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How to manage adults with hyponatraemia

saline infusionHyponatraemia, generally defined as a serum sodium less than 135mmol/L, is the most common electrolyte abnormality observed in hospital inpatients.1 It is estimated that mild hyponatraemia (serum sodium 125–135mmol/L) is observed in 15–30% of patients in hospital.2

Clinical features and mortality

The symptoms of hyponatraemia affect the central nervous system predominantly (see Box 1).3 Symptoms are more common when the serum sodium is less than 125mmol/L or when hyponatraemia develops rapidly.3 The degree of hyponatraemia is also linked with mortality — a newly admitted patient with severe hyponatraemia, ie, serum sodium <120mmol/L, is estimated to have a 60-fold increased risk of death.4


Assessment of a patient’s overall hydration status is important for categorising the type of hyponatraemia (see below) and choosing the most appropriate initial treatment.4

It is also necessary to rule out common causes of pseudohyponatraemia, such as elevated serum levels of lipids or proteins (which interfere with the laboratory test) or blood sampling from a proximal vein into which a hypotonic saline infusion is running. Examples of drugs that can cause hyponatraemia can be found in Box 2 (p263).

Investigations that should be undertaken are set out below.

Serum osmolarity It is necessary to test a patient’s serum osmolarity to confirm the presence of true hypo-osmolar hyponatraemia (ie, serum osmolarity <275mOsm/kg). By comparing measured and calculated serum osmolarity the osmolar gap be calculated; this can help identify if osmotic solutes, such as infused mannitol or glycine, are the cause of the hyponatraemia.5

Blood glucose High serum glucose promotes a shift of water out of cells, causing a dilution of serum sodium. The true serum sodium can be estimated by adding 1.5mmol/L of sodium for every 5mmol/L of glucose above the normal level.1 Treatment should be targeted at establishing normoglycaemia; serum sodium levels will return to normal once this is achieved, but only if high serum glucose is the underlying cause.

Urine osmolarity Assessing a patient’s urine osmolarity is useful for supporting or eliminating a diagnosis of syndrome of inappropriate antidiuretic hormone (SIADH).5 The usual physiological response to hyponatraemia is to produce maximally dilute urine (<100mOsm/kg). If a patient’s urine is inappropriately concentrated (>100mOsm/kg) this supports a diagnosis of SIADH.

Box 1: Severity of hyponatraemia4
 Mild 125-135 Alert –
 Moderate 120-125Nausea, headache, altered cognition23



 Confusion, stupor

Seizures, coma



Urinary sodium Measuring patients’ urinary sodium can help determine if their sodium loss is renal or extra-renal (eg, gastrointestinal). For instance, an appropriate physiological response to extra-renal loss would be to minimise renal sodium excretion (ie, urinary sodium <20mmol/L). It should be noted that concurrent diuretic therapy interferes with the interpretation of urinary sodium measurements.5

Hypovolaemic hyponatraemia

Patients with hypovolaemic hyponatraemia have extracellular fluid depletion and are also lacking total body sodium.

Potential causes of hypovolaemic hyponatraemia include:

  • Thiazide diuretic therapy (particularly for elderly patients)
  • Diarrhoea
  • Vomiting
  • Burns
  • Addison’s disease
  • Cerebral salt wasting syndrome, secondary to head injury or subarachnoid haemorrhage

Patients with hypovolaemic hyponatraemia will have a urine osmolarity >100mOsm/kg and urinary sodium either: <20mmol/L if secondary to gastrointestinal loss, burns, diuretic-related sodium depletion; or >20mmol/L if secondary to excessive current diuretic therapy, thiazide diuretic use, Addison’s disease or cerebral salt wasting syndrome.

A tetracosactide (ACTH) test should be carried out to exclude cortisone deficiency as a cause of hypovolaemic hyponatraemia.

The mainstay of management is rehydration with sodium chloride 0.9% solution, and discontinuation of diuretic therapy where appropriate.4 Correction or maintenance of other serum electrolytes is vital; correction of hypokalaemia is particularly important because low potassium can impair correction of hyponatraemia.5

Euvolaemic hyponatraemia

Euvolaemic hyponatraemia is a common type of hyponatraemia seen in hospital inpatients, especially in the post-operative period.1

A diagnosis of SIADH (characterised by hyponatraemia, serum osmolarity <270mOsm/kg, urine sodium >30mmol/L and urine osmolarity >100mOsm/kg) should be excluded, since it is the most common cause of euvolaemic hyponatraemia.4

Other potential causes of euvolaemic hyponatraemia include:

  • Infusion of hypotonic fluids
  • Excessive absorption of bladder irrigation fluids during urological procedures
  • Hypothyroidism

Thyroid function tests should be carried out for all patients suspected of having euvolaemic hyponatraemia.

Any medicines that could be the cause of euvolaemic hyponatraemia (see Box 2) should be stopped. This, along with fluid restriction, forms the backbone of initial management. Pharmacological treatment is considered second line. Drug treatment of hyponatraemia caused by SIADH is described in Box 3 (p264).

Box 2: Drug causes

Medicines that can cause hyponatraemia do so via a range of mechanisms.6

Some drugs affect water and sodium homeostasis:

  •    Diuretics — thiazides, indapamide, amiloride, loop diuretics

Some increase hypothalamic production of antidiuretic hormone (ie, cause syndrome of inappropriate antidiuretic hormone):

  • Antidepressants — tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine-oxidase inhibitors
  • Antipsychotics — phenothiazines, haloperidol
  • Antiepileptics — carbamazepine, oxcarbazepine, sodium valproate
  • Anticancer drugs — vinca alkaloids, platinum compounds, alkylating agents
  • Others — methotrexate, interferon alfa, opiates

Others potentiate the effects of antidiuretic hormone:

  • Antiepileptics — carbamazepine, lamotrigine
  • Hypoglycaemic medicines — tolbutamide
  • Non-steroidal anti-inflammatory drugs
  • Anticancer drugs — alkylating medicines

Hypervolaemic hyponatraemia

Often described as a dilutional hyponatraemia, hypervolaemic hyponatraemia occurs when a patient has a relative excess of extracellular water and a high or normal total body sodium.1

Potential causes of hypervolaemic hyponatraemia include:

  • Heart failure
  • Hepatic cirrhosis
  • Nephrotic syndrome l Primary polydipsia

Patients with hypervolaemic hyponatraemia will have a serum osmolarity <275mOsm/kg and urinary sodium of <20mmol/L (heart failure) or >40mmol/L (recent diuretic use).

Generally, treatment starts with fluid and sodium restriction. Long-term management focuses on addressing the underlying causes, such as cardiac failure or hepatic cirrhosis.

Treatment approaches

Although serious neurological effects are among the signs and symptoms of acute hyponatraemia, it is important to understand that rapid, uncontrolled correction of hyponatraemia can cause long-term neurological damage due to osmotic demyelination.

When serum sodium levels drop, neuronal cells excrete organic solutes and other molecules to maintain their osmotic balance. This protective process takes around 48–72 hours to reach its maximal effect; accordingly hyponatraemia tends to be classified as either acute, with a known duration of less than 48 hours, or chronic, where the duration is unknown or is longer than 48 hours.7

Guidance from an expert panel, published in 2007,7 recommends that, regardless of the treatment approach, rates of correction should not exceed 10–12mmol/L over 24 hours or 18mmol/L over 48 hours. Patients with severe malnutrition, advanced cirrhosis or alcoholism may be susceptible to osmotic demyelination at lower rates than these. Care should be taken when treating patients with cortisol deficiency or taking thiazide diuretics, because correcting their underlying volume depletion can lead to rapid “autocorrection” of hyponatraemia.7

For the critically hyponatraemic patient displaying serious neurological symptoms, higher initial rates of correction may be considered with hourly measurements of serum sodium. Hypertonic sodium chloride 3% solutions can be used at a rate of 1ml/kg/h to promote initial correction rates of 1.5–2mmol/h for the first 3–4 hours.4

Nevertheless, it is important to remain within the recommended 24-hour correction rates so the infusion should be stopped once life-threatening symptoms have resolved. Due to the intense monitoring requirements, patients with neurological symptoms with or without a serum sodium <120mmol/L should be managed in a critical care unit.

Fluid restriction Fluid restriction should be the first intervention for patients with hypervolaemic or euvolaemic hyponatraemia. Put simply, patients should not ingest more fluid than is lost in urine and insensible losses. Depending on the degree of hyponatraemia and severity of symptoms, fluid should be restricted to provide a negative fluid balance of around 500ml/day.

Box 3: Treatment of hyponatraemia caused by SIADH

Certain medicines can be used to treat hyponatraemia that occurs as a result of the syndrome of inappropriate antidiuretic hormone (SIADH).


Demeclocycline can be used at a dose of 150mg four times a day or 300mg twice a day; doses of up to 1,200mg/day have been used with caution (unlicensed). Demeclocycline is a tetracycline antibiotic that has a mechanism of action that inhibits vasopressin (ADH) receptors on the distal collecting tubule of the kidney and induces a nephrogenic diabetes insipidus. Demeclocycline can take four to 10 days to work. Side effects include photosensitivity, nephrotoxicity and extreme nausea. As for other tetracycline antibiotics, clinicians should ensure demeclocycline is not co-administered with dairy products, medicines containing calcium, magnesium, iron or zinc and, particularly, aluminium salts used in antacids.


Tolvaptan can be used at a dose of 15–60mg once daily. Tolvaptan selectively antagonises vasopressin-2 receptors in the renal tubule, decreasing the expression of water channels. This results in a reduction in the water permeability of the collecting duct, even in the presence of excess ADH, allowing an increase in free water clearance. Tolvaptan can cause a rapid rise in serum sodium concentration; therefore, dose escalation should be gradual, allowing at least two days before an increase and discontinuing if serum sodium correction rates exceed 12mmol/L in 24 hours. Side effects can be predicted from its mechanism of action and include dehydration and constipation. Drug interactions occur via cytochrome P450 3A4 hepatic enzymes.

Clinical approach

The following steps are appropriate in the clinical management of a patient with hyponatraemia:

  • Check serum osmolarity to confirm the patient has a true hypo-osmolar state
  • Confirm whether hyponatraemia is acute (<48 hours) or chronic (>48 hours)
  • Be aware of the patient’s current extracellular volume fluid status
  • Look for underlying causes of the patient’s hyponatraemia (medicines, nutritional intake, intravenous fluids, antibiotics diluted before administration)
  • Ensure urine osmolarity has been checked, especially in SIADH
  • If SIADH is suspected look for medication causes first l In hypervolaemic and euvolaemic hyponatraemia ensure appropriate fluid restriction is in place
  • Ensure rational, safe prescribing and dose escalation of medicines used to treat SIADH-induced hyponatraemia (including checking for drug interactions)
  • On discharge ensure there is a plan for monitoring sodium with the GP or secondary care clinician

James Allen is divisional pharmacist at University Hospital Southampton NHS Foundation Trust and pharmacist representative for the Society for Acute Medicine. Philip Newland-Jones is advanced specialist pharmacist for endocrine and diabetes at University Hospital Southampton NHS
Foundation Trust.


Citation: Clinical Pharmacist URI: 11108156

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