Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Cerebral edema in children with diabetic ketoacidosis

George S Jeha, MD
Morey W Haymond, MD
Section Editors
Joseph I Wolfsdorf, MB, BCh
Adrienne G Randolph, MD, MSc
Deputy Editor
Alison G Hoppin, MD


Cerebral edema (or cerebral injury) is an uncommon but potentially devastating consequence of diabetic ketoacidosis (DKA). It is far more common among children with DKA than among adults. Young children and those with newly diagnosed diabetes are at highest risk. Symptoms typically emerge during treatment for DKA, but may be present prior to initiation of therapy.

The pathophysiology, diagnosis, and treatment of cerebral edema in children with DKA will be discussed here. The diagnosis and treatment of DKA in children is discussed separately. (See "Clinical features and diagnosis of diabetic ketoacidosis in children" and "Treatment and complications of diabetic ketoacidosis in children".)


Clinically significant cerebral edema occurs in approximately 1 percent of episodes of DKA in children and has a mortality rate of 20 to 90 percent [1,2]. Overall mortality rates for diabetic ketoacidosis (DKA) in children and adolescents range from 0.15 to 0.51 percent in national population studies in Canada, the United Kingdom, and the United States [3-8]; 50 to 80 percent of diabetes-related deaths are caused by cerebral edema [1,2,9]. Other causes of death from DKA include aspiration pneumonia, multiple organ failure, gastric perforation, and traumatic hydrothorax [4].

Subclinical brain swelling, as detected by ventricular narrowing on a computed tomography (CT) scan, has been reported in the majority of children with DKA in some studies [10,11], while others reported much smaller proportions [12]. All of these studies were limited by small numbers and lack of appropriate control groups.

In a study of 41 children with DKA, the intercaudate width of the frontal horns of the lateral ventricles was measured by magnetic resonance imaging (MRI) [13]. The lateral ventricles were significantly smaller in patients during treatment for DKA than after recovery (mean width 9.3±0.3 versus 10.2±0.3 mm, respectively). Fifty-six percent of the children had ventricular narrowing during treatment, and these children were more likely to have mental status changes than those without narrowed ventricles (Glasgow coma scale [GCS] scores below 15 occurred in 12 of 22 with ventricular narrowing, versus 4 of 19 without).


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Sep 4, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Glaser N, Barnett P, McCaslin I, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. N Engl J Med 2001; 344:264.
  2. Edge JA, Hawkins MM, Winter DL, Dunger DB. The risk and outcome of cerebral oedema developing during diabetic ketoacidosis. Arch Dis Child 2001; 85:16.
  3. Levitsky L. Death from diabetes (DM) in hospitalized children (1970-1988). Pediatr Res 1991; 29:A195.
  4. Edge JA, Ford-Adams ME, Dunger DB. Causes of death in children with insulin dependent diabetes 1990-96. Arch Dis Child 1999; 81:318.
  5. Curtis JR, To T, Muirhead S, et al. Recent trends in hospitalization for diabetic ketoacidosis in ontario children. Diabetes Care 2002; 25:1591.
  6. Lawrence SE, Cummings EA, Gaboury I, Daneman D. Population-based study of incidence and risk factors for cerebral edema in pediatric diabetic ketoacidosis. J Pediatr 2005; 146:688.
  7. Decourcey DD, Steil GM, Wypij D, Agus MS. Increasing use of hypertonic saline over mannitol in the treatment of symptomatic cerebral edema in pediatric diabetic ketoacidosis: an 11-year retrospective analysis of mortality*. Pediatr Crit Care Med 2013; 14:694.
  8. Hsia DS, Tarai SG, Alimi A, et al. Fluid management in pediatric patients with DKA and rates of suspected clinical cerebral edema. Pediatr Diabetes 2015; 16:338.
  9. Wolfsdorf J, Glaser N, Sperling MA, American Diabetes Association. Diabetic ketoacidosis in infants, children, and adolescents: A consensus statement from the American Diabetes Association. Diabetes Care 2006; 29:1150.
  10. Krane EJ, Rockoff MA, Wallman JK, Wolfsdorf JI. Subclinical brain swelling in children during treatment of diabetic ketoacidosis. N Engl J Med 1985; 312:1147.
  11. Hoffman WH, Steinhart CM, el Gammal T, et al. Cranial CT in children and adolescents with diabetic ketoacidosis. AJNR Am J Neuroradiol 1988; 9:733.
  12. Smedman L, Escobar R, Hesser U, Persson B. Sub-clinical cerebral oedema does not occur regularly during treatment for diabetic ketoacidosis. Acta Paediatr 1997; 86:1172.
  13. Glaser NS, Wootton-Gorges SL, Buonocore MH, et al. Frequency of sub-clinical cerebral edema in children with diabetic ketoacidosis. Pediatr Diabetes 2006; 7:75.
  14. Edge JA, Roy Y, Bergomi A, et al. Conscious level in children with diabetic ketoacidosis is related to severity of acidosis and not to blood glucose concentration. Pediatr Diabetes 2006; 7:11.
  15. Levitsky LL. Symptomatic cerebral edema in diabetic ketoacidosis: the mechanism is clarified but still far from clear. J Pediatr 2004; 145:149.
  16. Dunger DB, Sperling MA, Acerini CL, et al. ESPE/LWPES consensus statement on diabetic ketoacidosis in children and adolescents. Arch Dis Child 2004; 89:188.
  17. Glasgow AM. Devastating cerebral edema in diabetic ketoacidosis before therapy. Diabetes Care 1991; 14:77.
  18. Dunger DB, Sperling MA, Acerini CL, et al. European Society for Paediatric Endocrinology/Lawson Wilkins Pediatric Endocrine Society consensus statement on diabetic ketoacidosis in children and adolescents. Pediatrics 2004; 113:e133.
  19. Harris GD, Fiordalisi I, Harris WL, et al. Minimizing the risk of brain herniation during treatment of diabetic ketoacidemia: a retrospective and prospective study. J Pediatr 1990; 117:22.
  20. Durr JA, Hoffman WH, Sklar AH, et al. Correlates of brain edema in uncontrolled IDDM. Diabetes 1992; 41:627.
  21. Silver SM, Clark EC, Schroeder BM, Sterns RH. Pathogenesis of cerebral edema after treatment of diabetic ketoacidosis. Kidney Int 1997; 51:1237.
  22. Arieff AI, Kleeman CR. Studies on mechanisms of cerebral edema in diabetic comas. Effects of hyperglycemia and rapid lowering of plasma glucose in normal rabbits. J Clin Invest 1973; 52:571.
  23. Wootton-Gorges SL, Buonocore MH, Kuppermann N, et al. Cerebral proton magnetic resonance spectroscopy in children with diabetic ketoacidosis. AJNR Am J Neuroradiol 2007; 28:895.
  24. Wootton-Gorges SL, Buonocore MH, Kuppermann N, et al. Detection of cerebral {beta}-hydroxy butyrate, acetoacetate, and lactate on proton MR spectroscopy in children with diabetic ketoacidosis. AJNR Am J Neuroradiol 2005; 26:1286.
  25. Hoffman WH, Andjelkovic AV, Zhang W, et al. Insulin and IGF-1 receptors, nitrotyrosin and cerebral neuronal deficits in two young patients with diabetic ketoacidosis and fatal brain edema. Brain Res 2010; 1343:168.
  26. Hoffman WH, Artlett CM, Zhang W, et al. Receptor for advanced glycation end products and neuronal deficit in the fatal brain edema of diabetic ketoacidosis. Brain Res 2008; 1238:154.
  27. Hoffman WH, Stamatovic SM, Andjelkovic AV. Inflammatory mediators and blood brain barrier disruption in fatal brain edema of diabetic ketoacidosis. Brain Res 2009; 1254:138.
  28. Glaser NS, Wootton-Gorges SL, Marcin JP, et al. Mechanism of cerebral edema in children with diabetic ketoacidosis. J Pediatr 2004; 145:164.
  29. Figueroa RE, Hoffman WH, Momin Z, et al. Study of subclinical cerebral edema in diabetic ketoacidosis by magnetic resonance imaging T2 relaxometry and apparent diffusion coefficient maps. Endocr Res 2005; 31:345.
  30. Vavilala MS, Richards TL, Roberts JS, et al. Change in blood-brain barrier permeability during pediatric diabetic ketoacidosis treatment. Pediatr Crit Care Med 2010; 11:332.
  31. Roberts JS, Vavilala MS, Schenkman KA, et al. Cerebral hyperemia and impaired cerebral autoregulation associated with diabetic ketoacidosis in critically ill children. Crit Care Med 2006; 34:2217.
  32. Fiordalisi I, Novotny WE, Holbert D, et al. An 18-yr prospective study of pediatric diabetic ketoacidosis: an approach to minimizing the risk of brain herniation during treatment. Pediatr Diabetes 2007; 8:142.
  33. Rosenbloom AL. Intracerebral crises during treatment of diabetic ketoacidosis. Diabetes Care 1990; 13:22.
  34. Edge JA, Jakes RW, Roy Y, et al. The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children. Diabetologia 2006; 49:2002.
  35. Hoorn EJ, Carlotti AP, Costa LA, et al. Preventing a drop in effective plasma osmolality to minimize the likelihood of cerebral edema during treatment of children with diabetic ketoacidosis. J Pediatr 2007; 150:467.
  36. Duck SC, Weldon VV, Pagliara AS, Haymond MW. Cerebral edema complicating therapy for diabetic ketoacidosis. Diabetes 1976; 25:111.
  37. Duck SC, Wyatt DT. Factors associated with brain herniation in the treatment of diabetic ketoacidosis. J Pediatr 1988; 113:10.
  38. Hale PM, Rezvani I, Braunstein AW, et al. Factors predicting cerebral edema in young children with diabetic ketoacidosis and new onset type I diabetes. Acta Paediatr 1997; 86:626.
  39. Bureau MA, Bégin R, Berthiaume Y, et al. Cerebral hypoxia from bicarbonate infusion in diabetic acidosis. J Pediatr 1980; 96:968.
  40. Mahoney CP, Vlcek BW, DelAguila M. Risk factors for developing brain herniation during diabetic ketoacidosis. Pediatr Neurol 1999; 21:721.
  41. Clements RS Jr, Blumenthal SA, Morrison AD, Winegrad AI. Increased cerebrospinal-fluid pressure during treatment of diabetic ketosis. Lancet 1971; 2:671.
  42. Muir AB, Quisling RG, Yang MC, Rosenbloom AL. Cerebral edema in childhood diabetic ketoacidosis: natural history, radiographic findings, and early identification. Diabetes Care 2004; 27:1541.
  43. Wolfsdorf JI, Allgrove J, Craig ME, et al. ISPAD Clinical Practice Consensus Guidelines 2014. Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatr Diabetes 2014; 15 Suppl 20:154.
  44. Wolfsdorf JI. The International Society of Pediatric and Adolescent Diabetes guidelines for management of diabetic ketoacidosis: Do the guidelines need to be modified? Pediatr Diabetes 2014; 15:277.
  45. Franklin B, Liu J, Ginsberg-Fellner F. Cerebral edema and ophthalmoplegia reversed by mannitol in a new case of insulin-dependent diabetes mellitus. Pediatrics 1982; 69:87.
  46. Shabbir N, Oberfield SE, Corrales R, et al. Recovery from symptomatic brain swelling in diabetic ketoacidosis. Clin Pediatr (Phila) 1992; 31:570.
  47. Roberts MD, Slover RH, Chase HP. Diabetic ketoacidosis with intracerebral complications. Pediatr Diabetes 2001; 2:109.
  48. Marcin JP, Glaser N, Barnett P, et al. Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema. J Pediatr 2002; 141:793.
  49. Kamat P, Vats A, Gross M, Checchia PA. Use of hypertonic saline for the treatment of altered mental status associated with diabetic ketoacidosis. Pediatr Crit Care Med 2003; 4:239.
  50. Curtis JR, Bohn D, Daneman D. Use of hypertonic saline in the treatment of cerebral edema in diabetic ketoacidosis (DKA). Pediatr Diabetes 2001; 2:191.