Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics.

BACKGROUND Cerebral edema is an uncommon but devastating complication of diabetic ketoacidosis in children. Risk factors for this complication have not been clearly defined. METHODS In this multicenter study, we identified 61 children who had been hospitalized for diabetic ketoacidosis within a 15-year period and in whom cerebral edema had developed. Two additional groups of children with diabetic ketoacidosis but without cerebral edema were also identified: 181 randomly selected children and 174 children matched to those in the cerebral-edema group with respect to age at presentation, onset of diabetes (established vs. newly diagnosed disease), initial serum glucose concentration, and initial venous pH. Using logistic regression we compared the three groups with respect to demographic characteristics and biochemical variables at presentation and compared the matched groups with respect to therapeutic interventions and changes in biochemical values during treatment. RESULTS A comparison of the children in the cerebral-edema group with those in the random control group showed that cerebral edema was significantly associated with lower initial partial pressures of arterial carbon dioxide (relative risk of cerebral edema for each decrease of 7.8 mm Hg [representing 1 SD], 3.4; 95 percent confidence interval, 1.9 to 6.3; P<0.001) and higher initial serum urea nitrogen concentrations (relative risk of cerebral edema for each increase of 9 mg per deciliter [3.2 mmol per liter] [representing 1 SD], 1.7; 95 percent confidence interval, 1.2 to 2.5; P=0.003). A comparison of the children with cerebral edema with those in the matched control group also showed that cerebral edema was associated with lower partial pressures of arterial carbon dioxide and higher serum urea nitrogen concentrations. Of the therapeutic variables, only treatment with bicarbonate was associated with cerebral edema, after adjustment for other covariates (relative risk, 4.2; 95 percent confidence interval, 1.5 to 12.1; P=0.008). CONCLUSIONS Children with diabetic ketoacidosis who have low partial pressures of arterial carbon dioxide and high serum urea nitrogen concentrations at presentation and who are treated with bicarbonate are at increased risk for cerebral edema.

[1]  L. Finberg,et al.  Safe management of diabetic ketoacidemia. , 1988, The Journal of pediatrics.

[2]  M. D. Jones Energy metabolism in the developing brain. , 1979, Seminars in perinatology.

[3]  B. Lin,et al.  Hyperglycemia triggers massive neutrophil deposition in brain following transient ischemia in rats , 2000, Neuroscience Letters.

[4]  D. Kleinbaum,et al.  Applied Regression Analysis and Other Multivariate Methods , 1978 .

[5]  G. Faich,et al.  The epidemiology of diabetic acidosis: a population-based study. , 1983, American journal of epidemiology.

[6]  A. Rosenbloom Intracerebral Crises During Treatment of Diabetic Ketoacidosis , 1990, Diabetes Care.

[7]  C. Steinhart,et al.  Cranial CT in children and adolescents with diabetic ketoacidosis. , 1988, AJNR. American journal of neuroradiology.

[8]  B. Efron,et al.  A Leisurely Look at the Bootstrap, the Jackknife, and , 1983 .

[9]  R. Willoughby,et al.  Textbook of Pediatric Intensive Care , 1996 .

[10]  M. Kappy,et al.  Cerebral Salt Wasting in Children: The Need for Recognition and Treatment , 1993 .

[11]  F. Ginsberg-Fellner,et al.  Cerebral edema and ophthalmoplegia reversed by mannitol in a new case of insulin-dependent diabetes mellitus. , 1982, Pediatrics.

[12]  J. Dorman,et al.  Why do children with diabetes die? , 1986, Acta endocrinologica. Supplementum.

[13]  A. Glasgow Devastating Cerebral Edema in Diabetic Ketoacidosis Before Therapy , 1991, Diabetes Care.

[14]  Y. Berthiaume,et al.  Cerebral hypoxia from bicarbonate infusion in diabetic acidosis. , 1980, The Journal of pediatrics.

[15]  A. Arieff,et al.  Cerebral edema in diabetic comas. II. Effects of hyperosmolality, hyperglycemia and insulin in diabetic rabbits. , 1974, The Journal of clinical endocrinology and metabolism.

[16]  R. Tannen,et al.  Fluids and electrolytes , 1986 .

[17]  D. Dunger,et al.  Causes of death in children with insulin dependent diabetes 1990–96 , 1999, Archives of disease in childhood.

[18]  S. Silver,et al.  Pathogenesis of cerebral edema after treatment of diabetic ketoacidosis. , 1997, Kidney international.

[19]  M. Katz Hyperglycemia-induced hyponatremia--calculation of expected serum sodium depression. , 1973, The New England journal of medicine.

[20]  B. Vlcek,et al.  Risk factors for developing brain herniation during diabetic ketoacidosis. , 1999, Pediatric neurology.

[21]  F. Marumo,et al.  Alterations in Plasma Concentrations of Natriuretic Peptides and Antidiuretic Hormone After Subarachnoid Hemorrhage , 1994, Stroke.

[22]  D. Rubin,et al.  Statistical Analysis with Missing Data. , 1989 .

[23]  C. C. Chen,et al.  The bootstrap and identification of prognostic factors via Cox's proportional hazards regression model. , 1985, Statistics in medicine.

[24]  H. Scheffé A METHOD FOR JUDGING ALL CONTRASTS IN THE ANALYSIS OF VARIANCE , 1953 .

[25]  J. Sotos,et al.  Cerebral oedema in diabetic ketoacidosis in children , 1990, The Lancet.

[26]  W. L. Harris,et al.  Minimizing the risk of brain herniation during treatment of diabetic ketoacidemia: a retrospective and prospective study. , 1990, The Journal of pediatrics.

[27]  P. Hammond,et al.  Cerebral oedema in diabetic ketoacidosis. , 1992, BMJ.

[28]  E. Krane,et al.  Subclinical brain swelling in children during treatment of diabetic ketoacidosis. , 1985, The New England journal of medicine.

[29]  R. Couch,et al.  Early Onset Fatal Cerebral Edema In Diabetic Ketoacidosis , 1991, Diabetes Care.

[30]  S. Duck,et al.  Factors associated with brain herniation in the treatment of diabetic ketoacidosis. , 1988, The Journal of pediatrics.

[31]  W. Bingaman,et al.  Malignant cerebral edema and intracranial hypertension. , 1995, Neurologic clinics.

[32]  L. Prockop Hyperglycemia, polyol accumulation, and increased intracranial pressure. , 1971, Archives of neurology.

[33]  R. Kairam,et al.  Recovery from Symptomatic Brain Swelling In Diabetic Ketoacidosis , 1992, Clinical pediatrics.

[34]  A. Muir Cerebral Edema in Diabetic Ketoacidosis: A Look Beyond Rehydration , 2000 .