Treatment and complications of diabetic ketoacidosis in children
- George S Jeha, MD
George S Jeha, MD
- Assistant Professor of Pediatrics
- Baylor College of Medicine
- Morey W Haymond, MD
Morey W Haymond, MD
- Professor of Pediatric Nutrition
- Baylor College of Medicine
- Section Editors
- Joseph I Wolfsdorf, MB, BCh
Joseph I Wolfsdorf, MB, BCh
- Section Editor — Pediatric Endocrinology
- Professor of Pediatrics
- Harvard Medical School
- Adrienne G Randolph, MD, MSc
Adrienne G Randolph, MD, MSc
- Section Editor — Pediatric Critical Care Medicine
- Professor of Anaesthesia and Pediatrics
- Harvard Medical School
Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus (T1DM), with a case fatality rate ranging from 0.15 percent to 0.31 percent [1-3]. DKA also can occur in children with type 2 DM (T2DM); this presentation is most common among youth of African-American descent [4-8]. (See "Classification of diabetes mellitus and genetic diabetic syndromes".)
The management of DKA in children will be reviewed here (table 1). There is limited experience in the management and outcomes of DKA in children with T2DM, although the same principles should apply. The clinical manifestations and diagnosis of DKA in children and the pathogenesis of DKA are discussed elsewhere. (See "Clinical features and diagnosis of diabetic ketoacidosis in children" and "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Epidemiology and pathogenesis".)
A consensus statement from the International Society for Pediatric and Adolescent Diabetes (ISPAD) in 2014 defined the following biochemical criteria for the diagnosis of diabetic ketoacidosis (DKA) :
●Hyperglycemia, defined as a blood glucose of >200 mg/dL (11 mmol/L) AND
●Metabolic acidosis, defined as a venous pH <7.3 or a plasma bicarbonate <15 mEq/L (15 mmol/L) AND
- Levitsky L. Death from diabetes (DM) in hospitalized children (1970-1988). Pediatr Res 1991; 29:A195.
- Edge JA, Ford-Adams ME, Dunger DB. Causes of death in children with insulin dependent diabetes 1990-96. Arch Dis Child 1999; 81:318.
- Curtis JR, To T, Muirhead S, et al. Recent trends in hospitalization for diabetic ketoacidosis in ontario children. Diabetes Care 2002; 25:1591.
- Pinhas-Hamiel O, Dolan LM, Zeitler PS. Diabetic ketoacidosis among obese African-American adolescents with NIDDM. Diabetes Care 1997; 20:484.
- Scott CR, Smith JM, Cradock MM, Pihoker C. Characteristics of youth-onset noninsulin-dependent diabetes mellitus and insulin-dependent diabetes mellitus at diagnosis. Pediatrics 1997; 100:84.
- Banerji MA. Impaired beta-cell and alpha-cell function in African-American children with type 2 diabetes mellitus--"Flatbush diabetes". J Pediatr Endocrinol Metab 2002; 15 Suppl 1:493.
- Sellers EA, Dean HJ. Diabetic ketoacidosis: a complication of type 2 diabetes in Canadian aboriginal youth. Diabetes Care 2000; 23:1202.
- Neufeld ND, Raffel LJ, Landon C, et al. Early presentation of type 2 diabetes in Mexican-American youth. Diabetes Care 1998; 21:80.
- 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.
- 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.
- 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.
- Rosenbloom AL. Hyperglycemic hyperosmolar state: an emerging pediatric problem. J Pediatr 2010; 156:180.
- Zeitler P, Haqq A, Rosenbloom A, et al. Hyperglycemic hyperosmolar syndrome in children: pathophysiological considerations and suggested guidelines for treatment. J Pediatr 2011; 158:9.
- 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.
- 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.
- 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.
- 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.
- DARROW DC, PRATT EL. Retention of water and electrolyte during recovery in a patient with diabetic acidosis. J Pediatr 1952; 41:688.
- Atchley DW, Loeb RF, Richards DW, et al. ON DIABETIC ACIDOSIS: A Detailed Study of Electrolyte Balances Following the Withdrawal and Reestablishment of Insulin Therapy. J Clin Invest 1933; 12:297.
- BUTLER AM, TALBOT NB. Metabolic studies in diabetic coma. Trans Assoc Am Physicians 1947; 60:102.
- Koves IH, Neutze J, Donath S, et al. The accuracy of clinical assessment of dehydration during diabetic ketoacidosis in childhood. Diabetes Care 2004; 27:2485.
- Wolfsdorf J, Craig ME, Daneman D, et al. Diabetic ketoacidosis. Pediatr Diabetes 2007; 8:28.
- 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.
- Hom J, Sinert R. Evidence-based emergency medicine/critically appraised topic. Is fluid therapy associated with cerebral edema in children with diabetic ketoacidosis? Ann Emerg Med 2008; 52:69.
- Brown TB. Cerebral oedema in childhood diabetic ketoacidosis: is treatment a factor? Emerg Med J 2004; 21:141.
- 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.
- Felner EI, White PC. Improving management of diabetic ketoacidosis in children. Pediatrics 2001; 108:735.
- Adrogué HJ, Barrero J, Eknoyan G. Salutary effects of modest fluid replacement in the treatment of adults with diabetic ketoacidosis. Use in patients without extreme volume deficit. JAMA 1989; 262:2108.
- Puttha R, Cooke D, Subbarayan A, et al. Low dose (0.05 units/kg/h) is comparable with standard dose (0.1 units/kg/h) intravenous insulin infusion for the initial treatment of diabetic ketoacidosis in children with type 1 diabetes-an observational study. Pediatr Diabetes 2010; 11:12.
- Carmody D, Naylor RN, Philipson LH. Insulin dosing in pediatric diabetic ketoacidosis: where to start? JAMA 2015; 313:2274.
- Luzi L, Barrett EJ, Groop LC, et al. Metabolic effects of low-dose insulin therapy on glucose metabolism in diabetic ketoacidosis. Diabetes 1988; 37:1470.
- Schade DS, Eaton RP. Dose response to insulin in man: differential effects on glucose and ketone body regulation. J Clin Endocrinol Metab 1977; 44:1038.
- Grimberg A, Cerri RW, Satin-Smith M, Cohen P. The "two bag system" for variable intravenous dextrose and fluid administration: benefits in diabetic ketoacidosis management. J Pediatr 1999; 134:376.
- Fisher JN, Shahshahani MN, Kitabchi AE. Diabetic ketoacidosis: low-dose insulin therapy by various routes. N Engl J Med 1977; 297:238.
- Della Manna T, Steinmetz L, Campos PR, et al. Subcutaneous use of a fast-acting insulin analog: an alternative treatment for pediatric patients with diabetic ketoacidosis. Diabetes Care 2005; 28:1856.
- Soler NG, FitzGerald MG, Wright AD, Malins JM. Comparative study of different insulin regimens in management of diabetic ketoacidosis. Lancet 1975; 2:1221.
- Duck SC, Weldon VV, Pagliara AS, Haymond MW. Cerebral edema complicating therapy for diabetic ketoacidosis. Diabetes 1976; 25:111.
- Duck SC, Wyatt DT. Factors associated with brain herniation in the treatment of diabetic ketoacidosis. J Pediatr 1988; 113:10.
- 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.
- 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.
- Durward A, Ferguson LP, Taylor D, et al. The temporal relationship between glucose-corrected serum sodium and neurological status in severe diabetic ketoacidosis. Arch Dis Child 2011; 96:50.
- Hillier TA, Abbott RD, Barrett EJ. Hyponatremia: evaluating the correction factor for hyperglycemia. Am J Med 1999; 106:399.
- Adrogué HJ, Wilson H, Boyd AE 3rd, et al. Plasma acid-base patterns in diabetic ketoacidosis. N Engl J Med 1982; 307:1603.
- Adrogué HJ, Eknoyan G, Suki WK. Diabetic ketoacidosis: role of the kidney in the acid-base homeostasis re-evaluated. Kidney Int 1984; 25:591.
- Oh MS, Carroll HJ, Uribarri J. Mechanism of normochloremic and hyperchloremic acidosis in diabetic ketoacidosis. Nephron 1990; 54:1.
- Noyes KJ, Crofton P, Bath LE, et al. Hydroxybutyrate near-patient testing to evaluate a new end-point for intravenous insulin therapy in the treatment of diabetic ketoacidosis in children. Pediatr Diabetes 2007; 8:150.
- Morris LR, Murphy MB, Kitabchi AE. Bicarbonate therapy in severe diabetic ketoacidosis. Ann Intern Med 1986; 105:836.
- Hale PJ, Crase J, Nattrass M. Metabolic effects of bicarbonate in the treatment of diabetic ketoacidosis. Br Med J (Clin Res Ed) 1984; 289:1035.
- Okuda Y, Adrogue HJ, Field JB, et al. Counterproductive effects of sodium bicarbonate in diabetic ketoacidosis. J Clin Endocrinol Metab 1996; 81:314.
- Zipf WB, Bacon GE, Spencer ML, et al. Hypocalcemia, hypomagnesemia, and transient hypoparathyroidism during therapy with potassium phosphate in diabetic ketoacidosis. Diabetes Care 1979; 2:265.
- Alberti KG, Emerson PM, Darley JH, Hockaday TD. 2,3-Diphosphoglycerate and tissue oxygenation in uncontrolled diabetes mellitus. Lancet 1972; 2:391.
- Gibby OM, Veale KE, Hayes TM, et al. Oxygen availability from the blood and the effect of phosphate replacement on erythrocyte 2,3-diphosphoglycerate and haemoglobin-oxygen affinity in diabetic ketoacidosis. Diabetologia 1978; 15:381.
- Fisher JN, Kitabchi AE. A randomized study of phosphate therapy in the treatment of diabetic ketoacidosis. J Clin Endocrinol Metab 1983; 57:177.
- Wilson HK, Keuer SP, Lea AS, et al. Phosphate therapy in diabetic ketoacidosis. Arch Intern Med 1982; 142:517.
- 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.
- 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.
- 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.
- Ghetti S, Lee JK, Sims CE, et al. Diabetic ketoacidosis and memory dysfunction in children with type 1 diabetes. J Pediatr 2010; 156:109.
- Wootton-Gorges SL, Buonocore MH, Caltagirone RA, et al. Progressive decrease in N-acetylaspartate/Creatine ratio in a teenager with type 1 diabetes and repeated episodes of ketoacidosis without clinically apparent cerebral edema: Evidence for permanent brain injury. AJNR Am J Neuroradiol 2010; 31:780.
- Worly JM, Fortenberry JD, Hansen I, et al. Deep venous thrombosis in children with diabetic ketoacidosis and femoral central venous catheters. Pediatrics 2004; 113:e57.
- Gutierrez JA, Bagatell R, Samson MP, et al. Femoral central venous catheter-associated deep venous thrombosis in children with diabetic ketoacidosis. Crit Care Med 2003; 31:80.
- Carl GF, Hoffman WH, Passmore GG, et al. Diabetic ketoacidosis promotes a prothrombotic state. Endocr Res 2003; 29:73.
- Haddad NG, Croffie JM, Eugster EA. Pancreatic enzyme elevations in children with diabetic ketoacidosis. J Pediatr 2004; 145:122.
- Vanelli M, Chiari G, Ghizzoni L, et al. Effectiveness of a prevention program for diabetic ketoacidosis in children. An 8-year study in schools and private practices. Diabetes Care 1999; 22:7.
- Drozda DJ, Dawson VA, Long DJ, et al. Assessment of the effect of a comprehensive diabetes management program on hospital admission rates of children with diabetes mellitus. Diabetes Educ 1990; 16:389.
- Beck JK, Logan KJ, Hamm RM, et al. Reimbursement for pediatric diabetes intensive case management: a model for chronic diseases? Pediatrics 2004; 113:e47.
- INITIAL RAPID ASSESSMENT
- Clinical assessment
- Laboratory testing
- Assessment of severity
- Moderate and severe DKA
- - Dehydration
- Initial volume expansion
- Subsequent fluid administration
- - Hyperglycemia
- - Electrolyte and acid-base disturbances
- Serum sodium
- Serum potassium
- Metabolic acidosis
- - Monitoring
- - Discontinuing the insulin infusion
- Mild DKA
- COMPLICATIONS AND MORTALITY
- Cerebral edema
- Cognitive impairment
- Venous thrombosis
- Cardiac arrhythmia
- Pancreatic enzyme elevations
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS