Hypernatraemia

Hypernatraemia is a serum sodium concentration over 145 mmol/L. It reflects a deficit of water relative to sodium, and therefore hyperosmolality, which draws water out of brain cells. It is nearly always the result of loss of water in a patient who cannot drink enough (infants, older adults, sedated or critically ill patients), and sometimes of sodium gain. The principles are to restore volume if the patient is shocked, replace the free water deficit slowly, and treat the cause.

Clinical relevance. Hypernatraemia occurs in up to 10% of hospital patients and is common in intensive care. Mortality rises with the level (over 40% with sodium over 160 mmol/L) because of the underlying illness and the brain injury.

Physiology. Thirst and ADH protect against hypernatraemia. A rise in osmolality of 1 to 2% stimulates thirst and ADH, so sustained hypernatraemia requires impaired thirst, no access to water, or ongoing water loss. Brain cells shrink acutely, and later generate osmolytes (idiogenic osmoles) over 24 to 48 hours, so rapid correction of chronic hypernatraemia causes cerebral oedema.

Classification by severity.

• Mild: 146 to 150 mmol/L.
• Moderate: 151 to 160 mmol/L.
• Severe: over 160 mmol/L.

Classification by duration. Acute (under 48 hours) after sodium loading, accidental salt ingestion, or a water drinking deficit in the very young. Chronic (48 hours or more, or unknown), where correction must be slow.

Classification by volume status.

• Hypovolaemic: loss of water and sodium, with water loss greater (gastrointestinal loss, sweating, burns, osmotic diuresis, diuretics, kidney disease).
• Euvolaemic: water loss with normal total sodium (diabetes insipidus, insensible loss, hypodipsia).
• Hypervolaemic: sodium gain (hypertonic saline, sodium bicarbonate, hypertonic feeds, salt ingestion, primary hyperaldosteronism, Cushing syndrome).

Key distinctions. A urine osmolality over 600 mOsm/kg with hypernatraemia suggests extrarenal water loss with intact ADH action. A dilute urine (under 300 mOsm/kg) with a high sodium indicates diabetes insipidus or osmotic diuresis.

History.

• Thirst, polyuria, nocturia, polydipsia, drinking ability and access to water, fluid intake, diet and feeds (enteral protein loads), vomiting, diarrhoea, fever, burns, and sweating.
• Drugs: lithium, demeclocycline, amphotericin B, foscarnet, cidofovir, ifosfamide, osmotic agents (mannitol), loop diuretics, laxatives (lactulose), hypertonic saline, sodium bicarbonate, and corticosteroids.
• Head injury, neurosurgery, pituitary disease, brain tumour, subarachnoid haemorrhage, hypercalcaemia, hypokalaemia, sickle cell disease, Sjogren syndrome, and previous kidney disease.
• Mental state, dementia, immobility and dependence on others for drinks.
• In infants: feeding difficulty, incorrectly prepared formula, diarrhoea, and fever.

Examination.

• Weight change, postural blood pressure, heart rate, capillary refill, skin turgor, mucous membranes, urine output.
• Neurological: irritability, lethargy, tremor, hyperreflexia, muscle twitching, spasticity, ataxia, seizures, focal signs, coma.
• Signs of kidney disease, hyperglycaemia, adrenal disease, and fever.
• In infants: fontanelle depression, doughy skin, high pitched cry.

Red flags.

• Sodium over 160 mmol/L, or a rapid rise (over 1 mmol/L each hour).
• Reduced consciousness, seizures, focal neurological signs (intracranial haemorrhage, subdural haematoma, venous sinus thrombosis).
• Hypovolaemic shock, oliguria, or kidney injury.
• Polyuria over 3 litres daily or urine output over 200 mL/hour (diabetes insipidus).
• Severe hyperglycaemia (hyperosmolar state).
• Infants with seizures or lethargy.
• Acute sodium loading (salt poisoning, hypertonic infusions, sea water ingestion).

Special groups. Infants and older adults are at highest risk. Pregnancy: gestational diabetes insipidus (vasopressinase). Patients on lithium have nephrogenic diabetes insipidus. Critically ill patients lose water through fever and ventilation and receive sodium in drugs and fluids.

Water loss without sodium (euvolaemic or mildly hypovolaemic).

• Central diabetes insipidus: head injury, neurosurgery, pituitary tumour, craniopharyngioma, infiltration (sarcoidosis, histiocytosis), hypoxic brain injury, brain death, autoimmune, genetic, idiopathic.
• Nephrogenic diabetes insipidus: lithium, hypercalcaemia, hypokalaemia, demeclocycline, amphotericin B, foscarnet, ifosfamide, sickle cell disease, Sjogren syndrome, amyloidosis, obstructive uropathy, chronic kidney disease, X linked genetic forms, and pregnancy related.
• Insensible losses: fever, burns, hyperventilation, ventilated patients with dry gas.
• Hypodipsia and adipsia: central nervous system lesions, older age, dementia.
• Primary polydipsia with hyperosmolality is rare.

Hypotonic fluid loss (hypovolaemic). Gastrointestinal loss (vomiting, diarrhoea, osmotic diarrhoea, nasogastric drainage), skin loss (sweating, burns), renal loss (osmotic diuresis in hyperglycaemia, mannitol, glycosuria, urea diuresis, loop diuretics, post obstructive diuresis, polyuric phase of acute tubular necrosis).

Sodium gain (hypervolaemic). Intravenous hypertonic saline, sodium bicarbonate, sodium containing antibiotics (piperacillin with tazobactam, flucloxacillin), hypertonic feeds, seawater ingestion, salt tablets or poisoning, infant formula errors, hypertonic dialysis, primary hyperaldosteronism, Cushing syndrome, and hypertonic enemas.

Other. Reset osmostat, laboratory error.

Step 1. Assess volume status and symptoms, take a drug and fluid history, and review recorded intake, output and weights.

Step 2. Laboratory tests: sodium, potassium, calcium, glucose, urea, creatinine, bicarbonate, serum osmolality, urine osmolality, urine sodium and potassium, 24 hour urine volume, and urinalysis. Serum osmolality is usually over 295 mOsm/kg.

Step 3. Interpret the urine.

• Urine osmolality over 600 mOsm/kg with a low urine volume: extrarenal water loss or inadequate intake, with normal ADH and renal response.
• Urine osmolality under 300 mOsm/kg with urine volume over 3 litres daily and a high serum sodium: diabetes insipidus (central or nephrogenic).
• Urine osmolality 300 to 600 mOsm/kg with polyuria: osmotic diuresis (check glucose, urea, mannitol) or partial diabetes insipidus.
• Urine sodium over 100 mmol/L with high serum sodium and volume expansion: sodium gain.

Step 4. Confirm diabetes insipidus.

• Desmopressin test (with fluid access under supervision): measure urine osmolality before and 30 to 60 minutes after desmopressin 2 micrograms IV or subcutaneously (or 10 micrograms intranasally). A rise of over 50% indicates central diabetes insipidus; a rise under 10% indicates nephrogenic diabetes insipidus.
• Water deprivation test (in patients with normal sodium) with urine osmolality, serum osmolality and weight at intervals, then desmopressin, under supervision. A plasma copeptin measure (baseline, or after hypertonic saline stimulation) distinguishes central and nephrogenic types and primary polydipsia in specialist units.
• MRI of the pituitary and hypothalamus for central diabetes insipidus (loss of the posterior pituitary bright spot), and anterior pituitary hormone tests.
• Genetic testing for nephrogenic forms in children.

Step 5. Calculate the water deficit.

• Total body water (litres) equals weight (kg) multiplied by 0.6 for young men, 0.5 for young women and older men, and 0.45 for older women.
• Water deficit (litres) equals total body water multiplied by (serum sodium divided by 140, minus 1). For a 70 kg man with sodium of 160 mmol/L: 42 litres multiplied by (160 divided by 140 minus 1) gives a deficit of about 6 litres.
• Add the ongoing losses (urine, gastrointestinal, insensible loss of about 500 to 800 mL daily, more with fever).

Interpretation. A high sodium with a concentrated urine means appropriate renal conservation of water and a fluid deficit from lack of access or extrarenal loss. A dilute urine in a hypernatraemic patient is always abnormal.

Limitations. The formulae ignore ongoing loss and change in total body water, and provide only an estimate; sodium must be measured frequently. A water deprivation test is unsafe in hypernatraemia.

Principles. Restore circulating volume first if there is shock, then replace the free water deficit at a rate that lowers the sodium slowly. In chronic hypernatraemia the maximum correction is 10 mmol/L in 24 hours (about 0.4 mmol/L/hour), to avoid cerebral oedema, seizures and death. Acute hypernatraemia (under 48 hours) can be corrected faster, up to 1 mmol/L/hour. Treat the cause and stop sodium loading.

Hypovolaemic shock or marked hypovolaemia. Isotonic saline 0.9% 500 mL IV boluses over 15 to 30 minutes until blood pressure and perfusion are restored (isotonic saline is hypotonic relative to the patient's serum, so it still lowers the sodium slightly). Then change to hypotonic fluid.

Replacement of free water.

• Oral or enteral water is preferred: give water by mouth or nasogastric tube, at a rate to meet the deficit over 48 to 72 hours.
• Intravenous: 5% glucose, or 0.45% saline (half-normal saline) when there is also sodium depletion, at 3 to 6 mL/kg/hour initially (about 200 to 400 mL/hour in adults), adjusted to a sodium fall of 0.3 to 0.5 mmol/L/hour. This is higher than maintenance because the deficit and the ongoing loss both need replacement.
• Calculation: infusion rate (mL/hour) equals the water deficit (mL) divided by the number of hours planned (48 to 72 hours for chronic hypernatraemia), added to maintenance (1.5 mL/kg/hour or 30 to 35 mL/kg/day) and ongoing losses.
• Monitoring: sodium every 4 hours (every 2 hours if over 160 mmol/L or a rapid fall), glucose every 6 hours when 5% glucose is used (hyperglycaemia and osmotic diuresis occur with large glucose loads; give insulin if glucose is over 10 mmol/L), potassium, urine output hourly, and weight daily. Slow the infusion if the sodium falls too quickly. If neurological deterioration occurs during correction, suspect cerebral oedema, stop hypotonic fluid, give isotonic saline, and consider hypertonic saline 3% 100 to 150 mL.
• Children: use the same principle, aiming for a fall of under 0.5 mmol/L/hour, with weight based fluids and specialist advice.

Central diabetes insipidus.

• Desmopressin 1 to 2 micrograms IV or subcutaneously every 12 hours (acute), or 0.1 to 0.2 mg orally two to three times daily (maximum 1.2 mg daily), or 10 to 40 micrograms intranasally in 1 to 3 divided doses, or sublingual 60 to 240 micrograms two to three times daily. The dose is titrated to a urine output of 1 to 2 mL/kg/hour and a nocturnal gap of 4 to 6 hours.
• Cautions: hyponatraemia and fluid overload if fluid intake is unrestricted. Allow a period of polyuria between doses once a week. Monitor sodium at 3 to 7 days after starting and after each dose change, then every 3 to 6 months. After head injury or surgery, diabetes insipidus can be transient or biphasic or triphasic, so use fixed small doses and monitor.
• Replace water by mouth in an awake patient (thirst is intact).

Nephrogenic diabetes insipidus.

• Stop or reduce the causative drug (lithium, with psychiatric advice and amiloride 5 to 10 mg orally once daily to reduce lithium uptake in the collecting duct, monitoring potassium and kidney function), correct hypercalcaemia and hypokalaemia, and relieve obstruction.
• Reduce solute load: sodium intake under 2 g daily and protein 1 g/kg daily.
• Hydrochlorothiazide 25 mg orally once or twice daily (maximum 50 mg daily; monitor sodium, potassium, calcium and lithium levels, which rise with thiazides; avoid in lithium treated patients without lithium monitoring) or indomethacin 25 mg orally two to three times daily (maximum 150 mg daily; monitor kidney function, gastrointestinal bleeding and potassium).
• Free water access and adequate intake.

Hypervolaemic hypernatraemia (sodium gain). Stop sodium containing infusions and drugs. Furosemide 20 to 40 mg IV (higher in kidney impairment; monitor urine output, potassium, magnesium and sodium), with replacement of the urine water loss by 5% glucose. Dialysis (haemodialysis or peritoneal dialysis with a lower sodium dialysate) in kidney failure or very high sodium (over 170 mmol/L). Treat hyperaldosteronism.

Osmotic diuresis. Treat hyperglycaemia (insulin 0.05 to 0.1 units/kg/hour IV in hyperosmolar states), stop mannitol, replace free water and electrolytes.

Hypovolaemic hypernatraemia from gastrointestinal or skin loss. Replace the volume, then the water deficit with 5% glucose or 0.45% saline, give potassium (20 to 40 mmol/L in the infusion), treat vomiting, diarrhoea and fever, and rehydrate burns with the fluid regimen for burns.

Seizures. Lorazepam 4 mg IV (0.1 mg/kg, maximum 4 mg, repeated once after 10 minutes). Avoid hypotonic fluid boluses, which can worsen cerebral oedema.

Monitoring. Sodium every 2 to 4 hours, osmolality and glucose every 6 hours, neurological observations hourly in severe cases, fluid balance, weight, and urine osmolality. CT of the head if there is deterioration (subdural haematoma, venous thrombosis, or cerebral oedema).

Referral and escalation. Critical care or high dependency for sodium over 160 mmol/L, neurological signs or shock. Endocrinology for diabetes insipidus and pituitary disease. Nephrology for kidney disease and dialysis. Paediatrics for infants. Geriatric services and dietetics for prevention.

Admission criteria. Sodium over 155 mmol/L, any neurological symptoms, shock, kidney injury, inability to take oral fluids, or a severe underlying cause. Mild hypernatraemia (146 to 150 mmol/L) in a patient who can drink may be managed at home with oral fluids and repeat testing.

Discharge and safety netting. Discharge when sodium is under 150 mmol/L and falling, the patient can drink adequately or is supported, and the cause is treated, with a check of sodium in 2 to 5 days. For diabetes insipidus, written advice on desmopressin and fluid intake. Patients return for thirst, polyuria, confusion, drowsiness, vomiting, fever or seizures. Prevention in older adults: scheduled drinks and care home review.