Background: Hyponatremia occurring as a result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common and potentially lethal complication in critically ill patients. Urea, by inducing renal water excretion and promoting sodium (Na) retention, has been well described as a treatment for chronic SIADH. However, there are limited data on its use for the treatment of SIADH as encountered in patients admitted to the intensive care unit (ICU). We assessed the effects of urea administration for treatment of SIADH in ICU patients. Methods: Data from ICU patients treated with urea for SIADH between January 2000 and August 2010 were reviewed. The time courses of Na and urea concentrations were analyzed by variance analysis (ANOVA). Results: Records from 24 patients were analyzed. The most common etiology of SIADH was neurological (18 patients). Before urea administration, the mean serum Na concentration was 124.8 ± 5.9 mEq/l. There was a significant increase in serum Na from the second day of treatment (131.4 ± 3.5 mEq/l, p < 0.001) and a normalization of mean serum Na by the fourth day (136.2 ± 4.1 mEq/l, p < 0.001). The mean serum urea concentration also increased (from 29.8 ± 11.1 mg/dl before urea to 57.6 ± 24.0 mg/dl on the first day of treatment, p < 0.001). Conclusions: Urea administration appears useful for the treatment of SIADH-associated hyponatremia in critically ill patients. Prospective randomized controlled studies are needed to confirm these results.

Keywords:
Syndrome of inappropriate antidiuretic hormone secretion, Hyponatremia, Urea, Sodium, Critically ill patients
1.
Adrogue HJ, Madias NE: Hyponatremia. N Engl J Med 2000;342:1581–1589.
2.
Hoorn EJ, Lindemans J, Zietse R: Development of severe hyponatraemia in hospitalized patients: treatment-related risk factors and inadequate management. Nephrol Dial Transplant 2006;21:70–76.
3.
Palmer BF: Hyponatremia in the intensive care unit. Semin Nephrol 2009;29:257–270.
4.
Funk GC, Lindner G, Druml W, Metnitz B, Schwarz C, Bauer P, Metnitz PG: Incidence and prognosis of dysnatremias present on ICU admission. Intensive Care Med 2010;36:304–311.
5.
Stelfox HT, Ahmed SB, Khandwala F, Zygun D, Shahpori R, Laupland K: The epidemiology of intensive care unit-acquired hyponatraemia and hypernatraemia in medical-surgical intensive care units. Crit Care 2008;12:R162.
6.
Wald R, Jaber BL, Price LL, Upadhyay A, Madias NE: Impact of hospital-associated hyponatremia on selected outcomes. Arch Intern Med 2010;170:294–302.
7.
Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G: Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med 2006;119:71.e1–e8.
8.
Smith DM, McKenna K, Thompson CJ: Hyponatraemia. Clin Endocrinol (Oxf) 2000;52:667–678.
9.
Palmer BF: Hyponatraemia in a neurosurgical patient: syndrome of inappropriate antidiuretic hormone secretion versus cerebral salt wasting. Nephrol Dial Transplant 2000;15:262–268.
10.
Bitew S, Imbriano L, Miyawaki N, Fishbane S, Maesaka JK: More on renal salt wasting without cerebral disease: response to saline infusion. Clin J Am Soc Nephrol 2009;4:309–315.
11.
Ellison DH, Berl T: Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med 2007;356:2064–2072.
12.
Murphy T, Dhar R, Diringer M: Conivaptan bolus dosing for the correction of hyponatremia in the neurointensive care unit. Neurocrit Care 2009;11:14–19.
13.
Lindner G, Schwarz C, Funk GC: Osmotic diuresis due to urea as the cause of hypernatraemia in critically ill patients. Nephrol Dial Transplant 2011, E-pub ahead of print.
14.
Decaux G, Brimioulle S, Genette F, Mockel J: Treatment of the syndrome of inappropriate secretion of antidiuretic hormone by urea. Am J Med 1980;69:99–106.
15.
Decaux G, Unger J, Brimioulle S, Mockel J: Hyponatremia in the syndrome of inappropriate secretion of antidiuretic hormone. Rapid correction with urea, sodium chloride, and water restriction therapy. JAMA 1982;247:471–474.
16.
Decaux G, Andres C, Gankam Kengne F, Soupart A: Treatment of euvolemic hyponatremia in the intensive care unit by urea. Crit Care 2010;14:R184.
17.
Decaux G, Musch W: Clinical laboratory evaluation of the syndrome of inappropriate secretion of antidiuretic hormone. Clin J Am Soc Nephrol 2008;3:1175–1184.
18.
Hannon MJ, Thompson CJ: The syndrome of inappropriate antidiuretic hormone: prevalence, causes and consequences. Eur J Endocrinol 2010;162(suppl 1):S5–S12.
19.
Knaus WA, Draper EA, Wagner DP, Zimmerman JE: Apache II: a severity of disease classification system. Crit Care Med 1985;13:818–829.
20.
Bankir L, Bouby N, Trinh-Trang-Tan MM, Ahloulay M, Promeneur D: Direct and indirect cost of urea excretion. Kidney Int 1996;49:1598–1607.
21.
Bankir L, Trinh-Trang-Tan MM: Urea and the kidney; in Brenner BM (ed): Brenner & Rector’s The Kidney, ed 6. Philadelphia, Saunders, 2000, vol 1, pp 636–679.
22.
Fenton RA, Knepper MA: Urea and renal function in the 21st century: insights from knockout mice. J Am Soc Nephrol 2007;18:679–688.
23.
Berl T: Impact of solute intake on urine flow and water excretion. J Am Soc Nephrol 2008;19:1076–1078.
24.
Soupart A, Schroeder B, Decaux G: Treatment of hyponatraemia by urea decreases risks of brain complications in rats. Brain osmolyte contents analysis. Nephrol Dial Transplant 2007;22:1856–1863.
25.
Brimioulle S, Orellana-Jimenez C, Aminian A, Vincent JL: Hyponatremia in neurological patients: cerebral salt wasting versus inappropriate antidiuretic hormone secretion. Intensive Care Med 2008;34:125–131.
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2012
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