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Hyponatremia is the most common electrolyte disorder in hospitalized patients. While the kidney is important in the pathogenesis of hyponatremia, the effect on the brain, rather than the underlying condition, is the reason for the high morbidity and mortality. Hyponatremia causes cerebral edema which, in turn, can lead to several life-threatening conditions such as pulmonary edema, cerebral infarction, respiratory arrest, and coma. Fraser and Arieff provide a comprehensive review of hyponatremic encephalopathy.
The basic defect in hyponatremia is the inability of the kidney to excrete free water. Other contributing factors include osmolality, tonicity, thirst, and their relationship to anti- diuretic hormone (ADH), which is often relatively increased in hyponatremic states.
Clinical Manifestations: Clinical manifestations are directly related to the development of cerebral edema, increased intracranial pressure, and cerebral hypoxia. The early symptoms are usually non-specific and include weakness, muscle cramps, and headache. Advanced manifestations include a spectrum of neurological abnormalities ranging from central diabetes insipidus, bizarre behavior, asterixis, and seizures to respiratory arrest, coma, permanent brain damage, and death.
Clinical Conditions Association with Hyponatremic Brain Damage: While brain damage can occur with both hyponatremic encephalopathy and improper treatment of hyponatremia, clinical data suggest that the former is the usual circumstance. A few clinical settings account for the majority of brain damage due to hyponatremia (see Table 1).
2. Young menstruant women, 25 ´ of brain damage
3. Prepubertal children
4. Post-operative state
5. Pharmacologic agents
6. Congestive heart failure
7. Adults with AIDS
a. Post-operative hyponatremia. This occurs in about 1% of cases and has an overall morbidity of 5%. In this setting, premenopausal young women are particularly at risk of developing brain edema and respiratory insufficiency, which occurs at a higher sodium level (117 + 7 mmol/L; range, 104-130 mmol/L) as compared with post-menopausal women (107+ mmol/L; range, 92-123 mmol/L).
b. Congestive heart failure. It is the most common cause of hyponatremia in the United States. Hyponatremia is of prognostic significance with a one-year mortality greater than 50%, although the actual number dying from hyponatremia per se are undetermined.
c. Pharmacologic agents. Many drugs interfere with the ability of the kidney to excrete free water (see Table 2). Thiazide-induced hyponatremia may represent an idiosyncratic drug reaction, with massive urinary sodium and potassium losses.
d. AIDS. The three major reasons for hyponatremia in AIDS are SIADH, volume deficiency with hypotonic fluid replacement, and adrenal insufficiency.
e. Psychogenic polydipsia. Patients with bipolar disorders cannot clear free water and have elevated ADH levels.
Hypoxia and Hyponatremic Encephalopathy. Hypoxemia is a very major contributing factor to brain damage in hyponatremia. In symptomatic patients, respiratory arrest can occur abruptly, and severe permanent brain damage may occur. Hypoxia decreases the effectiveness of compensatory changes in the brain by which the brain adapts to increases in cell-water. By severe blunting of the increase in NA+-K-ATPase transport activity, which is initiated by hyponatremia, hypoxia causes a net increase in brain water, with resultant brain edema.
Management of Hyponatremia
a. The Asymptomatic Patient. Hypertonic saline is not indicated, and normal saline should be used in volume-depleted patients. In SIADH, water restriction is often not practical because fluid intake has to be limited to less than 800 mL/d and, even so, serum sodium rarely exceeds 1-1.5 mmol/d. However, water restriction should always be attempted. Drugs such as demeclocycline can be useful in SIADH.
b. The Symptomatic Patient. This is a medical emergency, and the patient should be monitored in the intensive care unit. The therapy is outlined in Table 3.
1. Secure an airway
2. Hypertonic sodium chloride (514 mmol/L) administration by infusion pump to raise serum sodium by 1 mmol/L per hour. If seizures/raised intracranial pressure, increase rate of infusion to raise serum sodium by 4-5 mmol/L per hour until seizures stop.
3. Monitor serum sodium every 2 hrs. and adjust infusion rate. Sodium should not be elevated by more than 25 mmol/L in first 48 hours.
4. Loop diuretic may be used.
Complications of Therapy. Therapy of hyponatremia is not associated with brain damage. On the contrary, treatment of the symptomatic patient with hypertonic saline is associated with survival and recovery. Cerebral demyelinating lesions including central pontine myelinosis (CPM) develop in patients with hyponatremia when a) hyponatremia worsens during treatment; b) there is an absolute increase in sodium that exceeds 25 mmol/L in the first 24-48 hours of therapy; c) hypoxic event occurs; and d) severe liver disease is present. CPM has been associated with alcoholism, advanced liver disease, extensive burns, sepsis, Hodgkin's disease, and other malignancies.
Two anecdotes about hyponatremia-related brain damage can be put to rest. First, brain damage is not directly related to either a rapid decline in serum sodium or a particularly low level of serum sodium. Second, brain damage can occur in otherwise healthy individuals primarily as a result of brain edema in association with hypoxemia, with the highest risk (25-fold) being in premenopausal women. Unequivocally, the symptomatic hyponatremia patient with sodium less than 125 mmol/L is at risk of brain edema and possible permanent brain damage. To treat the symptomatic hyponatremic patient and bring the sodium up to the 120-125 mmol/L range is both medically correct and non-risky. Hyponatremia may be prevented in premenopausal young women and those undergoing surgical procedures by only using isotonic fluids and abandoning hypotonic replacement therapy.