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Syndrome of Inappropriate Antidiuretic Hormone Secretion Treatment & Management

  • Author: Christie P Thomas, MBBS, FRCP, FASN, FAHA; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
 
Updated: Oct 28, 2015
 

Approach Considerations

The treatment of SIADH and the rapidity of correction of hyponatremia depend on the degree of hyponatremia, on whether the patient is symptomatic, and on whether it is acute (<48 h) or chronic. The urine osmolality and creatinine clearance also must be considered when choosing the type of therapy. If no history is available to determine the duration of hyponatremia and if the patient is asymptomatic, it is reasonable to presume the condition is chronic. Diagnosis and treatment of the underlying cause of SIADH is also important.

Extreme hyponatremia and an inappropriate approach to its treatment can both have disastrous consequences; consultation with a nephrologist should be sought early in difficult cases. Correcting hyponatremia too rapidly may result in central pontine myelinolysis (CPM) with permanent neurologic deficits. It is important to remember that even severe hyponatremia can correct rapidly with just fluid restriction if that hyponatremia is associated with absent ADH secretion (eg, psychogenic polydipsia).

European guidelines for the treatment of syndrome of inappropriate antidiuresis include the following recommendations for management of moderate or profound hyponatremia[24] :

  • Restrict fluid intake as first-line treatment
  • Second-line treatments include increasing solute intake with 0.25–0.50 g/kg per day of urea or a combination of low-dose loop diuretics and oral sodium chloride
  • Use of lithium, demeclocycline, or vasopressin receptor antagonists is not recommended
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Emergent Care

Aggressive treatment of hyponatremia should always be weighed against the risk of inducing CMP. A rare but serious complication, CMP can develop one to several days after aggressive treatment of hyponatremia. Aggressive management of hyponatremia is indicated in patients with severe symptoms such as seizures, stupor, coma, and respiratory arrest, regardless of the degree of hyponatremia. Emergent treatment should also be strongly considered for those with moderate-to-severe hyponatremia with a documented duration of less than 48 hours.

The goal is to correct hyponatremia at a rate that does not cause neurologic complications. The objective is to raise serum Na+ levels by 0.5-1 mEq/h, and not more than 10-12 mEq in the first 24 hours, to bring the Na+ value to a maximum level of 125 -130 mEq/L. Administration of 3% hypertonic saline should be restricted to these emergent circumstances, and both neurological symptoms and serum Na+ should be monitored frequently to achieve the desired target and to prevent overcorrection.

Correction of serum Na+ levels by 6 mEq/L in 24 hours has been dubbed the "rule of sixes." The rule states that, "Six a day makes sense for safety; 6 in 6 hours for severe symptoms and stop."[25]

Other authors have recommended a rate of initial correction of 1-2 mEq/L/h in severely symptomatic patients until symptoms resolve (or for the first 3-4 h). However, total correction in the first 24 hours must not exceed 10-12 mEq. CMP has been reported in cases in which the initial correction exceeded 12 mEq and even in cases in which the correction was 9-10 mEq/24 h. This has led some authors to recommend a lower target of 8 mEq in 24 hours. In the special situation of exercise-induced hyponatremia with neurological symptoms, some authors recommend an immediate bolus of 100 mL of 3% hypertonic saline repeated every 10 minutes until symptoms resolve.[18]

Formulas for the dose and rate of hypertonic saline have been proposed based on a Na+ deficit to calculate the rate of administration of hypertonic fluids.[13] However, they have not been prospectively studied. Despite the correct use of these formulas, hyponatremia is often corrected too rapidly. Therefore, these formulas should serve only as guidelines. Patients still require frequent retesting of their serum Na+ concentration.[16]

The approximate Na+ deficit can be estimated by using the following formula (0.5 L/kg for females):

  • Na + Deficit (mEq) = (Desired Na + - Measured Na +) x 0.6 L/kg x Weight (kg)

Three-percent hypertonic saline has 513 mEq/L each of Na+ and Cl- and has an osmolality of 1026 mOsm/L. The volume of hypertonic saline needed to correct that deficit can be calculated as follows:

  • Volume of 3% Saline = (Na + Deficit)/513 mEq/L Na +

Assuming a rate of correction of chronic hyponatremia of 0.5 mEq/L per hour, the amount of time needed to correct a given degree of hyponatremia is as follows:

  • Time Needed for Correction = (Desired Na + - Measured Na +)/0.5 mEq/L per hour

The rate of infusion of hypertonic saline is as follows:

  • Rate = (Volume of 3% Saline)/(Time Needed for Correction)

Furosemide increases excretion of free water and has been used along with hypertonic saline in severe cases to limit treatment-induced volume expansion. The diuresis induced by furosemide has a urine solute concentration roughly equivalent to half-normal saline; thus, excretion of free water occurs. Electrolyte free water intake can be restricted. Combining furosemide with hypertonic saline and water restriction may lead to a faster rate of correction of serum Na and requires that serum Na+ osmolality and urine osmolality be checked frequently to monitor the change in serum Na+ values and to prevent overcorrection. Attention should also be paid to the prevention of severe hypokalemia in conjunction with treatment of hyponatremia.

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Acute Setting

In the acute setting (ie, < 48 h since onset) with moderate symptoms such as confusion, delirium, disorientation, nausea, and vomiting, treatment options for the hyponatremia include 3% hypertonic saline (513 mEq/L), loop diuretics with saline, vasopressin-2 receptor antagonists (aquaretics), and water restriction.

Depending on the rate of development of hyponatremia, the approach to correction varies. If an acute onset and moderate neurologic symptoms have occurred, the use of hypertonic saline may be warranted (discussed under Emergent Care). If symptoms are less severe (headache, irritability, inability to concentrate, altered mood) or absent, then vasopressin-2 receptor antagonists (aquaretics) or water restriction are both options. The patient's serum Na+ level and clinical status must be monitored often to determine the need for continued aggressive therapy.

Water restriction

The degree of water restriction depends on the prior water intake, the expected ongoing fluid losses, and the degree of hyponatremia. Water restriction to about 500-1500 mL/d (or even lower in some cases) is usually prescribed. Although easier to maintain in the hospital setting, this becomes difficult for patients to follow in an outpatient setting.

One of the functions of the kidneys is to excrete solutes in varying amounts of water. In persons with SIADH, urine osmolality is fixed at a certain value; for the kidneys to eliminate an "X" amount of solutes, a certain volume of water must be excreted. If water intake is lowered below total obligatory fluid losses (insensible losses plus volume of urine required to excrete the osmolar load), then serum osmolality rises because a net loss of water occurs. The insensible losses of relatively hypotonic fluids also contribute to net water loss. The key is sufficient restriction of water intake so that the excretion of free water from all sources is in excess of that taken in.

For example, consider a patient who has a net solute load of 900 mOsm/kg/day that must be excreted, and, because of SIADH, his or her urine osmolality is fixed at 600 mOsm/kg. This patient then excretes the solute load in 1.5 L of urine. On the other hand, if the urine osmolarity is fixed at 300 mOsm/kg, then 3 L of urine is required to excrete the same osmolar load. When water intake is restricted, the body mobilizes the free water already present to excrete this load. Thus, if urine output (plus insensible losses) exceeds water intake, a net water loss occurs and the serum Na+ level returns towards normal.

Vasopressin receptor antagonists

Inhibition of the AVP V2 receptor reduces the number of aquaporin-2 water channels in the renal collecting duct and decreases the water permeability of the collecting duct. Collectively, agents that competitively block ADH action and increase water excretion are called aquaretics, and they are useful in the treatment of the hyponatremia in SIADH. The term "vaptan" has been coined to officially name all the members of this new class of drugs.[3]

There are 2 aquaretics that are currently approved by the US Food and Drug Administration (FDA). Conivaptan is a parenteral nonpeptide dual AVP V1a- and V2-receptor antagonist, which is approved for use in hospitalized patients with euvolemic (dilutional) and hypervolemic hyponatremia. The drug is given as a 20-mg loading dose followed by a continuous infusion or as intermittent boluses, but it should not be used for more than 4 days. The pivotal studies in euvolemic hyponatremia showed that compared with fluid restriction alone, conivaptan together with a 2 L fluid restriction over 4 days increased serum Na by 6 mEq/L, with a median increase of 4 mEq/L by 23 hours.[26]

Tolvaptan is a selective oral V2 receptor antagonist also approved for use in hospitalized patients for hypervolemia and euvolemic hyponatremia.[27, 28] The drug is started at 15 mg once daily and titrated up to 60 mg daily as required, and it is best to avoid fluid restriction during the dose-finding phase. In the pivotal studies, which included patients with CHF, cirrhosis, and SIADH, tolvaptan compared with fluid restriction alone increased serum Na by 8 mEq/L over 30 days, although with withdrawal of the drug, serum Na+ falls back to that seen in the placebo group.[29]

This is a useful drug to consider in a patient in whom serum Na+ does not rise by 2 mEq in the first 24 hrs after a 1000-mL fluid restriction. Once the drug is initiated, the patient can be discharged in 24-48 hours if neurological symptoms have resolved or the patient was asymptomatic at presentation. If the underlying cause of SIADH has resolved, the drug can be withdrawn after 2-4 weeks, while carefully monitoring serum Na+ daily for the next 5 days. If the serum Na+ falls again and if is less than 125 for more than 48 hours, the patient may need to be admitted again before reinitiating tolvaptan. Tolvaptan can also be considered for long-term therapy of chronic hyponatremia.[30]

The vaptans can have a profound effect on serum Na and they should be used by physicians experienced in the management of hyponatremia. These drugs should be avoided in hypovolemic hyponatremia. The vaptans are more likely to be effective compared with fluid restriction alone in patients in whom the sum of urinary potassium and Na+ concentration is greater than the plasma concentration. They offer the benefit of prompt correction of serum Na+, producing water excretion without electrolyte excretion and eliminating the need for fluid restriction. The primary risk of using these drugs is an excessively rapid rate of correction of serum Na.

Furosemide

Furosemide and other loop diuretics can be used to increase the excretion of free water. Excess water that must be removed to correct the hyponatremia can be calculated using total body water (TBW). TBW equals body weight in kg multiplied by 0.6, assuming that the total body solute or water has not changed. The diuresis induced by furosemide has a urine solute concentration roughly equivalent to half-normal saline; thus, excretion of free water occurs. The excreted Na+ is replaced with 3% hypertonic saline or with normal saline (NaCl 154 mEq/L), thus avoiding a net Na+ loss while effecting a loss of free water.

Other sources of free water intake should be restricted as well. If the measured sum of urinary potassium and Na+ with furosemide is greater than the plasma Na, then hypertonic saline rather than normal saline should be used to replace excreted Na. Serum Na+ and osmolality and urine osmolality should be checked frequently to monitor the change in serum Na+ and the rate of correction.

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Chronic Setting

In the chronic asymptomatic setting, the principal options are fluid restriction and V2 receptor antagonists (see Acute Setting). If V2 receptor antagonists are not available or if local experience with these agents is very limited, other therapeutic modalities include chronic loop diuretics with increased salt intake, urea, mannitol, and demeclocycline.

Urea

Urea is a solute that must be excreted by the kidneys. Because urine osmolality is fixed in persons with SIADH, the obligatory urine volume can be increased by increasing the osmotic or solute load. Increased urinary loss of water decreases free water retention. This therapy can be used in chronic and acute settings if the urine osmolality is low and can increase the serum Na+ by up to 5 mEq/L/day. Urea is a relatively nontoxic compound and, as opposed to sodium chloride treatment, does not cause edema or increase body weight.

Urea can be administered on a long-term basis (0.5 g/kg body weight) without major adverse effects. Urea is available as a powder, which is dissolved in water and taken orally during or after meals. To avoid gastric upset, it can be taken with an antacid. Urea can also be used continuously in patients with cerebral hemorrhage via a gastric tube or intravenously to prevent a rapid fall in intracranial pressure.

Urea should be used with great care in patients with serum creatinine of 2 mg/dL or more, BUN 80 mg/dL or more, or bilirubin of 2 mg/dL or more, to avoid progressive azotemia, hyperammonemia, and hepatic encephalopathy. Hypernatremia and dehydration may occur if the patient does not have free access to water.

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Contributor Information and Disclosures
Author

Christie P Thomas, MBBS, FRCP, FASN, FAHA Professor, Department of Internal Medicine, Division of Nephrology, Departments of Pediatrics and Obstetrics and Gynecology, Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics

Christie P Thomas, MBBS, FRCP, FASN, FAHA is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, Royal College of Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Mony Fraer, MD, FACP, FASN Associate Professor, Division of Nephrology, Department of Medicine, University of Iowa Hospitals and Clinics; Staff Physician, Iowa City Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Specialty Editor Board

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, FACP, 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, FACP, 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

Disclosure: Nothing to disclose.

Acknowledgements

Howard A Bessen, MD Professor of Medicine, Department of Emergency Medicine, UCLA School of Medicine; Program Director, Harbor-UCLA Medical Center

Howard A Bessen, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Keenan Bora, MD Fellow, Medical Toxicology, Detroit Medical Center; Attending Physician, Medical Center Emergency Services, Detroit

Keenan Bora, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, and American Medical Association

Disclosure: Nothing to disclose.

Meher Chaudhry, MD Chief Resident, Department of Emergency Medicine, Detroit Receiving Hospital, University Health Center

Disclosure: Nothing to disclose.

Sonali Deshmukh, MBBS Consulting Staff, Omaha Nephrology, Nebraska

Sonali Deshmukh, MBBS is a member of the following medical societies: American Society of Nephrology

Disclosure: Nothing to disclose.

obert J Ferry Jr, MD Chief, Division of Pediatric Endocrinology and Metabolism, Le Bonheur Children's Hospital; Professor, Department of Pediatrics, University of Tennessee Health Science Center at Memphis; St. Jude Children's Research Hospital, Memphis, TN; Brigade Surgeon, 36th Sustainment Brigade, U.S. Army; Adjunct Professor, Pediatric Surgery Department, King Saud University, Riyadh, Saudi Arabia

Robert J Ferry Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society

Disclosure: Nutropin Speakers Bureau Honoraria Speaking and teaching; Genotropin Speakers Bureau Honoraria Speaking and teaching; Eli Lilly & Co. Grant/research funds Investigator; MacroGenics, Inc. Grant/research funds Investigator; Ipsen, S.A. (formerly Tercica, Inc.) Grant/research funds Investigator; NovoNordisk SA Grant/research funds Investigator; Diamyd Investigator

Stephen Kemp, MD, PhD Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas College of Medicine and Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

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

Disclosure: Dept of Veterans Affairs Grant/research funds Research

Lynne Lipton Levitsky, MD Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor of Pediatrics, Harvard Medical School

Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Pfizer Grant/research funds P.I.; Tercica Grant/research funds Other; Eli Lily Grant/research funds PI; NovoNordisk Grant/research funds PI

Chike Magnus Nzerue, MD Associate Dean for Clinical Affairs, Vice-Chairman of Internal Medicine, Meharry Medical College

Chike Magnus Nzerue, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Society of Nephrology, and National Kidney Foundation

Disclosure: Nothing to disclose.

Jose F Pascual-y-Baralt, MD Chief, Division of Pediatric Nephrology, San Antonio Military Pediatric Center; Clinical Professor, Department of Pediatrics, University of Texas Health Science Campus

Jose F Pascual-y-Baralt, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, American Society of Pediatric Nephrology, Association of Military Surgeons of the US, and International Society of Nephrology

Disclosure: Nothing to disclose.

Alexandr Rafailov, MD Staff Physician, Department of Emergency Medicine, State University of New York Downstate/Kings County Hospital

Disclosure: Nothing to disclose.

Arlan L Rosenbloom, MD Adjunct Distinguished Service Professor Emeritus of Pediatrics, University of Florida; Fellow of the American Academy of Pediatrics; Fellow of the American College of Epidemiology

Arlan L Rosenbloom, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Epidemiology, American Pediatric Society, Endocrine Society, Florida Pediatric Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Erik D Schraga, MD Consulting Staff, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates; Consulting Staff, Permanente Medical Group, Kaiser Permanente, Santa Clara Medical Center

Disclosure: Nothing to disclose.

Richard H Sinert, DO Associate Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center

Richard H Sinert, DO is a member of the following medical societies: American College of Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, Medscape

Disclosure: Nothing to disclose.

References
  1. Bartter FC, Schwartz WB. The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med. 1967 May. 42(5):790-806. [Medline].

  2. Sterns RH. Disorders of plasma sodium--causes, consequences, and correction. N Engl J Med. 2015 Jan 1. 372 (1):55-65. [Medline].

  3. Verbalis JG, Berl T. Disorders of water balance. Brenner BM. Brenner & Rector's The Kidney. 8th ed. Saunders; 2007. Vol 1: 459-491.

  4. Elhassan EA, Schrier RW. Hyponatremia: diagnosis, complications, and management including V2 receptor antagonists. Curr Opin Nephrol Hypertens. 2011 Mar. 20(2):161-8. [Medline].

  5. Kohen I, Voelker S, Manu P. Antipsychotic-induced hyponatremia: case report and literature review. Am J Ther. 2008 Sep-Oct. 15(5):492-4. [Medline].

  6. Vitting KE, Gardenswartz MH, Zabetakis PM, et al. Frequency of hyponatremia and nonosmolar vasopressin release in the acquired immunodeficiency syndrome. JAMA. 1990 Feb 16. 263(7):973-8. [Medline].

  7. Hoorn EJ, Lindemans J, Zietse R. Development of severe hyponatraemia in hospitalized patients: treatment-related risk factors and inadequate management. Nephrol Dial Transplant. 2006 Jan. 21(1):70-6. [Medline].

  8. Schrier RW. Body water homeostasis: clinical disorders of urinary dilution and concentration. J Am Soc Nephrol. 2006 Jul. 17(7):1820-32. [Medline].

  9. 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(6):R162. [Medline]. [Full Text].

  10. Upadhyay A, Jaber BL, Madias NE. Incidence and prevalence of hyponatremia. Am J Med. 2006 Jul. 119(7 Suppl 1):S30-5. [Medline].

  11. Ayus JC, Varon J, Arieff AI. Hyponatremia, cerebral edema, and noncardiogenic pulmonary edema in marathon runners. Ann Intern Med. 2000 May 2. 132(9):711-4. [Medline].

  12. Kumar S, Fowler M, Gonzalez-Toledo E, Jaffe SL. Central pontine myelinolysis, an update. Neurol Res. 2006 Apr. 28(3):360-6. [Medline].

  13. Ellison DH, Berl T. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007 May 17. 356(20):2064-72. [Medline].

  14. 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 Jan. 119(1):71.e1-8. [Medline].

  15. Usala RL, Fernandez SJ, Mete M, Cowen L, Shara NM, Barsony J, et al. Hyponatremia Is Associated With Increased Osteoporosis and Bone Fractures in a Large US Health System Population. J Clin Endocrinol Metab. 2015 Aug. 100 (8):3021-31. [Medline].

  16. Clayton JA, Le Jeune IR, Hall IP. Severe hyponatraemia in medical in-patients: aetiology, assessment and outcome. QJM. 2006 Aug. 99(8):505-11. [Medline].

  17. Decaux G. Is asymptomatic hyponatremia really asymptomatic?. Am J Med. 2006 Jul. 119(7 Suppl 1):S79-82. [Medline].

  18. Hew-Butler T, Noakes TD, Siegel AJ. Practical management of exercise-associated hyponatremic encephalopathy: the sodium paradox of non-osmotic vasopressin secretion. Clin J Sport Med. 2008 Jul. 18(4):350-4. [Medline].

  19. Sterns RH, Silver SM. Cerebral salt wasting versus SIADH: what difference?. J Am Soc Nephrol. 2008 Feb. 19(2):194-6. [Medline].

  20. Yee AH, Burns JD, Wijdicks EF. Cerebral salt wasting: pathophysiology, diagnosis, and treatment. Neurosurg Clin N Am. 2010 Apr. 21(2):339-52. [Medline].

  21. Tian W, Fu Y, Garcia-Elias A, et al. A loss-of-function nonsynonymous polymorphism in the osmoregulatory TRPV4 gene is associated with human hyponatremia. Proc Natl Acad Sci U S A. 2009 Aug 18. 106(33):14034-9. [Medline]. [Full Text].

  22. 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].

  23. Maesaka JK, Miyawaki N, Palaia T, Fishbane S, Durham JH. Renal salt wasting without cerebral disease: diagnostic value of urate determinations in hyponatremia. Kidney Int. 2007 Apr. 71 (8):822-6. [Medline].

  24. [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 Apr. 29 Suppl 2:i1-i39. [Medline].

  25. Sterns RH, Hix JK, Silver S. Treating profound hyponatremia: a strategy for controlled correction. Am J Kidney Dis. 2010 Oct. 56 (4):774-9. [Medline].

  26. Zeltser D, Rosansky S, van Rensburg H, Verbalis JG, Smith N. Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia. Am J Nephrol. 2007. 27(5):447-57. [Medline].

  27. Decker BC. Disorders of Water Excess: Hyponatremia. Dale DC, Federman DD, eds. ACP Medicine. BC Decker; 2007. Vol 1:

  28. Nemerovski C, Hutchinson DJ. Treatment of hypervolemic or euvolemic hyponatremia associated with heart failure, cirrhosis, or the syndrome of inappropriate antidiuretic hormone with tolvaptan: a clinical review. Clin Ther. 2010 Jun. 32(6):1015-32. [Medline].

  29. Schrier RW, Gross P, Gheorghiade M, Berl T, Verbalis JG, Czerwiec FS, et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006 Nov 16. 355(20):2099-112. [Medline].

  30. Berl T, Quittnat-Pelletier F, Verbalis JG, et al. Oral tolvaptan is safe and effective in chronic hyponatremia. J Am Soc Nephrol. 2010 Apr. 21(4):705-12. [Medline]. [Full Text].

  31. Gross P. Treatment of hyponatremia. Intern Med. 2008. 47(10):885-91. [Medline].

  32. Marik PE, Rivera R. Therapeutic effect of conivaptan bolus dosing in hyponatremic neurosurgical patients. Pharmacotherapy. 2013 Jan. 33(1):51-5. [Medline].

 
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