Highlights & Basics
- Syndrome of inappropriate antidiuretic hormone (SIADH) is defined as euvolemic, hypotonic hyponatremia secondary to impaired free water excretion, usually from excessive arginine vasopressin (AVP) release.
- Severe neurologic symptoms, such as altered mental status, seizure, and coma, may result from SIADH and these are always treated with hypertonic saline, with close monitoring to avoid overcorrection of serum sodium.
- Central pontine myelinolysis (osmotic demyelination syndrome) may occur with rapid correction of serum sodium in excess of 12 mEq/L/day.
- Vasopressin receptor antagonists (also known as vaptans) are a class of medications that compete with the antidiuretic hormone AVP for binding at the vasopressin receptor, permitting free water excretion.
Quick Reference
History & Exam
Key Factors
absence of hypovolemia
absence of hypervolemia
absence of signs of adrenal insufficiency or hypothyroidism
nausea
vomiting
altered mental status
headache
seizure
coma
Other Factors
no history of recent diuretic use
Diagnostics Tests
1st Tests to Order
serum sodium
serum osmolality
serum BUN
urine osmolality
urine sodium
Other Tests to consider
diagnostic trial with normal saline infusion
serum uric acid
fractional excretion of sodium
fractional excretion of urea
serum TSH
serum cortisol level
serum arginine vasopressin (AVP)
Treatment Options
acute
severe symptoms
acute (onset ≤48 hours)
chronic (onset >48 hours or unknown)
mild to moderate symptoms
acute (onset ≤48 hours)
chronic (onset >48 hours or unknown)
Definition
Classifications
Clinically accepted classification of SIADH
Vignette
Common Vignette
Epidemiology
Etiology
- Drugs: multiple drugs have been linked to increased AVP release or enhanced potential of AVP, including selelctive serotonin-reuptake inhibitors (SSRIs), amiodarone, carbamazepine, chlorpromazine, amitriptyline, and nonsteroidal anti-inflammatory drugs (NSAIDs), and many chemotherapeutic agents such as cyclophosphamide, vincristine, and vinblastine.
- Pulmonary processes: including pulmonary infections and lung cancers, especially small cell lung cancer.
- Malignancy: including lung, gastrointestinal, or genitourinary cancers; lymphomas; or sarcomas.
- Central nervous system (CNS) disorders: including CNS infections, brain trauma, subdural hematoma, subarachnoid hemorrhage, multiple sclerosis, Guillain-Barre syndrome, and acute intermittent porphyria.
- Other stimuli for AVP release: such as anesthesia and postoperative state, nausea, vomiting, pain, and endurance exercise.
- Nephrogenic syndrome of inappropriate antidiuresis or pseudo-SIADH. This is due to gain-of-function mutations in the vasopressin 2 (V2) receptor, which is constitutively active. This initiates aquaporin-2 placement into the apical membrane of cortical collecting duct cells and corresponding free water permeability, in face of appropriately low serum AVP levels.[3]
- The presence of an unknown antidiuretic substance (other than AVP) that stimulates the AVP V2 receptor.[1]
- Post-AVP V2 receptor defect. Aquaporin-2 channel activity is inappropriately stimulated downstream of the AVP V2 receptor. This could be via intracellular stimulation or dysfunction of the aquaporin-2 channel itself.[1]
Pathophysiology
Diagnostic Approach
Risk factors
History
Physical exam
- Tachycardia
- Orthostasis
- Dry mucous membranes
- Poor skin turgor.
- Cirrhosis (e.g., ascites or lower extremity edema)
- Congestive heart failure (e.g., orthopnea, paroxysmal nocturnal dyspnea, or lower extremity edema)
- Nephrosis (e.g., anasarca or lower extremity edema).
Investigations
- Hypotonic hyponatremia: low serum sodium and osmolality
- Euvolemic hyponatremia: high urine sodium, fractional excretion of sodium and urea; low BUN and serum uric acid levels
- Relatively concentrated urine: elevated urine osmolality while serum sodium and osmolality are low
- Exclusion of endocrinopathy: serum TSH and cortisol levels to rule out hypothyroidism and Addison disease, both of which cause euvolemic hyponatremia.
Risk Factors
History & Exam
Tests
Differential Diagnosis
Differentiating Signs/Symptoms
- Many patients are asymptomatic. Symptoms, if present, depend on the nature and severity of the underlying cause.
- Possible symptoms or signs of poorly controlled diabetes (polyuria, polydipsia) may be present if hyperglycemia is the cause.
- Eruptive xanthoma may be seen in patients with severe hyperlipidemia.
- Patients with hyperproteinemia may show signs of multiple myeloma or other rarer causes.
Differentiating Tests
- Suspicion is raised if measurement of serum glucose, lipids, and protein reveals one of these to be elevated.
- Elevated serum glucose: diagnosis is confirmed if calculation of the corrected serum sodium value reveals a normal sodium level. The equation is: corrected sodium (mEq/L) = measured sodium (mEq/L) + 0.016 [glucose (mg/dL) -100].
- Elevated serum lipid level, particularly triglyceride: normal serum osmolarity confirms diagnosis.
- Elevated serum protein, particularly, globulin (multiple myeloma): normal serum osmolarity confirms diagnosis.
Differentiating Signs/Symptoms
- History of poor oral intake, vomiting, diarrhea, or diuretic use help to distinguish hypovolemia from SIADH.
- Evidence of dry mucous membranes, skin tenting, and flat neck veins can accompany hypovolemia, although clinical assessment is poor at predicting volume status.[15]
Differentiating Tests
- Central venous pressure (CVP) <8.
- Urine sodium <20 mEq/L.
- Elevation in serum sodium with a diagnostic trial of 1 to 2 L of normal saline infusion.
Differentiating Signs/Symptoms
- Dyspnea, pulmonary edema, elevated jugular venous pressure, ascites, lower extremity edema.
Differentiating Tests
- CVP elevated.
- Urine sodium <40 mEq/L.
Psychogenic polydipsia
Differentiating Signs/Symptoms
- There may be a psychiatric history or excess fluid intake elicited during history.
Differentiating Tests
- Urine osmolality <100 mOsm/kg H₂O.
- 24-hour urine osmoles >600 mOsm.
Differentiating Signs/Symptoms
- Beer drinking or malnourished patients with poor dietary solute intake and high water intake. Low solute excretion limits water excretion, causing water retention.
Differentiating Tests
- Urine osmolality <100 mOsm/kg H₂O.
- 24-hour urine osmoles <300 mOsm.
Differentiating Signs/Symptoms
- Hypertension; edema may be present.
Differentiating Tests
- Elevated creatinine.
Addison disease
Differentiating Signs/Symptoms
- Pigmentation of skin and mucosa, weight loss, hypotension.
Differentiating Tests
- Low cortisol levels.
- Responds to steroid administration.
Hypothyroidism
Differentiating Signs/Symptoms
- Dry coarse skin, myxedema, hair loss, weight gain.
Differentiating Tests
- High TSH and low serum thyroid hormone levels.
- Responds to treatment with thyroid hormone.
Criteria
- Decreased effective serum osmolality (<275 mOsm/kg of H₂O)
- Urinary osmolality >100 mOsm/kg of H₂O during hypotonicity
- Urinary sodium >30 mEq/L with normal dietary salt and water intake
- Clinical euvolemia
- No orthostasis, tachycardia, decreased skin turgor, dry mucous membranes
- No clinical signs of excessive volume, edema, or ascites
- Normal thyroid and adrenal function
- No recent diuretic use.
- Plasma uric acid <4 mg/dL
- BUN <10 mg/dL
- Fractional sodium excretion >1%, fractional urea excretion >55%
- Failure to correct serum sodium with normal saline infusion
- Abnormal result on test of water load (<80% excretion of 20 mL of H₂O/kg body weight over 4 hours), or inadequate urinary dilution (<100 mOsm/kg H₂O)
- Elevated plasma arginine vasopressin (AVP) levels, despite the presence of hypotonicity and clinical euvolemia.
Screening
Treatment Approach
Acute hyponatremia (≤48 hours' duration) with severe symptoms
Chronic hyponatremia (>48 hours or unknown duration) with severe symptoms
All other patients
Persistent chronic SIADH
Treatment Options
severe symptoms
acute (onset ≤48 hours)
intravenous hypertonic saline + fluid restriction
Comments
- Severe symptoms include altered mental status, seizure, and coma. Acute hyponatremia may occur while a patient is hospitalized. Patients with acute development of hyponatremia may be more susceptible to symptoms at higher serum sodium levels than those with chronic hyponatremia.
- Intravenous hypertonic saline is required and serum sodium levels checked every 2 hours. Treatment goal is initially to elevate serum sodium by 1 to 2 mEq/L per hour until neurologic symptoms resolve.[21]
- In the emergency department, treatment may start with 50 mL 3% saline intravenous, followed by 200 mL intravenous infusion over 4 to 6 hours.[30] This treatment generally raises serum sodium by 8 to 10 mEq/L and moves patients out of the acute neurologic dangers of hyponatremia.[30] The rate of correction is then slowed to elevate serum sodium no more than 8 to 10 mEq/L in a 24-hour period thereafter.[14]
- There is a risk of central pontine myelinolysis (osmotic demyelination syndrome) in these patients. However, when hyponatremia has developed in ≤48 hours, the risk is less than in patients with more chronic development of hyponatremia. Therefore, more rapid correction, although not ideal, is less dangerous in patients with acute hyponatremia.
- Acute hyponatremia, once corrected, might be self-limited, if the causes of SIADH are removed. It may be necessary to continue free fluid restriction (1-1.5 L/day) after hypertonic saline therapy. Serum sodium is monitored daily until it stabilizes.
treat underlying cause
Comments
- The patient is investigated for the presence of an underlying disorder, such as infection, pain, nausea, or stress, SIADH-associated medication, or administration of hypotonic fluid, that may have led to hyponatremia.
- These disorders are treated and causative medications discontinued.
- All hypotonic fluids are also stopped.
furosemide
Primary Options
- furosemide
20 mg intravenously as a single dose initially, increase by 20 mg/dose increments every 6-12 hours according to response, maximum 600 mg/day
- furosemide
Comments
- Furosemide may be used in addition to hypertonic saline, especially if the patient is at risk for volume overload. It helps to correct hyponatremia by increasing free water excretion.
- If furosemide is used in addition to intravenous 3% saline, infusion rates may need to be reduced, so as to avoid overcorrection of hyponatremia.
- Urine sodium plus urine potassium is monitored to determine urine electrolyte and free water loss. With adequate furosemide dosing, urine sodium + urine potassium is likely to equal around 80 mEq/L (similar to half-normal saline). Correcting for above electrolyte losses by administering 3% saline (1/6 cc per cc urine if urine electrolytes 80 mEq/L) would lead to net free water clearance of 5/6 of urine output, which must be taken into consideration when correcting hyponatremia.[11]
- Hypokalemia is monitored and corrected with intravenous potassium replacement.
chronic (onset >48 hours or unknown)
intravenous hypertonic saline
Comments
- Severe neurologic symptoms include altered mental status, seizure, and coma.
- Intravenous hypertonic saline is required and serum sodium levels checked every 2 hours. Treatment goal is initially to elevate serum sodium by 1 to 2 mEq/L per hour, until neurologic symptoms resolve.[21]
- In the emergency department, treatment may start with 200 mL 3% saline intravenous infusion over 4 to 6 hours.[30] This treatment generally moves patients out of the acute neurologic dangers of hyponatremia.[30] The rate of correction is then slowed to elevate serum sodium no more than 10 mEq/L in a 24-hour period.[14]
- There is an increased risk of central pontine myelinolysis (osmotic demyelination syndrome) in chronically hyponatremic patients, so careful monitoring is of utmost importance. Central pontine myelinolysis may present with neurologic symptoms, including behavior disturbances, lethargy, dysarthria, dysphagia, paraparesis or quadriparesis, and coma.
- Seizures may also be seen but are less common.[21]
vasopressin receptor antagonist
Primary Options
- conivaptan
20 mg intravenously as a loading dose, followed by 20 mg infusion given over 24 hours, may increase to 40 mg infusion given over 24 hours if inadequate response, maximum 4 days total treatment
- conivaptan
Comments
- Following successful therapy with intravenous hypertonic saline, an intravenous vasopressin receptor antagonist is commenced.
- Conivaptan is a nonselective vasopressin receptor antagonist and affects both V1 and V2 receptors. Therefore, it is recommended that the patient is monitored for hypotension. This may occur with V1 receptor blockade and resultant vasodilation. Other adverse effects include a risk of infusion site reactions in up to 50% of patients.[14]
- Tolvaptan, a selective V2 receptor antagonist, has been demonstrated to be safe and effective, if monitored closely at initiation.[28] Serum sodium should be checked at baseline and 8 hours after the first dose, and then daily during titration period (up to 14 days).[26] Due to reports of potentially fatal liver injury, tolvaptan should not be used for more than 30 days, and it should be avoided in patients with underlying liver disease including cirrhosis. The drug should be discontinued immediately in patients with signs or symptoms of liver injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice, elevated LFTs).
- An increase in urine output is expected following treatment. Patients receiving tolvaptan should discontinue any previous fluid restriction and drink fluids freely though not excessively.[2]
treat underlying cause
Comments
- The patient is investigated for the presence of an underlying disorder, such as infection, pain, nausea, or stress, SIADH-associated medication, or administration of hypotonic fluid, that may have led to hyponatremia.
- These disorders are treated and causative medications discontinued.
- All hypotonic fluids are also stopped.
furosemide
Primary Options
- furosemide
20 mg intravenously as a single dose initially, increase by 20 mg/dose increments every 6-12 hours according to response, maximum 600 mg/day
- furosemide
Comments
- Furosemide may be used in addition to hypertonic saline, especially if the patient is at risk for volume overload. It helps to correct hyponatremia by increasing free water excretion.
- If furosemide is used in addition to intravenous 3% saline, infusion rates may need to be reduced, so as to avoid overcorrection of hyponatremia.
- Urine sodium plus urine potassium is monitored to determine urine electrolyte and free water loss. With adequate furosemide dosing, urine sodium + urine potassium is likely to equal around 80 mEq/L (similar to half-normal saline). Correcting for above electrolyte losses by administering 3% saline (1/6 cc per cc urine if urine electrolytes 80 mEq/L) would lead to net free water clearance of 5/6 of urine output, which must be taken into consideration when correcting hyponatremia.[11]
- Hypokalemia is monitored and corrected with intravenous potassium replacement.
mild to moderate symptoms
acute (onset ≤48 hours)
treat underlying cause
Comments
- Mild to moderate symptoms include nausea, vomiting, or headache.
- The patient is investigated for the presence of an underlying disorder, such as infection, pain, nausea, or stress, SIADH-associated medication, or administration of hypotonic fluid, that may have led to hyponatremia.
- These disorders are treated and causative medications discontinued.
- All hypotonic fluids are also stopped.
fluid restriction
Comments
- Fluid restriction of 1 to 1.5 L/day is required.
- Acute hyponatremia, once corrected, might be self-limited, if the causes of SIADH are removed.
- Serum sodium is monitored daily until it stabilizes.
chronic (onset >48 hours or unknown)
treat underlying cause
Comments
- Mild to moderate symptoms include nausea, vomiting, or headache.
- The patient is investigated for the presence of an underlying disorder, such as infection, pain, nausea, or stress, SIADH-associated medication, or administration of hypotonic fluid, that may have led to hyponatremia.
- These disorders are treated and causative medications discontinued.
- All hypotonic fluids are also stopped.
vasopressin receptor antagonist
Primary Options
- conivaptan
20 mg intravenously as a loading dose, followed by 20 mg infusion given over 24 hours, may increase to 40 mg infusion given over 24 hours if inadequate response, maximum 4 days total treatment
- conivaptan
Comments
- Vasopressin receptor antagonists are recommended initially for patients with chronic SIADH without severe neurologic symptoms.
- Conivaptan is a nonselective vasopressin receptor antagonist and affects both V1 and V2 receptors. Therefore, it is recommended that the patient is monitored for hypotension. This may occur with V1 receptor blockade and resultant vasodilation. Other adverse effects include a risk of infusion site reactions in up to 50% of patients.[14]
- Tolvaptan, a selective V2 receptor antagonist, has been demonstrated to be safe and effective, if monitored closely at initiation. Serum sodium should be checked at baseline and 8 hours after the first dose, and then daily during titration period (up to 14 days).[26] Due to reports of potentially fatal liver injury, tolvaptan should not be used for more than 30 days, and it should be avoided in patients with underlying liver disease including cirrhosis. The drug should be discontinued immediately in patients with signs or symptoms of liver injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice, elevated LFTs).
- An increase in urine output is expected following treatment. Patients receiving tolvaptan should discontinue any previous fluid restriction and drink fluids freely though not excessively.[2]
asymptomatic with sodium ≥125 mEq/L
fluid restriction + treat underlying cause
Comments
- Fluid restriction of 1 to 1.5 L/day is required.
- The patient is investigated for the presence of an underlying disorder, such as infection, pain, nausea, or stress, SIADH-associated medication, or administration of hypotonic fluid, that may have led to hyponatremia.
- These disorders are treated and causative medications discontinued.
- All hypotonic fluids are also stopped.
persistence of chronic SIADH
fluid restriction
Comments
- Fluid restriction of 1 to 1.5 L/day has been the mainstay of therapy for chronic SIADH therapy.
- Compliance with fluid restriction often limits this therapeutic option.
treat underlying cause
Comments
- The patient is investigated for the presence of an underlying disorder, such as infection, pain, nausea, or stress, SIADH-associated medication, or administration of hypotonic fluid, that may have led to hyponatremia.
- These disorders are treated and causative medications discontinued.
- All hypotonic fluids are also stopped.
tolvaptan
Primary Options
Comments
- If the patient is intolerant to fluid restriction, tolvaptan may be used.
- Tolvaptan, a selective V2 receptor antagonist, has been demonstrated to be safe and effective, if monitored closely at initiation. Serum sodium should be checked at baseline and 8 hours after the first dose, and then daily during titration period (up to 14 days).[26] Due to reports of potentially fatal liver injury, tolvaptan should not be used for more than 30 days, and it should be avoided in patients with underlying liver disease including cirrhosis. The drug should be discontinued immediately in patients with signs or symptoms of liver injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice, elevated LFTs). An increase in urine output is expected following treatment. Fluid restriction should be avoided.
sodium chloride + furosemide
Primary Options
sodium chloride
2-3 g/day orally
and
- furosemide
40 mg orally once daily
Comments
- If the patient is intolerant to fluid restriction, sodium chloride tablets may be administered, which can increase urine output and modestly improve serum sodium levels. This is heightened by co-administration of diuretics, which lower urine osmolality and improve water excretion.[29]
- Serum potassium will need to be monitored closely.
demeclocycline
Primary Options
- demeclocycline
900-1200 mg/day orally given in 3-4 divided doses initially, followed by 600-900 mg/day given in 3-4 divided doses
- demeclocycline
Comments
- If the patient is intolerant to fluid restriction, demeclocycline may be used.
- Demeclocycline is a bacteriostatic antibiotic that causes diminished responsiveness of the collecting tubule to arginine vasopressin (AVP).
- Demeclocycline is used without fluid restriction.
- Side effects such as skin photosensitivity and nephrotoxicity limit use.[14] Effects of therapy vary widely and therefore will require close monitoring.
Emerging Tx
Sodium-glucose co-transporter 2 (SGLT2) inhibitors
Prevention
Primary Prevention
Secondary Prevention
Follow-Up Overview
Prognosis
Persistent SIADH
Monitoring
Complications
Citations
Robertson GL. Regulation of arginine vasopressin in the syndrome of inappropriate antidiuresis. Am J Med. 2006 Jul;119(7 Suppl 1):S36-42.[Abstract]
Gross P. Clinical management of SIADH. Ther Adv Endocrinol Metab. 2012 Apr;3(2):61-73.[Abstract][Full Text]
Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol. 2014 Mar;170(3):G1-47.[Abstract][Full Text]
Ellison DH, Berl T. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007 May 17;356(20):2064-72.[Abstract]
Hoorn EJ, Zietse R. Diagnosis and Treatment of Hyponatremia: Compilation of the Guidelines. J Am Soc Nephrol. 2017 May;28(5):1340-1349.[Abstract][Full Text]
1. Robertson GL. Regulation of arginine vasopressin in the syndrome of inappropriate antidiuresis. Am J Med. 2006 Jul;119(7 Suppl 1):S36-42.[Abstract]
2. Gross P. Clinical management of SIADH. Ther Adv Endocrinol Metab. 2012 Apr;3(2):61-73.[Abstract][Full Text]
3. Feldman BJ, Rosenthal SM, Vargas GA, et al. Nephrogenic syndrome of inappropriate antidiuresis. N Engl J Med. 2005 May 5;352(18):1884-90.[Abstract][Full Text]
4. Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol. 2014 Mar;170(3):G1-47.[Abstract][Full Text]
5. Verbalis JG, Adler S, Schrier RW, et al. Efficacy and safety of oral tolvaptan therapy in patients with the syndrome of inappropriate antidiuretic hormone secretion. Eur J Endocrinol. 2011 May;164(5):725-32.[Abstract][Full Text]
6. Verbalis JG, Goldsmith SR, Greenberg A, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013 Oct;126(10 suppl 1):S1-42.[Abstract][Full Text]
7. Liamis G, Rodenburg EM, Hofman A, et al. Electrolyte disorders in community subjects: prevalence and risk factors. Am J Med. 2013 Mar;126(3):256-63.[Abstract][Full Text]
8. 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.[Abstract][Full Text]
9. Zhang X, Li XY. Prevalence of hyponatremia among older inpatients in a general hospital. Eur Geriatr Med. 2020 Aug;11(4):685-692.[Abstract][Full Text]
10. Robertson GL. Antidiuretic hormone: normal and disordered function. Endocrinol Metab Clin North Am. 2001 Sep;30(3):671-94, vii.[Abstract]
11. Lien YH, Shapiro JI. Hyponatremia: clinical diagnosis and management. Am J Med. 2007 Aug;120(8):653-8.[Abstract]
12. Upadhyay A, Jaber BL, Madias NE. Incidence and prevalence of hyponatremia. Am J Med. 2006 Jul;119(7 Suppl 1):S30-5.[Abstract]
13. Miller M, Morley JE, Rubenstein LZ. Hyponatremia in a nursing home population. J Am Geriatr Soc. 1995 Dec;43(12):1410-3.[Abstract]
14. Ellison DH, Berl T. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007 May 17;356(20):2064-72.[Abstract]
15. Chung HM, Kluge R, Schrier RW, et al. Clinical assessment of extracellular fluid volume in hyponatremia. Am J Med. 1987;83:905-908.[Abstract]
16. Diringer MN, Zazulia AR. Hyponatremia in neurologic patients: consequences and approaches to treatment. Neurologist. 2006;12:117-126.[Abstract]
17. Singh S, Bohn D, Carlotti A, et al. Cerebral salt wasting: truth, fallacies, theories, and challenges. Crit Care Med. 2002;30:2575-2579.[Abstract]
18. Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant. 2014 Apr;29 Suppl 2:i1-i39.[Abstract][Full Text]
19. Lien YH. Antidepressants and hyponatremia. Am J Med. 2018 Jan;131(1):7-8.[Abstract][Full Text]
20. Hoorn EJ, Zietse R. Diagnosis and Treatment of Hyponatremia: Compilation of the Guidelines. J Am Soc Nephrol. 2017 May;28(5):1340-1349.[Abstract][Full Text]
21. Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med. 2000 May 25;342(21):1581-9.[Abstract]
22. Decaux G, Soupart A. Treatment of symptomatic hyponatremia. Am J Med Sci. 2003 Jul;326(1):25-30.[Abstract]
23. Greenberg A, Verbalis JG. Vasopressin receptor antagonists. Kidney Int. 2006 Jun;69(12):2124-30.[Abstract]
24. 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.[Abstract][Full Text]
25. Dixon MB, Lien YH. Tolvaptan and its potential in the treatment of hyponatremia. Ther Clin Risk Manag. 2008 Dec;4(6):1149-55.[Abstract]
26. Berl T, Quittnat-Pelletier F, Verbalis JG, et al; SALTWATER Investigators. Oral tolvaptan is safe and effective in chronic hyponatremia. J Am Soc Nephrol. 2010 Apr;21(4):705-12.[Abstract]
27. Cawley MJ. Hyponatremia: current treatment strategies and the role of vasopressin antagonists. Ann Pharmacother. 2007 May;41(5):840-50.[Abstract]
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.[Abstract]
29. Decaux G, Waterlot Y, Genette F, et al. Inappropriate secretion of antidiuretic hormone treated with frusemide. Br Med J (Clin Res Ed). 1982 Jul 10;285(6335):89-90.[Abstract][Full Text]
30. Kokko JP. Symptomatic hyponatremia with hypoxia is a medical emergency. Kidney Int. 2006 Apr;69(8):1291-3.[Abstract]
31. Refardt J, Imber C, Sailer CO, et al. A Randomized Trial of Empagliflozin to Increase Plasma Sodium Levels in Patients with the Syndrome of Inappropriate Antidiuresis. J Am Soc Nephrol. 2020 Mar;31(3):615-624.[Abstract][Full Text]
32. Gross P, Reimann D, Henschkowski J, et al. Treatment of severe hyponatremia: conventional and novel aspects. J Am Soc Nephrol. 2001;12(suppl 1):S10-S14.[Abstract][Full Text]
33. Ayus JC, Caputo D, Bazerque F, et al. Treatment of hyponatremic encephalopathy with a 3% sodium chloride protocol: a case series. Am J Kidney Dis. 2015;65:435-442.[Abstract][Full Text]
Key Articles
Other Online Resources
Referenced Articles
Guidelines
Diagnostic
Summary
Evidence-based guidance on the diagnosis of adults with hypotonic hyponatremia.Published by
European Society of Endocrinology, European Society of Intensive Care Medicine, European Renal Association-European Dialysis and Transplant Association
Published
2014
Treatment
Summary
Evidence-based guidance on the management of adults with hypotonic hyponatremia.Published by
European Society of Endocrinology, European Society of Intensive Care Medicine, European Renal Association-European Dialysis and Transplant Association
Published
2014