Hyponatremia Follow-up

  • Author: Eric E Simon, MD; Chief Editor: Vecihi Batuman, MD, FASN  more...
Updated: Jul 26, 2016

Further Inpatient Care

Patients with hyponatremia from any cause require close attention to their electrolyte and fluid status.

Patients with symptomatic hyponatremia who are being actively treated often require several daily measurements of serum sodium to avoid a rate of correction that is too rapid.

After acute treatment, follow-up generally is dictated by the underlying etiology of the hyponatremia.



Clinical manifestations include clouding of consciousness, confusion, stupor, or coma. Seizures commonly occur with rapid reductions in serum sodium or with serum sodium concentrations of less than 115-120 mEq/L.

For unknown reasons, premenopausal women seem to have a less efficient osmotic adaptation. This increases their susceptibility to severe hyponatremia and rapid progression from minimal symptoms (eg, headache, nausea) to respiratory arrest. Cerebral edema and herniation have been found at autopsy.[35]

Correction of hyponatremia that is too rapid may cause permanent neurologic impairment. Central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM), complications of excessive correction of chronic hyponatremia, are now diagnosed by diffusion-weighted magnetic resonance imaging (MRI). Of note is that conventional CT and MRI scan findings typically lag behind the clinical manifestations of myelinosis by 2-4 weeks.[36]

The clinical course of these patients features initial encephalopathy secondary to hyponatremia, then improvement as the plasma Na concentration increases, and finally deterioration several days later. The disorder can resolve completely or result in permanent disability or death. This typical clinical course has been called the osmotic demyelination syndrome (ODS). The clinical neurologic picture may be confusing, as it may include a variety of findings from psychiatric, behavioral, and movement disorders, such as dysphagia and flaccid or spastic quadriparesis, depending on the involvement of extrapontine or central pontine myelinolysis. Disruption of the blood-brain barrier is presumed to play an important role in the pathogenesis of osmotic demyelination.

An increased susceptibility to osmotic demyelination is also observed in cirrhotic patients. In this setting, myoinositol, the most abundant organic osmolyte, is depleted because of glutamine- and hyponatremia-induced brain cell swelling. CPM is a common and often fatal complication of orthotopic liver transplantation, affecting up to 10% of patients who were hyponatremic prior to transplant.[37]



The prognosis for patients with hyponatremia is predicated upon the underlying etiology. A study by Doshi et al found that hyponatremia among patients with cancer is associated with extended hospital stays and higher mortality rates; however, whether long-term correction of hyponatremia would improve these outcomes is unclear.[38]

A meta-analysis of 15 studies encompassing 13,816 patients found that any improvement in hyponatremia was associated with a reduced risk of overall mortality (odds ratio [OR]=0.57). With the eight studies that reported a threshold for serum sodium improvement to >130 mmol/L, the association was even stronger (OR=0.51). The reduction in mortality risk persisted at 12-month follow-up (OR=0.55). Reduced mortality was more evident in older patients and in patients with lower serum sodium levels at enrollment.[39]




Patient Education

Patients to be treated with a fluid restriction often require education regarding the free water content of foods and an explanation of the need to limit the intake of liquids to a predetermined level.

Contributor Information and Disclosures

Eric E Simon, MD Professor of Medicine, Chief, Section of Nephrology and Hypertension, Tulane University School of Medicine; Director, Nephrology Training, Medical Director, Dialysis Clinic, Inc, Canal Street

Eric E Simon, MD is a member of the following medical societies: American Federation for Medical Research, American Heart Association, American Physiological Society, American Society of Nephrology, Central Society for Clinical and Translational Research, International Society of Nephrology, National Kidney Foundation, Phi Beta Kappa, American Society for Cell Biology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.


Seyed Mehrdad Hamrahian, MD Assistant Professor of Medicine, Jefferson Medical College of Thomas Jefferson University

Seyed Mehrdad Hamrahian, MD is a member of the following medical societies: American Society of Nephrology, International Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.

Federico J Teran, MD Instructor of Clinical Medicine, Section of Nephrology and Hypertension, Tulane University School of Medicine

Federico J Teran, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Nephrology, Louisiana State Medical Society, National Kidney Foundation, Renal Physicians Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Eleanor Lederer, MD, FASN Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD, FASN is a member of the following medical societies: American Association for the Advancement of Science, International Society of Nephrology, American Society for Biochemistry and Molecular Biology, American Federation for Medical Research, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, Kentucky Medical Association, National Kidney Foundation, Phi Beta Kappa

Disclosure: Received grant/research funds from Dept of Veterans Affairs for research; Received salary from American Society of Nephrology for asn council position; Received salary from University of Louisville for employment; Received salary from University of Louisville Physicians for employment; Received contract payment from American Physician Institute for Advanced Professional Studies, LLC for independent contractor; Received contract payment from Healthcare Quality Strategies, Inc for independent cont.

Chief Editor

Vecihi Batuman, MD, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

James H Sondheimer, MD, FACP, FASN Associate Professor of Medicine, Wayne State University School of Medicine; Medical Director of Hemodialysis, Harper University Hospital at Detroit Medical Center; Medical Director, DaVita Greenview Dialysis (Southfield)

James H Sondheimer, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Nephrology

Disclosure: Receive dialysis unit medical director fee (as independ ent contractor) for: DaVita .

  1. 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.

  2. [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].

  3. 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].

  4. 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].

  5. 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.

  6. 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].

  7. 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].

  8. 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].

  9. 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].

  10. Huang H, Jolly SE, Airy M, et al. Associations of dysnatremias with mortality in chronic kidney disease. Nephrol Dial Transplant. 2016 May 24. [Medline].

  11. 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].

  12. Hillier TA, Abbott RD, Barrett EJ. Hyponatremia: evaluating the correction factor for hyperglycemia. Am J Med. 1999 Apr. 106(4):399-403. [Medline].

  13. 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].

  14. 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].

  15. Palmer BF. Hyponatremia in patients with central nervous system disease: SIADH versus CSW. Trends Endocrinol Metab. 2003 May-Jun. 14(4):182-7. [Medline].

  16. 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].

  17. 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].

  18. 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].

  19. 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].

  20. 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].

  21. 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].

  22. 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].

  23. 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].

  24. 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].

  25. 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].

  26. 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].

  27. 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].

  28. 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].

  29. [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].

  30. Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med. 2000 May 25. 342(21):1581-9. [Medline].

  31. Vachharajani TJ, Zaman F, Abreo KD. Hyponatremia in critically ill patients. J Intensive Care Med. 2003 Jan-Feb. 18(1):3-8. [Medline].

  32. 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].

  33. 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].

  34. 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.

  35. Ayus JC, Wheeler JM, Arieff AI. Postoperative hyponatremic encephalopathy in menstruant women. Ann Intern Med. 1992 Dec 1. 117(11):891-7. [Medline].

  36. 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].

  37. 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].

  38. 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].

  39. 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].

  40. Zenenberg RD, Carluccio AL, Merlin MA. Hyponatremia: evaluation and management. Hosp Pract (Minneap). 2010 Feb. 38(1):89-96. [Medline].

  41. Zeidel ML. Hyponatremia: mechanisms and newer treatments. Endocr Pract. 2010 Sep-Oct. 16(5):882-7. [Medline].

  42. 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].

  43. 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.

  44. Gines P, Berl T, Bernardi M, et al. Hyponatremia in cirrhosis: from pathogenesis to treatment. Hepatology. 1998 Sep. 28(3):851-64. [Medline].

  45. 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].

  46. 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].

  47. 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.

  48. Pham PC, Pham PM, Pham PT. Vasopressin excess and hyponatremia. Am J Kidney Dis. 2006 May. 47(5):727-37. [Medline].

  49. 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.

  50. 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].

  51. Saunders R. Tolvaptan Corrects Hyponatremia in Cancer Patients. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/814821. Accessed: December 2, 2013.

  52. Schrier RW, Abraham WT. Hormones and hemodynamics in heart failure. N Engl J Med. 1999 Aug 19. 341(8):577-85. [Medline].

  53. 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].

  54. 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].

  55. 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].

  56. 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].

  57. 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.

Central pontine myelinolysis, MRI FLAIR
Extrapontine myelinolysis T2
Medscape Consult
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.