Regardless of etiology, hyponatremia primarily affects the CNS. As the Na⁺ concentration drops below 125 mEq/L, changes in cognition and motor function occur commonly. Confusion and seizures often occur at serum values less than 120 mEq/L, particularly if the decline occurs acutely. The severity of the complications increases rapidly with a declining Na⁺ concentration; half of all patients with severe hyponatremia (Na⁺ < 105 mEq/L) die.

While clearly there are risks from hyponatremia, there are also risks of treating it. Even though there are no definitive studies of the topic, it is generally agreed that the speed of correction should be in proportion to the chronicity of the problem. Unfortunately, the clinician oftentimes does not know the duration of hyponatremia. Practically speaking, most symptomatic hyponatremic patients should have the Na⁺ corrected to an initial level of 120 to 130 mEq/L over a 12- to 24-h period, at an hourly rate not to exceed 1 to 2 mEq/L. (Without little supporting data, some experts sanction rapid normalization of hyponatremia, even when severe, if <1 to 2 days duration.) Slower correction (i.e., 0.5 mEq/L/h) is prudent in patients with chronic hyponatremia. Rapid correction of long-standing hyponatremia is associated with serious neurologic sequelae—central pontine myelinolysis (CPM). CPM is a CNS demyelinating syndrome characterized by weakness, dysarthria, dysphagia, coma, and potentially death. Risk factors include not only the rate of hyponatremia correction but also severity of the hyponatremia, advanced age, preexisting liver or CNS disorders, diuretic use, and alcoholism.

The treatment of hyponatremia depends on its cause and severity. In hypervolemic hyponatremia, restrictions of salt and fluid are the mainstays of therapy. However, diuretics or dialysis may be required when renal function is impaired. In most patients with hypovolemic hyponatremia, isotonic saline should be used to restore circulating volume. In isovolemic hyponatremia, free water restriction and treatment of the underlying disorder are preferred. In less-acute cases of SIADH, hyponatremia may respond to demeclocycline (600 to 1,200 mg/day). Rarely vaprisol (40 mg IV over 24 h) may be useful.

Most patients with severe and symptomatic hyponatremia (stupor, coma, seizures, etc.) require hypertonic saline and/or diuretics to achieve safe serum Na⁺ with adequate speed. (Remember that 0.9% saline is significantly “hypertonic” for severely hyponatremic patients.) Relatively small increases in serum Na⁺ on the order of 5% should decrease cerebral edema. One should slow correction once life-threatening manifestations have improved, typically to approximately 0.5 mEq/L/h. One way to calculate the amount of Na⁺ to be given using 3% saline follows. Multiply the desired change in serum Na⁺ times the estimated total body water to get the number of mEq of Na⁺ to be administered. Divide that amount by the concentration of Na⁺ in the fluid to be infused (513 mEq/L for 3% saline) to obtain the total volume to be administered. Then divide the total volume by the time over which the correction is desired to yield the infusion rate.

Example: A 60-kg woman with normal preoperative electrolytes develops seizures postoperatively while receiving hypotonic fluid. The serum Na⁺ is 116 mEq.

Calculation to raise the serum Na⁺ to 120 mEq over 4 h is as follows:

Hypernatremia, defined as a serum Na⁺ level more than 145 mEq/L, occurs when more water than Na⁺ is lost from the body or when highly concentrated Na⁺ solutions are administered or ingested. Hypernatremia is rare in patients with intact ADH secretion, a sensitive thirst mechanism, and access to free water. Hence, it is primarily a disease of patients who are unable to obtain and drink fresh water (e.g., infants, elderly, bedridden, and critically ill), particularly those simultaneously sustaining increased water losses (e.g., diuretics, sweating). Hypernatremia implies hyperosmolarity, the major mechanism of toxicity.

Similar to hyponatremia, the problem can logically be thought of in three categories: high, normal, or low extracellular volume. Hypervolemic hypernatremia occurs from ingestion or infusion of hypertonic Na⁺ containing solutions. For example, “normal” saline (0.9% NaCl) is modestly hypertonic (Na⁺ 154 mEq/L, 308 mOsm/L) and without adequate free water, it tends to raise the serum Na⁺ concentration while expanding extracellular volume. Hypernatremia is much more common when osmolarity is intentionally increased by hypertonic (3%) saline (Na⁺ 513 mEq/L, 1,026 mOsm/L) or unintentionally by sodium bicarbonate (NaHCO₃) with a Na⁺ of 595 mEq/L and 1,190 mOsm/L. Even though data on effectiveness are limited, 3% saline is now a widely used therapy for intracranial hypertension from cerebral edema. In this setting, serum hypertonicity attracts water from cerebrospinal fluid and brain cells thereby facilitating cerebral blood flow. For effect, serum Na⁺ is typically maintained in the 145 to 155 mEq/L range (roughly 300 to 320 mOsm/L). Hypertonic saline is now also being used for field resuscitation of hemorrhagic shock because the fluid is low in cost, does not require refrigeration or cross-matching, and produces substantial intravascular volume expansion for the amount of fluid that must be transported. Hypernatremia can be an unintended consequence of NaHCO₃ if large volumes are administered to treat metabolic acidosis or cyclic antidepressant overdose. For patients with impaired Na⁺ clearance, the Na⁺-K⁺ ion exchange resin, Kayexalate, can raise serum Na⁺ by transferring significant salt loads across the bowel wall. Na⁺ accumulations from primary hyperaldosteronism or salt or sea water ingestion are rare causes of hypernatremia.

Extracellular volume is normal, at least initially in a number of hypernatremic conditions. For example, both central and nephrogenic diabetes insipidus (DI) produce hypernatremia by preventing appropriate water reabsorption by the distal convoluted tubules and collecting ducts of the kidney. In central DI, ADH secretion is inadequate and in nephrogenic DI, the kidney does not respond normally to the secreted ADH. Hypernatremia with
near normal extracellular volume can also result from insensible (skin and lung) water losses of burns, tachypnea, or hyperthermia (high fever, heatstroke, neuroleptic malignant syndrome, malignant hyperthermia, etc.). Note that a high minute ventilation does not cause dehydration in mechanically ventilated patients because fully humidified gas is used.

Hypernatremia can also result from conditions that cause low extracellular volume such as vomiting, diarrhea, and osmotic diuretics such as glucose, mannitol, or glycerol. In each case, the tonicity of the fluid lost must be less than that of serum for hypernatremia to develop.

Regardless of cause, the common symptoms of hypernatremia are thirst, nausea, vomiting, agitation, stupor, and coma. Unfortunately, all these symptoms are nonspecific, hence their cause often goes unrecognized. The history and physical examination typically lead to the correct diagnosis. It is usually obvious when NaHCO₃, 3% NaCl, or osmotic diuretics have been administered. The impressive urine output of the volume-replete patient with full-blown DI (up to 1 to 2 L/h) is also almost always noted. It is important to note that the diagnosis of DI may be missed if free water losses have progressed to the point that profound intravascular volume depletion has occurred. Caution must be exercised in the diagnosis of DI; in the unstable, volume-depleted patient in the ICU, the often recommended “water deprivation test” may prove harmful. A better strategy is to replace the circulating volume and empirically give a trial of ADH. When hemodynamically stable, additional endocrine testing, including a water deprivation test, may be safely performed. Although hypernatremia usually does not present a diagnostic challenge, the urinary osmolarity can be particularly helpful if the etiology is unclear (Table 13-3).

Treatment of hypernatremia consists of the replacement of water (either given enterally or as D₅W or a hypotonic NaCl solution), with frequent evaluation of electrolytes and osmolality. The speed of correction should depend on the chronicity of the problem and the severity of neurologic symptoms, but as a general rule, correction at a rate of 0.5 to 2 mEq/L each hour is an appropriate target. Expert recommendations also suggest that correction rates not exceed 12 mEq/L in a day or 18 mEq/L over two days. Like hyponatremia, very rapid correction, especially of longstanding hypernatremia, can precipitate CPM or cerebral edema. The latter condition results from rapid swelling of neurons which have accumulated “idiogenic osmoles” in an attempt to match the tonicity of serum during hypernatremia. If endogenous ADH is deficient or ineffective, it may be replaced with desmopressin (DDAVP), an ADH analog (see Chapter 32). In the less common cases of hypernatremia resulting from Na⁺ gain, such as after the NaHCO₃ administration (cardiac arrest), the use of loop diuretics addition to Na⁺ poor fluid may be necessary.

Unnecessarily precise calculations of “water deficit” are often performed in hypernatremia. It is important to recognize that the use of the conventional water deficit formula—Water deficit = (0.6 × weight) × (1 – [140/serum sodium concentration])—has limitations. It may underestimate the free water need in cases of hypotonic fluid losses (e.g., vomiting) and does not take into account the ongoing insensible losses. Because Na⁺ concentrations less than 155 mEq/L rarely concern clinicians, by the time the decision is made to treat hypernatremia in
the average sized adult, water deficits average 4 to 6L. If the goal is to correct the deficit over 1 to 2 days, IV infusion of D₅W at 200 mL/h is usually effective unless the initial Na⁺ concentration is much higher or ongoing water losses are substantial.