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

Serum osmolal gap

Michael Emmett, MD
Section Editor
Richard H Sterns, MD
Deputy Editor
John P Forman, MD, MSc


The serum (or plasma) osmolality is determined by the concentrations of the different solutes in the plasma. In normal subjects, sodium salts (chloride and bicarbonate), glucose, and urea are the primary circulating solutes. Although a variety of formulas have been evaluated to predict the plasma osmolality [1], most studies have concluded that serum osmolality (Sosm) can be best estimated from the following formula [1-5]:

 Calculated Sosm   =   (2  x  serum [Na])  +  [glucose, in mg/dL]/18  + [blood urea nitrogen, in mg/dL]/2.8

or, with standard units (all of which are in mmol/L):

 Calculated Sosm   =   (2  x  serum [Na])  +  [glucose]  + [urea]

The serum sodium is multiplied by two to account for accompanying anions (chloride and bicarbonate) and, in the first formula, the divisors 18 and 2.8 convert units of mg/dL into mosmol/kg (calculator 1) or, for standard units, (calculator 2) [6].


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: Aug 25, 2014.
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. Rasouli M, Kalantari KR. Comparison of methods for calculating serum osmolality: multivariate linear regression analysis. Clin Chem Lab Med 2005; 43:635.
  2. Worthley LI, Guerin M, Pain RW. For calculating osmolality, the simplest formula is the best. Anaesth Intensive Care 1987; 15:199.
  3. Schelling JR, Howard RL, Winter SD, Linas SL. Increased osmolal gap in alcoholic ketoacidosis and lactic acidosis. Ann Intern Med 1990; 113:580.
  4. Lynd LD, Richardson KJ, Purssell RA, et al. An evaluation of the osmole gap as a screening test for toxic alcohol poisoning. BMC Emerg Med 2008; 8:5.
  5. Purssell RA, Pudek M, Brubacher J, Abu-Laban RB. Derivation and validation of a formula to calculate the contribution of ethanol to the osmolal gap. Ann Emerg Med 2001; 38:653.
  6. Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, McGraw-Hill, New York 2001. p.607.
  7. Walker JA, Schwartzbard A, Krauss EA, et al. The missing gap. A pitfall in the diagnosis of alcohol intoxication by osmometry. Arch Intern Med 1986; 146:1843.
  8. Sweeney TE, Beuchat CA. Limitations of methods of osmometry: measuring the osmolality of biological fluids. Am J Physiol 1993; 264:R469.
  9. Sklar AH, Linas SL. The osmolal gap in renal failure. Ann Intern Med 1983; 98:481.
  10. Glasser L, Sternglanz PD, Combie J, Robinson A. Serum osmolality and its applicability to drug overdose. Am J Clin Pathol 1973; 60:695.
  11. Gennari FJ. Current concepts. Serum osmolality. Uses and limitations. N Engl J Med 1984; 310:102.
  12. Robinson AG, Loeb JN. Ethanol ingestion--commonest cause of elevated plasma osmolality? N Engl J Med 1971; 284:1253.
  13. Jacobsen D, Bredesen JE, Eide I, Ostborg J. Anion and osmolal gaps in the diagnosis of methanol and ethylene glycol poisoning. Acta Med Scand 1982; 212:17.
  14. Gabow PA. Ethylene glycol intoxication. Am J Kidney Dis 1988; 11:277.
  15. Calvery HO, Klumpp TG. The toxicity for human beings of diethylene glycol with sulfanilamide. South Med J 1939; 32:1105.
  16. Rentz ED, Lewis L, Mujica OJ, et al. Outbreak of acute renal failure in Panama in 2006: a case-control study. Bull World Health Organ 2008; 86:749.
  17. Schep LJ, Slaughter RJ, Temple WA, Beasley DM. Diethylene glycol poisoning. Clin Toxicol (Phila) 2009; 47:525.
  18. Morelle J, Kanaan N, Hantson P. The Case: Cranial nerve palsy and acute renal failure after a 'special drink'. Kidney Int 2010; 77:559.
  19. Arroliga AC, Shehab N, McCarthy K, Gonzales JP. Relationship of continuous infusion lorazepam to serum propylene glycol concentration in critically ill adults. Crit Care Med 2004; 32:1709.
  20. Miller MA, Forni A, Yogaratnam D. Propylene glycol-induced lactic acidosis in a patient receiving continuous infusion pentobarbital. Ann Pharmacother 2008; 42:1502.
  21. Bledsoe KA, Kramer AH. Propylene glycol toxicity complicating use of barbiturate coma. Neurocrit Care 2008; 9:122.
  22. Zosel A, Egelhoff E, Heard K. Severe lactic acidosis after an iatrogenic propylene glycol overdose. Pharmacotherapy 2010; 30:219.
  23. Zar T, Graeber C, Perazella MA. Recognition, treatment, and prevention of propylene glycol toxicity. Semin Dial 2007; 20:217.
  24. Kraut JA, Kurtz I. Toxic alcohol ingestions: clinical features, diagnosis, and management. Clin J Am Soc Nephrol 2008; 3:208.
  25. Braden GL, Strayhorn CH, Germain MJ, et al. Increased osmolal gap in alcoholic acidosis. Arch Intern Med 1993; 153:2377.
  26. Guglielminotti J, Pernet P, Maury E, et al. Osmolar gap hyponatremia in critically ill patients: evidence for the sick cell syndrome? Crit Care Med 2002; 30:1051.
  27. Inaba H, Hirasawa H, Mizuguchi T. Serum osmolality gap in postoperative patients in intensive care. Lancet 1987; 1:1331.