Approach

Treatment goals are normalisation of fluid balance, control of symptoms, avoidance of complications, and maintained quality of life.

Correction of hypernatraemia

If hypernatraemia is a feature at presentation (unusual), correction of water deficit is important. Oral or enteral fluid replacement is the preferred route, as this leads to a smoother change in serum electrolytes. Intravenous hypotonic fluids (dextrose 5% and sodium chloride [NaCl] 0.45%) may be necessary in some patients.

If parenteral correction is required, the infusion rate is determined by the tonicity of the infusate chosen, the degree of hypernatraemia, the desired rate of correction, the ongoing water losses and the estimated deficit in total body water.[55] Pre-existing treatment with desmopressin will lead to more rapid reduction in serum sodium as renal water loss is reduced. Slower rates of fluid administration are required in this position, with regular serum sodium tests.

Several formulae help in calculating the water deficits and infusate rates.[55] Ongoing water losses also need to be considered. Such formulae are guides. Key is the recognition that correction is taking place in a dynamic (the patient) rather than static system. Frequent electrolyte assessments are required to manage the clinical situation safely.

  • The free water deficit may be calculated on the basis of the estimated percentage of total body water (TBW) and the baseline serum sodium (Na) concentration.[55]

    • Free water deficit = total body water × (serum Na/140) -1.

    • TBW = body weight × correction factor based on patient age and sex (children and adult men, 0.6; adult women and older men, 0.5; older women, 0.45).

  • As infusions vary in their sodium concentration, an alternative formula (taking into account the effect of giving 1 litre of a particular infusate) may also be used.[55] For example, 0.45% NaCl contains 77 mmol/L sodium; 5% dextrose contains no sodium.

    • Change in serum sodium = (infusion Na - serum Na)/(TBW +1).[55]

Acute hypernatraemia:

  • Rapid correction of hypernatraemia improves prognosis without increasing the risk of cerebral oedema.[55] Reducing the serum sodium concentration by up to 1 mmol/L (1 mEq/L) per hour may be appropriate.[55]

Chronic hypernatraemia or hypernatraemia of unknown duration:

  • The rate of correction of serum sodium should be at a maximal rate of 0.5 mmol/L/hour (0.5 mEq/L/hour) to reduce the risk of iatrogenic cerebral oedema.[55] Reduction 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]

Arginine vasopressin deficiency (AVP-D; previously known as central diabetes insipidus)

The long-acting, synthetic arginine vasopressin (AVP) analogue desmopressin (also known as DDAVP) is the treatment of choice as replacement for endogenous AVP. Desmopressin is effective in pregnancy-associated AVP-D, as it is not metabolised by placental vasopressinase/oxytocinase. Oral, intranasal, and parenteral formulations are available. Parenteral desmopressin is 5 to 20 times more potent than an intranasal administration, and may be preferred in the acute setting. Desmopressin treatment in small children can result in rapid changes in serum osmolality.[61] Similarly, intravenous fluid administration and desmopressin replacement (in parallel) risk hyponatraemia. Low doses of desmopressin should be used initially and clinical and biochemical response assessed on a regular basis.[61]

Acute presentation

  • Treatment is with parenteral or oral desmopressin started at the lowest possible dose.

  • Urine output and thirst typically respond within 1 to 2 hours. Therapeutic effect persists for 6 to 8 hours.

  • Subsequent dose titration should be based upon clinical and biochemical response.

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

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

  • Patients who develop AVP-D following pituitary surgery or traumatic brain injury may experience fluctuations in fluid balance and require careful monitoring.

Chronic AVP-D

  • The treatment of choice is desmopressin.[62]

  • Dosing is tailored on an individual basis, starting with a low dose. A single nocturnal dose is sufficient in some with mild AVP-D.[3]

  • Patients may be advised to delay, reduce, or omit treatment on 1 day per week, to allow unloading of excess water and prevent hyponatraemia associated with slight over-treatment (‘desmopressin escape’).[63]

Arginine vasopressin resistance (AVP-R; previously known as nephrogenic diabetes insipidus)

Treatment for AVP-R is challenging. Desmopressin is generally ineffective due to renal resistance. High-dose desmopressin can be partially effective in some with variable acquired nephron insensitivity.

The mainstay of treatment is adequate fluid intake to match output and insensible losses. Adequate intake may be difficult, especially during intercurrent illness, as urine output can be up to 12 litres per day.[10]

Any underlying cause, if identified, should be corrected.

  • Drug-induced AVP-R may resolve following discontinuation of the offending drug.[64] However, AVP-R secondary to lithium therapy often does not resolve.[41]

  • Any underlying kidney disease should be treated.

  • AVP-R secondary to hypercalcaemia or hypokalaemia commonly resolves following correction of the electrolyte disorder.

Other treatment modalities for AVP-R include low-sodium diet (<500 mg/day), thiazide diuretics, or indometacin.[1][53]​​ Combinations of these approaches can act synergistically. Treatment rarely restores urine output to normal.

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