Hyponatraemia

Hyponatraemia is a serum sodium concentration under 135 mmol/L. It is the commonest electrolyte disorder in hospital patients and reflects an excess of water relative to sodium. Harm comes from two sources: cerebral oedema when the sodium falls quickly, and osmotic demyelination when chronic hyponatraemia is corrected too fast. Management therefore turns on symptoms, duration and the rate of correction rather than on the number alone.

Clinical relevance. Hyponatraemia is present in up to 30% of hospital patients and is associated with falls, fractures, gait disturbance, longer stay and higher mortality. Acute symptomatic hyponatraemia is a neurological emergency.

Physiology. Sodium concentration is set by water balance, controlled by antidiuretic hormone (ADH) released in response to raised osmolality, hypovolaemia, nausea, pain, drugs and stress. The brain adapts to hypo-osmolality over 24 to 48 hours by losing intracellular solutes, which protects against swelling but makes rapid correction dangerous.

Classification by severity (laboratory).

• Mild: 130 to 134 mmol/L.
• Moderate: 125 to 129 mmol/L.
• Profound: under 125 mmol/L.

Classification by duration. Acute when documented to have developed in under 48 hours (marathon runners, postoperative patients, MDMA use, psychogenic polydipsia, bowel preparation, transurethral resection). Chronic when present for 48 hours or more, or when the duration is unknown, which is assumed to be the case unless proved otherwise.

Classification by symptoms.

• Mild symptoms: nausea without vomiting, headache, poor concentration, unsteady gait.
• Moderately severe: nausea with vomiting, confusion, headache.
• Severe: vomiting, seizures, reduced consciousness (Glasgow Coma Scale of 8 or less), cardiorespiratory distress, coma.

Classification by tonicity and volume status.

• Hypertonic hyponatraemia: raised osmolality from hyperglycaemia, mannitol, or contrast. Sodium falls about 2.4 mmol/L for each 5.6 mmol/L rise in glucose over normal.
• Isotonic (pseudo) hyponatraemia: artefact from severe hyperlipidaemia or paraproteinaemia with indirect ion selective electrodes.
• Hypotonic hyponatraemia, true hyponatraemia: hypovolaemic (sodium and water loss, with sodium loss greater), euvolaemic (water excess with normal total sodium, including the syndrome of inappropriate ADH secretion), and hypervolaemic (heart failure, cirrhosis, nephrotic syndrome, kidney failure).

Key distinctions. The urine sodium and osmolality, together with a careful volume assessment, separate renal from extrarenal loss and SIADH from low solute intake. Hyponatraemia with a serum osmolality over 295 mOsm/kg or with a normal osmolality is not treated with sodium.

History.

• Onset and speed: recent surgery, marathon or endurance exercise, ecstasy use, large volumes of fluid, bowel preparation, hospital admission with hypotonic infusions.
• Symptoms: nausea, vomiting, headache, lethargy, confusion, cramps, falls, seizures, shortness of breath.
• Losses: vomiting, diarrhoea, burns, sweating, polyuria, adrenal or thyroid symptoms.
• Intake: water intake, alcohol (beer), tea and toast diet, low protein diet, psychiatric polydipsia.
• Drugs: thiazide diuretics, indapamide, loop diuretics, SSRIs, SNRIs, tricyclic antidepressants, carbamazepine, oxcarbazepine, antipsychotics, desmopressin, oxytocin, cyclophosphamide, vincristine, opioids, proton pump inhibitors, NSAIDs, trimethoprim, MDMA, amiodarone.
• Medical history: heart failure, cirrhosis, kidney disease, lung disease (pneumonia, tuberculosis, small cell cancer), brain disease (stroke, subarachnoid haemorrhage, meningitis, head injury), HIV, cancer, adrenal or thyroid disease.

Examination.

• Vital signs including postural blood pressure, heart rate, temperature and weight.
• Volume status: mucous membranes, skin turgor, jugular venous pressure, oedema, ascites, pleural effusion, capillary refill. Clinical assessment is imprecise, so urine tests and response to fluid help.
• Neurological: Glasgow Coma Scale, orientation, gait, asterixis, reflexes, seizures, papilloedema.
• Signs of hypothyroidism, adrenal insufficiency (pigmentation, hypotension), cirrhosis, heart failure, and malignancy.

Red flags.

• Seizures, reduced consciousness, or Glasgow Coma Scale falling (cerebral oedema).
• Vomiting with headache, or respiratory distress with crackles (neurogenic pulmonary oedema).
• Acute onset (under 48 hours) with any neurological symptom, especially in premenopausal women, children, neurosurgical or postoperative patients, and after marathon running or MDMA use.
• Serum sodium under 120 mmol/L, or a fall of over 10 mmol/L in 24 hours.
• Subarachnoid haemorrhage, head injury or brain tumour.
• Risk factors for osmotic demyelination: sodium of 105 mmol/L or less, hypokalaemia, alcohol use disorder, malnutrition, advanced liver disease, and hypovolaemia with brisk water diuresis after replacement.
• Adrenal crisis (hypotension, hyperkalaemia, hypoglycaemia).
• Hypovolaemic shock.

Special groups. Premenopausal women and children are at higher risk of cerebral oedema in acute hyponatraemia. Older adults are at risk from thiazides and SSRIs. Newborns and infants are at risk from hypotonic fluids. Pregnancy: oxytocin infusion with large volumes of fluid. Postoperative patients and those with pain, nausea or opioids have non-osmotic ADH release.

Hypertonic and isotonic hyponatraemia. Hyperglycaemia, mannitol, glycine (irrigation), radiocontrast, severe hypertriglyceridaemia, paraproteinaemia (myeloma), and intravenous immunoglobulin.

Hypovolaemic hypotonic hyponatraemia.

• Renal loss (urine sodium over 30 mmol/L): thiazide diuretics, loop diuretics, mineralocorticoid deficiency (Addison disease), cerebral salt wasting, salt losing nephropathy, osmotic diuresis (glucose, urea, mannitol), bicarbonaturia, ketonuria.
• Extrarenal loss (urine sodium under 30 mmol/L): vomiting, diarrhoea, burns, sweating, pancreatitis, bowel obstruction, third space loss, haemorrhage.

Euvolaemic hypotonic hyponatraemia.

• Syndrome of inappropriate ADH secretion (SIADH): malignancy (small cell lung cancer, head and neck, pancreas, lymphoma), pulmonary disease (pneumonia, tuberculosis, asthma, positive pressure ventilation), central nervous system disease (stroke, haemorrhage, trauma, infection, tumour, Guillain-Barre syndrome), drugs, HIV, pain, nausea, and postoperative state.
• Endocrine: hypothyroidism, secondary adrenal insufficiency (glucocorticoid deficiency).
• Low solute intake: tea and toast diet, beer potomania, malnutrition.
• Primary polydipsia (psychogenic, exercise associated, drug related).
• Exercise associated hyponatraemia.

Hypervolaemic hypotonic hyponatraemia. Heart failure, cirrhosis with ascites, nephrotic syndrome, advanced kidney disease, and capillary leak states.

Other. Reset osmostat, pregnancy (mild), and sampling from a drip arm.

Step 1. Assess severity and symptoms. If the patient has severe symptoms, start treatment at once while the tests are running.

Step 2. Confirm true hypotonic hyponatraemia: serum osmolality (hypotonic if under 275 mOsm/kg), glucose, lipids and total protein. Repeat the sodium from a venous or blood gas sample if it is unexpected.

Step 3. Core tests: urea, creatinine, potassium, bicarbonate, calcium, urate, liver tests, thyroid function, morning cortisol (or short synacthen test), triglycerides, and urinalysis. Urine osmolality, urine sodium and urine potassium on a spot sample before fluid or diuretic treatment.

Step 4. Interpret urine tests together with volume status.

• Urine osmolality under 100 mOsm/kg: primary polydipsia, low solute intake (beer potomania), or reset osmostat.
• Urine osmolality over 100 mOsm/kg with urine sodium under 30 mmol/L: extrarenal loss, heart failure, cirrhosis, nephrotic syndrome (low effective circulating volume).
• Urine osmolality over 100 mOsm/kg with urine sodium over 30 mmol/L: renal loss (diuretics, adrenal insufficiency, cerebral salt wasting, kidney disease) or SIADH, separated by volume status and serum urate (under 240 micromol/L supports SIADH, as does fractional urate excretion over 12%).
• The ratio of urine sodium plus potassium to serum sodium over 1 predicts poor response to fluid restriction.

Step 5. Diagnostic features of SIADH: hypotonic hyponatraemia, urine osmolality over 100 mOsm/kg, urine sodium over 30 mmol/L on a normal salt intake, clinical euvolaemia, no recent diuretics, and normal adrenal, thyroid and kidney function. Response to isotonic saline 0.9% 1 litre distinguishes hypovolaemia (sodium rises) from SIADH (sodium falls or is unchanged).

Step 6. Search for the cause of SIADH: chest radiograph and CT of chest, abdomen and pelvis for malignancy, CT or MRI of the head, drug review, and HIV testing.

Interpretation. Hypovolaemic hyponatraemia improves with isotonic saline. Euvolaemic hyponatraemia with a urine osmolality over 100 mOsm/kg is SIADH once adrenal and thyroid disease are excluded.

Limitations. Volume assessment is inaccurate. Urine tests are unreliable after diuretics. Pseudohyponatraemia depends on the analyser (direct ion selective electrodes avoid it).

Principles. Treat on the basis of symptoms and duration, not the number alone. In chronic hyponatraemia, correct slowly: the sodium should rise by no more than 10 mmol/L in the first 24 hours and 8 mmol/L in each 24 hours after. The limit is no more than 8 mmol/L in 24 hours in patients at high risk of osmotic demyelination (sodium of 105 mmol/L or less, hypokalaemia, alcohol use disorder, malnutrition, advanced liver disease).

Stop hypotonic fluids and the causative drug, and check sodium before and after every intervention.

Severe symptoms (seizures, coma, vomiting, cardiorespiratory distress): emergency treatment.

• Hypertonic saline 3% (513 mmol/L) 150 mL IV over 20 minutes (or 2 mL/kg if weight is under 50 kg), through a large peripheral vein or central line, in a monitored setting. Check the serum sodium 20 minutes after the infusion.
• Repeat the 150 mL bolus up to 2 more times at 20 minute intervals if symptoms persist. Continue until symptoms improve or the sodium has risen by 5 mmol/L (aim for a rise of 5 to 6 mmol/L in the first hours, enough to reverse cerebral oedema). Stop hypertonic saline as soon as symptoms improve.
• Seizures: treat with lorazepam 4 mg IV (0.1 mg/kg, maximum 4 mg, repeated once after 10 minutes) while sodium is corrected. Intubate and ventilate for coma with respiratory failure.
• After the rise of 5 mmol/L, stop 3% saline, keep the line open with isotonic saline 0.9% 20 mL/hour, treat the cause, and set a limit of 10 mmol/L in the first 24 hours (8 mmol/L if at high risk).
• Monitoring: sodium every 20 minutes during boluses, then every 2 hours for 6 hours, then every 4 to 6 hours for 48 hours. Check urine output hourly.

Moderately severe symptoms (nausea with vomiting, confusion, headache). Hypertonic saline 3% 150 mL IV over 20 minutes once, then recheck the sodium, aiming for a rise of 5 mmol/L in 24 hours. Alternatively infuse 3% saline 0.5 to 2 mL/kg/hour with sodium checks every 4 hours. Urgent causes of symptoms (intracranial pathology) are considered.

Mild symptoms or no symptoms. Stop the cause, treat the underlying condition, and restrict or give fluid by type. No hypertonic saline is needed. Avoid correction faster than 10 mmol/L in 24 hours.

Hypovolaemic hyponatraemia.

• Isotonic saline 0.9% 500 mL to 1 litre IV over 1 hour, then 1 litre over 4 to 8 hours, adjusted to volume status and sodium response. Stop thiazides and loop diuretics, and treat diarrhoea, vomiting and bleeding.
• Warning: once volume is restored, ADH switches off and a brisk water diuresis can raise the sodium by 2 mmol/L or more each hour. Measure urine output hourly and sodium every 2 to 4 hours.
• If urine output is over 100 mL/hour and the sodium is rising too fast, give desmopressin 2 micrograms IV or subcutaneously every 8 hours.
• Replace urine losses with 5% glucose (3 mL/kg over 1 hour, repeated as needed) to relower the sodium, with hourly sodium checks.
• Replace potassium (it raises the sodium): each 1 mmol of potassium has the same effect as 1 mmol of sodium.
• Adrenal insufficiency: hydrocortisone 100 mg IV, then 50 mg IV every 6 hours (or 200 mg over 24 hours by infusion), with isotonic saline. Follow with oral hydrocortisone 15 to 25 mg daily in divided doses and fludrocortisone 50 to 100 micrograms daily when mineralocorticoid deficiency is confirmed.

Euvolaemic hyponatraemia (SIADH and related states).

• Fluid restriction 500 to 1000 mL daily (include all drinks and the water in food), aiming for a deficit between intake and urine output plus insensible loss. Strict restriction (500 mL) is needed when the urine sodium plus potassium over serum sodium ratio is over 1. Expect a rise of 1 to 2 mmol/L daily. Stop SIADH inducing drugs.
• When restriction fails or is unsuitable: urea 15 to 30 g orally once daily (dissolved in 50 to 100 mL water or juice; monitor sodium, urea and creatinine; avoid in kidney failure and hepatic encephalopathy).
• Alternatively, sodium chloride tablets 1 g (17 mmol) orally three times daily with furosemide 20 mg orally once daily (monitor potassium, volume status, blood pressure and creatinine; avoid in heart failure with oedema).
• Alternatively, empagliflozin 10 to 25 mg orally once daily (monitor volume status, glucose and genital infection; avoid in type 1 diabetes and recurrent genital infections).
• Tolvaptan 15 mg orally once daily in hospital only, increased after 24 hours to 30 mg and then 60 mg (maximum 60 mg daily).
• Check sodium at 6 and 24 hours after each dose, with no fluid restriction in the first 24 hours.
• Avoid in liver disease (risk of liver injury), hypovolaemia, anuria, and with strong CYP3A inhibitors. Limit to 30 days. Stop if the rise is over 8 to 10 mmol/L in 24 hours. Used only when other measures have failed in patients at lower risk of overcorrection.
• Demeclocycline 600 to 1200 mg orally daily in two divided doses is a last option (nephrotoxic; monitor creatinine; photosensitivity).
• Treat the cause: hypothyroidism with levothyroxine (25 to 50 micrograms daily, increased every 4 to 6 weeks), stop SSRIs, carbamazepine or other causative drugs, and treat cancer, infection or pain.
• Low solute intake (tea and toast, beer potomania): the sodium can rise rapidly once solute and food are given; give a normal diet with protein and salt, and do not give large volumes of saline. These patients are at high risk of overcorrection, so monitor urine output and sodium every 2 to 4 hours.
• Primary polydipsia: restrict water intake to about 1 to 1.5 litres daily with psychiatric support.
• Exercise associated hyponatraemia with encephalopathy: 3% saline 100 mL IV bolus over 10 minutes, repeated up to 3 times at 10 minute intervals; never give hypotonic fluids to athletes with suspected hyponatraemia.

Hypervolaemic hyponatraemia (heart failure, cirrhosis, nephrotic syndrome, kidney failure).

• Fluid restriction 1 litre daily (500 to 800 mL if the sodium is under 125 mmol/L), sodium restriction (under 2 g daily), and treatment of the cause.
• Furosemide 40 to 80 mg IV or orally once or twice daily, increased to the response (monitor sodium, potassium, creatinine and weight daily).
• Heart failure: optimise treatment and consider adding acetazolamide 250 to 500 mg once daily if bicarbonate is raised. In cirrhosis, albumin 25% 1 g/kg IV (maximum 100 g) once daily for 2 days in selected patients. Tolvaptan should be avoided in cirrhosis. Hypertonic saline only for severe symptoms.

Hypertonic hyponatraemia. Treat hyperglycaemia with insulin and fluids, and expect the sodium to rise as glucose falls.

Prevention of osmotic demyelination. Avoid overcorrection, monitor sodium every 2 to 4 hours, and if the limit is exceeded relower the sodium immediately. Give desmopressin 2 micrograms IV or subcutaneously every 6 to 8 hours (for up to 24 to 48 hours) and 5% glucose 3 mL/kg/hour IV, measuring sodium hourly. Osmotic demyelination presents 2 to 6 days after correction with dysarthria, dysphagia, spastic quadriparesis, confusion, or locked in syndrome, and MRI is the best test.

Monitoring. Sodium every 20 minutes during boluses and every 2 to 6 hours afterwards, urine output and osmolality, fluid balance, daily weight, potassium and glucose, and neurological observations hourly in severe cases.

Referral and escalation. Critical care or high dependency for severe symptoms and 3% saline infusions. Endocrinology for adrenal, pituitary and thyroid disease. Nephrology for kidney disease and refractory cases. Oncology when SIADH reveals cancer. Neurology or neurosurgery for CNS causes. Pharmacy for drug review.

Admission criteria. Sodium under 125 mmol/L, any neurological symptoms, acute onset, rapidly falling sodium, risk factors for overcorrection, hypovolaemic shock, or an unwell patient. Mild asymptomatic hyponatraemia (130 to 134 mmol/L) can be treated in the community.

Discharge and safety netting. Discharge when sodium is rising or stable, over 125 mmol/L, symptoms have resolved, and the cause is being treated, with a sodium check in 2 to 7 days. Written advice on fluid restriction, drug changes, and salt intake. Patients return for headache, confusion, vomiting, drowsiness, falls, or seizures.