Hyponatraemia

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

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

acute onset (<48 hours) and/or symptomatic

1st line – hypertonic (3%) saline infusion

Back

1st line –

hypertonic (3%) saline infusion

Cerebral oedema occurs more frequently when hyponatraemia develops acutely (i.e., <48 hours). In patients with cerebral oedema, symptoms are usually severe (e.g., nausea/vomiting, altered mental status, somnolence, seizures, coma).[2]

All patients with acute onset of hyponatraemia and/or symptoms should be treated promptly with hypertonic 3% saline.[2][3][5]

Usual regimen is 100-300 mL of hypertonic 3% saline (or 2-4 mL/kg) given in 100 mL increments over 10-20 minutes (usually as a bolus infusion) until symptom improvement occurs.[3][5] Evidence suggests that a ‘rapid intermittent bolus’ regime of fluid administration may be more effective at achieving the desired hourly reduction in sodium levels than a slow continuous infusion.[48]

Recommendations regarding the rate of serum sodium correction vary, with some sources recommending a rate of 3-6 mmol/L/day, while others recommend a more aggressive rate of 8-12 mmol/L/day (in the first 24 hours).[2][49][50] A rate of 1-2 mmol/L/hour can be used for several hours if symptoms are severe.[24] A rate of <8 mmol/L/day is recommended to prevent myelinolysis.[24][Figure caption and citation for the preceding image starts]: Brain magnetic resonance imaging of a patient with central pontine myelinolysis showing hypointensity within the basis pontisBMJ Case Reports 2013; doi:10.1136/bcr-2013-009970 [Citation ends]. com.bmj.content.model.Caption@130f636 A more conservative approach to sodium correction is recommended in patients who have mild symptoms or who are asymptomatic.

Avoid giving hypotonic fluids as this can worsen cerebral oedema.

Once desired serum sodium concentration is achieved, hypertonic 3% saline can be stopped and fluid repletion continued with a suitable fluid according to clinical conditions and to correct any ongoing losses.[5]

Plus – supportive care

Back

Plus –

supportive care

Treatment recommended for ALL patients in selected patient group

Supportive care (e.g., establishing intravenous access, giving supplemental oxygen, seizure control, intubation) should be initiated depending on the presentation.[3]

Serum sodium concentration should be tested every 2 hours to guide therapy until stabilisation occurs and hypertonic saline is no longer required. It should then be tested every 4-6 hours for 24 hours, and every 24 hours thereafter to monitor the ongoing rate of correction.[3]

Urine output should also be monitored as spontaneous diuresis can occur, which may lead to overcorrection of the serum sodium concentration. If urine output changes abruptly, serum sodium levels should be reassessed. A urine output of <2400 mL/24 hours (or 100 mL/hour) has been proposed as a safe upper limit during hyponatraemia correction, but this has yet to be validated.[51] Urine studies should be obtained as early as possible as they may be affected by the administration of intravenous fluids.

Plus – treat underlying cause

Back

Plus –

treat underlying cause

Treatment recommended for ALL patients in selected patient group

Once the patient is stabilised, the underlying cause should be addressed.

Patients who do not improve may require further diagnostic assessment.

ONGOING

chronic onset (≥48 hours) or asymptomatic

hypovolaemic

1st line – isotonic fluid infusion

Back

1st line –

isotonic fluid infusion

Isotonic intravenous fluids (e.g., normal saline 0.9% or a balanced solution such as lactated Ringer's solution) should be administered in 250-1000 mL boluses to maintain blood pressure. Boluses can be repeated as necessary, and then followed by an infusion of 0.5 to 1 mL/kg/hour to replete intravascular volume until signs and symptoms are no longer present.[2] It is important that hypotonic fluids be avoided in these patients.

Recommendations regarding the rate of serum sodium correction vary. In patients with mild symptoms, or who are asymptomatic, 3-6 mmol/L/day may be appropriate. A rate of <8 mmol/L/day is recommended to prevent myelinolysis.[24]

Serum sodium concentration should be tested every 8-12 hours for 24 hours, and every 24 hours thereafter. It should be reassessed after repletion of volume as a concomitant disorder that is causing hyponatraemia may be present.

Plus – treat underlying cause

Back

Plus –

treat underlying cause

Treatment recommended for ALL patients in selected patient group

Underlying cause should be treated (e.g., treating severe nausea/vomiting, stopping diuretics if possible, treating mineralocorticoid deficiency).

hypervolaemic

1st line – fluid restriction

Back

1st line –

fluid restriction

All patients should be placed on fluid restriction (including all oral and intravenous fluids) of 1 L/day.[2][3] This should be adjusted based on measured urine output and set at 500 mL less than daily urine volume (e.g., a patient producing 1200 mL/day of urine should be placed on 700 mL/day fluid restriction). This conservative approach should increase the serum sodium concentration gradually (i.e., <8 mmol/L/day) and helps to prevent myelinolysis, which can occur if sodium levels are corrected too quickly.

Electrolyte-free water excretion may be calculated. It is particularly useful in patients who are not responding to the general fluid restriction measures, and helps to determine the amount of free water restriction required to correct the serum sodium concentration.

Electrolyte-free water excretion = V × [1 - (UNa + UK)/(PNa)], where V is the urine flow rate, UNa is the urine concentration of sodium (mmol/L), UK is the urine concentration of potassium (mmol/L), and PNa is the plasma concentration of sodium (mmol/L).

If the value is positive, free water intake should be restricted to less than the electrolyte-free water excretion value, if feasible, in order to induce a negative free water balance. If the value is very low, this may be difficult to achieve. If the value is negative, free water restriction will not be effective and alternative treatment options (e.g., vaptans) should be considered.[43][44]

Serum sodium concentration should be tested every 8-12 hours for 24 hours, and every 24 hours thereafter.

Plus – treat underlying cause

Back

Plus –

treat underlying cause

Treatment recommended for ALL patients in selected patient group

Underlying cause should be treated. For patients with hypervolaemic hyponatraemia, causes include acute kidney injury/chronic kidney disease, congestive heart failure, cirrhosis, and nephrotic syndrome.

Consider – loop diuretic or spironolactone

Back

Consider –

loop diuretic or spironolactone

Additional treatment recommended for SOME patients in selected patient group

A diuretic can be added if hypervolaemia is present and the underlying condition warrants it.[3]

Choice of agent depends on the underlying condition. Loop diuretics are recommended in patients with congestive heart failure or nephrotic syndrome, while spironolactone (an aldosterone receptor antagonist) is recommended in patients with cirrhosis and ascites. Thiazide diuretics should be avoided as they tend to worsen hyponatraemia.

The rate of correction of serum sodium should be closely monitored when using these agents and kept to <8 mmol/L/day to prevent myelinolysis.

Primary options

furosemide: 20-80 mg orally every 6-8 hours, increase dose gradually according to response, usual dose 40-120 mg/day, maximum 600 mg/day; 20-40 mg intravenously initially, increase dose by 20-40 mg every 2 hours as needed to achieve clinical response

spironolactone: 25 mg/day orally initially given as a single dose or in 2 divided doses, increase gradually according to response, maximum 200 mg/day

2nd line – vasopressin receptor antagonist + discontinue fluid restriction

Back

2nd line –

vasopressin receptor antagonist + discontinue fluid restriction

If fluid restriction fails, a vasopressin receptor antagonist (also known as a vaptan) should be considered.[3]

Vaptans directly block the action of vasopressin on the kidneys, thereby reducing water retention.[3][17] They have been shown to be safe and effective at slowly correcting serum sodium levels; however, they have not been shown to be associated with mortality benefits when used for the long-term treatment of congestive heart failure or hypervolaemic hyponatraemia.[52][53] [ ] There are also concerns that these drugs are associated with liver dysfunction.

Once a vaptan is started, fluid restriction is lifted in order to prevent overcorrection.[3][54] One systematic review found that treatment with a vaptan increased the risk of overcorrection by approximately 3% compared with placebo.[53]

Primary options

tolvaptan: 15 mg orally once daily initially, increase gradually according to response, maximum 60 mg/day for up to 30 days

3rd line – urea

Back

3rd line –

urea

Oral urea is supported as an alternative to vaptans in European and US hyponatraemia guidelines, although evidence from large multicentre randomised trials is lacking. The treatment is generally well tolerated and may be used in outpatient settings.[2][9][55][56][57]

Primary options

urea: 15-60 g/day orally given in 1-4 divided doses, titrate according to serum sodium level, maximum 180 g/day

euvolaemic

1st line – fluid restriction

Back

1st line –

fluid restriction

Serum sodium concentration should be tested every 8-12 hours for 24 hours, and every 24 hours thereafter.

Plus – treat underlying cause

Back

Plus –

treat underlying cause

Treatment recommended for ALL patients in selected patient group

Underlying cause should be treated. For patients with euvolaemic hyponatraemia causes include causative medications and excess fluid intake (e.g., exercise, surgery, primary polydipsia, potomania). The syndrome of inappropriate antidiuretic hormone (SIADH) is characterised by hypotonic hyponatraemia, concentrated urine, and a euvolaemic state. See Syndrome of inappropriate antidiuretic hormone (Treatment algorithm).

2nd line – vasopressin receptor antagonist + discontinue fluid restriction

Back

2nd line –

vasopressin receptor antagonist + discontinue fluid restriction

If fluid restriction fails, a vasopressin receptor antagonist (also known as a vaptan) should be considered.[3]

Vaptans directly block the action of vasopressin on the kidneys, thereby reducing water retention.[3][17] They have been shown to be safe and effective at slowly correcting serum sodium levels; however, they have not been shown to be associated with mortality benefits when used for the long-term treatment of euvolaemic hyponatraemia.[52][53] [ ] There are also concerns that these drugs are associated with liver dysfunction.

Primary options

tolvaptan: 15 mg orally once daily initially, increase gradually according to response, maximum 60 mg/day for up to 30 days

3rd line – urea

Back

3rd line –

urea

Primary options

urea: 15-60 g/day orally given in 1-4 divided doses, titrate according to serum sodium level, maximum 180 g/day

overcorrection of serum sodium concentration

1st line – stop active treatment + initiate free water intake and/or desmopressin

Back

1st line –

stop active treatment + initiate free water intake and/or desmopressin

If an overcorrection of more than 8-12 mmol/L/day of serum sodium concentration occurs, then prompt intervention is required to lower the serum sodium concentration.[2]

All active treatment should be stopped and treatment with free water intake and/or desmopressin should be initiated.

The Adrogue-Madias formula can be used to determine the sodium-lowering effect of 1 litre of fluid (e.g., dextrose 5% in water): change in serum sodium concentration (per 1 litre) = (infusate sodium concentration - serum sodium concentration)/(total body water + 1); where serum sodium concentration is in mmol/L and total body water is in litres. Total body water in the equation can be estimated by using the following simple calculations: 0.5 × body weight in kilograms (for women and elderly men); 0.6 × body weight in kilograms (for younger men or children). Sodium concentration of common fluids (per litre): normal saline (0.9%): 154 mmol/L; lactated Ringer's solution: 130 mmol/L; dextrose 5% in water: 0 mmol/L; enteral water: 0 mmol/L. The sodium concentration of the infusate fluid must be known in order to use this formula, and the equation fails to take the ongoing water and electrolyte losses through urine and stool into account.[2][24]

The formula may be inadequate at predicting serum sodium levels in individual patients. For this reason, some physicians recommend paying careful attention to the initial changes in the serum sodium level and starting with 50% to 75% of the calculated infusion rate, and then adjusting the rate according to the serum sodium level.

Primary options

desmopressin: 1-2 micrograms intravenously twice daily

Use of this content is subject to our disclaimer