eMedicine Specialties > Emergency Medicine > Endocrine & Metabolic

Hypernatremia

Author: Steven L Stephanides, MD, Attending Physician, Department of Emergency Medicine, Eisenhower Medical Center
Contributor Information and Disclosures

Updated: Aug 18, 2009

Introduction

Background

Sodium levels are tightly controlled in a healthy individual by regulation of urine concentration and production and regulation of the thirst response. In patients with an intact thirst response, hypernatremia (defined as a serum sodium level >145 mEq/L) is a rare entity. When hypernatremia does occur, it is associated with a high mortality rate (>50% in most studies).

Given this high mortality rate, the emergency physician must be able to recognize and treat this condition. Accordingly, this article discusses the patients in whom hypernatremia should be suspected and a treatment strategy for patients in whom the condition is discovered.

In general, hypernatremia can be caused by derangement of the thirst response or the behavioral response thereto (primarily in infants, psychiatric patients, and elderly patients who are institutionalized), by problems with the renal concentrating mechanism (diabetes insipidus [DI]) secondary to kidney pathology (nephrogenic DI) or difficulty with the neurohormonal control of this concentrating mechanism (central DI), or by losses of free water from other sources.

Assessment and treatment of a hypernatremic patient focuses on 2 important questions:

• What is the patient's volume status?
• Is the problem acute or chronic?

Pathophysiology

Water homeostasis results from the balance between water intake and the combined water loss from renal excretion, respiratory, skin, and GI sources. Under normal conditions, water intake and losses are matched. To maintain salt homeostasis, the kidneys similarly adjust urine concentration to match salt intake and loss.

Hypernatremia results from disequilibrium of one or both of these balances. Most commonly, the disorder is caused by a relative free water loss, although it can be caused by salt loading. The various ways in which these equilibria can be disturbed are discussed in Causes.

When hypernatremia (of any etiology) occurs, cells become dehydrated. Either the osmotic load of the increased sodium acts to extract water from the cells or a portion of the burden of the body's free water deficit is borne by the cell. (Sodium, primarily an extracellular ion, is actively pumped out of most cells and is the primary determinant of serum osmolarity.) Dehydrated cells shrink from water extraction.

Cells immediately respond to combat this shrinkage and osmotic force by transporting electrolytes across the cell membrane, thus altering rest potentials of electrically active membranes. After an hour of hypernatremia, intracellular organic solutes are generated in an effort to restore cell volume and to avoid structural damage. This protective mechanism is important to remember when treating a patient with hypernatremia. Cerebral edema ensues if water replacement proceeds at a rate that does not allow for excretion or metabolism of accumulated solutes.

The effects of cellular dehydration are seen principally in the CNS, where stretching of shrunken neurons and alteration of membrane potentials from electrolyte flux lead to ineffective functioning. If shrinkage is severe enough, stretching and rupture of bridging veins may cause intracranial hemorrhage.

Frequency

United States

Hypernatremia occurs in approximately 1% of hospitalized patients. The condition usually develops after hospital admission. An incidence closer to 2% has been reported in debilitated elderly persons and in breastfed infants.^1,2

International

Pediatric patients in developing nations may be at increased risk for hypernatremia because infant feeding may be complicated by poor maternal milk production (secondary to nutritional status) and errors in reconstitution of powdered formula.

Mortality/Morbidity

The mortality rate from hypernatremia is high, especially among elderly patients. Mortality rates of 42-75% have been reported for acute changes and 10-60% for chronic hypernatremia. Because patients with hypernatremia often have other serious comorbidities, precisely evaluating the degree of mortality directly due to hypernatremia is difficult. Morbidity in survivors is high, with many patients experiencing permanent neurologic deficits.

• Most deaths are due to an underlying disease process, rather than the hypernatremia itself. Delays in treatment (or inadequate treatment) of hypernatremia increase mortality.
• In hospitalized patients, persistent hypernatremia and protracted hypotension have been associated with a very poor prognosis.

Sex

Hypernatremia is diagnosed in males and females in equal numbers.

Age

Patients who present to the hospital with hypernatremia tend to be at the extremes of age. Breastfed infants occasionally present with hypernatremia in the first weeks of life, and elderly patients who are institutionalized are especially heavily represented.

Clinical

History

The history in the hypernatremic patient often points to the etiology of the syndrome. Search for any cause of extrarenal fluid losses (eg, burns, vomiting, diarrhea, fevers). Investigate the patient's perception of his or her fluid status and corrective measures he or she has taken. Does the patient complain of polyuria or polydipsia (ie, signs of DI or osmotic diuresis)? Does the patient have an intact thirst response? (This often is impaired in elderly persons.) A diminished thirst response is an indication to investigate the hypothalamus for a lesion in the thirst centers. For unclear reasons, patients with DI often crave ice-cold water.

In infants, seek sources of extrarenal losses, and investigate the patient's dietary habits. Hypernatremia in infants is often caused by improper preparation of formula or poor maternal milk production.³

In patients who are hospitalized, reviewing the medicines and feedings the patient has received in search of an iatrogenic sodium load is imperative. Commonly identified sources include the administration of sodium bicarbonate during an arrest, high-sodium tube feedings, or overaggressive infusion of 3% isotonic sodium chloride solution. Pharmaceutical causes of nephrogenic DI should also be considered (see Causes).

Symptoms of hypernatremia tend to be nonspecific. Anorexia, restlessness, nausea, and vomiting occur early. These symptoms are followed by altered mental status, lethargy or irritability, and, eventually, stupor or coma. Musculoskeletal symptoms may include twitching, hyperreflexia, ataxia, or tremor. Neurologic symptoms are generally nonfocal (eg, mental status changes, ataxia, seizure), but focal deficits such as hemiparesis have been reported.

Physical

Physical examination findings in hypernatremia are nonspecific.

• Assessment of overall fluid status is important when determining the cause of the hypernatremia. Note signs of volume status, including mucous membranes, skin turgor, orthostatic vital signs, and neck veins.
• Because neurologic deficits are common in hypernatremia, perform a thorough neurologic examination.
• Significant hypovolemia can result when hypotonic fluid losses cause hypernatremia. The physical findings are those of dehydration or even hypovolemic shock, with tachycardia, orthostasis, and hypotension.

Causes

The most common cause of hypernatremia in elderly or institutionalized patients is lack of free water intake adequate to meet losses. Thirst is the body's main defense against increased serum tonicity. The thirst drive is activated through 2 pathways, one responsive to decreased intravascular volume and the other responsive to even slight increases in serum osmolarity. Most patients with an intact thirst mechanism and access to water can prevent the development of hypernatremia. Even patients with a defective renal concentrating mechanism (eg, patients with DI who may produce up to 20 L of urine a day) generally can keep up with water losses if they are allowed free access to water.

Some patients, however, cannot respond to their thirst drive. Infants and elderly patients who are debilitated depend on caregivers to provide fluids. Similarly, institutionalized patients may have limited access to water secondary to either external or internal constraints (eg, no access to water in their room, they believe the water is poisoned and refuse to drink it). Intrinsic water losses cannot be avoided, and some urine must be produced, even if it is maximally concentrated. Without access to water, these patients encounter a free water deficit, and their serum sodium level increases.

In some instances, the difficulty stems from an inability of the kidneys to concentrate the urine. This is known as diabetes insipidus (DI). DI can be due to a lack of a central stimulus to concentrate the urine (ie, lack of antidiuretic hormone [ADH] production [central DI]) or to a lack of renal response to such stimulus (ie, nephrogenic DI). The kidneys can fail to respond secondary to resistance to vasopressin or due to loss of the medullary-concentrating gradient for urine.

The differential diagnosis is most easily managed if the physician considers the patient's volume status.

• Hypovolemic hypernatremia (ie, water deficit >sodium deficit)
  • Extrarenal losses - Diarrhea, vomiting, fistulas, significant burns
  • Renal losses - Osmotic diuretics, diuretics, postobstructive diuresis, intrinsic renal disease
  • Adipsic hypernatremia is secondary to decreased thirst. This can be behavioral or, rarely, secondary to damage to the hypothalamic thirst centers.
• Hypervolemic hypernatremia (ie, sodium gains >water gains)
  • Hypertonic saline
  • Sodium bicarbonate administration
  • Accidental salt ingestion (eg, error in preparation of infant formula)
  • Mineralocorticoid excess (Cushing syndrome)
• Euvolemic hypernatremia
  • Extrarenal losses - Increased insensible loss (eg, hyperventilation)
  • Renal losses - Central DI, nephrogenic DI
    • These patients appear euvolemic because most of the free water loss is from intracellular and interstitial spaces, with less than 10% occurring from the intravascular space.
    • Typically, symptoms result if serum sodium level is more than 160-170 mEq/L.
• Central DI differential diagnosis
  • Head trauma
  • Suprasellar or intrasellar tumors
  • Granulomas (sarcoidosis, Wegener granulomatosis, tuberculosis, syphilis)
  • Histocytosis (eosinophilic granuloma)
  • Infectious (encephalitis, meningitis, Guillain-Barré syndrome)
  • Vascular (cerebral aneurysm, thrombosis, hemorrhage, Sheehan syndrome)
  • Congenital
  • Transient DI of pregnancy
• Nephrogenic DI (deficient renal response to ADH) differential diagnosis
  • Advanced renal disease (interstitial disease)
  • Electrolyte disturbances - Hypokalemia, hypercalcemia
  • Systemic diseases - Sickle cell disease, Sjögren syndrome, amyloidosis, Fanconi syndrome, sarcoidosis, renal tubular acidosis, light-chain nephropathy
  • Dietary disturbances - Excessive water intake, decreased salt intake, decreased protein intake
  • Drugs - Lithium, demeclocycline, colchicine, vinblastine, amphotericin B, gentamicin, furosemide, angiographic dyes, osmotic diuretics
  • Miscellaneous - Postobstructive diuresis, diuretic phase of acute renal failure, osmotic diuresis, paroxysmal hypertension

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