/ON. Our study does not allow suggesting certain thresholds of citrulline nor I-FABP that could be used for bedside decision-making with regard to EN. This study was a planned sub-study of the iSOFA study (ClinicalTrials.gov Identifier: NCT02613000).
Competing Interests: Declaration of competing interest Annika Reintam Blaser, Joel Starkopf and Martin Padar report a grant from Fresenius Kabi to the University of Tartu with the purpose of funding this study. Joel Starkopf reports receiving speaker honoraria from Fresenius Kabi. Liis Starkopf has nothing to disclose. Alastair Forbes reports receiving speaker honoraria from Fresenius Kabi, B. Braun and Baxter. Michael Hiesmayr reports affiliation as member of advisory board at Fresenius Kabi, receiving institutional grants to Medical University of Vienna from Fresenius Kabi and Abbott and speaker honoraria from Fresenius Kabi. Stephan M. Jakob reports that the Department of Intensive Care Medicine has, or has had in the past, research & development/consulting contracts with Edwards Lifesciences Services GmbH, Phagenesis Limited and Nestlé. The money was paid into a departmental fund, Stephan M. Jakob did not receive any financial gain. The Department of Intensive Care Medicine has received in the past unrestricted educational grants from the following organizations for organizing bi-annual postgraduate courses in the fields of critical care ultrasound, management of ECMO and mechanical ventilation: Pierre Fabre Pharma AG (formerly known as RobaPharm), Pfizer AG, Bard Medica S.A., Abbott AG, Anandic Medical Systems, PanGas AG Healthcare, Orion Pharma, Bracco, Edwards Lifesciences AG, Hamilton Medical AG, Fresenius Kabi (Schweiz) AG, Getinge Group Maquet AG, Dräger Schweiz AG, Teleflex Medical GmbH. Olav Rooijackers reports receiving grants from Fresenius Kabi and personal fees from Fresenius Kabi, Nutricia and Nestlé. Jan Wernerman has nothing to disclose. Sven Erik Ojavee has nothing to disclose. Annika Reintam Blaser reports receiving speaker and/or consulting honoraria from Fresenius Kabi, Nestlé and VIPUN Medical. Fresenius Kabi provided a grant to the University of Tartu (not directly to Annika Reintam Blaser, Joel Starkopf nor Martin Padar, all affiliated to the University of Tartu) to cover costs of biomarkers measurements. Medical University of Vienna did not fund this study and did not receive any funding from Fresenius Kabi related to this study.
(Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)