Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

severe symptoms

1st line – intravenous hypertonic saline + fluid restriction

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ACUTE
|
severe symptoms
|
acute (onset ≤48 hours)
1st line – 

intravenous hypertonic saline + fluid restriction

Severe neurological symptoms include altered mental status, seizure, and coma. Acute hyponatraemia may occur while a patient is hospitalised. Patients with acute development of hyponatraemia may be more susceptible to symptoms at higher serum sodium levels than those with chronic hyponatraemia.

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 mmol/L (1-2 mEq/L) per hour until neurological symptoms resolve.[22]

In the emergency department, treatment may start with 50 mL 3% saline intravenous, followed by 200 mL intravenous infusion over 4 to 6 hours.[33] This treatment generally raises serum sodium by 8 to 10 mmol/L (8-10 mEq/L) and moves patients out of the acute neurological dangers of hyponatraemia.[33] The rate of correction is then slowed to elevate serum sodium no more than 8 to 10 mmol/L (8-10 mEq/L) in a 24-hour period thereafter.[16]

There is a risk of central pontine myelinolysis (osmotic demyelination syndrome) in these patients. However, when hyponatraemia has developed in ≤48 hours, the risk is less than in patients with more chronic development of hyponatraemia. Therefore, more rapid correction, although not ideal, is less dangerous in patients with acute hyponatraemia.

Acute hyponatraemia, once corrected, might be self-limiting, 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 stabilises.

Plus – treat underlying cause

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ACUTE
|
severe symptoms
|
acute (onset ≤48 hours)
Plus – 

treat underlying cause

Treatment recommended for ALL patients in selected patient group

The patient is investigated for the presence of an underlying disorder, such as infection, pain, nausea, or stress, SIADH-associated medicine, or administration of hypotonic fluid, that may have led to hyponatraemia.

These disorders are treated and causative medicines discontinued.

All hypotonic fluids are also stopped.

Consider – furosemide

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ACUTE
|
severe symptoms
|
acute (onset ≤48 hours)
Consider – 

furosemide

Additional treatment recommended for SOME patients in selected patient group

Furosemide may be used in addition to hypertonic saline, especially if the patient is at risk for volume overload. It helps to correct hyponatraemia 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 hyponatraemia.

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 mmol/L (80 mEq/L) (similar to half-normal saline). Correcting for above electrolyte losses by administering 3% saline (1/6 mL per mL urine if urine electrolytes 80 mmol/L [80 mEq/L]) would lead to net free water clearance of 5/6 of urine output, which must be taken into consideration when correcting hyponatraemia.[12]

Hypokalaemia is monitored and corrected with intravenous potassium replacement.

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

1st line – intravenous hypertonic saline

Back
ACUTE
|
severe symptoms
|
chronic (onset >48 hours or unknown)
1st line – 

intravenous hypertonic saline

Severe neurological 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 mmol/L (1-2 mEq/L) per hour, until neurological symptoms resolve.[22]

In the emergency department, treatment may start with 200 mL 3% saline intravenous infusion over 4 to 6 hours.[33] This treatment generally moves patients out of the acute neurological dangers of hyponatraemia.[33] The rate of correction is then slowed to elevate serum sodium no more than 10 mmol/L (10 mEq/L) in a 24-hour period.[16]

There is an increased risk of central pontine myelinolysis (osmotic demyelination syndrome) in chronically hyponatraemic patients, so careful monitoring is of utmost importance. Central pontine myelinolysis may present with neurological symptoms, including behaviour disturbances, lethargy, dysarthria, dysphagia, paraparesis or quadriparesis, and coma.

Seizures may also be seen but are less common.[22]

Malnutrition, potassium depletion, and hepatic failure increase the risk of developing central pontine myelinolysis.[22][23] One large multi-centre study in 2023 found a high incidence of overcorrection of sodium in hospitalised hyponatraemic patients, but a relatively low incidence of osmotic demyelination syndrome. While this is an interesting finding, it does not downplay the importance of slow correction of sodium in the chronic hyponatraemic patient.​[24]​

Plus – vasopressin receptor antagonist

Back
ACUTE
|
severe symptoms
|
chronic (onset >48 hours or unknown)
Plus – 

vasopressin receptor antagonist

Treatment recommended for ALL patients in selected patient group

Following successful therapy with intravenous hypertonic saline, an intravenous vasopressin receptor antagonist is commenced.

Conivaptan is a non-selective 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.[16]

Tolvaptan, a selective V2 receptor antagonist, has been demonstrated to be safe and effective, if monitored closely at initiation.[30] Serum sodium should be checked at baseline and 8 hours after the first dose, and then daily during titration period (up to 14 days).[28] 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]

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

OR

tolvaptan: 15 mg orally once daily initially

More

Plus – treat underlying cause

Back
ACUTE
|
severe symptoms
|
chronic (onset >48 hours or unknown)
Plus – 

treat underlying cause

Treatment recommended for ALL patients in selected patient group

The patient is investigated for the presence of an underlying disorder, such as infection, pain, nausea or stress, SIADH-associated medicine, or administration of hypotonic fluid, that may have led to hyponatraemia.

These disorders are treated and causative medicines discontinued.

All hypotonic fluids are also stopped.

Consider – furosemide

Back
ACUTE
|
severe symptoms
|
chronic (onset >48 hours or unknown)
Consider – 

furosemide

Additional treatment recommended for SOME patients in selected patient group

Furosemide may be used in addition to hypertonic saline, especially if the patient is at risk for volume overload. It helps to correct hyponatraemia 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 hyponatraemia.

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 mmol/L (80 mEq/L) (similar to half-normal saline). Correcting for above electrolyte losses by administering 3% saline (1/6 mL per mL urine if urine electrolytes 80 mmol/L [80 mEq/L]) would lead to net free water clearance of 5/6 of urine output, which must be taken into consideration when correcting hyponatraemia.[12]

Hypokalaemia is monitored and corrected with intravenous potassium replacement.

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

mild to moderate symptoms

1st line – treat underlying cause

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ACUTE
|
mild to moderate symptoms
|
acute (onset ≤48 hours)
1st line – 

treat underlying cause

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 hyponatraemia.

These disorders are treated and causative medications discontinued.

All hypotonic fluids are also stopped.

Plus – fluid restriction

Back
ACUTE
|
mild to moderate symptoms
|
acute (onset ≤48 hours)
Plus – 

fluid restriction

Treatment recommended for ALL patients in selected patient group

Fluid restriction of 1 to 1.5 L/day is required.

Acute hyponatraemia, once corrected, might be self-limiting, if the causes of SIADH are removed.

Serum sodium is monitored daily until it stabilises.

1st line – treat underlying cause

Back
ACUTE
|
mild to moderate symptoms
|
chronic (onset >48 hours or unknown)
1st line – 

treat underlying cause

The patient is investigated for the presence of an underlying disorder, such as infection, pain, nausea, or stress, SIADH-associated medicine, or administration of hypotonic fluid, that may have led to hyponatraemia.

These disorders are treated and causative medicines discontinued.

All hypotonic fluids are also stopped.

Plus – vasopressin receptor antagonist

Back
ACUTE
|
mild to moderate symptoms
|
chronic (onset >48 hours or unknown)
Plus – 

vasopressin receptor antagonist

Treatment recommended for ALL patients in selected patient group

Vasopressin receptor antagonists are recommended initially for patients with chronic SIADH without severe neurological symptoms.

Conivaptan is a non-selective 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.[16]

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).[28] 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]

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

OR

tolvaptan: 15 mg orally once daily initially

More

asymptomatic with sodium ≥125 mmol/L (≥125 mEq/L)

1st line – fluid restriction + treat underlying cause

Back
ACUTE
|
asymptomatic with sodium ≥125 mmol/L (≥125 mEq/L)
1st line – 

fluid restriction + treat underlying cause

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 hyponatraemia.

These disorders are treated and causative medications discontinued.

All hypotonic fluids are also stopped.

ONGOING

persistence of chronic SIADH

1st line – fluid restriction

Back
ONGOING
|
persistence of chronic SIADH
1st line – 

fluid restriction

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.

Plus – treat underlying cause

Back
ONGOING
|
persistence of chronic SIADH
Plus – 

treat underlying cause

Treatment recommended for ALL patients in selected patient group

The patient is investigated for the presence of an underlying disorder, such as infection, pain, nausea, or stress, SIADH-associated medicine, or administration of hypotonic fluid, that may have led to hyponatraemia.

These disorders are treated and causative medicines discontinued.

All hypotonic fluids are also stopped.

2nd line – tolvaptan

Back
ONGOING
|
persistence of chronic SIADH
2nd line – 

tolvaptan

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).[28] 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. However, in select patients with persistent chronic SIADH, tolvaptan may be continued beyond 30 days (for longer-term treatment) at the lowest effective dose with very close monitoring, although there is limited data to support this approach.[31]​ 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.

Primary options

tolvaptan: 15 mg orally once daily initially

More

3rd line – sodium chloride + furosemide

Back
ONGOING
|
persistence of chronic SIADH
3rd line – 

sodium chloride + furosemide

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.[32]

Serum potassium will need to be monitored closely.

Primary options

sodium chloride: 2-3 g/day orally

and

furosemide: 40 mg orally once daily

4th line – demeclocycline

Back
ONGOING
|
persistence of chronic SIADH
4th line – 

demeclocycline

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.[16] Effects of therapy vary widely and therefore will require close monitoring.

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

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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