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Dysnatremia: Hypernatremia

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Also known as: Hyperosmolarity

1. Description of the problem

Hypernatremia is a hyperosmolar state that results from disturbances in water balance. It is most often the result of water loss in excess of effective plasma solute (either pure water loss or loss of hypotonic fluid) and less commonly due to hypertonic sodium gain. Free water loss can occur at the level of the kidneys, the gastrointestinal (GI) tract, the skin or respiratory tract.

Hypernatremia stimulates the osmoreceptors in the hypothalamus, causing release of vasopressin, also known as antidiuretic hormone (ADH), when the plasma osmolality rises approximately to 285 mOsm/kg and the development of hypernatremia when it exceeds 290 mOsm/kg. Vasopressin secretion stimulates renal water conservation and the production of a concentrated urine while thirst (and the subsequent increase in water intake) is the ultimate body defense against hypernatremia. Given the role of thirst and water ingestion in defending against hypernatremia, it is most likely to develop in infants and in adults with altered mental status, impaired thirst mechanism or limited access to water.

Clinical Features

Given osmotic equilibration across all body fluids, hypernatremia results in the efflux of water out of the intracellular compartment. Cellular dehydration, at the level of the brain, results in neurologic symptoms ranging from weakness, irritability, altered mentation to intracerebral bleed, seizures, coma and death. These symptoms are usually seen at serum Na level greater than 158 mEq/L and their reversibility varies between patients. Symptoms depend on the rate, magnitude and duration of hypernatremia. Patients with chronic hypernatremia that develops slowly may be asymptomatic due to intracellular osmotic adaptation.

Patients with hypernatremia may be volume overloaded in case of Na excess, volume depleted in case of hypotonic fluid loss or euvolemic during the initial stages of pure free water loss.

Patients with hypernatremia of greater than 24 hours’ duration are at increased risk of brain edema if the serum sodium concentration is rapidly corrected to normal.

Key Management Points

The primary treatment of hypernatremia is water repletion, followed by specific treatment to address the underlying etiology:

1. If the patient is volume depleted, initial therapy should focus on correction of volume deficits to ensure hemodynamic stability.

2. Once intravascular volume is restored, the hypernatremia should be corrected by administration of free water. Enteral water administration is preferable (either oral or via nasogastric tube). If adequate enteral administration is not possible, then 5% dextrose in water can be given intravenously. (Sterile water cannot be given intravenously, as local hypotonicity at the site of infusion can cause intravascular hemolysis).

The volume of free water administered should be based on calculation of the free-water deficit: Free-water deficit = total body water (TBW) multiplied by (140-serum Na/140)—where TBW is the estimated total body water calculated as approximately 60% of body weight in men and 50% of total body weight in women. In addition to replacing existing deficits, ongoing measurable water losses (most commonly renal and GI) and insensible water losses must also be replaced. Insensible losses in adults can usually be estimated as 30 to 50 mL/hour (0.5 mL/kg/h), but will be increased in the setting of fever or increased ambient temperature.

3. In symptomatic patients, the initial rate of correction of the serum sodium concentration should be no faster than 1 to 2 mEq/L/h with the rate of correction slowed once neurologic symptoms abate. As a general rule of thumb, 50% of the free-water deficit can be corrected in the first 24 hours with the remainder of the deficit corrected over the ensuing 24 to 48 hours.

4. The sources of free-water loss need to be Identified and treated: If GI in origin, use antimotility agents, discard cathartics and use proton pump inhibitors, as appropriate. If cutaneous, use cooling blankets. If diabetes insipidus (DI), treat appropriately with hormone replacement (if hypothalamic), limit daily solute load, discontinue lithium, and use thiazide diuretics. If due to osmotic diuresis, institute insulin therapy when hyperglycemia is present, discontinue use of mannitol, adjust total parenteral nutrition (TPN) prescription.

2. Emergency Management

1. If volume depletion is present, restore intravascular volume with isotonic saline.

2. Once intravascular volume is restored, begin correction of the free-water deficit with enteral water or intravenous 5% dextrose in water based on the estimated free-water deficit.

3. If neurologic symptoms are present, target an initial rapid (1-2 mEq/L/h) correction of the serum sodium concentration for a few hours until there is an initial improvement in neurologic status. The overall goal should be to correct half of the free-water deficit over the first 24 hours and completely correct the sodium concentration over the subsequent 1 to 2 days.

4. Monitor the response to treatment closely with measurement of the serum sodium concentration every 2 to 4 hours and with frequent neurologic examinations.

5. The development or worsening of neurologic symptoms after initial improvement should raise suspicion of cerebral edema. Free-water administration should be stopped and the patient monitored. Once symptoms attributable to cerebral edema resolve, free-water replacement can be resumed, albeit at slower rates.

6. If volume overload is present, diuretics may need to be given along with free water. In patients with renal failure and massive volume overload, dialysis may be necessary.

7. The underlying etiology of water loss needs to be identified and treated. If polyuria is present and urine osmolarity is low, raising suspicion of diabetes insipidus, a clinical trial of vasopressin or desmopressin can be instituted.

Management points not to be missed

Although overly rapid correction can lead to cerebral edema, seizures, irreversible neurologic damage and death, inadequate treatment is also associated with increased risk of neurologic complications and death.

3. Diagnosis

The diagnosis of hypernatremia is made based on laboratory testing. The specific etiology depends on assessment of volume status and source of fluid losses:

Euvolemic hypernatremia develops in the setting of inadequate water intake along with normal or excessive insensible or renal free-water losses:

– Primary hypodipsia

– Essential hypernatremia

– Hypothalamic lesions affecting the “osmostat”: Increased insensible losses—hyperpyrexia, mechanical ventilation with inadequate humidification, burns

– Increased renal free-water losses: hypothalamic DI, nephrogenic DI

Hypovolemic hypernatremia develops as the result of hypotonic fluid loss or from isotonic fluid sequestration in the presence of insufficient water intake:

– Cutaneous losses: severe burn injury, profuse sweating

– GI losses: vomiting, nasogastric suction, diarrhea

– Renal losses: osmotic diuresis (eg, hyperglycemia), diuretics, adrenocortical insufficiency, diuretic phase of acute kidney injury, postobstructive diuresis, renal salt wasting, isotonic fluid sequestration, bowel obstruction, pancreatitis, peritonitis, ileus

Hypervolemic hypernatremia: The co-existence of hypernatremia with ECF volume expansion is unusual and most often is iatrogenic in origin, resulting from administration of fluids such as hypertonic saline or hypertonic sodium bicarbonate.

Diagnostic testing should include serum electrolytes, plasma osmolality, urine electrolytes, urine osmolality.

The urine osmolarity should be greater than 700 mOsm/L in the presence of hypernatremia if renal concentrating ability is intact. If the urine osmolality is greater than 700 mOsm/L, it indicates that renal water conservation is normal and that the hypernatremia is due to non-renal water losses or primary hypodipsia.

A urine osmolality of less than 300 mOsm/L in the setting of hypernatremia suggests a diagnosis of DI. Intermediate values of urine osmolality may reflect partial forms of DI or primary kidney disease.


Hypernatremia most commonly results from the loss of water in excess of effective plasma solute. This can occur in the form of free-water loss or hypotonic fluid loss.

Free water loss

– Insensible: insensible losses from skin and respiratory tract average 800 to 1000 mL per day. Hypernatremia can develop if insensible losses are increased.

– Renal: DI is characterized by a lack of ADH action due to impaired secretion (hypothalamic DI) or effect (nephrogenic DI). This leads to the production of large amounts of dilute urine, leading to polyuria and polydipsia.

Hypotonic fluid loss

– GI: osmotic diarrhea from lactulose, certain infections and malabsorption, vomiting, NG drainage, enterocutaneous fistula

– Skin: burn injury, excessive sweating

– Renal: Osmotic diuresis from hyperglycemia, mannitol, high-protein intake; loop diuretics that impair urinary concentration by affecting the countercurrent mechanism in the medulla; postobstructive diuresis; recovery from ATN

Occasionally, Hypernatremia results from gain of hypertonic solution, as seen with administration of hypertonic saline, hyperosmolar sodium bicarbonate solution, TPN or excessive salt ingestion.

Defects in thirst and hypodipsia are necessary for the maintenance of the hypernatremic state.

Primary hypodipsia can be due to altered mental status, but it can result from any hypothalamic lesions affecting the osmostat (trauma, tumors, granulomatous disease, hydrocephalus and vascular lesions). Geriatric hypodipsia in the elderly population can occur without anatomic abnormalities.

Essential hypernatremia is due to malfunction of osmoreceptors, leading to ADH release only in response to volume and not osmolarity.

Reset osmostat is seen in states of primary mineralocorticoid excess such as primary hyperaldosteronism leading to chronic volume expansion. It is characterized by an increased osmotic threshold for ADH release.


Hypernatremia is seen in 0.5% to 2% of the general population. In the outpatient setting, it mostly affects the elderly with altered mental status or impaired thirst mechanism who develop an acute illness. In the inpatient setting, the reported incidence is 1%.

In hospitalized patients hypernatremia is most often iatrogenic, resulting from inadequate water administration in patients with predictably increased water losses or from the use of hypertonic solutions.


Hypernatremia is an indicator of poor prognosis, with associated mortality rates in excess of 40%. Poor outcome is generally not a result of hypernatremia per se, but more a reflection of disease severity and underlying comorbidities. Hypernatremia that persists longer than 72 hours is more likely to contribute to mortality.

What’s the evidence?

Rose, BD, Post, TW. Clinical physiology of acid-base and electrolyte disorders. 2001. pp. 764-775. (Review of hypernatremia with focus on pathophysiology.)

Adrogué, HJ, Madias, NE. “Hypernatremia”. N Engl J Med. vol. 342. 2000. pp. 1493(Review of hypernatremia with formula to estimate rate of correction and clinical examples.)

Lindner, G, Funk, GC, Schwarz, C. “Hypernatremia in the critically ill is an independent risk factor for mortality”. Am J Kidney Dis. vol. 50. 2007. pp. 952(Retrospective analysis of the impact of hypernatremia on mortality in intensive care units.)

Palevsky, PM, Bhagrath, R, Greenberg, A. “Hypernatremia in hospitalized patients”. Ann Intern Med. vol. 124. 1996. pp. 197(Prospective cohort study looking at the development of hypernatremia in hospitalized patients, risk factors and delay in therapy.)

Palevsky, PM. “Hypernatremia”. Semin Nephrol. vol. 18. 1998. pp. 20-30. (Review of hypernatremia, epidemiology and pathophysiology)

Snyder, NA, Feigal, DW, Arieff, AI. “Hypernatremia in elderly patients. A heterogeneous, morbid, and iatrogenic entity”. Ann Intern Med. vol. 107. 1987. pp. 309-19. (Study that examines the development of hypernatremia in hospitalized elderly patients, causes and morbidity.)

Ayus, JC, Armstrong, DL, Arieff, AI. “Effects of hypernatraemia in the central nervous system and its therapy in rats and rabbits”. J Physiol. vol. 492. 1996. pp. 243-55. (Shows the deleterious effects of hypernatremia and rapid correction in animal models.)

Phillips, PA, Rolls, BJ, Ledingham, JG, Forsling, ML, Morton, JJ, Crowe, MJ, Wollner, L. “Reduced thirst after water deprivation in healthy elderly men”. N Engl J Med. vol. 311. 1984. pp. 753-9. (Study that shows that healthy older men exhibit less thirst and water intake after water deprivation as compared to younger individuals and despite higher vasopressin levels, show less urinary concentrating abilities.)

Lien, YH, Shapiro, JI, Chan, L. “Effects of hypernatremia on organic brain osmoles”. J Clin Invest. vol. 85. 1990. pp. 1427-1435. (Animal studies looking at accumulation of organic brain osmoles with hypernatremia of varying degree and chronicity.)