Glutamine Randomized Studies in Early Life: The Unsolved Riddle of Experimental and Clinical Studies

Abstract

Glutamine may have benefits during immaturity or critical illness in early life but its effects on outcome end hardpoints are controversial. Our aim was to review randomized studies on glutamine supplementation in pups, infants, and children examining whether glutamine affects outcome. Experimental work has proposed various mechanisms of glutamine action but none of the randomized studies in early life showed any effect on mortality and only a few showed some effect on inflammatory response, organ function, and a trend for infection control. Although apparently safe in animal models (pups), premature infants, and critically ill children, glutamine supplementation does not reduce mortality or late onset sepsis, and its routine use cannot be recommended in these sensitive populations. Large prospectively stratified trials are needed to better define the crucial interrelations of “glutamine-heat shock proteins-stress response” in critical illness and to identify the specific subgroups of premature neonates and critically ill infants or children who may have a greater need for glutamine and who may eventually benefit from its supplementation. The methodological problems noted in the reviewed randomized experimental and clinical trials should be seriously considered in any future well-designed large blinded randomized controlled trial involving glutamine supplementation in critical illness.

Nutrición parenteral en situaciones clínicas especiales

“…En relación a los inmunonutrientes, aunque arginina, ácidos grasos n-3 y glutamina han mostrado efectos antioxidantes, no existe evidencia científica en el paciente pediátrico crítico que avale el uso de estas sustancias en el momento actual (28,41).…”

The effect of 2 mMol glutamine supplementation on HSP70 and TNF-α release by LPS stimulated blood from healthy children

“…In studies of glutamine supplementation in pre-term infants [45e50], infants with gastrointestinal disease and surgery [51,52], children with burns [53,54] and malnutrition [55e57], little or no benefit on survival, late onset sepsis or duration of hospital stay have been described [18]. In addition recent evidence indicates that either hypo-glutamine <430 mmol/L [58] or hyper-glutamine levels >930 mmol/L are associated with increased mortality [59,60].…”

“…Since the results from Heyland and Dhaliwal [64] describing the increased risk of mortality following the use of glutamine in sepsis, supplementation is no longer recommended [65]. Furthermore, the effect of glutamine supplementation has not been elucidated in critically ill children and so its use cannot be recommended in immune competent children [18]. Further work is required to understand what the role of glutamine is in critically ill children.…”

“…A recent analysis considering the effect of HSP70 in animal models compared to humans indicate that whilst HSP70 confers an almost entirely protective effect in animals (97.1%) the same may not be true in humans, with only a 50% protective effect demonstrated [1]. Therefore the clinical benefit of HSP70 upregulation during times of stress remains unclear, especially as both low and high levels in children and adults are associated with increased risk in children and adults mortality and infection risk [1,18]. In adults following trauma HSP70 levels 15 ng/ml is associated with increased mortality [19], conversely, levels !60 ng/ml is associated with increased mortality in traumatic brain injury [20] and severe sepsis in adults [21] and children [22].…”

Polymyxin B hemoperfusion in septic shock: nothing overmuch (Meden Agan)!

“…Last decades the concept of targeted interventions to decrease the circulating mediators of sepsis to intercept the dysregulated host response grew enthusiasm, and endotoxin was a reliable target to consider for therapy. Treatment interventions at various steps of the endotoxin pathway, including the heat shock protein-72 and -90 "danger signal" induction (3), have been tested experimentally in human in vivo and in vitro studies (4,5) without convincing results (6,7). Attempts to remove endotoxin with monoclonal antibodies failed, so extracorporeal removal by hemoperfusion was introduced using polymyxin B cartridges, where endotoxin can be bound and neutralized (8).…”