How to manage adults with hyponatraemia

Low serum sodium levels are commonly encountered in hospital inpatients. What should be considered to manage them appropriately?

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In short

Hyponatraemia is associated with significant mortality and morbidity and is the most common electrolyte abnormality in hospital inpatients. Appropriate treatment can only be instituted after an accurate assessment of patients’ overall volume status.

Although serious neurological symptoms are observed with acute hyponatraemia, controlled correction is required to avoid rapid correction, which is itself associated with longterm neurological damage

Hyponatraemia, 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

Box 1: Severity of hyponatraemia4

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

Diagnosis

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.

Box 2: Drug causes

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.

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

Testing urinary sodium can help ascertain whether a patient’s sodium loss is renal or extra-renal

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.

Box 3: Treatment of hyponatraemia caused by SIADH

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 
  • 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.

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
  • 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

References

  1. Smith MD, McKenna K, Thompson CJ. Hyponatraemia. Clinical Endocrinology 2000;52:667–78.
  2. Schrier RW, Bansal S. Diagnosis and management of hyponatremia in acute illness. Current Opinion in Critical Care. 2008;14:627–34.
  3. Adrogue HJ, Madias NE. Hyponatraemia. New England Journal of Medicine. 2000;342:1581–9.
  4. Chirag V, Warren H, Benjamin F. Management of hyponatremia: Providing treatment and avoiding harm. Cleveland Clinic Journal of Medicine 2010;77:715–26.
  5. Freda BJ, Davidson MB, Hall PM. Evaluation of hyponatremia: a little physiology goes a long way. Cleveland Clinic Journal of Medicine 2004;71:639–50.
  6. Liamis G, Haralampos M, Elisat M. A review of druginduced hyponatraemia: American Journal of Kidney Diseases 2008;52:144–53.
  7. Verbalis JG, Goldsmith SR, Greenberg A, et al. Hyponatraemia treatment guidelines 2007: expert panel recommendations. American Journal of Medicine 2007;120(suppl 1):S1–S21.

NOTE
Clinical Pharmacist PRACTICE TOOLS do not constitute formal practice guidance. Articles in the series have been commissioned from independent authors who have summarised useful clinical skills.

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Citation
Clinical Pharmacist, CP, 2012;()::DOI:10.1211/PJ.2021.1.86479