Abstract
Cerebral edema is the most frequent serious complication of diabetic ketoacidosis (DKA) in children, occurring in 1% to 5% of DKA episodes. The rates of mortality and permanent neurologic morbidity from this complication are high. The pathophysiologic mechanisms underlying DKA-related cerebral edema are unclear. A number of past and more recent studies have investigated biochemical and therapeutic risk factors for the development of cerebral edema. Recent studies have shown that a higher initial serum urea nitrogen concentration and lower initial partial pressure of carbon dioxide are associated with the development of cerebral edema. This and other information suggests that the pathophysiology of DKA-related cerebral edema may involve cerebral ischemia.
Similar content being viewed by others
References and Recommended Reading
Faich G, Fishbein H, Ellis E: The epidemiology of diabetic acidosis: a population-based study. Am J Epidemiol 1983, 117:551–558.
Pinkney J, Bingley P, Sawtell P: Presentation and progress of childhood diabetes mellitus: a prospective population-based study. Diabetologia 1994, 37:70–74.
Glaser N, Barnett P, McCaslin I, et al.: Risk factors for cerebral edema in children with diabetic ketoacidosis. N Engl J Med 2001, 344:264–269. Multivariate statistical methods are used to compare children with DKA-related cerebral edema with children in two control groups. The authors demonstrate that a lower initial PCO2 value and higher serum urea nitrogen concentration are associated with cerebral edema. A lesser rise in serum sodium concentration during treatment and administration of bicarbonate was also associated with cerebral edema.
Bello F, Sotos J: Cerebral oedema in diabetic ketoacidosis in children. Lancet 1990, 336:64.
Mahoney C, Vlcek B, Del Aguila M: Risk factors for developing brain herniation during diabetic ketoacidosis. Pediatr Neurol 1999, 21:721–727. The initial PCO2 value was found to be the most important predictor of cerebral edema in children with DKA, in agreement with the results of Glaser et al. [3].
Duck S, Wyatt D: Factors associated with brain herniation in the treatment of diabetic ketoacidosis. J Pediatr 1988, 113:10–14.
Rosenbloom A: Intracerebral crises during treatment of diabetic ketoacidosis. Diabetes Care 1990, 13:22–33.
Scibilia J, Finegold D, Dorman J, et al.: Why do children with diabetes die? Acta Endocrinol Suppl 1986, 279:326–333.
Edge J, Ford-Adams M, Dunger D: Causes of death in children with insulin-dependent diabetes 1990-1996. Arch Dis Child 1999, 81:318–323.
Sperling M: Diabetic ketoacidosis. Pediatr Clin North Am 1984, 31:591–610.
Harris G, Fiordalisi I, Harris W, et al.: Minimizing the risk of brain herniation during treatment of diabetic ketoacidemia: a retrospective and prospective study. J Pediatr 1990, 117:22–31.
Harris G, Fiordalisi I, Finberg L: Safe management of diabetic ketoacidemia. J Pediatr 1988, 113:65–67.
Hoffman W, Steinhart C, El Gammal T, et al.: Cranial CT in children and adolescents with diabetic ketoacidosis. AJNR Am J Neuroradiol 1988, 9:733–739.
Krane E, Rockoff M, Wallman J, Wolfsdorf J: Subclinical brain swelling in children during treatment of diabetic ketoacidosis. N Engl J Med 1985, 312:1147–1151.
Glasgow A: Devastating cerebral edema in diabetic ketoacidosis before therapy. Diabetes Care 1991, 14:77–78.
Couch R, Acott P, Wong G: Early onset of fatal cerebral edema in diabetic ketoacidosis. Diabetes Care 1991, 14:78–79.
Arieff A, Kleeman C: Cerebral edema in diabetic comas: II: effects of hyperosmolality, hyperglycemia and insulin in diabetic rabbits. J Clin Endocrinol Metab 1974, 38:1057–1067.
Hammond P, Wallis S: Cerebral oedema in diabetic ketoacidosis. BMJ 1992, 305:203–204.
Prockop L: Hyperglycemia, polyol accumulation, and increased intracranial pressure. Arch Neurol 1971, 25:126–140.
Van Der Meulen J, Klip A, Grinstein S: Possible mechanisms for cerebral oedema in diabetic ketoacidosis. Lancet 1987, 2:306–308.
Muir A: Cerebral edema in diabetic ketoacidosis: a look beyond rehydration. J Clin Endocrinol Metab 2000, 85:509–513. The author describes controversies regarding the pathogenesis of DKA-related cerebral edema and provides evidence in favor of or against specific hypotheses.
Harati Y: Diabetes and the nervous system. Endocrinol Metab Clin North Am 1996, 25:325–359.
Dietrich W: Inflammatory factors regulating the blood-brain barrier. In Inflammatory Cells and Mediators in CNS Diseases. Edited by Feuerstein G. Newark: Harwood Academic Publishers; 1999:137–155.
Lin B, Ginsberg M, Busto R, Li L: Hyperglycemia triggers massive neutrophil deposition in brain following transient ischemia in rats. Neurosci Lett 2000, 278:1–4.
Isales C, Min L, Hoffman W: Acetoacetate and B-hydroxybutyrate differentially regulate endothelin-1 and vascular endothelial growth factor in mouse brain microvascular endothelial cells. J Diabetes Complications 1999, 13:91–97.
Hale P, Rezvani I, Braunstein A, et al.: Factors predicting cerebral edema in young children with diabetic ketoacidosis and new onset type I diabetes. Acta Paediatr 1997, 86:626–631.
Durr J, Hoffman W, Sklar A, et al.: Correlates of brain edema in uncontrolled IDDM. Diabetes 1992, 41:627–632.
Harris G, Fiordalisi I: Physiologic management of diabetic ketoacidemia: a 5-year prospective pediatric experience in 231 episodes. Arch Pediatr Adolesc Med 1994, 148:1046–1052.
Ganong C, Kappy M: Cerebral salt wasting in children: the need for recognition and treatment. Am J Dis Child 1993, 147:167–169.
Wijdicks E, Ropper A, Hunnicutt E, et al.: Atrial natriuretic factor and salt wasting after aneurysmal subarachnoid hemorrhage. Stroke 1991, 22:1519–1524.
Isotani E, Suzuki R, Tomita K, et al.: Alterations in plasma concentrations of natriuretic peptides and antidiuretic hormone after subarachnoid hemorrhage. Stroke 1994, 25:2198–2203.
Zwienenberg M, Muizelaar J: Severe pediatric head injury: the role of hyperemia revisited. J Neurotrauma 1999, 16:937–943.
Marion D, Firlik A, McLaughlin M: Hyperventilation therapy for severe traumatic brain injury. New Horiz 1995, 3:439–447.
Muizelaar J, Marmarou A, Ward J, et al.: Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg 1991, 75:731–739.
Bureau M, Begin R, Berthiaume Y, et al.: Cerebral hypoxia from bicarbonate infusion in diabetic acidosis. J Pediatr 1980, 96:968–973.
Assal J, Aoki T, Manzano F, Kozak G: Metabolic effects of sodium bicarbonate in management of diabetic ketoacidosis. Diabetes 1973, 23:405–411.
Muir A, Quisling R, Rosenbloom A: Early diagnosis of cerebral edema in children with diabetic ketoacidosis. Diabetes 2000, 49(suppl):A92-A93. The authors demonstrate that symptoms and signs of neurologic dysfunction are frequently present prior to acute neurologic decompensation in children with DKA-related cerebral edema. They also show that when focal cerebral edema occurs brain areas with high ATP demand are frequently affected, suggesting that cerebral ischemia might be involved.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Glaser, N. Cerebral edema in children with diabetic ketoacidosis. Curr Diab Rep 1, 41–46 (2001). https://doi.org/10.1007/s11892-001-0009-7
Issue Date:
DOI: https://doi.org/10.1007/s11892-001-0009-7