Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment

Irl B Hirsch, MD
Michael Emmett, MD
Section Editor
David M Nathan, MD
Deputy Editor
Jean E Mulder, MD


Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS, also known as hyperosmotic hyperglycemic nonketotic state [HHNK]) are two of the most serious acute complications of diabetes. They are part of the spectrum of hyperglycemia, and each represents an extreme in the spectrum.

The treatment of DKA and HHS in adults will be reviewed here. The epidemiology, pathogenesis, clinical features, evaluation, and diagnosis of these disorders are discussed separately. DKA in children is also reviewed separately.

(See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Epidemiology and pathogenesis".)

(See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis".)

(See "Clinical features and diagnosis of diabetic ketoacidosis in children and adolescents".)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Jan 13, 2017.
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 ©2017 UpToDate, Inc.
  1. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 2009; 32:1335.
  2. Arieff AI, Carroll HJ. Nonketotic hyperosmolar coma with hyperglycemia: clinical features, pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of therapy in 37 cases. Medicine (Baltimore) 1972; 51:73.
  3. Kitabchi AE, Umpierrez GE, Fisher JN, et al. Thirty years of personal experience in hyperglycemic crises: diabetic ketoacidosis and hyperglycemic hyperosmolar state. J Clin Endocrinol Metab 2008; 93:1541.
  4. Morris LR, Kitabchi AE. Efficacy of low-dose insulin therapy for severely obtunded patients in diabetic ketoacidosis. Diabetes Care 1980; 3:53.
  5. Daugirdas JT, Kronfol NO, Tzamaloukas AH, Ing TS. Hyperosmolar coma: cellular dehydration and the serum sodium concentration. Ann Intern Med 1989; 110:855.
  6. Fulop M, Tannenbaum H, Dreyer N. Ketotic hyperosmolar coma. Lancet 1973; 2:635.
  7. Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th, McGraw-Hill, New York 2001. p.809-815.
  8. Barrett EJ, DeFronzo RA. Diabetic ketoacidosis: diagnosis and treatment. Hosp Pract (Off Ed) 1984; 19:89.
  9. Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care 2001; 24:131.
  10. Bratusch-Marrain PR, Komajati M, Waldhausal W. The effect of hyperosmolarity on glucose metabolism. Pract Cardiol 1985; 11:153.
  11. Kitabchi AE, Umpierrez GE, Murphy MB. Diabetic ketoacidosis and hyperglycemic hypersmolar state. In: International Textbook of Diabetes Mellitus, 3rd, DeFronzo RA, Ferrannini E, Keen H, Zimmet P (Eds), John Wiley & Sons, Chichester, UK 2004. p.1101.
  12. Nyenwe EA, Kitabchi AE. Evidence-based management of hyperglycemic emergencies in diabetes mellitus. Diabetes Res Clin Pract 2011; 94:340.
  13. Savage MW, Dhatariya KK, Kilvert A, et al. Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis. Diabet Med 2011; 28:508.
  14. Hillman K. Fluid resuscitation in diabetic emergencies--a reappraisal. Intensive Care Med 1987; 13:4.
  15. Waldhäusl W, Kleinberger G, Korn A, et al. Severe hyperglycemia: effects of rehydration on endocrine derangements and blood glucose concentration. Diabetes 1979; 28:577.
  16. Ennis ED, Stahl EJ, Kreisberg RA. The hyperosmolar hyperglycemic syndrome. Diabetes Rev 1994; 2:115.
  17. Wachtel TJ. The diabetic hyperosmolar state. Clin Geriatr Med 1990; 6:797.
  18. Abramson E, Arky R. Diabetic acidosis with initial hypokalemia. Therapeutic implications. JAMA 1966; 196:401.
  19. Beigelman PM. Potassium in severe diabetic ketoacidosis. Am J Med 1973; 54:419.
  20. Murthy K, Harrington JT, Siegel RD. Profound hypokalemia in diabetic ketoacidosis: a therapeutic challenge. Endocr Pract 2005; 11:331.
  21. Adrogué HJ, Lederer ED, Suki WN, Eknoyan G. Determinants of plasma potassium levels in diabetic ketoacidosis. Medicine (Baltimore) 1986; 65:163.
  22. Umpierrez GE, Jones S, Smiley D, et al. Insulin analogs versus human insulin in the treatment of patients with diabetic ketoacidosis: a randomized controlled trial. Diabetes Care 2009; 32:1164.
  23. 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.
  24. Kitabchi AE, Fisher JN, Murphy MB, Rumbak MJ. Diabetic ketoacidosis and the hyperglycemic hyperosmolar nonketotic state. In: Joslin's Diabetes Mellitus, 13th, Kahn CR, Weir GC (Eds), Lea & Febiger, Philadelphia 1994. p.738.
  25. Brown PM, Tompkins CV, Juul S, Sönksen PH. Mechanism of action of insulin in diabetic patients: a dose-related effect on glucose production and utilisation. Br Med J 1978; 1:1239.
  26. Rosenthal NR, Barrett EJ. An assessment of insulin action in hyperosmolar hyperglycemic nonketotic diabetic patients. J Clin Endocrinol Metab 1985; 60:607.
  27. Page MM, Alberti KG, Greenwood R, et al. Treatment of diabetic coma with continuous low-dose infusion of insulin. Br Med J 1974; 2:687.
  28. Padilla AJ, Loeb JN. "Low-dose" versus "high-dose" insulin regimens in the management of uncontrolled diabetes. A survey. Am J Med 1977; 63:843.
  29. Kitabchi AE, Murphy MB, Spencer J, et al. Is a priming dose of insulin necessary in a low-dose insulin protocol for the treatment of diabetic ketoacidosis? Diabetes Care 2008; 31:2081.
  30. Fisher JN, Shahshahani MN, Kitabchi AE. Diabetic ketoacidosis: low-dose insulin therapy by various routes. N Engl J Med 1977; 297:238.
  31. Umpierrez GE, Latif K, Stoever J, et al. Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis. Am J Med 2004; 117:291.
  32. Umpierrez GE, Cuervo R, Karabell A, et al. Treatment of diabetic ketoacidosis with subcutaneous insulin aspart. Diabetes Care 2004; 27:1873.
  33. Viallon A, Zeni F, Lafond P, et al. Does bicarbonate therapy improve the management of severe diabetic ketoacidosis? Crit Care Med 1999; 27:2690.
  34. Morris LR, Murphy MB, Kitabchi AE. Bicarbonate therapy in severe diabetic ketoacidosis. Ann Intern Med 1986; 105:836.
  35. Lever E, Jaspan JB. Sodium bicarbonate therapy in severe diabetic ketoacidosis. Am J Med 1983; 75:263.
  36. Latif KA, Freire AX, Kitabchi AE, et al. The use of alkali therapy in severe diabetic ketoacidosis. Diabetes Care 2002; 25:2113.
  37. Narins RG, Cohen JJ. Bicarbonate therapy for organic acidosis: the case for its continued use. Ann Intern Med 1987; 106:615.
  38. Okuda Y, Adrogue HJ, Field JB, et al. Counterproductive effects of sodium bicarbonate in diabetic ketoacidosis. J Clin Endocrinol Metab 1996; 81:314.
  39. 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.
  40. Mitchell JH, Wildenthal K, Johnson RL Jr. The effects of acid-base disturbances on cardiovascular and pulmonary function. Kidney Int 1972; 1:375.
  41. Kraut JA, Madias NE. Treatment of acute metabolic acidosis: a pathophysiologic approach. Nat Rev Nephrol 2012; 8:589.
  42. DeFronzo RA, Matzuda M, Barret E. Diabetic ketoacidosis: a combined metabolic-nephrologic approach to therapy. Diabetes Rev 1994; 2:209.
  43. Fraley DS, Adler S. Correction of hyperkalemia by bicarbonate despite constant blood pH. Kidney Int 1977; 12:354.
  44. Kreisberg RA. Phosphorus deficiency and hypophosphatemia. Hosp Pract 1977; 12:121.
  45. Kebler R, McDonald FD, Cadnapaphornchai P. Dynamic changes in serum phosphorus levels in diabetic ketoacidosis. Am J Med 1985; 79:571.
  46. RAINEY RL, ESTES PW, NEELY CL, AMICK LD. Myoglobinuria following diabetic acidosis with electromyographic evaluation. Arch Intern Med 1963; 111:564.
  47. Casteels K, Beckers D, Wouters C, Van Geet C. Rhabdomyolysis in diabetic ketoacidosis. Pediatr Diabetes 2003; 4:29.
  48. Shilo S, Werner D, Hershko C. Acute hemolytic anemia caused by severe hypophosphatemia in diabetic ketoacidosis. Acta Haematol 1985; 73:55.
  49. Fisher JN, Kitabchi AE. A randomized study of phosphate therapy in the treatment of diabetic ketoacidosis. J Clin Endocrinol Metab 1983; 57:177.
  50. Keller U, Berger W. Prevention of hypophosphatemia by phosphate infusion during treatment of diabetic ketoacidosis and hyperosmolar coma. Diabetes 1980; 29:87.
  51. Wilson HK, Keuer SP, Lea AS, et al. Phosphate therapy in diabetic ketoacidosis. Arch Intern Med 1982; 142:517.
  52. Barsotti MM. Potassium phosphate and potassium chloride in the treatment of DKA. Diabetes Care 1980; 3:569.
  53. Winter RJ, Harris CJ, Phillips LS, Green OC. Diabetic ketoacidosis. Induction of hypocalcemia and hypomagnesemia by phosphate therapy. Am J Med 1979; 67:897.
  54. 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.
  55. Middleton P, Kelly AM, Brown J, Robertson M. Agreement between arterial and central venous values for pH, bicarbonate, base excess, and lactate. Emerg Med J 2006; 23:622.
  56. Loh TP, Saw S, Sethi SK. Bedside monitoring of blood ketone for management of diabetic ketoacidosis: proceed with care. Diabet Med 2012; 29:827.
  57. Sulway MJ, Malins JM. Acetone in diabetic ketoacidosis. Lancet 1970; 2:736.
  58. Reichard GA Jr, Skutches CL, Hoeldtke RD, Owen OE. Acetone metabolism in humans during diabetic ketoacidosis. Diabetes 1986; 35:668.
  59. Oh MS, Carroll HJ, Goldstein DA, Fein IA. Hyperchloremic acidosis during the recovery phase of diabetic ketosis. Ann Intern Med 1978; 89:925.
  60. Oh MS, Carroll HJ, Uribarri J. Mechanism of normochloremic and hyperchloremic acidosis in diabetic ketoacidosis. Nephron 1990; 54:1.
  61. Kitabchi AE, Ayyagari V, Guerra SM. The efficacy of low-dose versus conventional therapy of insulin for treatment of diabetic ketoacidosis. Ann Intern Med 1976; 84:633.
  62. 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.
  63. Sprung CL, Rackow EC, Fein IA. Pulmonary edema; a complication of diabetic ketoacidosis. Chest 1980; 77:687.
  64. Powner D, Snyder JV, Grenvik A. Altered pulmonary capillary permeability complicating recovery from diabetic ketoacidosis. Chest 1975; 68:253.
  65. Brun-Buisson CJ, Bonnet F, Bergeret S, et al. Recurrent high-permeability pulmonary edema associated with diabetic ketoacidosis. Crit Care Med 1985; 13:55.