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(For hypernatremia in neonates, see Neonatal Hypernatremia.)
Hypernatremia is a serum sodium concentration > 145 mEq/L. It implies a deficit of total body water relative to total body sodium, caused by water intake being less than water losses. A major symptom is thirst; other clinical manifestations are primarily neurologic (due to an osmotic shift of water out of brain cells), including confusion, neuromuscular excitability, seizures, and coma. Diagnosis requires measurement of serum sodium and sometimes other laboratory tests. Treatment is usually controlled water replacement. When the response to treatment is poor, testing (eg, monitored water deprivation or administration of vasopressin) is directed at detecting causes other than decreased water intake.
Hypernatremia reflects a deficit of total body water (TBW) relative to total body sodium content. Because total body sodium content is reflected by ECF volume status, hypernatremia must be considered along with status of the ECF volume: hypovolemia, euvolemia, and hypervolemia. Note that the ECF volume is not the same as effective plasma volume. For example, decreased effective plasma volume may occur with decreased ECF volume (as with diuretic use or hemorrhagic shock), but it may also occur with an increased ECF volume (eg, in heart failure, hypoalbuminemia, or capillary leak syndrome).
Hypernatremia usually involves an impaired thirst mechanism or limited access to water, either as contributing factors or primary causes. The severity of the underlying disorder that results in an inability to drink in response to thirst and the effects of hyperosmolality on the brain are thought to be responsible for a high mortality rate in hospitalized adults with hypernatremia. There are several common causes of hypernatremia (see Table: Principal Causes of Hypernatremia).
Principal Causes of Hypernatremia
Hypernatremia associated with hypovolemia occurs with sodium loss accompanied by a relatively greater loss of water from the body. Common extrarenal causes include most of those that cause hyponatremia and volume depletion. Either hypernatremia or hyponatremia can occur with severe volume loss, depending on the relative amounts of sodium and water lost and the amount of water ingested before presentation.
Renal causes of hypernatremia and volume depletion include therapy with diuretics. Loop diuretics inhibit sodium reabsorption in the concentrating portion of the nephrons and can increase water clearance. Osmotic diuresis can also impair renal concentrating capacity because of a hypertonic substance present in the tubular lumen of the distal nephron. Glycerol, mannitol, and occasionally urea can cause osmotic diuresis resulting in hypernatremia.
The most common cause of hypernatremia due to osmotic diuresis is hyperglycemia in patients with diabetes. Because glucose does not penetrate cells in the absence of insulin , hyperglycemia further dehydrates the ICF compartment. The degree of hyperosmolality in hyperglycemia may be obscured by the lowering of serum sodium resulting from movement of water out of cells into the ECF ( translational hyponatremia). Patients with renal disease can also be predisposed to hypernatremia when their kidneys are unable to maximally concentrate urine.
Hypernatremia with euvolemia is a decrease in TBW with near-normal total body sodium (pure water deficit). Extrarenal causes of water loss, such as excessive sweating, result in some sodium loss, but because sweat is hypotonic, hypernatremia can result before significant hypovolemia. A deficit of almost purely water also occurs in central diabetes insipidus and nephrogenic diabetes insipidus.
Essential hypernatremia (primary hypodipsia) occasionally occurs in children with brain damage and in chronically ill elderly adults. It is characterized by an impaired thirst mechanism (eg, caused by lesions of the brain’s thirst center). Altered osmotic trigger for vasopressin release is another possible cause of euvolemic hypernatremia; some lesions cause both an impaired thirst mechanism and an altered osmotic trigger. The nonosmotic release of vasopressin appears intact, and these patients are generally euvolemic.
Hypernatremia in rare cases is associated with volume overload. In this case, hypernatremia results from a grossly elevated sodium intake associated with limited access to water. One example is the excessive administration of hypertonic sodium bicarbonate during treatment of lactic acidosis. Hypernatremia can also be caused by the administration of hypertonic saline or incorrectly formulated hyperalimentation.
Hypernatremia is common among the elderly, particularly postoperative patients and those receiving tube feedings or parenteral nutrition. Other contributing factors may include the following:
Dependence on others to obtain water
Impaired thirst mechanism
Impaired renal concentrating capacity (due to diuretics, impaired vasopressin release, or nephron loss accompanying aging or other renal disease)
Impaired angiotensin II production (which may contribute directly to the impaired thirst mechanism)
The major symptom of hypernatremia is thirst. The absence of thirst in conscious patients with hypernatremia suggests an impaired thirst mechanism. Patients with difficulty communicating or ambulating may be unable to express thirst or obtain access to water. Sometimes patients with difficulty communicating express thirst by becoming agitated.
The major signs of hypernatremia result from CNS dysfunction due to brain cell shrinkage. Confusion, neuromuscular excitability, hyperreflexia, seizures, or coma may result. Cerebrovascular damage with subcortical or subarachnoid hemorrhage and venous thromboses have been described in children who died of severe hypernatremia.
In chronic hypernatremia, osmotically active substances are generated in CNS cells (idiogenic osmoles) and increase intracellular osmolality. Therefore, the degree of brain cell dehydration and resultant CNS symptoms are less severe in chronic than in acute hypernatremia.
When hypernatremia occurs with abnormal total body sodium, the typical symptoms of volume depletion or volume overload are present. Patients with renal concentrating defects typically excrete a large volume of hypotonic urine. When losses are extrarenal, the route of water loss is often evident (eg, vomiting, diarrhea, excessive sweating), and the urinary sodium concentration is low.
The diagnosis is clinical and by measuring serum sodium. In patients who do not respond to simple rehydration or in whom hypernatremia recurs despite adequate access to water, further diagnostic testing is warranted. Determination of the underlying disorder requires assessment of urine volume and osmolality, particularly after water deprivation.
In patients with increased urine output, a water deprivation test is occasionally used to differentiate among several polyuric states, such as central diabetes insipidus and nephrogenic diabetes insipidus.
Replacement of intravascular volume and of free water is the main goal of treatment. Oral hydration is effective in conscious patients without significant GI dysfunction. In severe hypernatremia or in patients unable to drink because of continued vomiting or mental status changes, IV hydration is preferred. Hypernatremia that has occurred within the last 24 h should be corrected over the next 24 h. However, hypernatremia that is chronic or of unknown duration should be corrected over 48 h, and the serum osmolality should be lowered at a rate of no faster than 0.5 mOsm/L/h to avoid cerebral edema caused by excess brain solute. The amount of water (in liters) necessary to replace existing deficits may be estimated by the following formula:
where TBW is in liters and is estimated by multiplying weight in kilograms by 0.6 for men and by 0.5 for women; serum sodium is in mEq/L. This formula assumes constant total body sodium content. In patients with hypernatremia and depletion of total body sodium content (ie, who have volume depletion), the free water deficit is greater than that estimated by the formula.
In patients with hypernatremia and ECF volume overload (excess total body sodium content), the free water deficit can be replaced with 5% D/W, which can be supplemented with a loop diuretic. However, too-rapid infusion of 5% D/W may cause glucosuria, thereby increasing salt-free water excretion and hypertonicity, especially in patients with diabetes mellitus. Other electrolytes, including serum potassium, should be monitored and should be replaced as needed.
In patients with hypernatremia and euvolemia, free water can be replaced using either 5% D/W or 0.45% saline.
Treatment of patients with central diabetes insipidus and acquired nephrogenic diabetes insipidus are discussed elsewhere.
In patients with hypernatremia and hypovolemia, particularly in patients with diabetes with nonketotic hyperglycemic coma, 0.45% saline can be given as an alternative to a combination of 0.9% normal saline and 5% D/W to replenish sodium and free water. Alternatively, ECF volume and free water can be replaced separately, using the formula given previously to estimate the free water deficit. When severe acidosis (pH <7.10) is present, sodium bicarbonate solution can be added to 5% D/W or 0.45% saline, as long as the final solution remains hypotonic.
Hypernatremia is usually caused by limited access to water or an impaired thirst mechanism, and less commonly by diabetes insipidus.
Manifestations include confusion, neuromuscular excitability, hyperreflexia, seizures, and coma.
Patients who do not respond to simple rehydration or in whom there is no obvious cause may need assessment of urine volume and osmolality, particularly after water deprivation.
Replace intravascular volume and free water orally or intravenously at a rate dictated by how acutely (< 24 hr) or chronically (>24 hr) the hypernatremia has developed, while watching other serum electrolyte levels (especially potassium and bicarbonate) as well.
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