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Treatment of hyponatremia: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) and reset osmostat

INTRODUCTION

Hyponatremia in the syndrome of inappropriate antidiuretic hormone secretion (SIADH) results from ADH-induced retention of ingested or infused water. Although water excretion is impaired, sodium handling is intact since there is no abnormality in volume-regulating mechanisms such as the renin-angiotensin-aldosterone system or atrial natriuretic peptide [1].

The treatment of hyponatremia due to SIADH (including the reset osmostat variant) will be reviewed here. The choice of therapy of SIADH is dependent upon a number of factors including the degree of hyponatremia, the presence or absence of symptoms, and, to some degree, the urine osmolality.

The pathogenesis and etiology of the SIADH and a general review of the treatment of hyponatremia due to a variety of causes are discussed separately. (See "Pathophysiology and etiology of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)" and "Overview of the treatment of hyponatremia in adults".)

PATHOGENESIS

To understand the approach to therapy of hyponatremia in SIADH, it is worthwhile to briefly review the pathogenesis of hyponatremia in this disorder. Among patients with SIADH, the combination of water retention and secondary solute (sodium plus potassium) loss accounts for essentially all of the reduction in serum sodium [2,3].

These changes occur in the following sequence [3,4]:

                           

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Literature review current through: Aug 2014. | This topic last updated: Jul 22, 2014.
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References
Top
  1. Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, McGraw-Hill, New York 2001. p.729.
  2. Cooke CR, Turin MD, Walker WG. The syndrome of inappropriate antidiuretic hormone secretion (SIADH): pathophysiologic mechanisms in solute and volume regulation. Medicine (Baltimore) 1979; 58:240.
  3. Verbalis JG. Pathogenesis of hyponatremia in an experimental model of the syndrome of inappropriate antidiuresis. Am J Physiol 1994; 267:R1617.
  4. Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med 2000; 342:1581.
  5. Rose BD. New approach to disturbances in the plasma sodium concentration. Am J Med 1986; 81:1033.
  6. Ellison DH, Berl T. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med 2007; 356:2064.
  7. Wijdicks EF, Vermeulen M, Murray GD, et al. The effects of treating hypertension following aneurysmal subarachnoid hemorrhage. Clin Neurol Neurosurg 1990; 92:111.
  8. Sterns RH, Silver SM. Cerebral salt wasting versus SIADH: what difference? J Am Soc Nephrol 2008; 19:194.
  9. Woo CH, Rao VA, Sheridan W, Flint AC. Performance characteristics of a sliding-scale hypertonic saline infusion protocol for the treatment of acute neurologic hyponatremia. Neurocrit Care 2009; 11:228.
  10. Steele A, Gowrishankar M, Abrahamson S, et al. Postoperative hyponatremia despite near-isotonic saline infusion: a phenomenon of desalination. Ann Intern Med 1997; 126:20.
  11. Sterns RH, Nigwekar SU, Hix JK. The treatment of hyponatremia. Semin Nephrol 2009; 29:282.
  12. Decaux G, Waterlot Y, Genette F, et al. Inappropriate secretion of antidiuretic hormone treated with frusemide. Br Med J (Clin Res Ed) 1982; 285:89.
  13. Decaux G, Brimioulle S, Genette F, Mockel J. Treatment of the syndrome of inappropriate secretion of antidiuretic hormone by urea. Am J Med 1980; 69:99.
  14. Decaux G, Genette F. Urea for long-term treatment of syndrome of inappropriate secretion of antidiuretic hormone. Br Med J (Clin Res Ed) 1981; 283:1081.
  15. Verbalis JG, Goldsmith SR, Greenberg A, et al. Hyponatremia treatment guidelines 2007: expert panel recommendations. Am J Med 2007; 120:S1.
  16. Greenberg A, Verbalis JG. Vasopressin receptor antagonists. Kidney Int 2006; 69:2124.
  17. Schrier RW, Gross P, Gheorghiade M, et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med 2006; 355:2099.
  18. Soupart A, Gross P, Legros JJ, et al. Successful long-term treatment of hyponatremia in syndrome of inappropriate antidiuretic hormone secretion with satavaptan (SR121463B), an orally active nonpeptide vasopressin V2-receptor antagonist. Clin J Am Soc Nephrol 2006; 1:1154.
  19. Zeltser D, Rosansky S, van Rensburg H, et al. Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia. Am J Nephrol 2007; 27:447.
  20. Saito T, Ishikawa S, Abe K, et al. Acute aquaresis by the nonpeptide arginine vasopressin (AVP) antagonist OPC-31260 improves hyponatremia in patients with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). J Clin Endocrinol Metab 1997; 82:1054.
  21. Murphy T, Dhar R, Diringer M. Conivaptan bolus dosing for the correction of hyponatremia in the neurointensive care unit. Neurocrit Care 2009; 11:14.
  22. Abraham WT, Decaux G, Josiassen RC, et al. Oral lixivaptan effectively increases serum sodium concentrations in outpatients with euvolemic hyponatremia. Kidney Int 2012; 82:1215.
  23. Abraham WT, Hensen J, Gross PA, et al. Lixivaptan safely and effectively corrects serum sodium concentrations in hospitalized patients with euvolemic hyponatremia. Kidney Int 2012; 82:1223.
  24. Borne RT, Krantz MJ. Lixivaptan for hyponatremia--the numbers game. JAMA 2012; 308:2345.
  25. Berl T, Quittnat-Pelletier F, Verbalis JG, et al. Oral tolvaptan is safe and effective in chronic hyponatremia. J Am Soc Nephrol 2010; 21:705.
  26. Higashihara E, Torres VE, Chapman AB, et al. Tolvaptan in autosomal dominant polycystic kidney disease: three years' experience. Clin J Am Soc Nephrol 2011; 6:2499.
  27. Torres VE, Chapman AB, Devuyst O, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 2012; 367:2407.
  28. Samsca (tolvaptan): Drug Warning - Potential Risk of Liver Injury. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm336669.htm?source=govdelivery (Accessed on January 28, 2013).
  29. Samsca (Tolvaptan): Drug Safety Communication - FDA Limits Duration and Usage Due To Possible Liver Injury Leading to Organ Transplant or Death. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm350185.htm (Accessed on May 20, 2013).
  30. Forrest JN Jr, Cox M, Hong C, et al. Superiority of demeclocycline over lithium in the treatment of chronic syndrome of inappropriate secretion of antidiuretic hormone. N Engl J Med 1978; 298:173.
  31. Cox M, Guzzo J, Morrison G, Singer I. Demeclocycline and therapy of hyponatremia. Ann Intern Med 1977; 86:113.
  32. Grünfeld JP, Rossier BC. Lithium nephrotoxicity revisited. Nat Rev Nephrol 2009; 5:270.
  33. Renneboog B, Musch W, Vandemergel X, et al. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med 2006; 119:71.e1.
  34. Sterns RH, Hix JK, Silver S. Treatment of hyponatremia. Curr Opin Nephrol Hypertens 2010; 19:493.
  35. Adrogué HJ, Madias NE. The challenge of hyponatremia. J Am Soc Nephrol 2012; 23:1140.
  36. Ayus JC, Wheeler JM, Arieff AI. Postoperative hyponatremic encephalopathy in menstruant women. Ann Intern Med 1992; 117:891.
  37. Arieff AI, Ayus JC. Endometrial ablation complicated by fatal hyponatremic encephalopathy. JAMA 1993; 270:1230.
  38. Ayus JC, Arieff A, Moritz ML. Hyponatremia in marathon runners. N Engl J Med 2005; 353:427.
  39. Hew-Butler T, Ayus JC, Kipps C, et al. Statement of the Second International Exercise-Associated Hyponatremia Consensus Development Conference, New Zealand, 2007. Clin J Sport Med 2008; 18:111.
  40. Siegel AJ, Verbalis JG, Clement S, et al. Hyponatremia in marathon runners due to inappropriate arginine vasopressin secretion. Am J Med 2007; 120:461.e11.
  41. Robertson GL. Regulation of arginine vasopressin in the syndrome of inappropriate antidiuresis. Am J Med 2006; 119:S36.
  42. Robertson GL, Shelton RL, Athar S. The osmoregulation of vasopressin. Kidney Int 1976; 10:25.
  43. DeFronzo RA, Goldberg M, Agus ZS. Normal diluting capacity in hyponatremic patients. Reset osmostat or a variant of the syndrome of inappropriate antidiuretic hormone secretion. Ann Intern Med 1976; 84:538.
  44. Kahn T. Reset osmostat and salt and water retention in the course of severe hyponatremia. Medicine (Baltimore) 2003; 82:170.
  45. Hill AR, Uribarri J, Mann J, Berl T. Altered water metabolism in tuberculosis: role of vasopressin. Am J Med 1990; 88:357.