Hypernatremia

GENERAL PRINCIPLES

• Hypernatremia is defined as a plasma [Na⁺] >145 mEq/L and represents a state of hyperosmolality (see “Disorders of Sodium Concentration” section).

• Hypernatremia may be caused by a primary Na⁺ gain or a water deficit, the latter being much more common. Normally, this hyperosmolar state stimulates thirst and the excretion of a maximally concentrated urine. For hypernatremia to persist, one or both of these compensatory mechanisms must be impaired.

• Impaired thirst response may occur in situations where access to water is limited, often due to physical restrictions (institutionalized, handicapped, postoperative, or intubated patients) or mental impairment (delirium, dementia).

• Hypernatremia due to water loss. The loss of water must occur in excess of electrolyte losses to raise [Na⁺].

î Nonrenal water loss may be due to evaporation from the skin and respiratory tract (insensible losses) or loss from the GI tract. Diarrhea is the most common GI cause of hypernatremia. Osmotic diarrhea (induced by lactulose, sorbitol, or malabsorption of carbohydrate) and viral gastroenteritis, in particular, result in disproportional water loss.

î Renal water loss results from either osmotic diuresis or diabetes insipidus (DI).

■ Osmotic diuresis is frequently associated with glycosuria and high osmolar feeds. In addition, increased urea generation from accelerated catabolism, high-protein feeds, and stress-dose

steroids can also result in an osmotic diuresis.

■ Hypernatremia secondary to nonosmotic urinary water loss is usually caused by impaired vasopressin secretion (central diabetes insipidus [CDI]) or resistance to the actions of vasopressin (nephrogenic diabetes insipidus [NDI]). Partial defects occur more commonly than complete defects in both types.

■ The most common cause of CDI is destruction of the neurohypophysis from trauma, neurosurgery, granulomatous disease, neoplasms, vascular accidents, or infection.

■ NDI may either be inherited or acquired. Acquired NDI often results from a disruption to the renal concentrating mechanism due to drugs (lithium, demeclocycline, amphotericin), electrolyte disorders (hypercalcemia, hypokalemia), medullary washout (loop diuretics), and intrinsic renal diseases.

• Hypernatremia due to primary Na⁺ gain occurs infrequently because of the kidney's capacity to excrete the retained Na⁺. However, it can rarely occur after repetitive hypertonic saline administration or chronic mineralocorticoid excess.

• Transcellular water shift from ECF to ICF can occur in circumstances of transient intracellular hyperosmolality, as in seizures or rhabdomyolysis.

DIAGNOSIS

Clinical Presentation

• Hypernatremia results in contraction of brain cells as water shifts to attenuate the rising ECF osmolality. Thus, the most severe symptoms of hypernatremia are neurologic, including altered mental status, weakness, neuromuscular irritability, focal neurologic deficits, and, occasionally, coma or seizures. As with hyponatremia, the severity of the clinical manifestations is related to the acuity and magnitude of the rise in plasma [Na⁺]. Chronic hypernatremia is generally less symptomatic as a result of adaptive mechanisms designed to defend cell volume.

• CDI and NDI generally present with complaints of polyuria and thirst. Signs of volume depletion or neurologic dysfunction are generally absent unless the patient has an associated thirst abnormality.

Diagnostic Testing

Urine osmolality and the response to DDAVP can help narrow the differential diagnosis for hypernatremia (Figure 12-2).

Figure 12-2 Algorithm depicting the diagnostic approach to hypernatremia.BUN, blood urea nitrogen; ↑Ca⁺, hypercalcemia; CDI, central diabetes insipidus; DDAVP, desmopressin acetate; ECF, extracellular fluid; GI, gastrointestinal; NDI, nephrogenic

diabetes insipidus; tK⁺, hypokalemia; (+), conditions with increase in urine osmolality in response to desmopressin acetate; (-), conditions with little increase in urine osmolality in response to desmopressin acetate.

• The appropriate renal response to hypernatremia is a small volume of concentrated urine (urine osmolality >800 mOsm/L).

• Response to DDAVP. Complete forms of CDI and NDI can be distinguished by administering the vasopressin analog DDAVP (10 μg intranasally) after careful water restriction. The urine osmolality should increase by at least 50% in complete CDI and does not change in NDI. The diagnosis is sometimes difficult when partial defects are present.

TREATMENT

• Rate of correction

î Aggressive correction of symptomatic hypernatremia is potentially dangerous, although the risk is not as well defined as overcorrection in hyponatremia. Out of an abundance of caution, the water deficit should be reduced gradually and plasma [Na⁺] levels should be reduced by no more than 10­12 mEq/L/d.

î In chronic hypernatremia, the risk of treatment-related complications may be increased because of the cerebral adaptation to the chronic hyperosmolar state. The plasma [Na⁺] should be lowered at a more moderate rate (between 5 and 8 mEq/L/d).

• Intervention

î The mainstay of management is the administration of water, preferably by mouth or nasogastric tube. Alternatively, 5% dextrose in water (D5W) or quarter NS can be given via IV

■ The extent of the free water deficit can be calculated by the equation:

■ This free water deficit provides a target amount of water that should be replaced to correct the hypernatremia.

■ The rate of water administration can be estimated by dividing this amount by the time frame over which hypernatremia should be normalized to achieve the target rate of correction outlined above.

? Example: For a 3-L free water deficit that you wish to correct over 24 hours, the D5W can be run at 3 L/24 h = 125 mL/h.

? It should be noted that this equation does NOT account for ongoing free water losses. Using this equation alone without considering ongoing losses through GI or renal excretion may result in an underestimation of the amount of water required to correct a patient's hypernatremia.

■ No single equation adequately captures the dynamic input and output of free water in a patient. Because of this, it is critically important to recheck laboratory data to ensure that an appropriate rate of correction is being achieved.

î Specific therapies for the underlying cause

■ Hypovolemic hypernatremia. In patients with mild volume depletion, Na⁺-containing solutions such as 0.45% NS can be used to replenish the ECF as well as the water deficit. If patients have severe or symptomatic volume depletion, correction of volume status with isotonic fluid should take precedence over correction of the hyperosmolar state. Once the patient is hemodynamically stable, hypotonic fluid can be given to replace the free water deficit.

■ Hypernatremia from primary Na⁺ gain is unusual. Cessation of iatrogenic Na⁺ is typically sufficient.

■ DI without hypernatremia. DI is best treated by removing the underlying cause. Despite the renal water loss, DI should not result in hypernatremia if the thirst mechanism remains intact. However, treatment is sometimes required to alleviate symptomatic polyuria.

? CDI. Because the polyuria is the result of impaired secretion of vasopressin, treatment is best accomplished with the administration of DDAVP, a vasopressin analog.

? NDI. A low-Na⁺ diet combined with thiazide diuretics will decrease polyuria by inducing mild volume depletion. This enhances proximal reabsorption of salt and water, thus decreasing urinary free water loss. Decreasing protein intake will further decrease urine output by minimizing the solute load that must be excreted.