BACKGROUND: The neurological prognostication is crucial for the management of refractory out-of-hospital cardiac arrest (OHCA) patients. Despite treatment advances, ischemia-reperfusion brain injury remains a critical factor affecting neurological outcomes. This study evaluated the utility of intestinal fatty acid-binding protein (I-FABP) and its relationship with non-occlusive mesenteric ischemia (NOMI) for neurological prognostication, comparing patients with refractory cardiac arrest treated with extracorporeal cardiopulmonary resuscitation (ECPR) compared to those treated with conventional CPR. METHODS: This is a single-center prospective pilot study. We compared I-FABP levels in OHCA patients recruited from June 2022 to October 2023. Blood samples for I-FABP examination were collected at admission, 24, and 48 h and analyzed against 30-day neurological outcomes and NOMI occurrence. ROC analysis determined I-FABP cut-off values for predicting poor neurological outcomes (Cerebral Performance Category (CPC) 3-5) in ECPR and CPR groups. RESULTS: Among the 68 patients admitted for OHCA, 22 received ECPR and 46 conventional CPR. I-FABP cut-off values for predicting poor neurological outcomes were: at admission > 0.95 ng/mL for ECPR vs. 1.64 ng/mL for CPR (AUC 0.55 vs. 0.38); at 24 h > 0.04 ng/mL vs. 0.4 ng/mL (AUC 0.7 vs. 0.51); at 48 h > 0.18 ng/mL vs. 0.53 ng/mL (AUC 0.77 vs. 0.41). However, compared to NSE AUCs, I-FABP showed significantly worse outcomes prediction in all time points.I-FABP was unreliable in predicting neurological outcomes and also showed no consistent elevation in NOMI patients. CONCLUSION: Compared to neuron-specific enolase, I-FABP does not appear to be a predictor of outcome in patients with refractory cardiac arrest. Clinical manifestations of NOMI are not consistently associated with elevated I-FABP levels.

1st Faculty of Medicine Charles University Prague Czech Republic

2nd Department of Cardiovascular Medicine General University Hospital Prague 1st Faculty of Medicine Charles University Prague Prague Czech Republic

3rd Department of Internal Medicine 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czech Republic

Critical Care Research Group Brisbane Queensland Australia

Department of Anesthesiology and Intensive Care Medicine 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czech Republic

Institute of Heart Diseases Wroclaw Medical University Wroclaw Poland

Institute of Medical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

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Grunau B., Kime N., Leroux B., et al. Association of intra-arrest transport vs continued on-scene resuscitation with survival to hospital discharge among patients with out-of-hospital cardiac arrest. JAMA. 2020;324(11) doi: 10.1001/jama.2020.14185. PubMed DOI PMC

Yan S., Gan Y., Jiang N., et al. The global survival rate among adult out-of-hospital cardiac arrest patients who received cardiopulmonary resuscitation: a systematic review and meta-analysis. Crit Care. 2020;24(1) doi: 10.1186/s13054-020-2773-2. PubMed DOI PMC

Lunz D., Calabrò L., Belliato M., et al. Extracorporeal membrane oxygenation for refractory cardiac arrest: a retrospective multicenter study. Intensive Care Med. 2020;46(5):973–982. doi: 10.1007/s00134-020-05926-6. PubMed DOI

Mørk S.R., Stengaard C., Linde L., et al. Mechanical circulatory support for refractory out-of-hospital cardiac arrest: a Danish nationwide multicenter study. Crit Care. 2021;25(1) doi: 10.1186/s13054-021-03606-5. PubMed DOI PMC

Nolan J.P., Sandroni C., Böttiger B.W., et al. European resuscitation council and European society of intensive care medicine guidelines 2021: post-resuscitation care. Resuscitation. 2021;161:220–269. doi: 10.1016/j.resuscitation.2021.02.012. PubMed DOI

Piton G., Belin N., Barrot L., et al. Enterocyte Damage: A PIECE IN THE PUZZLE OF POST–CARDIAC ARREST SYNDROME. Shock. 2015;44(5):438–444. https://doi.org/10.109/SHK.0000000000000440. PubMed

Hoftun Farbu B., Langeland H., Ueland T., et al. Intestinal injury in cardiac arrest is associated with multiple organ dysfunction: A prospective cohort study. Resuscitation. 2023;185 doi: 10.1016/j.resuscitation.2023.109748. PubMed DOI

Krychtiuk K.A., Richter B., Lenz M., et al. Epinephrine treatment but not time to ROSC is associated with intestinal injury in patients with cardiac arrest. Resuscitation. 2020;155:32–38. doi: 10.1016/j.resuscitation.2020.05.046. PubMed DOI

Grimaldi D., Guivarch E., Neveux N., et al. Markers of intestinal injury are associated with endotoxemia in successfully resuscitated patients. Resuscitation. 2013;84(1):60–65. doi: 10.1016/j.resuscitation.2012.06.010. PubMed DOI

Schriefl C., Steininger P., Clodi C., et al. The association of early diarrhea after successful resuscitation following out-of-hospital cardiac arrest with neurological outcome. Medicine. 2021;100(49) doi: 10.1097/MD.0000000000028164. PubMed DOI PMC

Annborn M., Dankiewicz J., Erlinge D., et al. Procalcitonin after cardiac arrest – An indicator of severity of illness, ischemia-reperfusion injury and outcome. Resuscitation. 2013;84(6):782–787. doi: 10.1016/j.resuscitation.2013.01.004. PubMed DOI

Brodska H., Smalcova J., Kavalkova P., et al. Biomarkers for neuroprognostication after standard versus extracorporeal cardiopulmonary resuscitation – A sub-analysis of Prague-OHCA study. Resuscitation. 2024;199 doi: 10.1016/j.resuscitation.2024.110219. PubMed DOI

Bailey R.W., Bulkley G.B., Hamilton S.R., Morris J.B., Haglund U.H. Protection of the small intestine from nonocclusive mesenteric ischemic injury due to cardiogenic shock. Am J Surg. 1987;153(1):108–116. doi: 10.1016/0002-9610(87)90210-8. PubMed DOI

Bourcier S., Klug J., Nguyen L.S. Non-occlusive mesenteric ischemia: Diagnostic challenges and perspectives in the era of artificial intelligence. World J Gastroenterol. 2021;27(26):4088–4103. doi: 10.3748/wjg.v27.i26.4088. PubMed DOI PMC

Konan A., Piton G., Ronot M., et al. Abdominal atherosclerosis is not a risk factor of nonocclusive mesenteric ischemia among critically ill patients: a propensity matching study. Ann Intensive Care. 2022;12(1) doi: 10.1186/s13613-022-01096-4. PubMed DOI PMC

Mazzei M.A., Gentili F., Mazzei F.G., Grassi R., Volterrani L. Non-occlusive mesenteric ischaemia: CT findings, clinical outcomes and assessment of the diameter of the superior mesenteric artery: Don’t forget the reperfusion process! Br J Radiol. 2019;92(1093) doi: 10.1259/bjr.20180736. PubMed DOI PMC

Kammerer S., Schuelke C., Berkemeyer S., et al. The role of multislice computed tomography (MSCT) angiography in the diagnosis and therapy of non-occlusive mesenteric ischemia (NOMI): Could MSCT replace DSA in diagnosis? PLoS One. 2018;13(3) doi: 10.1371/journal.pone.0193698. PubMed DOI PMC

Chen Z., Liu X., Shou C., Yang W., Yu J. Advances in the diagnosis of non-occlusive mesenteric ischemia and challenges in intra-abdominal sepsis patients: a narrative review. PeerJ. 2023;11 doi: 10.7717/peerj.15307. PubMed DOI PMC

Korth U., Krieter H., Denz C., et al. Intestinal ischaemia during cardiac arrest and resuscitation: comparative analysis of extracellular metabolites by microdialysis. Resuscitation. 2003;58(2):209–217. doi: 10.1016/S0300-9572(03)00119-9. PubMed DOI

Kanda T., Nakatomi Y., Ishikawa H., et al. Intestinal fatty acid-binding protein as a sensitive marker of intestinal ischemia. Dig Dis Sci. 1992;37(9):1362–1367. doi: 10.1007/BF01296004. PubMed DOI

Huang X., Zhou Y., Sun Y., Wang Q. Intestinal fatty acid binding protein: A rising therapeutic target in lipid metabolism. Prog Lipid Res. 2022;87 doi: 10.1016/j.plipres.2022.101178. PubMed DOI

Bernier-Latmani J., González-Loyola A., Petrova T.V. Mechanisms and functions of intestinal vascular specialization. J Exp Med. 2024;221(1) doi: 10.1084/jem.20222008. PubMed DOI PMC

Stahl K., Busch M., Maschke S.K., et al. A retrospective analysis of nonocclusive mesenteric ischemia in medical and surgical ICU patients: clinical data on demography, clinical signs, and survival. J Intensive Care Med. 2020;35(11):1162–1172. doi: 10.1177/0885066619837911. PubMed DOI PMC

Guo H., Chen D., Chen M.-M., Liu X.-L., Liu J. Early identification of non-occlusive acute mesenteric ischemia. Journal of Translational. Crit Care Med. 2024;6(4) doi: 10.1097/JTCCM-D-24-00017. DOI

Mallick R., Basak S., Duttaroy A.K. Fatty acids and evolving roles of their proteins in neurological, cardiovascular disorders and cancers. Prog Lipid Res. 2021;83 doi: 10.1016/j.plipres.2021.101116. PubMed DOI

Liu R.-Z., Mita R., Beaulieu M., Gao Z., Godbout R. Fatty acid binding proteins in brain development and disease. Int J Dev Biol. 2010;54(8–9):1229–1239. doi: 10.1387/ijdb.092976rl. PubMed DOI

Bourcier S., Ulmann G., Jamme M., et al. A multicentric prospective observational study of diagnosis and prognosis features in ICU mesenteric ischemia: the DIAGOMI study. Ann Intensive Care. 2022;12(1) doi: 10.1186/s13613-022-01092-8. PubMed DOI PMC

Farbu B.H., Lydersen S., Mohus R.M., et al. The detrimental effects of intestinal injury mediated by inflammation are limited in cardiac arrest patients: A prospective cohort study. Resuscitation plus. 2024;18 doi: 10.1016/j.resplu.2024.100639. PubMed DOI PMC

Yellon D.M., Hausenloy D.J. Myocardial Reperfusion Injury. N Engl J Med. 2007;357(11):1121–1135. doi: 10.1056/NEJMra071667. PubMed DOI

Katz A., Brosnahan S.B., Papadopoulos J., Parnia S., Lam J.Q. Pharmacologic neuroprotection in ischemic brain injury after cardiac arrest. Ann N Y Acad Sci. 2022;1507(1):49–59. doi: 10.1111/nyas.14613. PubMed DOI

Bertacco A., Dehner C.A., Caturegli G., et al. Modulation of Intestinal Microbiome Prevents Intestinal Ischemic Injury. Front Physiol. 2017;8 doi: 10.3389/fphys.2017.01064. PubMed DOI PMC

Lezutekong J.N., Nikhanj A., Oudit G.Y. Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in cardiovascular disease. Clin Sci. 2018;132(8):901–904. doi: 10.1042/CS20180172. PubMed DOI

Singh V., Lee G.D., Son H.W., et al. Butyrate producers, “The Sentinel of Gut”: Their intestinal significance with and beyond butyrate, and prospective use as microbial therapeutics. Front Microbiol. 2023;13 doi: 10.3389/fmicb.2022.1103836. PubMed DOI PMC