Hypernatremia

Hypernatremia is defined as an increase in extracellular sodium concentration and may be accompanied by the presence of low, normal, or high total-body sodium content. The major causes of hypernatremia are excessive loss of water, inadequate intake of water, a lack of ADH, or excessive intake of sodium (e.g., with solutions containing a high sodium concentration such as sodium bicarbonate).

Diabetes insipidus may result from a deficiency of vasopressin or inability of the kidney to produce a hypertonic medullary interstitium. Diabetes insipidus is characterized by production of a large volume of dilute urine. Deficiency of vasopressin is called central diabetes insipidus and is an endocrine disorder. Vasopressin deficiency is seen after pituitary surgery, basal skull fracture, and severe head injury. Conversely, nephrogenic diabetes insipidus results if the kidney cannot produce a hypertonic medullary interstitium and is unable to concentrate urine. Nephrogenic diabetes insipidus may result from renal tubule cell insensitivity to the effects of vasopressin. Nephrogenic diabetes insipidus may result from any systemic or kidney disease that impairs tubular function. In central or nephrogenic diabetes insipidus, the patient loses a significant amount of body water in a short period, which can cause profound hypovolemia if the patient does not have adequate access to water.

Approximately 50% of patients with central diabetes insipidus are classified as having idiopathic disease. This condition is thought to be caused by an autoimmune process affecting the response of the hypothalamus to hypertonicity. Patients with nephrogenic diabetes insipidus have marked increases in the plasma levels of

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Patients with continued urine output of more than 100 mL/hour who develop hypernatremia should be evaluated for diabetes insipidus by determining the osmolalities of urine and serum. If the urine osmolality is less than 300 mOsm/L and serum sodium exceeds 150 mEq/L, the diagnosis of diabetes insipidus is suggested. In patients with central diabetes insipidus, 1-deamino-8-D-arginine vasopressin (DDAVP), a vasopressin analog also known as desmopressin acetate, may be administered to correct the deficiency in vasopressin. The underlying cause of nephrogenic diabetes insipidus should be found and treated if possible.

In the presence of an intact thirst mechanism, a slight increase in serum sodium concentration (e.g., 3 to 4 mmol/L) above baseline values elicits intense thirst. The lack of thirst in the presence of hypernatremia in a mentally alert patient indicates a defect in the osmoreceptor or in the cortical thirst center. The most common objective sign of hypernatremia is lethargy or mental status changes, which can proceed to coma and convulsions. Additional signs and symptoms of hypernatremia include thirst, shock, peripheral edema, myoclonus, ascites, muscular tremor, muscular rigidity, hyperactive reflexes, pleural effusion, and expanded intravascular fluid volume. With acute and severe hypernatremia, the osmotic shift of water from the cells can lead to shrink-age of the brain with tearing of the meningeal vessels and intracranial hemorrhage. Slowly developing hypernatremia is usually well tolerated because of the brain's ability to regulate its volume. Treatment involves restoring normal osmolality and volume and includes removal of excess sodium by the administration of diuretics and hypotonic crystalloid solutions, by identification and removal of solutes, or by some combination of these approaches. The speed of correction depends on the rate of development of hypernatremia and associated symptoms. Because chronic hypernatremia is well tolerated, rapid correction offers no advantage and may be extremely harmful or lethal because it may result in brain edema.^{[35] [36]} Typically, a maximum of 10% of the serum sodium concentration, or about 0.7 mmol/L per hour, should be the

TABLE 46-6 -- Drugs causing nephrogenic diabetes insipidus

Lithium

Foscarnet

Glyburide

Demeclocycline

Methoxyflurane

Amphotericin B

TABLE 46-7 -- Major causes of hypernatremia

Causes	Mechanisms
Impaired thirst	Coma, essential hypernatremia
Solute (osmotic) diuresis	Mannitol administration, diabetic ketoacidosis, nonketotic hyperosmolar coma
Excessive water losses: renal	Pituitary diabetes insipidus, nephrogenic diabetes insipidus
Excessive water losses: extrarenal	Sweating
Combined disorders	Coma plus hypertonic nasogastric feeding
Adapted from Andreoli TE: Disorders of fluid volume, electrolyte, and acid-base balance. In Wyngaarden JB, Smith LH Jr (eds): Cecil Textbook of Medicine, 17th ed. Philadelphia, WB Saunders, 1985, p 528.

goal rate of correction. Hypernatremia increases the minimum alveolar concentration of inhalational anesthetic agents, possibly because of enhanced sodium conductance during depolarization of excitatory membranes^[37] ( Table 46-7 ).