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Does this patient have hypernatremia?


Hypernatremia indicates hypertonicity leading to a decrease in cell volume. Plasma Na+ concentration is regulated within 1-2% of normal values (140 ± 3 meq/L). The clinical manifestations are largely a consequence of the shrinkage of brain cells and attendant neurologic signs and symptoms.

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Hypernatremia may result from lack of water intake, water losses in excess of Na+ losses, or from excess Na+ intake or retention. Except for isolated conditions (eg, cholera), the Na+ concentration of sweat, respiratory secretions, emesis and feces, and even urine, is lower than that of plasma. Thus, unless water is replenished, there is a tendency for the development of hyperosmolality and hypernatremia even with optimal secretion of vasopressin and a normal renal response to the hormone.


The possibility of hypernatremia should be considered in children and adults with changes in mental status or infants with lethargy and weakness. In more severe cases, patients may display confusion, twitching, seizures, and coma. Death may ensue in the most severe cases.


Several important questions can be highly enlightening.

  • Is the person very old or very young? Hypernatremia occurs in individuals whose ability to obtain water independently is limited: the elderly and infants.

  • Is the person debilitated or immobilized? Is access to water limited? Hypernatremia may ensue in patients with a partial defect, on in extreme cases with no defect, in vasopressin (antidiuretic hormone; see below) secretion or action. This may occur when they are prevented access to water when they would have otherwise been able to drink freely.

  • Is there loss of fluid from the gastrointestinal tract in the form of copious emesis or watery diarrhea?

  • Is there an osmotic or solute diuresis occurring as with uncontrolled diabetes mellitus or a highly catabolic state?

  • Is there a concurrent electrolyte abnormality such as hypokalemia or hypercalcemia?

  • Does the person have a new or old neurological abnormality or brain injury? Hypernatremia may be the first sign of the presence or recurrence of a brain tumor or other lesion.

  • Is there a history of polyuria or polydipsia? What fluids does the person prefer to drink? Typically, individuals with diabetes insipidus prefer ice water.

  • If the person is awake and alert, does he/she experience thirst?

  • Is there a history of psychiatric illness? Hypernatremia often accompanies acute lithium overdose or toxicity with chronic lithium therapy.

  • What other medications does the person take?

  • Has the individual recently undergone brain surgery, particularly transsphenoidal hypophysectomy or other procedure in the vicinity of the hypothalamus or pituitary stalk?

  • In evaluating infants, is there a family history of diabetes insipidus or neonatal death due to dehydration?

  • In infants, it is important to note if they are ingesting formula or being breast fed. Are the feedings premixed or do they require formulation at home and/or are other foods being given the infant or child?

  • Does the infant have severe dermatologic problems?

  • In adults, has a large amount of salt been ingested acutely?

  • For hospitalized patients, has there been a history of recent resuscitation? What is the volume and composition of fluids that have been administered?

  • If the patient has undergone recent surgery, what was the anesthetic and surgical procedure?

  • Less commonly, is there a recent history of extreme exercise activity, primary mineralocorticoid excess, or postpartum state?

Physical findings

Neurologic findings such as disorientation, acute memory loss, confusion, myoclonus, focal or generalized seizure activity, or coma may be present. The neurologic signs may be due directly to the hypernatremia or may represent an underlying neurologic defect associated with or leading to an abnormal plasma Na+ concentration. When water losses are accompanied by sodium losses, patients may display signs of volume depletion.

With profound volume depletion, such as patients who develop hypernatremia due to osmotic diuresis or enteric losses (see below), postural hypotension or even frank hypotension may occur. Poor skin turgor and decreased jugular venous pressure may be present. More rarely, when hypernatremia is due to excess ingestion or infusion of Na+ salts, individuals may exhibit signs of volume overload such as peripheral edema or pulmonary edema.

Conditions that present with similar findings

It may be difficult to distinguish the neurologic defects due directly to the changes in plasma osmolality from neurologic findings due to underlying brain lesions, such as seizures, tumors, progressive dementia, or infiltrative diseases. Hypercalcemia may also present with lethargy, obtundation and coma. Complicating the diagnosis, high plasma Ca2+ concentration also results in concurrent hypernatremia due to impaired urinary concentrating ability.

What is the differential diagnosis of hypernatremia?

In all the cases below, hypernatremia occurs when the water losses are not replenished regardless of the etiology.

Hypodipsic states
  • Elderly individuals – The threshold for thirst is increased in the very elderly.

  • Primary hypodipsia with normal vasopressin secretion: including tumors in the region of the hypothalamus and third ventricle, granulomatous or other diseases that infiltrate these regions/structures (e.g., sarcoidosis, tuberculosis, histiocytosis X, MPO-ANCA, malaria), or post-surgical damage to these structures.

  • Hypodipsia with/without complete or partial central diabetes insipidus (etiologies as in primary hypodipsia; autoantibodies directed to circumventricular brain sites with normal structures on imaging).

  • Essential hypernatremia.

Extrarenal losses of water in excess of Na+
  • Gastrointestinal losses: emesis, osmotic diarrheas, enteral losses hyperosmotic tube feedings

  • Increased dermatologic losses: fever, burns, exposure to high ambient temperature, rigorous exercise, hereditary ichthyosis (Netherton syndrome)

Renal losses of water in excess of Na+
  • Central (neurogenic) diabetes insipidus (DI) – lack of vasopressin secretion, may be complete or partial Hereditary: autosomal dominant, autosomal recessive, Wolfram syndrome

  • Acquired: idiopathic (autoimmune), primary brain tumors, trauma, neurosurgery, infiltrative diseases, hypoxic encephalopathy, lymphocytic infundibulo-neurohypophysitis, or ischemia, increased catabolism of vasopressin postpartum (usually self-limited), and drugs or other agents (Table II)

  • Nephrogenic diabetes insipidus – impaired vasopressin action on the renal collecting duct, may be complete or partial

    Hereditary: X-linked recessive (V2 receptor mutation), autosomal recessive (aquaporin 2 mutation)

    Hereditary diseases which may have renal concentrating defects: mutations associated with Bartter syndrome or familial hypocalciuric hypercalcemia, nephronophthisis, familial hypomagnesiemia with hypercalciuria and nephrocalcinosis, apparent mineralocorticoid excess syndromes

    Acquired: protein malnutrition, electrolyte abnormalities (e.g., hypokalemia, hypercalcemia), sickle cell disease, interstitial diseases of the kidney, infiltrative diseases of the kidney, vasopressin antagonists, other drugs or agents (Table II), tubular dysfunction associated with or in the recovery phase of acute kidney injury (may be self-limited)

  • Other

    Resetting of osmostat for vasopressin secretion: occurs with primary mineralocorticoid excess

    Water shift into cells: extreme exercise (water shift into muscle), typically transient

    Osmotic diuresis: sodium linked glucose transporter (SGLT1) inhibitors

Table II.

Drugs and Ingestions Predisposing to Hypernatremia

Excess Na intake
  • Use of hypertonic saline or sodium bicarbonate solutions

  • Administration of large volumes of isotonic sodium chloride for resuscitation

  • Dialysis against high Na+ dialysate

  • High sodium infant formula or hypertonic breast milk

  • Ingestion of soy sauce, “bamboo” salt (jukyeom), salt tablets, etc. without concurrent water ingestion,

  • Accidental excess Na+ concentration in whirlpool baths for burn patients

What tests to perform?

Hypernatremia at presentation

If the person is already hypernatremic, the concurrent measurement of urine osmolality, Uosm and plasma Na+ (or plasma osmolality, Posm) and plasma K+ concentration is the first and most important step in the evaluation (Table I).

Table I.

Urine Osmolality in Patients with Hypernatremia: Response to Vasopressin

  • If PNa+ is > 150 meq/L, endogenous vasopressin should have been secreted and the urine should be maximally concentrated (Uosm > 800 mosm/kgH2O). If the urine is not concentrated, a partial or complete defect in vasopressin release or action is present. The response to administration of vasopressin (5 units aqueous vasopressin subcutaneously or 2 μg dDAVP intravenously) or (10 μg dDAVP intranasally) should then be evaluated. (The intravenous route for dDAVP is preferable for testing to assure the full absorption of the drug.)

  • In central diabetes insipidus, the administration of exogenous vasopressin should result in at least a 50% increase in Uosm. Failure to do so strongly suggests a nephrogenic etiology.

  • Caution should be exerted in interpreting these results in cases of (1) hypovolemia and (2) results in the intermediate range. Even in complete central diabetes insipidus, the Uosm may exceed 400 mosm/kgH2O since, in volume depletion, the kidney may still be able to concentrate urine to osmolality exceeding that of plasma due to decreased delivery of fluid to the distal nephron with some ability of the distal tubules to reabsorb water even in the absence of vasopressin.

  • In hypodipsic states the response to water ingestion helps discriminate between the two forms.

    In primary hypodipsia with or without concomitant partial diabetes insipidus, water intake is sufficient to re-establish normal plasma Na+ concentration.

    In patients with essential hypernatremia, water administration does not decrease plasma Na+ concentration. It appears that the osmoreceptors in the hypothalamus are reset or less sensitive to changes in plasma osmolality and imbibition of water suppresses vasopressin and the ingested water is excreted at higher plasma Na+ concentrations.

  • In both primary hypodipsia and essential hypernatremia, the volume (baro) receptor function remains intact and vasopressin is released in response to hypovolemia or hypotension. This can be used to verify the diagnosis of essential hypernatremia. Infusion of hypertonic saline will increase both plasma Na+ concentration (which should increase vasopressin secretion) and extracellular volume (which should inhibit vasopressin secretion). In a normal individual, vasopressin will increase and Uosm would increase. In a person with essential hypernatremia, Uosm typically decreases since baroreceptor inhibition of vasopressin predominates.

Polyuria and polydipsia

More mild cases of hypernatremia (plasma Na+ concentrations 144 – 149 meq/L) may present in patients who are awake and alert but complain of polyuria defined as > 3L urine per day. Diagnosis can be made using the water restriction test.

In hospitalized patients where high solute loads to the kidney may occur (e.g., total parenteral nutrition, relief of urinary obstruction, etc.), total urinary osmole excretion should be measured to exclude the possibility of a solute diuresis as the cause of polyuria.

Water restriction test

Water (and all other fluids) are completely restricted.

  • Body weight, and Uosm are measured at the beginning of the water restriction and hourly.

  • Plasma Na+ concentration and/or Posm are measured at the beginning and every 2 hours.

  • Water restriction is continued until two consecutive Uosm values show no further increase (< 30 mosm/kgH2O difference between specimens) or Posm equals 295 – 300 mosm/kgH2O.

  • Once Uosm is stable, 5 units aqueous vasopressin subcutaneously or 2 μg dDAVP intravenously is given. dDAVP may also be given as 10 μg by intranasal insufflation if absorption is not a concern.

  • Hourly measurements of Uosm are continued

  • Maximum weight loss should not be permitted beyond 3 – 5% of body weight.

Interpretation of water restriction test

  • In normal individuals, water restriction will increase Posm and plasma Na+ concentration. Endogenous vasopressin will be secreted and Uosm will increase as urine flow rate decreases. Administration of exogenous vasopressin should not further increase Uosm.

  • Water restriction in individuals with complete or partial diabetes insipidus will result in Uosm values similar to those listed for spontaneous hypernatremia (Table I). Exogenous vasopressin will increase Uosm substantially only in patients with complete (100 – 800% rise) or partial (15 – 50% rise) central diabetes insipidus.

  • Individuals with nephrotic diabetes insipidus, especially the acquired types, are only partially resistant to vasopressin. Administration of vasopressin will thus result in a modest increase in Uosm (30 – 45%). This may be difficult to distinguish from partial central diabetes insipidus, except that patients with partial central diabetes insipidus usually have Uosm > 300 mosm/kgH2O at the end of water restriction (before vasopressin administration). In contrast, patients with nephrogenic diabetes insipidus have Uosm < 300 mosm/kgH2O after water restriction and remains more dilute than plasma after exogenous vasopressin.

  • Hypertonic saline (3%) is infused at 0.05 ml/kg/min for no more than 2 hours

  • Uosm, urine flow rate and plasma Na+ concentrations are followed.

  • Diagnostic criteria are identical to those for spontaneous hypernatremia (Table I)

  • Care must be exercised to avoid volume overload, pulmonary edema, or induction of severe hypernatremia.

  • This test is particularly helpful in identifying essential hypernatremia.

Spurious Hypernatremia

  • Hypernatremia may be spurious or artefactual such that plasma Na+ concentration is normal but the reported laboratory value is high. This may occur with contamination of the sample during collection with infused fluids or fluids used for catheter-lock procedures.

Diagnostic challenges and special circumstances

  • Postpartum polyuria due to increased activity of vasopressinase activity will not be corrected by vasopressin but will respond to dDAVP, as the absence of the amino group prevents catabolism by the peptidase. Thus, it is advisable to use dDAVP in evaluations of all women presenting with polyuria or hypernatremia in the peripartum period.

  • In hospitalized patients, polyuria is most commonly caused by solute diuresis due to administration of large volumes of saline, high protein parenteral feeding, hypertonic saline, or vasopressin antagonists. Depending on the type of fluid administered and the ability of the patient to ingest water, hypernatremia may or may not be present.

    Uosm < 250 mosm/kgH2O indicates administration of large volumes of hypotonic fluids or an undiagnosed disorder in water metabolism. A water restriction test should be performed to discriminate between these etiologies. The duration of water restriction should be given careful consideration so as not to risk excessive changes in plasma Na+ concentration. If diabetes insipidus is suspected, it is advisable to perform the restriction in an observed environment with periodic evaluations of plasma Na+ and urine osmolality.

    Uosm > or = 300 mosm/kgH2O strongly suggests a solute or osmotic diuresis. (Partial central or nephrogenic diabetes insipidus may also present this way so caution should be exercised.) If due to solute diuresis, checking plasma glucose, the protein composition of enteral/parenteral feeds, urine glucose, Na+ and urea concentrations will help identify the responsible solute.

  • Hypernatremia after neurosurgical procedures (typically after transsphenoidal hypophysectomy) or trauma to the hypothalamus, infundibular stalk or posterior pituitary displays a triphasic pattern. Patients should also be evaluated for more common causes of polyuria or excess water loss in the post-operative period, such as concurrent administration of mannitol or hyperglycemia resulting from glucocorticoid therapy.

    Initial polyuric phase occurs on postoperative day 1 and may persist up to 5 days.

    Antidiuretic phase lasts from ~6 days to 2 weeks and is due to release of vasopressin from the degenerating neurohypophysis. This phase is characterized by potential hyponatremia rather than hypernatremia

    Long term central diabetes insipidus results after depletion of neurohypophysial vasopressin stores. The central diabetes insipidus may be complete or partial. Some patients may recover without long lasting effects.

  • Permissive hypernatremia is becoming increasingly utilized to prevent elevated intracranial pressures. There are no controlled trials. Caution should be exerted to avoid excessively high concentrations of plasma Na+.

  • Rare cases of salt poisoning have occurred in children.

Ancillary studies

Ancillary studies should be considered in patients presenting with hypernatremia when history and clinical signs indicate there may be an underlying structural, functional, or hereditary abnormality.

  • Renal function assessed by serum creatinine, BUN and estimated glomerular filtration rate (GFR) should be ascertained. Patients with more advanced renal dysfunction from any etiology may display a moderate impairment in maximum concentrating ability unless they become severely volume depleted. These individuals are not typically polyuric (although many complain of frequency) but may be predisposed to developing hypernatremia when confronted with another insult (eg, diarrhea).

  • The presence of other electrolyte disturbances such as hypokalemia and metabolic alkalosis may point to more rare etiologies such as Bartter syndrome or primary mineralocorticoid excess. If indicated, serum aldosterone and/or cortisol should be evaluated.

  • Imaging of the brain with special attention to the sella turcica and hypothalamus is best accomplished by MRI/MRA. Characteristic findings of craniopharyngioma or other tumors or of infiltrative diseases (sarcoidosis, histiocytosis X) may be present. If primary excess mineralocorticoid is found, imaging of the adrenal glands is in order. This can be accomplished by MR but CT imaging is also acceptable. All polyuric states can result in dilation of the urinary tract and bladder and should be evaluated by renal and pelvic ultrasound. Bilateral hydronephrosis with renal failure has been known to occur, so frequent voiding and double voiding should be recommended if polyuria cannot be limited.

  • Genetic testing for hereditary causes of either central diabetes insipidus or nephrogenic diabetes insipidus is not yet broadly available.

  • Testing for antibodies to anti-rabphilin-3A or subfornical organ (not yet commercially or broadly available).

  • If spurious or artefactual hypernatremia is suspected, verification with assessment of plasma osmolality is recommended.

How should patients with hypernatremia be managed?

General considerations

It is recommended that plasma Na+ concentration be decreased by no more than 0.5 meq/L per hour. Overly rapid correction of hypernatremia may result in cerebral edema, seizures, permanent neurologic deficit, and even death. This rate is similar to earlier recommendations for correction of hyponatremia which have recently been changed to no more than 6 meq/L in 24 hr or 10 meq/L in 48 hr. Parallel studies in hypernatremia have not yet been done, but slower correction may also be wise in hypernatremic conditions. During osmotic adaptation for hypernatremia, brain cells gain intracellular electrolytes and organic solutes. Water re-enters the cells thereby restoring cell volume toward normal. Reducing plasma Na+ concentration (and Posm) too quickly or by too great an amount leads to water entry into the brain cells and cell volume increasing to values greater than normal.

Restoration of pure water deficit

  • Obtain current plasma Na+. Measure Uosm, Na+, K+, and hourly urinary volume (V).

  • Calculate the water deficit based on total body water content being ~60% of lean body weight.

Water deficit (in L) = (0.6 * lean body weight [in kg])* ({measured plasma [Na+]/140} – 1)

For elderly patients, particularly females, the normal body water may be closer to 50%, so that 0.5 rather than 0.6 should be used in the formula above. Newborn infants may be 70% total body water but slight underestimation may be safer in these as well as in adults. Caution should be exerted in calculation of patients who are morbidly obese in whom the proportion of body water in adipose tissue can be considerable. Generally, adipose tissue is ~ 10% water. This factor may be used to refine the above formula. For example, in a 150 kg male whose lean body weight would be 70 kg, one would use 0.6 * 70 kg + 0.1 * 80 kg = 50 L).

  • Evaluate ongoing extrarenal water losses: insensible losses (typically 30 – 50 ml/h), emesis, diarrhea, sweat, nasogastric drainage, fluids lost via other drains

  • Evaluate ongoing urinary water loss by calculating electrolyte-free water reabsorption:

Electrolyte free water reabsorption (TeCH2O) = V * ({[UNa+ + UK+]/PNa+} – 1)

  • A negative value for TeCH2O indicates the volume of ongoing urinary water losses that need to be replaced

  • Fluid administration to replace losses may take on different forms.

  • Water can be given orally or intravenously as 5% dextrose in water.

  • If hypotension is present due to severe volume depletion, fluid replacement should begin with isotonic saline to restore volume and blood pressure

  • Consideration should be given to other fluids that are being administered concurrently (e.g., vehicle for infusions or intermittent drugs administration, enteral fluids, etc.).

  • If volume depletion is also present, half-isotonic saline may be given. 1L of this solute would be identical to administering 500 ml isotonic saline and 500 ml free water.

  • Calculations of water deficit and electrolyte free water reabsorption are approximations at best. Caution should be exerted especially in the very young, the elderly, and the morbidly obese (water content of fat is ~10% but may make significant overall contribution in the morbidly obese). Moreover, extra renal ongoing losses are often difficult to quantitate. Therefore, serial measurements of plasma Na+ concentration are imperative, usually every 4 – 6 hours during replacement therapy.

  • When vasopressin replacement is required, this is best accomplished with dDAVP (desmopressin, des-amino-D-arginine vasopressin). In contrast to vasopressin itself, the antidiuretic activity of dDAVP is 1000 times greater than its vasoactive effect. It is administered by intranasal insufflation twice daily at 5 – 20 μg doses. An oral form is available. Roughly 0.1 mg orally is equivalent to 2.5 – 5 μg intranasally, but there is considerable variation on absorption and action depending on whether it is taken on an empty stomach or with meals. Titration of the dose is recommended. In infants, where intranasal dDAVP is not practical, bucally administered dDAVP 1 – 5 μg twice daily has been effective.

  • Since hypoosmolality cannot suppress exogenous vasopressin, there is risk of developing water retention and hyponatremia in patients on dDAVP who imbibe excess water. Thus, it is advisable to begin treatment with dDAVP with one nighttime dose and titrate the daytime dose to avoid troubling polyuria. Some patients may prefer to take a daytime nasal dose when they observe their urine output increase, rather than on a routine basis.

  • Low Na+ diet and thiazide diuretics have been used to minimize urine output in patients, particularly with partial central diabetes insipidus (see mechanism below). Other agents are now rarely used. Chlorpropamide has come into disuse due to the risk of hypoglycemia. The risk:benefit ratio of clofibrate and carbamazepine is also less attractive although they can enhance vasopressin secretion or action, respectively, in patients that have some endogenous vasopressin.

Long term treatment of nephrogenic diabetes insipidus

Long term treatment of nephrogenic diabetes insipidus is typically used in patients with symptomatic polyuria.

  • Thiazide diuretics with a low Na+and low protein diet are the mainstay of treatment. The mechanism of action of these interventions is due to induction of volume depletion with enhanced salt and water reabsorption in the proximal tubule thereby decreasing fluid delivery to the diluting segment. Limiting Na+ and protein intake limits solute excretion so that obligate water excretion is also curtailed. Loop diuretics should not be used as they impair the formation of an adequate medullary interstitium.

  • Amiloride, a K+-sparing diuretic may be useful in counteracting hypokalemia (which would aggravate nephrogenic diabetes insipidus). It is also indicated in patients with acute or chronic lithium toxicity as it prevents lithium accumulation in the principal cell. It has also been used as a preventive measure in patients at high risk for lithium toxicity and nephrogenic diabetes insipidus.

  • Renal prostaglandins counteract the renal tubular response to vasopressin. Nonsteroidal anti-inflammatory drugs (NSAIDS) inhibit renal prostaglandin synthesis and thus have proven of some benefit to increase Uosm by 50 to 100%. However, thiazide plus amiloride may have fewer side effects.

Hypodipsia or adipsia
  • Individuals with primary hypodipsia without diabetes insipidus can be treated by prescribed water intake, typically 1.5 – 2 L per day. If the patient has no concurrent disorders that affect Na+ balance (e.g., heart failure), then assessment of daily weight with replacement of water equivalent to weight loss (1 kg = 1 L). This can be particularly helpful if the individual is subject to greater water losses (e.g., exercise) or suffering from an acute disorder (e.g., diarrhea).

  • Treatment of patients with hypodipsia with partial central diabetes insipidus or essential hypernatremia is more difficult. Administration of water to these individuals often suppresses endogenous vasopressin and aggravates the polyuria. The plasma Na+ concentration thus remains high. Chlorpropamide has been used with success in these patients, but hyponatremia remains a risk. Hypernatremia due to Na+ overload and volume expansion is best treated by elimination of the excess total body Na+.

    Further salt intake should be prevented.

    Urinary Na+ excretion can be facilitated with administration of diuretics and replacing the consequent urinary Na+ and water losses with oral water or intravenous 5% dextrose in water.

    In severe cases, dialysis against a hypotonic dialysate has been used, but the dialysis prescription needs to be adjusted to achieve an appropriate rate of decrease in plasma Na+ concentration (0.5 meq/L/hr) and avoid inducing cerebral edema.

What happens to patients with hypernatremia?

Epidemiology, clinical course, and complications

As noted earlier, hypernatremia occurs in the very young, the very old, and in patients with prior neurologic disorders or who are incapacitated and cannot achieve water intake. Hospitalized patients are also at risk due to administration of hypertonic fluids (hypertonic saline, sodium bicarbonate) or having their oral intake limited due to a variety of reasons. Hypernatremia has been associated with increased mortality in patients with a number of underlying conditions.

  • Elevated plasma Na+ concentration (>150 meq/L) at the time of admission is an independent risk factor for hospital mortality.

  • The incidence of hypernatremia in ICU settings is increasing. Overall ICU mortality is higher in hypernatremic vs normonatremic patients with 90-day mortality as high as 60% with plasma Na+ concentrations > 160 meq/L. One year mortality is 57%. Mortality is independently associated with low systolic blood pressure, low pH, pneumonia, and mean sodium correction rate < 0.134 mmol/L/h.

  • Hypernatremia has been proposed as a potential prognostic marker for mortality in neurological patients in the ICU (sensitivity, 79.4%; specificity, 74.5%).

  • Hypernatremia (plasma Na+ > 150 meq/L) is associated with increased mortality in patient populations including geriatric individuals and patients presenting with hip fracture, liver transplantation, and preoperative screening.

  • Hypernatremia (3.2%) is less common than hyponatremia (5.3%) in hospitalized heart failure patients but hospital mortality in the hypernatremic group was substantial (6.7%).

  • In patients with chronic kidney disease, hypernatremia is associated with increased (36%) mortality due to non-cardiovascular disorders or malignancy.

  • Correction of hypernatremia by continuous dialytic modalities at a rate > 1 meq/L/hr is associated with increased mortality.

  • If plasma Na+ concentration rises too quickly during the evolution of hypernatremia, osmotic demyelination may occur similar to that resulting from too rapid a correction of hyponatremia. Patients typically die of underlying illness. Cerebral edema, herniation, and death can occur with too rapid a correction of hypernatremia.

  • Osmotic demyelination manifesting as abnormal involuntary movements and verified by MR imaging has also been observed in infants presenting with dehydration and de novo severe hypernatremia associated.

  • In geriatric patients on psychotropic medications, the combination of plasma Na+ > 140 meq/L and urine specific gravity < 1.010 is associated with a 26.3% incidence of acute kidney injury over the next 5 years.

  • Hypernatremia occurring with hyperglycemia in preterm infants increases the risk of intracranial hemorrhage by more than two-fold.

  • Hypernatremia in infancy is associated with developmental delay.

What is the physiology of water balance?

  • The distribution of water between the extracellular and intracellular body fluid compartments is determined by osmotic forces. If an osmotic gradient is established, water will move from the compartment of low osmolality to that with higher osmolality until a new equilibrium is established and the osmotic pressures are equalized. Since Na+ ions are restricted to the extracellular compartment, Na+ is the major solute contributing to extracellular osmolality. Thus, changes in plasma Na+ concentration generally parallel changes in plasma osmolality. Therefore, at equilibrium, plasma Na+ concentration can be used as in index of osmolality of both body fluid compartments. Under normal physiologic conditions, water intake and excretion are highly regulated such that total body osmolality and, hence, plasma Na+ concentration are maintained within very narrow limits. A change in the absolute amounts of Na+ and water will result in a change in the size of the body fluid compartments, volume regulation. Osmoregulation results in the control of the ratio of solutes and water such that a change in the concentration of plasma Na+ will reflect a change in body water content.

  • Water balance is maintained by functions that regulate water intake and water loss. Water intake can occur by drinking fluids as well as from water content and metabolism of food. In clinical settings, water intake can also occur via sources such as intravenous fluids, tube feedings, and lavage. Water may be lost via urine and gastrointestinal sources but also from the skin and respiratory tract. Water intake will tend to decrease plasma Na+ concentration and water losses will increase plasma Na+ concentration.

  • Changes in plasma osmolality are sensed by osmoreceptors in the brain areas surrounding the third ventricle, and hypothalamus sense changes in osmolality and regulate thirst sensation and the release of vasopressin. Vasopressin, or antidiuretic hormone, increases the water permeability of the collecting duct thereby enhancing renal tubular water reabsorption. As a result, urinary water excretion is minimized. The importance of thirst and water seeking behavior should not be discounted since individuals that lack vasopressin maintain water balance as long as they are able to drink. Overall, the mechanisms for maintaining normal water balance and osmotic regulation are able to control plasma Na+ concentration within ~1 – 2% of normal values.

Pathophysiology of hypernatremia

Hypernatremia may result from lack of water intake, water losses in excess of Na+ losses, or from excess Na+ intake or retention. Except for isolated conditions (eg, cholera), the Na+ concentration of sweat, respiratory secretions, emesis and feces, and even urine, is lower than that of plasma. Thus, unless water is replenished, there is a tendency for the development of hyperosmolality and hypernatremia even with optimal secretion of vasopressin and a normal renal response to the hormone. The disorders resulting from dysregulation are listed above under “Differential diagnosis.”.

How to utilize team care?

Nursing care

Nursing care for severe hypernatremia (arbitrarily set at plasma Na+> 155 meq/L) is best achieved in the intensive care unit (ICU) setting. However, regardless of the setting, strict measurement and accurate recording of oral intake, parenteral intake, the composition of the fluids, and output from all sources is important. Nursing care also provides close monitoring of the patient’s neurological status at the time of diagnosis and during restoration of fluid balance. Nursing staff need to be made aware of the importance of providing access to water for debilitated, paralyzed, or otherwise incapacitated individuals who cannot achieve water on their own.


Pharmacists are invaluable members of the care team. They may be able to provide more complete information regarding the formulation of parenteral feedings and means to modify the formulation, if needed, as well as special formulations of fluid (eg, 1/4-isotonic or 1/3 isotonic saline) if not routinely available. Dialogue with the pharmacist regarding the vehicle provided for other drug infusions for the patient may be helpful in estimating the nature and quantity of all fluid intake.


Dietitians can provide appropriate oral fluid intake and better quantification of it. They may also assist in formulation of enteral or parenteral feedings to avoid solute diuresis.

Other considerations

Length of stay
  • Length of stay is increased in hospital acquired hypernatremia. Length of stay in the intensive care unit (ICU) was 7 days for hypernatremic vs 2 days for normonatremic patients. Overall hospital stay was also increased to 24 days vs 12 days.