Catecholamine Use is Associated With Enterocyte Damage in Critically Ill Patients

Abstract

Small bowel damage is frequent but underdiagnosed among critically ill patients with shock. High catecholamine doses may have a deleterious effect on mesenteric blood flow. Plasma intestinal fatty acid-binding protein (I-FABP) concentration is a marker of enterocyte damage, whereas plasma citrulline concentration is a marker of functional enterocyte mass. We hypothesized that high doses of catecholamines in critically ill patients may be associated with enterocyte damage. This study aimed to determine the link between catecholamine use and dose with enterocyte damage. This is a prospective observational study performed in a large regional university teaching hospital. Critically ill patients requiring epinephrine and/or norepinephrine at admission to a medical intensive care unit (ICU) were included, as well as controls not receiving catecholamines. We evaluated at admission plasma I-FABP and citrulline concentrations, abdominal perfusion pressure (APP), and variables relating to prognosis and treatment. Patients were categorized according to the quartiles of catecholamine dose at ICU admission. Sixty critically ill patients receiving catecholamines and 27 not receiving catecholamines were included. Plasma I-FABP was higher among patients receiving catecholamine than in controls. Among patients receiving catecholamines, a dose of 0.48 γ kg min or more at ICU admission was associated with a higher I-FABP concentration. A Sepsis-related Organ Failure Assessment score higher than 11 and plasma I-FABP more than 524 pg mL at ICU admission were independently associated with 28-day mortality (odds ratio, 4.0 [1.24-12.95] and odds ratio, 4.90 [1.44-16.6], respectively). Catecholamine use is associated with I-FABP elevation in critically ill patients. Critically ill patients receiving more than 0.48 γ kg min of epinephrine and/or norepinephrine at ICU admission have high I-FABP concentrations. This suggests that enterocyte damage reflects the severity of shock, and an adverse effect of catecholamines per se is possible.

Induced Hypothermia Preserves the Functional Enterocyte Mass in A Porcine Multiple Trauma Model

“…In particular, the microvascular mucosal oxygenation appears to be improved after severe traumatic insults (22,28). However, Besides plasma citrulline as a marker for the functional enterocyte mass, iFABP has been described as a valid marker for enterocyte necrosis following shock (8,9,15,29). In contrast to the expected decrease of plasma citrulline, iFABP did not increase significantly in TN.…”

“…Citrulline is an amino acid synthesized in small bowel enterocytes from glutamine and is constantly released to the blood (8). Decreased levels have been associated with a diminished mass of functional enterocytes due to different gut disorders (9,10,15,16). iFABP is a cytoplasmic protein, exclusively expressed by enterocytes (14).…”

Enterocyte Damage

“…First, it is likely that ensuring a sufficient mean arterial pressure may limit the level of enterocyte damage, but excessive catecholamine dose may be deleterious on the small bowel mucosa (35,36); second, it is possible that early enteral nutrition can limit small bowel mucosal damage; third, ciclosporin use might theoretically limit the cellular damage by inhibiting the apoptotic signal originating from the mitochondria, but this treatment requires further investigations in the context of cardiac arrest (37).…”

Intestinal permeability induced by lipopolysaccharide and measured by lactulose, rhamnose and mannitol sugars in chickens

“…Increased IP models are well established in humans (Ni et al, 2015;Piton et al, 2015), pigs , rats and mice (Williams et al, 2013;Ruan et al, 2014). Dextran sodium sulphate (DSS) ingestion, fasting (Kuttappan et al, 2015;Vicuna et al, 2015b), dexamethasone (Vicuna et al, 2015a) and wire floor stress (Wideman et al, 2012) have recently been employed as models of increased IP in chickens.…”