Diabetic Ketoacidosis in Infants, Children, and Adolescents: A consensus statement from the American Diabetes Association
Authors: J. Wolfsdorf
Journal: Diabetes Care (2006)

he adage "A child is not a miniature adult" is most appropriate when considering diabetic ketoacidosis (DKA).The fundamental pathophysiology of this potentially life-threatening complication is the same as in adults.However, the child differs from the adult in a number of characteristics.1) The younger the child, the more difficult it is to obtain the classical history of polyuria, polydipsia, and weight loss.Infants and toddlers in DKA may be misdiagnosed as having pneumonia, reactive airways disease (asthma), or bronchiolitis and therefore treated with glucocorticoids and/or sympathomimetic agents that only compound and exacerbate the metabolic derangements.Because the diagnosis of diabetes is not suspected as it evolves, the duration of symptoms may be longer, leading to more severe dehydration and acidosis and ultimately to obtundation and coma.Even in developed countries, some 15-70% of all newly diagnosed infants and children with diabetes present with DKA (1-8).Generally, the rates of DKA are inversely proportional to rates of diabetes in that community, but throughout the U.S., the overall rates of DKA at diagnosis have remained fairly constant at ϳ25% (6).DKA, defined by blood bicarbonate Ͻ15 mmol/l and/or pH Ͻ7.25 (Ͻ7.3 if arterial or capillary), was present in 23.3% of a carefully analyzed cohort.However, the prevalence of DKA decreased significantly with age from 36% in children Ͻ5 years of age to 16% in those Ͼ14 years but did not differ significantly by sex or ethnicity (6).2) The higher basal metabolic rate and large surface area relative to total body mass in children requires greater precision in delivering fluids and electrolytes.The degree of dehydration is expressed as a function of body weight, i.e., 10% dehydration implies 10% loss of total body weight as water.However, the calculation of basal requirements, although a constant per unit of surface area, must be carefully adjusted when calculating per unit mass because the amount of fluid per kilogram declines as the infant or child grows.3) Cerebral and other autoregulatory mechanisms may not be as well developed in younger children.Hence, greater severity at presentation in younger children together with less maturity of autoregulatory systems combine to predispose children to cerebral edema, which occurs in ϳ0.5-1% of all episodes of DKA in children and is the most common cause of mortality in children with DKA (9 -12).Only a minority of deaths in DKA are attributable to other causes, such as sepsis, other infections (including mucormycosis), aspiration pneumonia, pulmonary edema, acute respiratory distress syn-drome, pneumomediastinum, hypo-or hyperkalemia, cardiac arrhythmias, central nervous system (CNS) hematoma or thrombosis, and rhabdomyolysis.Currently, the etiology, pathophysiology, and ideal treatment are poorly understood, but these are areas of intense investigation.Because cerebral edema occurs in the context of DKA, reduction of the incidence of DKA should be a major goal of treating children with diabetes.The reported mortality rates in children with DKA are constant in national populationbased studies varying from ϳ0.15 to 0.3%.Once cerebral edema develops, death occurs in some 20 -25%, and significant morbidity, including pituitary insufficiency, occurs in 10 -25% of survivors.Where medical services are less well developed, the risk of dying from DKA is greater, and children may die before receiving treatment.Overall, cerebral edema accounts for ϳ60 -90% of all DKA-related deaths in children.4) Whereas delay in diagnosis is the major cause of DKA in previously unrecognized disease in younger children, omission of insulin is the leading cause of recurrent DKA, most prevalent among adolescents.In this group, some 5% of patients account for Ͼ25% of all admission for DKA (11).These important differences between children and adults require careful attention to issues of management.Here, we briefly review the pathophysiology of DKA in childhood and discuss recommended treatment protocols.Current concepts of cerebral edema are presented.We conclude with recommendations and strategies for the prediction and prevention of DKA and, hence, its complications in infants, children, and adolescents.These considerations and recommendations are in agreement with those recently endorsed by the Lawson Wilkins Pediatric Endocrine Society (LWPES), European Society for Pediatric Endocrinology (ESPE), and the International Society for Pediatric and Adolescent Diabetes (ISPAD).