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

INITIAL

hypernatraemia at any stage

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oral/intravenous fluids

Hypotonic fluid replacement is required. Oral and enteral fluid is preferred if possible, as this leads to a smoother change in serum electrolytes.

Intravenous 5% dextrose and 0.45% sodium chloride may be necessary in some patients. If parenteral correction is required, the infusion rates are determined by the tonicity of the infusate chosen, the degree of hypernatraemia, the desired rate of correction, ongoing water losses, and the estimated deficit in total body water.[55]

Regular serum sodium tests are required.

If the hypernatraemia is acute, reducing the serum sodium concentration by up to 1 mmol/L (1 mEq/L) per hour may be appropriate.[55]

If the hypernatraemia is long-standing or is of uncertain duration, the rate of correction should be at a maximal rate of 0.5 mmol/L (0.5 mEq/L) per hour to reduce the risk of iatrogenic cerebral oedema.[55]​ Decrease in serum sodium should be limited to 10 mmol/L (10 mEq/L) per 24 hours, to a target serum sodium of 145 mmol/L (145 mEq/L).[55]

ACUTE

acute arginine vasopressin deficiency (AVP-D)

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desmopressin

Treatment is with parenteral or oral desmopressin (a synthetic, long-acting analogue of arginine vasopressin [AVP], also known as DDAVP).

Careful management of fluid intake is crucial to prevent water overload and hyponatraemia, a common side effect of desmopressin therapy.[3]​ Desmopressin treatment in small children is challenging and can result in rapid changes in serum osmolality.[65]​ The concurrent use of intravenous fluids and desmopressin further increases the risk of hyponatraemia.

To minimise the risk of hyponatraemia, treatment should be started at the lowest possible dose, with subsequent dose titration based upon clinical status and serum sodium level.​[65]

Primary options

desmopressin: children <4 years of age: 0.1 to 0.8 mg/day orally given in 2 divided doses; children 4-12 years of age: 0.1 to 1.2 mg/day orally given in 2-3 divided doses; children ≥12 years of age and adults: 0.1 to 1.2 mg/day orally given in 2-3 divided doses, or 2-4 micrograms/day subcutaneously/intravenously given in 1-2 divided doses

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oral/intravenous fluids

Additional treatment recommended for SOME patients in selected patient group

Patients who are conscious should be encouraged to drink to thirst.

Intravenous 5% dextrose and 0.45% sodium chloride may be necessary in some patients.

Regular monitoring, with serial measurements of serum sodium and urine and serum osmolality, is recommended.

Lower rates of fluid administration may be required in patients treated with desmopressin in parallel with intravenous fluids.

Serum sodium should be corrected at a maximal rate of 0.5 mmol/L (0.5 mEq/L) per hour to reduce the risk of iatrogenic cerebral oedema.[55]​ The decrease in serum sodium should be limited to 10 mmol/L (10 mEq/L) over 24 hours, to target nadir of 145 mmol/L (145 mEq/L).[55]

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desmopressin

If polyuria is present, urine osmolality is low, or if hypernatraemia is present, arginine vasopressin deficiency (AVP-D) is likely and treatment should be given with parenteral or oral desmopressin (a synthetic, long-acting analogue of arginine vasopressin [AVP], also known as DDAVP).

Careful management of fluid intake is crucial to prevent water overload and hyponatraemia, a common side effect of desmopressin therapy.[3]​ Desmopressin treatment in small children can result in rapid changes in serum osmolality.[65]​ The concurrent use of intravenous fluids and desmopressin further increases the risk of hyponatraemia.

To minimise the risk of hyponatraemia, patients should be started at the lowest possible dose of desmopressin, with subsequent titration based upon clinical status and serum sodium level.​[65]​ As postoperative AVP-D is often transient initially, desmopressin should be prescribed on an ‘as required’ basis according to urine output and electrolyte assessment. A triple-phase response may occur - beginning with AVP-D, followed by a transient syndrome of inappropriate antidiuretic hormone (SIADH), and ultimately leading to either permanent AVP-D or full recovery of AVP function.[12] Careful monitoring of fluid balance and serum sodium is essential throughout this period. Positive fluid balance and falling plasma sodium indicate SIADH, at which point desmopressin should be held and fluid intake restricted.[3]

Primary options

desmopressin: children <4 years of age: 0.1 to 0.8 mg/day orally given in 2 divided doses; children 4-12 years of age: 0.1 to 1.2 mg/day orally given in 2-3 divided doses; children ≥12 years of age and adults: 0.1 to 1.2 mg/day orally given in 2-3 divided doses, or 2-4 micrograms/day subcutaneously/intravenously given in 1-2 divided doses

Back
Consider – 

oral/intravenous fluids

Additional treatment recommended for SOME patients in selected patient group

Patients who are conscious should be encouraged to drink to thirst.

Intravenous 5% dextrose and 0.45% sodium chloride may be necessary in some patients.

Regular monitoring, with serial measurements of serum sodium and urine and serum osmolality, is recommended.

Lower rates of fluid administration may be required in patients treated with desmopressin in parallel with intravenous fluids.

Serum sodium should be corrected at a maximal rate of 0.5 mmol/L (0.5 mEq/L) per hour to reduce the risk of iatrogenic cerebral oedema.[55]​ The decrease in serum sodium should be limited to 10 mmol/L (10 mEq/L) over 24 hours, to target nadir of 145 mmol/L (145 mEq/L).[55]

ONGOING

chronic arginine vasopressin deficiency (AVP-D)

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desmopressin

The treatment of choice is the synthetic, long-acting arginine vasopressin (AVP) analogue desmopressin (also known as DDAVP).[66] Oral, intranasal, and parenteral formulations are available. Patient preference is important in choosing formulation, and an individualised dosing schedule is required.

Treatment should be started at low dose, with increments based on response and serum sodium test results. The average duration of action per dose is 6 to 18 hours.

In some patients with mild AVP-D, a single night-time dose may be sufficient to control symptoms.[3]​​

Treatment of AVP-D in small children is challenging. Rapid changes in serum osmolality can occur.[65]

Patients may be advised to delay, reduce, or omit treatment on 1 day per week, to allow off-loading of excess water and prevent hyponatraemia, which is a common adverse effect.[67]​ Specific strategies include a 'delayed dose' (waiting for aquaresis once or twice per week before resuming drug treatment), a 'regular delayed dose' (delaying each dose until polyuria develops for a daily low-grade aquaresis), or 'weekly omission of a tablet' (though this can be uncomfortable).[3]​ Most desmopressin-associated hyponatraemia is mild and asymptomatic, and responds to withholding a dose.[3]

Primary options

desmopressin: children <4 years of age: 0.1 to 0.8 mg/day orally given in 2 divided doses; children 4-12 years of age: 0.1 to 1.2 mg/day orally given in 2-3 divided doses; children ≥12 years of age and adults: 0.1 to 1.2 mg/day orally given in 2-3 divided doses, or 2-4 micrograms/day subcutaneously/intravenously given in 1-2 divided doses

OR

desmopressin nasal: (0.01%) children ≥3 months of age: 5-30 micrograms/day intranasally given in 1-2 divided doses; children ≥12 years of age and adults: 10-40 micrograms/day intranasally given in 1-3 divided doses

arginine vasopressin resistance (AVP-R)

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maintenance of adequate fluid intake

The mainstay of treatment is adequate fluid intake to match output and insensible losses.

Adequate intake may be difficult, especially during intercurrent illness, as urinary excretion can be up to 12 litres per day.[10]

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treatment of underlying cause

Treatment recommended for ALL patients in selected patient group

Any underlying cause, if identified, should be corrected.

Drug-induced AVP-R may resolve following discontinuation of the offending drug.[68] However, AVP-R secondary to lithium is often irreversible.[43]

Any underlying renal disease should be treated.

AVP-R secondary to hypercalcaemia or hypokalaemia should resolve following treatment of the electrolyte disorder.

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sodium restriction and/or pharmacotherapy

Additional treatment recommended for SOME patients in selected patient group

A low-sodium diet (<500 mg/day), thiazide diuretics, or indometacin may reduce urine output.​[1]​​

As these agents may act synergistically, combination therapy can be used.

Given the potential for dehydration and nephrotoxicity, a nephrology specialist should be consulted if pharmacotherapy is considered.

Primary options

hydrochlorothiazide: children: 1-3 mg/kg/day orally given in 2 divided doses; adults: 12.5 to 50 mg orally once daily

OR

indometacin: children ≥2 years of age: 2 mg/kg/day orally given in 2-4 divided doses, maximum 150 mg/day; adults: 25-50 mg orally two to three times daily, maximum 200 mg/day

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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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