History and exam
Key diagnostic factors
common
hospital stay
Hospital-acquired hypernatremia is the most common form of hypernatremia, and it is iatrogenic in some cases.[12][13][14][15]
Hypernatremia is more likely to occur in a hospital setting, and these patients are more likely to be hypervolemic (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 hypernatremia 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 hypovolemic hypernatremia 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 hypernatremia 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 hemorrhage, seizures, stupor, coma, and death.[2][66]
diarrhea or vomiting
Severe watery diarrhea (e.g., Clostridium difficile infection, laxative ingestion) or prolonged vomiting may result in hypernatremia due to water loss.
impaired thirst
weight loss
May indicate hypovolemia.
oliguria
May indicate hypovolemia or renal dysfunction.
orthostatic hypotension
May indicate hypovolemia.
decreased jugular venous pressure
May indicate hypovolemia.
other signs of hypovolemia
Other signs (e.g., tachycardia, dry mucous membranes) may also indicate hypovolemia.
uncommon
polyuria, polydipsia, increased thirst
Severe symptoms suggest diabetes insipidus which is characterized 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 hypernatremia due to insensible fluid loss.
Risk factors
strong
inability to drink water/limited access to water
Neonates
Neonates may develop hypernatremic dehydration due to inadequate fluid intake, usually related to poor lactation or insufficient maternal milk supply.[69] Neonatal hypernatremic dehydration is associated with a free water deficit.[70] The neonate may present with nonspecific 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 mEq/L/hour, with gradual correction over 48 hours.[69][70]
infancy
Infants are at risk of hypernatremia 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 hypernatremia 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 hypovolemic hypernatremia 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 hypernatremia had a renal concentrating defect.[47]
The large amounts of normal saline (0.9%) given to anuric or oliguric patients does not result in hypernatremia. 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 hypervolemic despite the high urinary-output state. Therefore, hypernatremia is often associated with immediate negative water balance, but not with volume depletion.
gastrointestinal disorders
Severe watery diarrhea (e.g., viral gastroenteritis) or prolonged vomiting can often result in hypernatremia.
insensible water losses
Exercise, fever, heat exposure, and burns may lead to hypernatremia due to free water losses.
diabetes insipidus
An uncommon cause of hypernatremia. In one prospective cohort study which included 103 participants, <6% of hypernatremic patients had diabetes insipidus.[12]
use of specific drugs
Lithium, a mood stabilizer, 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.
Hypernatremia due to profuse diarrhea has been reported in patients treated with activated charcoal/sorbitol for poisoning.[28][29]
Sodium polystyrene sulfonate/sorbitol has been associated with hypernatremia when used to treat patients with hyperkalemia.
Laxative or bowel cleansing agents can cause severe diarrhea.
High-dose corticosteroids, e.g., used in the treatment of sepsis, increase the risk of hypernatremia.[58]
Fosfomycin (when administered intravenously) has been associated with hypernatremia, 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 hypernatremia.[2]
Hypernatremia 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 hemodialysis 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 pediatric 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 hypernatremia.
A history of traumatic brain injury or any other insult to the brain (e.g., vascular syndromes, infections, tumors, or aggressive surgery for craniopharyngioma, Rathke cleft cyst, or other hypothalamic tumors) is often present in patients with central diabetes insipidus.[2]
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