- Author: Eric E Simon, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
Hyponatremia is an important and common electrolyte abnormality that can be seen in isolation or, as most often is the case, as a complication of other medical illnesses (eg, heart failure, liver failure, renal failure, pneumonia). The normal serum sodium level is 135-145 mEq/L. Hyponatremia is defined as a serum sodium level of less than 135 mEq/L. Joint European guidelines classify hyponatremia in adults according to serum sodium concentration, as follows[1, 2] :
Mild: 130-134 mmol/L
Moderate: 125-129 mmol/L
Profound: <125 mmol/L
Signs and symptoms
Symptoms range from nausea and malaise, with mild reduction in the serum sodium, to lethargy, decreased level of consciousness, headache, and (if severe) seizures and coma. Overt neurologic symptoms most often are due to very low serum sodium levels (usually <115 mEq/L), resulting in intracerebral osmotic fluid shifts and brain edema.
Hyponatremia is classified according to volume status, as follows:
Hypovolemic hyponatremia: decrease in total body water with greater decrease in total body sodium
Euvolemic hyponatremia: normal body sodium with increase in total body water
Hypervolemic hyponatremia: increase in total body sodium with greater increase in total body water
Hyponatremia can be further subclassified according to effective osmolality, as follows:
See Clinical Presentation for more detail.
There are three essential laboratory tests in the evaluation of patients with hyponatremia that, together with the history and the physical examination, help to establish the primary underlying etiologic mechanism: urine osmolality, serum osmolality, and urinary sodium concentration.
Urine osmolality helps differentiate between conditions associated with impaired free-water excretion and primary polydipsia. A urine osmolality greater than 100 mOsm/kg indicates impaired ability of the kidneys to dilute the urine.
Serum osmolality readily differentiates between true hyponatremia and pseudohyponatremia. The latter may be secondary to hyperlipidemia or hyperproteinemia, or may be hypertonic hyponatremia associated with elevated glucose, mannitol, glycine (posturologic or postgynecologic procedure), sucrose, or maltose (contained in IgG formulations).
Urinary sodium concentration
Urinary sodium concentration helps differentiate between hyponatremia secondary to hypovolemia and syndrome of inappropriate antidiuretic hormone secretion (SIADH). With SIADH (and salt-wasting syndrome), the urine sodium is greater than 20-40 mEq/L. With hypovolemia, the urine sodium typically measures less than 25 mEq/L. However, if sodium intake in a patient with SIADH (or salt-wasting) happens to be low, then urine sodium may fall below 25 mEq/L.
See Workup for more detail.
Hypotonic hyponatremia accounts for most clinical cases of hyponatremia and can be treated with fluids. Acute hyponatremia (duration < 48 hours) can be safely corrected more quickly than chronic hyponatremia. The treatment of hypertonic and pseudohyponatremia is directed at the underlying disorder in the absence of symptoms.
Intravenous fluids and water restriction
Administer isotonic saline to patients who are hypovolemic to replace the contracted intravascular volume. Patients with hypovolemia secondary to diuretics may also need potassium repletion, which, like sodium, is osmotically active.
Treat patients who are hypervolemic with salt and fluid restriction, plus loop diuretics, and correction of the underlying condition. The use of a V2 receptor antagonist may be considered.
For euvolemic, asymptomatic hyponatremic patients, free water restriction (< 1 L/day) is generally the treatment of choice. There is no role for hypertonic saline in these patients.
When treating patients with overtly symptomatic hyponatremia (eg, seizures, severe neurologic deficits), hypertonic (3%) saline should be used.
Conivaptan, a V1A and V2 vasopressin receptor antagonist, is available only for intravenous use and is approved for use in the hospital setting for euvolemic and hypervolemic hyponatremia. It is contraindicated in hypovolemic patients. It induces both a water and sodium diuresis with improvement in plasma sodium levels.
See Treatment and Medication for more detail.
Hypoosmolality (serum osmolality <280 mOsm/kg) always indicates excess total body water relative to body solutes or excess water relative to solute in the extracellular fluid (ECF), as water moves freely between the intracellular and the extracellular compartments. This imbalance can be due to solute depletion, solute dilution, or a combination of both.
Under normal conditions, renal handling of water is sufficient to excrete as much as 15-20 L of free water per day. Further, the body's response to a decreased osmolality is decreased thirst. Thus, hyponatremia can occur only when some condition impairs normal free water excretion. Generally, hyponatremia is of clinical significance only when it reflects a drop in the serum osmolality (ie, hypotonic hyponatremia), which is measured directly via osmometry or is calculated as 2(Na) mEq/L + serum glucose (mg/dL)/18 + BUN (mg/dL)/2.8. Note that urea is not an effective osmole, so when the urea levels are very high, the measured osmolality should be corrected for the contribution of urea.
The recommendations for treatment of hyponatremia rely on the current understanding of CNS adaptation to an altered serum osmolality. In the setting of an acute drop in the serum osmolality, neuronal cell swelling occurs due to the water shift from the extracellular space to the intracellular space (ie, Starling forces). Swelling of the brain cells elicits the following two osmoregulatory responses:
It inhibits both arginine vasopressin secretion from neurons in the hypothalamus and hypothalamic thirst center. This leads to excess water elimination as dilute urine.
There is an immediate cellular adaptation with loss of electrolytes, and over the next few days, there is a more gradual loss of organic intracellular osmolytes. 
Therefore, correction of hyponatremia must take into account the chronicity of the condition. Acute hyponatremia (duration < 48 h) can be safely corrected more quickly than chronic hyponatremia. Correction of serum sodium that is too rapid can precipitate severe neurologic complications. Most individuals who present for diagnosis, versus individuals who develop it while in an inpatient setting, have had hyponatremia for some time, so the condition is chronic, and correction should proceed accordingly.
The incidence of hyponatremia depends largely on the patient population and the criteria used to establish the diagnosis. Among hospitalized patients, 15-20% have a serum sodium level of <135 mEq/L, while only 1-4% have a serum sodium level of less than 130 mEq/L. The prevalence of hyponatremia is lower in the ambulatory setting.
Severe hyponatremia (<125 mEq/L) has a high mortality rate. In patients whose serum sodium level falls below 105 mEq/L, and especially in alcoholics, the mortality is over 50%.
In patients with acute ST-elevation myocardial infarction, the presence of hyponatremia on admission or early development of hyponatremia is an independent predictor of 30-day mortality, and the prognosis worsens with the severity of hyponatremia. Bae et al reported that in hospitalized survivors of acute myocardial infarction, the presence of hyponatremia at discharge was an independent predictor of 12-month mortality. The study involved 1290 patients.
Similarly, cirrhotic patients with persistent ascites and a low serum sodium level awaiting transplant have a high mortality risk despite low severity (MELD) scores (see the MELD Score calculator). The independent predictors—ascites and hyponatremia—are findings indicative of hemodynamic decompensation.[8, 9]
A study by Huang et al indicated that in patients with chronic kidney disease, hyponatremia and hypernatremia are associated with an increased risk for all-cause mortality and for deaths unrelated to cardiovascular problems or malignancy. Hyponatremia was also found to be linked to an increased risk for cardiovascular- and malignancy-related mortality in these patients. The study included 45,333 patients with stage 3 or 4 chronic kidney disease, 9.2% of whom had dysnatremia.
Race-, Sex-, and Age-related Demographics
Hyponatremia affects all races.
No sexual predilection exists for hyponatremia. However, symptoms are more likely to occur in young women than in men. Hyponatremia is more common in elderly persons, because they have anhigher rate of comorbid conditions (eg, cardiac, hepatic, or renal failure) that can lead to hyponatremia.
Barclay L, Nainggolan L. New European Guidelines Address Hyponatremia Management. Medscape Medical News. Available at http://www.medscape.com/viewarticle/821130. Accessed: March 1, 2014.
[Guideline] Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant. 2014 Feb 25. [Medline].
Singhi S, Jayashre M. Free water excess is not the main cause for hyponatremia in critically ill children receiving conventional maintenance fluids. Indian Pediatr. 2009 Jul. 46(7):577-83. [Medline].
Gross P, Reimann D, Henschkowski J, Damian M. Treatment of severe hyponatremia: conventional and novel aspects. J Am Soc Nephrol. 2001 Feb. 12 Suppl 17:S10-4. [Medline].
Dubois GD, Arieff AI. Treatment of hyponatremia: the case for rapid correction. Narins RG, ed. Controversies in Nephrology and Hypertension. New York: Churchill Livingstone Inc; 1984. 393-407.
Goldberg A, Hammerman H, Petcherski S, et al. Prognostic importance of hyponatremia in acute ST-elevation myocardial infarction. Am J Med. 2004 Aug 15. 117(4):242-8. [Medline].
Bae MH, Kim JH, Jang SY, et al. Hyponatremia at discharge as a predictor of 12-month clinical outcomes in hospital survivors after acute myocardial infarction. Heart Vessels. 2016 Jun 2. [Medline].
Heuman DM, Abou-Assi SG, Habib A, Williams LM, Stravitz RT, Sanyal AJ. Persistent ascites and low serum sodium identify patients with cirrhosis and low MELD scores who are at high risk for early death. Hepatology. 2004 Oct. 40(4):802-10. [Medline].
Kim MY, Baik SK, Yea CJ, et al. Hepatic venous pressure gradient can predict the development of hepatocellular carcinoma and hyponatremia in decompensated alcoholic cirrhosis. Eur J Gastroenterol Hepatol. 2009 Nov. 21(11):1241-6. [Medline].
Huang H, Jolly SE, Airy M, et al. Associations of dysnatremias with mortality in chronic kidney disease. Nephrol Dial Transplant. 2016 May 24. [Medline].
Bettari L, Fiuzat M, Shaw LK, Wojdyla DM, Metra M, Felker GM, et al. Hyponatremia and long-term outcomes in chronic heart failure-an observational study from the duke databank for cardiovascular diseases. J Card Fail. 2012 Jan. 18(1):74-81. [Medline].
Hillier TA, Abbott RD, Barrett EJ. Hyponatremia: evaluating the correction factor for hyperglycemia. Am J Med. 1999 Apr. 106(4):399-403. [Medline].
Issa MM, Young MR, Bullock AR, Bouet R, Petros JA. Dilutional hyponatremia of TURP syndrome: a historical event in the 21st century. Urology. 2004 Aug. 64(2):298-301. [Medline].
Palmer BF. Hyponatraemia in a neurosurgical patient: syndrome of inappropriate antidiuretic hormone secretion versus cerebral salt wasting. Nephrol Dial Transplant. 2000 Feb. 15(2):262-8. [Medline].
Palmer BF. Hyponatremia in patients with central nervous system disease: SIADH versus CSW. Trends Endocrinol Metab. 2003 May-Jun. 14(4):182-7. [Medline].
Yang CH, Lin YC, Chou PH, Chen HC, Chan CH. A Case Report of Late Onset Mania Caused by Hyponatremia in a Patient With Empty Sella Syndrome. Medicine (Baltimore). 2016 Feb. 95 (6):e2629. [Medline].
Smith D, Moore K, Tormey W, Baylis PH, Thompson CJ. Downward resetting of the osmotic threshold for thirst in patients with SIADH. Am J Physiol Endocrinol Metab. 2004 Nov. 287(5):E1019-23. [Medline].
Skippen P, Adderley R, Bennett M, et al. Iatrogenic hyponatremia in hospitalized children: Can it be avoided?. Paediatr Child Health. 2008 Jul. 13(6):502-6. [Medline]. [Full Text].
Thaler SM, Teitelbaum I, Berl T. "Beer potomania" in non-beer drinkers: effect of low dietary solute intake. Am J Kidney Dis. 1998 Jun. 31(6):1028-31. [Medline].
Goldman MB, Luchins DJ, Robertson GL. Mechanisms of altered water metabolism in psychotic patients with polydipsia and hyponatremia. N Engl J Med. 1988 Feb 18. 318(7):397-403. [Medline].
Danz M, Pöttgen K, Tönjes PM, Hinkelbein J, Braunecker S. Hyponatremia among Triathletes in the Ironman European Championship. N Engl J Med. 2016 Mar 10. 374 (10):997-8. [Medline].
Kratz A, Siegel AJ, Verbalis JG, et al. Sodium status of collapsed marathon runners. Arch Pathol Lab Med. 2005 Feb. 129(2):227-30. [Medline].
Almond CS, Shin AY, Fortescue EB, et al. Hyponatremia among runners in the Boston Marathon. N Engl J Med. 2005 Apr 14. 352(15):1550-6. [Medline].
Hew-Butler T, Almond C, Ayus JC, et al. Consensus statement of the 1st International Exercise-Associated Hyponatremia Consensus Development Conference, Cape Town, South Africa 2005. Clin J Sport Med. 2005 Jul. 15(4):208-13. [Medline].
Baker J, Cotter JD, Gerrard DF, Bell ML, Walker RJ. Effects of indomethacin and celecoxib on renal function in athletes. Med Sci Sports Exerc. 2005 May. 37(5):712-7. [Medline].
Feldman BJ, Rosenthal SM, Vargas GA, et al. Nephrogenic syndrome of inappropriate antidiuresis. N Engl J Med. 2005 May 5. 352(18):1884-90. [Medline].
Trivelli A, Ghiggeri GM, Canepa A, Oddone M, Bava G, Perfumo F. Hyponatremic-hypertensive syndrome with extensive and reversible renal defects. Pediatr Nephrol. 2005 Jan. 20(1):102-4. [Medline].
Sherlock M, O'Sullivan E, Agha A, et al. Incidence and pathophysiology of severe hyponatraemia in neurosurgical patients. Postgrad Med J. 2009 Apr. 85(1002):171-5. [Medline].
[Guideline] Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013 Oct. 126 (10 Suppl 1):S1-42. [Medline].
Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med. 2000 May 25. 342(21):1581-9. [Medline].
Vachharajani TJ, Zaman F, Abreo KD. Hyponatremia in critically ill patients. J Intensive Care Med. 2003 Jan-Feb. 18(1):3-8. [Medline].
Dixon MB, Lien YH. Tolvaptan and its potential in the treatment of hyponatremia. Ther Clin Risk Manag. 2008 Dec. 4(6):1149-55. [Medline]. [Full Text].
Farmakis D, Filippatos G, Kremastinos DT, Gheorghiade M. Vasopressin and vasopressin antagonists in heart failure and hyponatremia. Curr Heart Fail Rep. 2008 Jun. 5(2):91-6. [Medline].
FDA drug safety communication - FDA Limits Duration and Usage Due To Possible Liver Injury Leading to Organ Transplant or Death. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm350185.htm. Accessed: May 2, 2013.
Ayus JC, Wheeler JM, Arieff AI. Postoperative hyponatremic encephalopathy in menstruant women. Ann Intern Med. 1992 Dec 1. 117(11):891-7. [Medline].
Ruzek KA, Campeau NG, Miller GM. Early diagnosis of central pontine myelinolysis with diffusion-weighted imaging. AJNR Am J Neuroradiol. 2004 Feb. 25(2):210-3. [Medline].
Yu J, Zheng SS, Liang TB, Shen Y, Wang WL, Ke QH. Possible causes of central pontine myelinolysis after liver transplantation. World J Gastroenterol. 2004 Sep 1. 10(17):2540-3. [Medline].
Doshi SM, Shah P, Lei X, Lahoti A, Salahudeen AK. Hyponatremia in hospitalized cancer patients and its impact on clinical outcomes. Am J Kidney Dis. 2012 Feb. 59(2):222-8. [Medline].
Corona G, Giuliani C, Verbalis JG, Forti G, Maggi M, Peri A. Hyponatremia improvement is associated with a reduced risk of mortality: evidence from a meta-analysis. PLoS One. 2015. 10 (4):e0124105. [Medline]. [Full Text].
Zenenberg RD, Carluccio AL, Merlin MA. Hyponatremia: evaluation and management. Hosp Pract (Minneap). 2010 Feb. 38(1):89-96. [Medline].
Zeidel ML. Hyponatremia: mechanisms and newer treatments. Endocr Pract. 2010 Sep-Oct. 16(5):882-7. [Medline].
Budisavljevic MN, Stewart L, Sahn SA, Ploth DW. Hyponatremia associated with 3,4-methylenedioxymethylamphetamine ("Ecstasy") abuse. Am J Med Sci. 2003 Aug. 326(2):89-93. [Medline].
FDA Limits Use of Samsca (Tolvaptan) Due to Liver Injury Risk. Medscape Medical News. Available at http://www.medscape.com/viewarticle/803356. Accessed: May 8, 2013.
Gines P, Berl T, Bernardi M, et al. Hyponatremia in cirrhosis: from pathogenesis to treatment. Hepatology. 1998 Sep. 28(3):851-64. [Medline].
Glassock RJ, Cohen AH, Danovitch G, Parsa KP. Human immunodeficiency virus (HIV) infection and the kidney. Ann Intern Med. 1990 Jan 1. 112(1):35-49. [Medline].
Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007 Mar 28. 297(12):1319-31. [Medline].
Lowes R. Tolvaptan Poses Risk for Serious Liver Damage, FDA Warns. Medscape Medical News. January 25, 2013. Available at http://www.medscape.com/viewarticle/778200. Accessed: January 29, 2013.
Pham PC, Pham PM, Pham PT. Vasopressin excess and hyponatremia. Am J Kidney Dis. 2006 May. 47(5):727-37. [Medline].
Salahudeen AK, Ali N, George M, Lahoti A, Palla S. Tolvaptan in hospitalized cancer patients with hyponatremia: A double-blind, randomized, placebo-controlled clinical trial on efficacy and safety. Cancer. Wiley Online Library. Available at http://onlinelibrary.wiley.com/doi/10.1002/cncr.28468/abstract. Accessed: December 2, 2013.
Santos BC, Chevaile A, Hebert MJ, Zagajeski J, Gullans SR. A combination of NaCl and urea enhances survival of IMCD cells to hyperosmolality. Am J Physiol. 1998 Jun. 274(6 Pt 2):F1167-73. [Medline].
Saunders R. Tolvaptan Corrects Hyponatremia in Cancer Patients. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/814821. Accessed: December 2, 2013.
Schrier RW, Abraham WT. Hormones and hemodynamics in heart failure. N Engl J Med. 1999 Aug 19. 341(8):577-85. [Medline].
Schrier RW, Gross P, Gheorghiade M, et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006 Nov 16. 355(20):2099-112. [Medline].
Silver SM, Kozlowski SA, Baer JE, Rogers SJ, Sterns RH. Glycine-induced hyponatremia in the rat: a model of post-prostatectomy syndrome. Kidney Int. 1995 Jan. 47(1):262-8. [Medline].
Silver SM, Schroeder BM, Bernstein P, Sterns RH. Brain adaptation to acute hyponatremia in young rats. Am J Physiol. 1999 Jun. 276(6 Pt 2):R1595-9. [Medline].
Sterns RH. The syndrome of inappropriate antidiuretic hormone secretion of unknown origin. Am J Kidney Dis. 1999 Jan. 33(1):161-3; discussion 163-5. [Medline].
McCall B. US and Europe Differ on Use of Vaptans in Hyponatremia. Medscape Medical News. Available at http://www.medscape.com/viewarticle/845338. May 26, 2015; Accessed: June 19, 2015.