NOREPINEPHRINE CONTRIBUTES TO ENTEROCYTE DAMAGE IN SEPTIC SHOCK PATIENTS: A PROSPECTIVE COHORT STUDY

Objectives: In septic patients, both systemic inflammation and splanchnic hypoperfusion may cause enterocyte damage. Catecholamines may exert additional detrimental effects on mesenteric blood flow in these patients, and thereby contribute to this damage. Enterocyte damage itself results in impairment of gut barrier function and consequent translocation of bacteria/toxins. This may contribute to multiple organ failure and death by sustaining or amplifying the systemic inflammatory response. The aim of the study was 2-fold: to investigate which factors contribute to enterocyte damage in septic patients, and to assess whether enterocyte damage is associated with a sustained or amplified systemic inflammatory response. Methods: In this prospective observational cohort study in 129 patients with septic shock admitted to the ICU, we serially measured plasma levels of Intestinal Fatty Acid-Binding Protein (I-FABP, a marker for enterocyte damage) and of cytokines Tumor Necrosis Factor (TNF)-alpha, Interferon (IFN)-gamma, Interleukin (IL)-1b, IL-6, IL-8, IL-1 Receptor Antagonist (RA), and IL-10. Clinical data were collected from electronic patient files. Results: A total of 129 patients were included in the study. The median age of the patients was 67 years [56-74]. The median norepinephrine infusion rate was 0.2mg/kg/min [0.1-0.5]. Overall, 28-day mortality was 31 (24%). Similar to previous work, I-FABP levels at admission were independently associated with mortality (odds ratio 3.101 [1.138-8.448]). Acute Physiology and Chronic Health Evaluation II score and an increase in norepinephrine infusion rate between days 1 and 3 were independently associated with area under curve I-FABP levels, whereas mean arterial pressure and creatinine levels were not. No correlations were found between any of the measured cytokines and plasma I-FABP levels. Furthermore, high I-FABP levelswere not related with the subsequent course of cytokine levels. Conclusions: In patients with septic shock, norepinephrine use is associated with more enterocyte damage. Although enterocyte damage is associated with increased 28-day mortality, it is not associated with a sustained or amplified systemic inflammatory response.