Hypernatremia

Hypernatremia is a common clinical problem, observed in up to 2% of the general hospital population and 15% of patients admitted to the intensive care unit.¹^–⁴ In the outpatient setting, hypernatremia is most prevalent in the geriatric patient population; in hospitalized patients, it is observed in all age groups.^1,⁵ Mortality rates in patients with hypernatremia can range as high as 70%.¹^–⁶ Although the high mortality rate no doubt reflects the severity of underlying disease in these patients, there is significant morbidity related to hypernatremia itself. Neurologic sequelae from hypernatremia are common, particularly in the pediatric population.⁶

Maintaining a normal serum sodium concentration (135–145 mEq/L) is dependent on the balance between water intake and water excretion. Hypernatremia results from a deficit of free water that leads to an increase in serum tonicity. The usual mechanism underlying the development of hypernatremia is inadequate water intake and increased free water loss, but it can also result from the intake of hypertonic sodium solutions. Hypernatremia may be associated with volume depletion, euvolemia, or hypervolemia, depending on the balance of salt and water loss and intake. Sodium content is low, normal, or high, respectively, in each of these circumstances. Relative sodium and volume status has important implications for the treatment of hypernatremic patients.

The brain is particularly susceptible to the effects of hypernatremia. When the sodium concentration in plasma is higher than normal, water moves across cytosolic membranes (from the inside of cells to the outside of cells) to preserve osmotic equilibrium. As a consequence of intracellular dehydration, there is a net loss of brain volume, which in turn places mechanical stress on cerebral vessels, possibly resulting in bleeding.⁶ With chronic hypernatremia, however, cellular adaptation occurs. Under these circumstances, so-called idiogenic osmoles accumulate in brain cells, minimizing cellular dehydration. Importantly, the presence of these idiogenic osmoles presents a risk for the development of cerebral edema during the treatment of hypernatremia.

The symptoms of hypernatremia are nonspecific and often difficult to separate from those of underlying illnesses in hospitalized patients. Central nervous system (CNS) abnormalities are most common and can include confusion, weakness, and lethargy in the early stages, progressing to seizures, coma, and death in later stages. The CNS symptoms result from the movement of water out of the brain cells rather than the hypernatremia per se. Neurologic deterioration can be seen during treatment as a result of the development of cerebral edema. Signs of volume depletion or volume overload may be present, depending on the cause of the hypernatremia.

The treatment of hypernatremia is water repletion (Box 13-1). Assuming total body water is 60%, the water deficit may be estimated as follows:

The percentage of water relative to total body weight is actually closer to 50% in women and about 50% in the elderly of both genders. Treatment should be instituted at a rate that balances the risk of hypernatremia with the risk of too rapid correction, particularly in cases of chronic hypernatremia. Half the calculated deficit should be replaced within the first 12 to 24 hours at a rate of sodium concentration correction not over 2 mEq/L per hour. The remainder of the water deficit can be replaced over the next 48 hours. The rapidity of replacement should be determined by the acuteness of onset and severity of symptoms.

Neurologic status has to be closely monitored during replacement for evidence of the development of cerebral edema. Ongoing replacement of fluid and electrolyte losses is also necessary during treatment. In patients with volume depletion and hemodynamic instability associated with hypernatremia, volume replacement with isotonic saline is initially indicated. Once hemodynamic stability is achieved, water replacement can be initiated. Hypotonic saline (e.g., 0.45% saline) may be preferable to water as the replacement fluid for these patients. If hypernatremia is associated with hypervolemia (e.g., as a consequence of treatment with hypertonic saline or hypertonic sodium bicarbonate solution), treatment should be directed toward reducing sodium intake while inducing sodium loss. In these patients, diuretics can be used along with free water (5% dextrose) infusion. Dialysis may be necessary if renal failure is present.

Hyponatremia

Hyponatremia is one of the most common electrolyte abnormalities seen in hospitalized patients. It occurs in 2% to 4% of hospitalized patients and up to 30% of patients in intensive care units.⁷^–¹⁰ Mortality for patients with acute hyponatremia is reportedly as high as 50%, whereas mortality for those with chronic hyponatremia is 10% to 20%.⁷^–¹¹

Hyponatremia is a water problem, not a sodium problem; there is always an excess of water relative to sodium when hyponatremia is present. In hyponatremia, water excretion by the kidney is impaired. Patients who are hyponatremic may be hypovolemic (water deficit and sodium deficit), euvolemic (water excess and normal sodium content), or hypervolemic (water excess and sodium excess). As is the case with hypernatremia, the patient’s volume status has implications for the treatment of hyponatremia.

In the presence of hyponatremia, there is a decrease in extracellular tonicity relative to the intracellular space. The osmotic gap causes movement of water from the extracellular space into the intracellular space and results in cell swelling. In the CNS, cellular swelling manifests as cerebral edema and results in the symptoms associated with hyponatremia. The degree of cerebral cell swelling correlates with the severity of symptoms observed. The CNS adapts to hyponatremia in two ways. First, cerebral edema causes an increase in interstitial hydrostatic pressure and results in the movement of fluid from the interstitial space into the cerebrospinal fluid (CSF), leading to some amelioration of cerebral edema, assuming normal CSF production and resorption physiology. Second, solutes are lost from cells, resulting in a decrease in intracellular osmolarity and thus movement of water out of cells. The solutes lost initially are sodium and potassium, followed by organic solutes over the next several days. Because of cerebral adaptation, the severity of neurologic symptoms is related to the acuity and magnitude of the hyponatremia. If hyponatremia develops gradually, brain cells can compensate by decreasing intracellular osmolarity through the loss of osmolytes, thereby limiting the degree of cerebral edema and resultant neurologic dysfunction. Importantly, during the correction of chronic hyponatremia, the regeneration of these osmolytes lags, and cerebral dehydration can occur with rapid correction.

In acute hyponatremia, nausea, vomiting, lethargy, and confusion can progress to coma, seizures, eventual cerebral herniation, and death.^11,¹² The elderly and the young are more likely to be symptomatic from hyponatremia.⁹ Menstruating women also tend to be more symptomatic and are at greater risk for neurologic complications from acute hyponatremia.¹¹ Early in the development of hyponatremia, the symptoms are difficult to separate from those related to the underlying disease process. Hyponatremic patients who have clinically significant space-occupying lesions in the CNS should be aggressively treated. Meanwhile, efforts should be made to determine the cause of hyponatremia by assessing intravascular volume status, measuring urine output, seeking the presence of exogenous sugars or sugar alcohols (e.g., mannitol), and determining urine sodium concentration and osmolarity.

Treatment of hyponatremia is dependent on the acuteness of the hyponatremia and the presence and severity of symptoms (Box 13-2). Acute (<48 hours) or chronic (>48 hours) symptomatic hyponatremia (e.g., seizures) requires immediate therapy. However, the optimal approach for the treatment of these patients is controversial.¹²^–¹⁴ The controversy results from reports of the occurrence of a central demyelination syndrome associated with the correction of hyponatremia in some patients.¹⁵^–²² This syndrome appears to be more common with chronic hyponatremia (>48 hours), overcorrection of hyponatremia, large corrections (>12 to 25 mEq/L per 24 hours), and rapid correction (>1 to 2 mEq/L per hour).¹⁹^–²²