History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include: an inability to drink water/limited access to water; infancy; older age; renal concentrating defect; gastrointestinal disorders (e.g., severe vomiting or diarrhoea); insensible water losses (e.g., fever, exercise, heat exposure, burns); diabetes insipidus; use of specific drugs (e.g., lithium); large salt intake or administration; traumatic brain injury; or primary hypodipsia.

hospital stay

Hospital-acquired hypernatraemia is the most common form of hypernatraemia, and it is iatrogenic in some cases.[12]​​[13][14][15]

Hypernatraemia is more likely to occur in a hospital setting, and these patients are more likely to be hypervolaemic (particularly if they have been treated in the intensive care unit), have a history of being hypotensive, and have received large amounts of normal saline (0.9%).[6][7][8][11][42][44]

older age/nursing home resident

Older patients are particularly at risk of hypernatraemia due to various factors, including an inability to concentrate urine properly, lack of thirst (e.g., due to dementia), an inability to access water (e.g., due to altered mental status from illness, stroke, immobility), and/or increased insensible losses (e.g., fever and/or infection). Older patients living in nursing homes are most likely to develop hypovolaemic hypernatraemia due to inadequate free water intake, especially patients with dementia.[2][71]​ They may also have fever and/or infection.[2][12]​​[23][24][25][26]

central nervous system manifestations

If hypernatraemia is acute, the higher osmolality in the extracellular space causes water to move out of brain cells causing the brain to shrink. This shrinkage can lead to neurological consequences, including lethargy, weakness, and irritability.

Severe manifestations can include intracranial haemorrhage, seizures, stupor, coma, and death.[2][66]

diarrhoea or vomiting

Severe watery diarrhoea (e.g., Clostridium difficile infection, laxative ingestion) or prolonged vomiting may result in hypernatraemia due to water loss.

impaired thirst

Can occur in older patients, especially those with dementia.[2][71]

Adipsia or hypodipsia is a very rare cause of hypovolaemic hypernatraemia and can be seen in patients with normal mental status who lack a sense of thirst while hypernatraemic.[31][32][33]​​[76]

weight loss

May indicate hypovolaemia.

oliguria

May indicate hypovolaemia or renal dysfunction.

orthostatic hypotension

May indicate hypovolaemia.

decreased jugular venous pressure

May indicate hypovolaemia.

other signs of hypovolaemia

Other signs (e.g., tachycardia, dry mucous membranes) may also indicate hypovolaemia.

uncommon

polyuria, polydipsia, increased thirst

Severe symptoms suggest diabetes insipidus which is characterised by the output of a large volume of dilute urine.

Other diagnostic factors

uncommon

fever

May indicate the presence of an infection which can be associated with hypernatraemia due to insensible fluid loss.

Risk factors

strong

inability to drink water/limited access to water

Prevalent among ventilated patients in the intensive care unit.[1]​ Patients may be unable to drink water, even when awake.

Demented or delirious patients are also at risk.[2] These patients may not be able to drink water in response to thirst.

Neonates

Neonates may develop hypernatraemic dehydration due to inadequate fluid intake, usually related to poor lactation or insufficient maternal milk supply.[69] Neonatal hypernatraemic dehydration​ is associated with a free water deficit.[70] The neonate​ may present with non-specific features such as jaundice, high temperature, poor oral intake, lethargy and low urine output.[69] Correction of sodium levels in neonates should be undertaken​ cautiously to avoid adverse effects. There is no consensus as to method or rate of correction, though common recommendations are to correct sodium levels by no more that 0.5 mmol/L/hour, with gradual correction over 48 hours.[69][70]​​

infancy

Infants are at risk of hypernatraemia if they ingest a large volume of salt inadvertently, as they often do not have free access to water.

Central diabetes insipidus can be a congenital condition, usually due to a vasopressin (V2) mutation on the X chromosome.[54] Congenital nephrogenic diabetes insipidus is rare.

older age

Older patients are particularly at risk of hypernatraemia due to various factors, including an inability to concentrate urine properly, lack of thirst (e.g., due to dementia), an inability to access water (e.g., due to altered mental status from illness, stroke, immobility), and/or increased insensible losses (e.g., fever and/or infection). Older patients living in nursing homes are most likely to develop hypovolaemic hypernatraemia due to inadequate free water intake, especially patients with dementia.[2][71]

renal concentrating defect

Common causes include diuretic administration, osmotic diuresis, obstructive uropathy, and renal failure.[12]​​[41][54] In one study, 94% of patients with hypernatraemia had a renal concentrating defect.[47]​​

The large amounts of normal saline (0.9%) given to anuric or oliguric patients does not result in hypernatraemia. Rather, the rise in serum sodium concentration is dependent on the excretion of a large volume of urine (as renal function recovers) that does not contain much salt in the face of inadequate replenishment with oral water.[72] Most of these patients are hypervolaemic despite the high urinary-output state. Therefore, hypernatraemia is often associated with immediate negative water balance, but not with volume depletion.

gastrointestinal disorders

Severe watery diarrhoea (e.g., viral gastroenteritis) or prolonged vomiting can often result in hypernatraemia.

insensible water losses

Exercise, fever, heat exposure, and burns may lead to hypernatraemia due to free water losses.

diabetes insipidus

An uncommon cause of hypernatraemia. In one prospective cohort study which included 103 participants, <6% of hypernatraemic patients had diabetes insipidus.​[12]​​

use of specific drugs

Lithium, a mood stabiliser, is commonly associated with nephrogenic diabetes insipidus in adults, usually after chronic administration. This is possibly due to a significant down-regulation of the aquaporin 2 collecting duct (AQP2) gene.[52][54] Patients on chronic lithium therapy have a 50% chance of developing nephrogenic diabetes insipidus, which can sometimes persist even after lithium therapy is stopped.[55]

Other drugs reported to cause diabetes insipidus more rarely include: vasopressin receptor antagonists, demeclocycline, ethanol, foscarnet, temozolomide, dexmedetomidine, cisplatin, aminoglycosides, amphotericin B, penicillin derivatives, vitamin A or D excess, colchicine, vinblastine, and phenytoin.[2][53][56][59][60][61]

Loop diuretics cause an increase in free water excretion.

Intravenous mannitol can cause osmotic diuresis.

Hypernatraemia due to profuse diarrhoea has been reported in patients treated with activated charcoal/sorbitol for poisoning.[28][29]

Sodium polystyrene sulfonate/sorbitol has been associated with hypernatraemia when used to treat patients with hyperkalaemia.

Laxative or bowel cleansing agents can cause severe diarrhoea.

High-dose corticosteroids, e.g., used in the treatment of sepsis, increase the risk of hypernatraemia.[58]

Fosfomycin (when administered intravenously) has been associated with hypernatraemia, as has topiramate.[73][74]​​​​​​​​

large salt intake or administration

Common among patients with severe metabolic acidosis who have received multiple bolus doses of hypertonic sodium bicarbonate; however, large salt intake is the least common cause of hypernatraemia.[2]

Hypernatraemia has been associated with deliberate ingestion of household-strength bleach (sodium hypochlorite), inadvertent infusion with 5% saline (rather than 5% dextrose), sea water drowning (in survivors thereof), inappropriately high concentration of sodium bicarbonate or sodium chloride in dialysate for haemodialysis treatment, ingestion of bamboo salt (sea salt roasted in bamboo tubes), or massive intake of seasoning soy sauce or general excessive salt ingestion (usually in paediatric patients mistaking salt for sugar).[2]​​[34][35][36][37]​​​​[38][39]​​

traumatic brain injury

Patients with traumatic brain injury are often given hypertonic saline and/or mannitol (the latter causing osmotic diuresis), which can lead to hypernatraemia.

A history of traumatic brain injury or any other insult to the brain (e.g., vascular syndromes, infections, tumours, or aggressive surgery for craniopharyngioma, Rathke's cleft cyst, or other hypothalamic tumours) is often present in patients with central diabetes insipidus.[2]

primary hypodipsia

Patients with primary hypodipsia, which may be caused by a brain tumour, a congenital hypothalamic lesion, or granulomatous disease, are likely to be hypovolaemic and become hypernatraemic due to an impaired thirst mechanism.[31][32]

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