Insulin therapy in the pediatric intensive care unit

Background & aims: Hyperglycemia is a major risk factor for increased morbidity and mortality in the intensive care unit. Insulin therapy has emerged in adult intensive care units and several pediatric studies are currently being conducted. This review discusses hyperglycemia and the effects of insulin on metabolic and non-metabolic pathways, with a focus on pediatric critical illness. Methods: A PubMed search was performed by using the following keywords and limits (("hyperglycemia"[MeSH terms] or ("insulin resistance"[MeSH major topic]) and ("critical care"[MeSH terms] or "critical illness"[MeSH terms])) in different combinations with ("metabolism"[MeSH terms] or "metabolic networks and pathways"[MeSH terms]) and ("outcome"[all fields]) and ("infant"[MeSH terms] or "child"[MeSH terms] or "adolescent"[MeSH terms]). Quality assessment of selected studies included clinical pertinence, publication in peer-reviewed journals, objectivity of measurements and techniques used to minimize bias. Reference lists of such studies were included. Results: The magnitude and duration of hyperglycemia are associated with increased morbidity and mortality in the pediatric intensive care unit (PICU), but prospective, randomized controlled studies with insulin therapy have not been published yet. Evidence concerning the mechanism and the effect of insulin on glucose and lipid metabolism in pediatric critical illness is scarce. More is known about the positive effect on protein homeostasis, especially in severely burned children. The effect in septic children is less clear and seems age dependent. Some non-metabolic properties of insulin such as the modulation of inflammation, endothelial dysfunction and coagulopathy have not been fully investigated in children. Conclusion: Future studies on the effect of insulin on morbidity and mortality as well as on the mechanisms through which insulin exerts these effects are necessary in critically ill children. We propose these studies to be conducted under standardized conditions including precise definitions of hyperglycemia and rates of glucose intake.

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