Hyponatremia is one of the most commonly encountered electrolyte abnormalities occurring in up to 22% of hospitalized patients. Hyponatremia usually reflects excess water retention relative to sodium rather than sodium deficiency. Volume status and serum osmolality are essential to determine etiology. Treatment depends on several factors, including the cause, overall volume status of the patient, severity of hyponatremic symptoms, and duration of hyponatremia at presentation. Vasopressin antagonists like tolvaptan seem promising for the treatment of euvolemic and hypervolemic hyponatremia in heart failure. Low sodium concentrations cause cerebral edema, but the overly rapid sodium correction can also lead to iatrogenic cerebral osmotic demyelination syndrome. Demyelination may occur days after sodium correction or initial neurologic recovery from hyponatremia. The following case report analyzes the role of vasopressin antagonists in the treatment of hyponatremia and the need for daily dosing of tolvaptan and the monitoring of serum sodium levels to avoid rapid overcorrection which can result in osmotic demyelination syndrome (ODS). 1. Introduction Hyponatremia which is defined as serum sodium levels less than 135？mmol/L is often encountered in patients with heart failure. Patients with heart failure develop hyponatremia due to the activation of neurohormonal system leading to decrease in sodium levels. Treatment options for hyponatremia in heart failure, such as water restriction or the use of hypertonic saline with loop diuretics, have limited efficacy. AVP-receptor antagonists increase sodium levels effectively and their use has proven to be effective in correcting sodium levels and improving the outcome of these patients. However, their safety in terms of overcorrecting sodium levels with daily doses of 15–60？mg of tolvaptan is still debatable. Rapid correction of sodium levels in chronic hyponatremia patients has been shown to cause hypernatremia and osmotic demyelination syndrome (ODS) with grave consequences. We report a case of a 51-year-old male who was admitted with chronic hypervolemic hyponatremia. He developed acute hypernatremia and osmotic demyelination syndrome due to administration of tolvaptan and diuretics. We raise the question of dosing of vasopressin antagonists only after checking daily sodium levels and monitoring urine output. 2. Case Presentation A 51-year-old male with past medical history of coronary artery disease and peripheral vascular disease presented to the hospital with progressive shortness of breath and bilateral
References
[1]
M. Fukagawa, K. Kurokawa, and M. A. Papadakis, “Fluid and electrolyte disorders,” in Current Medical Diagnosis and Treatment, S. J. Mc Phee, M. A. Papadakis, and L. M. Tierney Jr., Eds., pp. 757–762, McGraw-Hill, New York, NY, USA, 47th edition, 2008.
[2]
N. A. Boon, N. R. Colledge, B. R. Walker, and J. A. Hunter, Davidson's Principles and Practice of Medicine, Integrated Water and Electrolyte Balance, Churchill Livingstone, Edinburgh, Scotland, 10th edition, 2006.
[3]
K. C. Cho, “Electrolyte and acid-base disorders,” in Current Medical Diagnosis and Treatment 2014, M. A. Papadakis, S. J. McPhee, M. W. Rabow, and T. G. Berger, Eds., chapter 21, McGraw-Hill, New York, NY, USA, 2013.
[4]
G. M. Felker, K. L. Lee, D. A. Bull, et al., “Diuretic strategies in patients with acute decompensated heart failure,” The New England Journal of Medicine, vol. 364, no. 9, pp. 797–805, 2011.
[5]
M. Thibonnier, D. M. Conarty, J. A. Preston, P. L. Wilkins, L. N. Berti-Mattera, and R. Mattera, “Molecular pharmacology of human vasopressin receptors,” Advances in Experimental Medicine and Biology, vol. 449, pp. 251–276, 1998.
[6]
A. W. Wallace, C. M. Tunin, and A. A. Shoukas, “Effects of vasopressin on pulmonary and systemic vascular mechanics,” The American Journal of Physiology, vol. 257, no. 4, part 2, pp. H1228–H1234, 1989.
[7]
J. Howl, T. Ismail, A. J. Strain, C. J. Kirk, D. Anderson, and M. Wheatley, “Characterization of the human liver vasopressin receptor. Profound differences between human and rat vasopressin-receptor-mediated responses suggest only a minor role for vasopressin in regulating human hepatic function,” Biochemical Journal, vol. 276, part 1, pp. 189–195, 1991.
[8]
A. Tanoue, S. Ito, K. Honda et al., “The vasopressin V1b receptor critically regulates hypothalamic-pituitary-adrenal axis activity under both stress and resting conditions,” Journal of Clinical Investigation, vol. 113, no. 2, pp. 302–309, 2004.
[9]
J. G. Verbalis, “Vasopressin V2 receptor antagonists,” Journal of Molecular Endocrinology, vol. 29, no. 1, pp. 1–9, 2002.
[10]
Samsca (Tolvaptan), Package Insert, Otsuka America Pharmaceutical, Rockville, Md, USA, 2009.
[11]
J. M. Topf, S. Rankin, and P. Murray, “Electrolyte disorders in critical care,” in Principles of Critical Care, J. B. Hall, G. A. Schmidt, and L. D. Wood, Eds., chapter 76, McGraw-Hill, New York, NY, USA, 3rd edition, 2005.
[12]
R. W. Schrier, S. Sharma, and D. Shchekochikhin, “Hyponatraemia: more than just a marker of disease severity?” Nature Reviews Nephrology, vol. 9, no. 1, pp. 37–50, 2013.
[13]
Y.-H. H. Lien and J. I. Shapiro, “Hyponatremia: clinical diagnosis and management,” The American Journal of Medicine, vol. 120, no. 8, pp. 653–658, 2007.
[14]
S. Pradhan, R. Jha, M. N. Singh, S. Gupta, R. V. Phadke, and V. Kher, “Central pontine myelinolysis following ‘slow’ correction of hyponatremia,” Clinical Neurology and Neurosurgery, vol. 97, no. 4, pp. 340–343, 1995.
[15]
S. Oya, K. Tsutsumi, K. Ueki, and T. Kirino, “Reinduction of hyponatremia to treat central pontine myelinolysis,” Neurology, vol. 57, no. 10, pp. 1931–1932, 2001.
[16]
F. Gankam Kengne, A. Soupart, R. Pochet, J.-P. Brion, and G. Decaux, “Re-induction of hyponatremia after rapid overcorrection of hyponatremia reduces mortality in rats,” Kidney International, vol. 76, no. 6, pp. 614–621, 2009.
