Changes in Arginine Metabolism during Sepsis and Critical Illness in Children

Abstract

Arginine is an important amino acid during disease and healing because of functions in the immune system and as precursor of nitric oxide (NO). In critically ill adults and children, plasma arginine and citrulline concentrations are substantially decreased, indicating an arginine-deficient state. Arginine availability is reduced because of increased arginine disposal in combination with reduced de novo arginine synthesis. The latter is most likely caused by reduced citrulline availability. As a result, NO synthesis may be impaired, which might compromise microcirculation. These metabolic changes seem to be dependent on the severity of inflammation. Arginine or citrulline supplementation in severe inflammation might therefore be beneficial. Possibly, the use of protein-energy-enriched formulas may be a first step to improve arginine availability and NO synthesis. In critically ill children, arginine metabolism and supplementation is however a virtually unexplored field. Since pediatric sepsis is a significant health problem, which differs in epidemiology and pathophysiology from sepsis in adults, and because of the scarcity of data in this population, studies focused on pathophysiological mechanisms and possible interventions in arginine metabolism in pediatric critical illness are warranted.

Clinical Characteristics Associated With Postoperative Intestinal Epithelial Barrier Dysfunction in Children With Congenital Heart Disease*

“…A larger sample size, across several centers would be needed to control for illness severity. While citrulline is a product of glutamine metabolism and could be altered in the setting of sepsis 38 , none of our patients were septic, so it is unlikely that this is impacting our results. Claudin 3 is expressed in the lung and lung injury could confound our results 39 .…”

Disease indicators for sepsis and analysis of sepsis treatment in children using the continuous blood purification technique

“…The interaction between the host and the microorganism activates the natural immunity pathway and triggers defensive mechanisms in the host, including body fluid composition and cells. Mononuclear cells release the pro-inflammatory markers and cytokines IL-1, IL-6, and TNF-α (Betue and Deutz, 2013;Qin et al, 2013). Sepsis is a pathological process involving the excessive cells and humoral immunity caused by infection with bacteria and toxins.…”

24-Hour protein, arginine and citrulline metabolism in fed critically ill children – A stable isotope tracer study

“…Arginine is especially of interest, because it has functions in the immune system and is the precursor of nitric oxide (NO). As sepsis and critical illness are considered arginine-deficient states, arginine supplementation might be beneficial (4). However scarce data exist on arginine metabolism and NO synthesis in critically ill children.…”

“…The reference method to study protein and arginine metabolism is considered to be stable isotope tracer techniques with measurement of amino acid appearances (4, 5). Usually an experimental protocol of 4–8 hours is used of which the results are extrapolated to 24-hour metabolism for recommendations of daily protein intake (6–9) or insight in arginine metabolism (10).…”

“…Therefore, we also do not know whether short duration tracer protocols (4–8 h) represent 24-hour protein and arginine metabolism in children. We anticipated that children at the pediatric intensive care unit (PICU) have an altered day-night cycle as a result of artificial light exposure, continuous care, sedation and hormonal changes related to the acute stress response (15, 16).…”