Hyponatraemia

Introduction

Hyponatraemia is defined as a serum sodium below 135 mmol/L and is the commonest electrolyte disturbance in clinical practice, present in up to 30% of hospital inpatients. It is independently associated with increased mortality, longer admissions and, even when mild and chronic, with falls, fractures and cognitive impairment.¹

Severity is graded mild (130-134 mmol/L), moderate (125-129 mmol/L) and severe (below 125 mmol/L) - but as with potassium, symptoms and the rate of fall matter more than the absolute number. A sodium of 125 developing over hours is far more dangerous than 118 developing over weeks.

Classification and causes

Step 1 - measure the serum osmolality

Step 2 - assess volume status

Syndrome of inappropriate ADH secretion (SIADH)

SIADH is a diagnosis of exclusion and the commonest cause of euvolaemic hyponatraemia. ADH is secreted despite a low plasma osmolality, causing inappropriate water retention.

• Diagnostic criteria: hypotonic hyponatraemia (serum osmolality <275), inappropriately concentrated urine (urine osmolality >100 mOsm/kg), urinary sodium >30 mmol/L, clinical euvolaemia, and normal thyroid, adrenal and renal function with no recent diuretics
• Malignancy - classically small cell lung cancer; also pancreatic, prostate and lymphoma
• CNS disease - stroke, subarachnoid haemorrhage, meningitis, encephalitis, head injury, tumours
• Pulmonary disease - pneumonia, tuberculosis, lung abscess, and positive-pressure ventilation
• Drugs - SSRIs and other antidepressants, carbamazepine, antipsychotics, NSAIDs, opiates, chemotherapy (cyclophosphamide, vincristine), PPIs, MDMA
• Surgery and pain - postoperative ADH release is very common and compounded by hypotonic IV fluids
• Other - HIV, porphyria, and idiopathic (particularly in older people)

Clinical features

Symptoms result from water moving into brain cells down the osmotic gradient, causing cerebral oedema. Their severity depends far more on the rate of fall than on the absolute sodium, because the brain adapts to slowly developing hyponatraemia by extruding organic osmolytes - an adaptation that is also what makes rapid correction dangerous.

By severity

• Mild / chronic: often asymptomatic, or non-specific - nausea, headache, malaise, lethargy, poor concentration. Importantly, even 'asymptomatic' chronic hyponatraemia is associated with gait instability, falls, fractures and osteoporosis in older people, and with subtle cognitive impairment
• Moderate: confusion, disorientation, vomiting, muscle cramps, weakness, restlessness
• Severe: seizures, reduced GCS, coma, respiratory arrest, and features of raised intracranial pressure from cerebral oedema - this constitutes a medical emergency

Assessing the patient

• Volume status is the central clinical task - JVP, skin turgor, mucous membranes, postural blood pressure, capillary refill, oedema, ascites, and crucially the fluid balance chart and daily weights
• Duration - establish whether this is acute (<48 hours) or chronic (>48 hours), using previous results where available. This determines how fast correction may proceed
• Drug history - thiazides, SSRIs, carbamazepine, antipsychotics, PPIs, NSAIDs, desmopressin; drugs are among the commonest causes
• Fluid intake history - including recent IV fluids (especially hypotonic), excessive water or beer intake, and endurance exercise
• Look for the underlying cause - respiratory examination and smoking history (small cell lung cancer), neurological examination, signs of heart failure or chronic liver disease, and features of hypothyroidism or Addison's disease (pigmentation, postural hypotension)

Investigations

• Serum osmolality - the essential first step, to exclude pseudo- and hypertonic hyponatraemia
• Urine osmolality - <100 mOsm/kg indicates appropriately dilute urine and suggests primary polydipsia or low solute intake; >100 indicates ADH is acting, appropriately or otherwise
• Urinary sodium - <20 mmol/L suggests hypovolaemia with appropriate renal conservation, or an oedematous state (heart failure, cirrhosis); >30 mmol/L suggests renal salt loss, diuretics, adrenal insufficiency or SIADH
• U&Es, creatinine and eGFR
• Glucose - to correct for hyperglycaemia and exclude a hypertonic cause
• Thyroid function tests - hypothyroidism must be excluded before diagnosing SIADH
• 9 am cortisol, and a short Synacthen test if indicated - adrenal insufficiency must be excluded before diagnosing SIADH; it is readily treatable and easily missed
• Lipid profile and total protein / paraproteins - if pseudohyponatraemia is suspected
• Liver function tests and albumin - cirrhosis
• Chest X-ray - essential if SIADH is diagnosed, looking for small cell lung cancer, pneumonia or tuberculosis; consider CT chest if suspicion is high
• CT head - if there are neurological signs or a CNS cause is suspected
• Daily weights and accurate fluid balance - often more informative than any single blood test

Management

Severe symptomatic hyponatraemia - a medical emergency

1. Indications: seizures, reduced consciousness, coma, or severe vomiting attributable to hyponatraemia - regardless of the absolute level
2. Give hypertonic 3% sodium chloride: typically 150 mL over 20 minutes, repeated up to two or three times, with sodium checked after each bolus
3. The target is symptom relief, not normalisation - aim to raise sodium by 4-6 mmol/L, which is usually enough to stop seizures and reverse cerebral oedema
4. Manage in a high-dependency or critical care setting with close monitoring, and involve senior, critical care and nephrology input early
5. Once symptoms resolve, stop the hypertonic saline and revert to treating the underlying cause within the 24-hour correction limit
6. Protect the airway, treat seizures, and correct coexisting hypokalaemia (which itself raises sodium as it is corrected, contributing to over-rapid rise)

Treatment by category

Complications

Of the hyponatraemia itself

• Cerebral oedema, seizures, coma and death - particularly with acute severe hyponatraemia
• Brainstem herniation and respiratory arrest in extreme cases
• Falls, gait instability and fractures - even mild chronic hyponatraemia impairs balance and attention, and is associated with osteoporosis
• Cognitive impairment and delirium
• Prolonged hospital stay and increased mortality - hyponatraemia is an independent marker of poor outcome across many conditions

Of over-rapid correction - osmotic demyelination syndrome

• Central pontine myelinolysis and extrapontine myelinolysis - demyelination caused by rapid osmotic shift out of adapted brain cells
• Classically biphasic: the patient initially improves as sodium rises, then deteriorates 2 to 6 days later
• Clinical features: dysarthria, dysphagia, spastic quadriparesis, pseudobulbar palsy, behavioural change, and in the worst cases the 'locked-in' syndrome
• MRI changes lag behind the clinical picture by days - a normal early scan does not exclude the diagnosis
• Often irreversible, though partial or occasionally substantial recovery does occur with supportive care and rehabilitation
• Risk factors: chronic hyponatraemia, sodium below 105 mmol/L, alcohol dependence, malnutrition, liver disease and transplantation, hypokalaemia, and advanced age
• Entirely preventable by respecting correction limits - which is why they are worth memorising

Red flags

Prognosis

Prognosis is determined largely by the underlying cause rather than by the sodium concentration itself. Hyponatraemia from a thiazide, an SSRI or a self-limiting episode of vomiting resolves completely once the cause is removed, with no lasting consequence. By contrast, hyponatraemia complicating advanced heart failure, cirrhosis or malignancy is a well-established marker of disease severity and an independent predictor of mortality - the low sodium is a signal of how unwell the patient is, and correcting the number without addressing the disease achieves little.

Even mild chronic hyponatraemia is not benign, which is a change in thinking worth appreciating. Long regarded as an incidental finding to be tolerated, it is now recognised to cause subtle cognitive impairment, unsteadiness, falls, fractures and osteoporosis, particularly in older people. There is therefore a reasonable argument for investigating and treating persistent mild hyponatraemia rather than simply noting it.

The outcome of treatment depends almost entirely on the rate of correction. Appropriately managed hyponatraemia, even when severe, generally resolves without neurological sequelae, and hypertonic saline given for seizures or coma is highly effective. Osmotic demyelination syndrome is the feared exception: it is frequently irreversible, can leave patients with devastating deficits including a locked-in state, and is almost entirely iatrogenic and preventable. Some recovery is possible with supportive care and rehabilitation, but the prognosis is poor once established. The practical conclusion is a slightly counterintuitive one that examiners like to test: in chronic hyponatraemia, the danger lies less in the low sodium than in correcting it too enthusiastically - the aim is to relieve symptoms and then to proceed slowly, deliberately and with frequent monitoring.