Cerebral correlates of hyponatremia.

Hyponatremia, defined as a serum sodium concentration ([Na+]) less than 135 mEq/L, is commonly caused by elevated levels of the hormone arginine vasopressin (AVP), which causes water retention. The principal organ affected by disease-related morbidity is the brain. The neurologic complications associated with hyponatremia are attributable to cerebral edema and increased intracranial pressure, caused by the osmotically driven movement of water from the extracellular compartment into brain cells. Although neurologic symptoms induced by hyponatremia are limited by an adaptive brain mechanism known as "regulatory volume decrease," an overly rapid correction of serum [Na+] before the reversal of this adaptive response can also produce neurologic damage. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a frequent cause of hyponatremia related to central nervous system disorders, neurosurgery, or the use of psychoactive drugs. Fluid restriction is the standard of care for patients with SIADH who are asymptomatic or who have only mild symptoms, but patients with severe or symptomatic hyponatremia require more aggressive therapy. Infusion of hypertonic saline is the usual approach to the treatment of symptomatic hyponatremia, but patients require frequent monitoring. Pharmacologic agents such as demeclocycline and lithium may be effective in some patients but are associated with undesirable adverse events. The AVPreceptor antagonists are a new therapeutic class for the treatment of hyponatremia. The first agent in this class approved for the treatment of euvolemic hyponatremia in hospitalized patients is conivaptan. Two other agents, tolvaptan and lixivaptan, are being evaluated in patients with euvolemic and hypervolemic hyponatremia. The AVP-receptor antagonists block the effects of elevated AVP and promote aquaresis, the electrolyte-sparing excretion of water, resulting in the correction of serum [Na+]. These agents may also have intrinsic neuroprotective effects.