Hypernatremia

Description

Hypernatremia is defined as a serum [Na⁺] >145 mEq/L; it indicates an absolute or relative water deficit.
Major causes include
- Excessive loss of water
- Inadequate water intake
- Lack of antidiuretic hormone (ADH)
- Excessive sodium intake from iatrogenic causes or accidental administration
Hypernatremia results in a hypertonic, hyperosmolar state within the extravascular compartment that draws water from the intracellular compartment causing cell shrinkage. This concept is harnessed therapeutically in patients with intracranial hypertension to decrease intracranial volume.

Epidemiology

Incidence

Found in ~1% of hospitalized patients.

Prevalence

Increased in patients who are intubated, have altered mental status, and where access to water is compromised (e.g., infants and elderly). In infants, it is usually associated with diarrhea or severe febrile illness.
Diagnosed equally among males and females.

Morbidity

Severe hypernatremia, defined by a [Na⁺] >160 mEq/L, or rapid onset of less than 12 hours, can result in intracranial bleeding, convulsions, neurologic deficits, and coma.
Chronic hyperosmolality and hypotonic fluid treatments can also cause cerebral edema, convulsions, coma, and death.

Mortality

Varies widely and is dependent on the severity of the condition and the rapidity of onset.

Acute changes: 42–75%
Chronic changes: 10–60%

Etiology/Risk Factors

Inadequate water intake (no gain in sodium)
- Restricted access to water; seen in nursing home or hospitalized persons who are dependent on others to meet fluid requirements.
- Impaired thirst mechanisms can result from a defect in the osmoreceptor or cortical thirst center as well as structural lesions involving the hypothalamus.
Hypotonic fluid loss
- Diabetic insipidus: Both central and nephrogenic causes
- Gastrointestinal (GI) losses: Diarrhea, vomiting, fistula
- Burns
- Peritoneal dialysis
- Insensible losses: Skin (excessive sweating), respiratory tract
- Renal losses: Osmotic diuresis as a result of hyperglycemia or diuretic therapy (mannitol), postobstructive diuresis
Sodium overload (in excess of body water)
- Excessive sodium intake: Iatrogenic causes include IV sodium bicarbonate or hypertonic saline (3% normal saline contains 30 g/L of sodium chloride which is equivalent to a [Na⁺] of 513 mEq/L); excessive PO salt intake.
- Mineralocorticoid excess: Cushing's syndrome, hyperaldosteronism
Medications that affect the function of the renal collection system: Lithium, glyburide, foscarnet, demeclocycline, amphotericin B, methoxyflurane.

Physiology/Pathophysiology

Under normal conditions, the sodium concentration is tightly regulated and maintained within a narrow range. Increases in sodium stimulate a strong thirst sensation and ADH release from the pituitary gland to re-establish normal levels. Physiological values are crucial to a myriad of functions within the human body:
- Maintains normal electrophysiological balance of the cell membrane. The normal transmembrane potential is maintained by the Na⁺/K⁺-ATPase pump, which pumps 3 sodium ions out of the cell for every 2 potassium ions transported into the cell.
- Maintains water homeostasis (water follows sodium)
- Maintains normal extracellular and intracellular osmolality
- Conducts electrical impulses in nerves, muscle, and cardiac tissue via specialized sodium channels.
- Regulates blood pressure BP via aldosterone's effects
General effects of hypernatremia: Hypertonic hyperosmolality that causes movement of water from the intracellular to extracellular space and results in intracellular compartment shrinkage.
Hypernatremia and the central nervous system: To offset cellular shrinkage, the brain increases intracellular solute uptake. Adverse effects include
- Intracranial bleeding. The brain is pulled away from the calvarium and can cause tearing of the bridging veins. Intraparenchymal bleeding results from capillary enlargement and rupture from cell shrinkage.
- Encephalopathy. Cellular shrinkage disrupts synaptic transmission and brain cell function.
Hypernatremia and the cardiovascular system. Rapid increases in serum sodium result in volume overload (fluid shifting out of the intracellular space) and can overwhelm the left ventricle with resultant dysfunction. Fluid may "backup" into the pulmonary vasculature and result in cardiogenic pulmonary edema. Conversely, the administration of hypertonic saline has been used to treat severe hypovolemia (e.g., trauma) by drawing water into the vasculature/circulation.
Hypernatremia and the renal system. Studies in rats have shown that an acute increase in serum sodium leads to renal vasodilatation. Hypertonic saline infusions stimulate vasopressin and oxytocin, alter sympathetic activity, cause transient hypertension, and result in a sustained increase in renal blood flow.
Central diabetes insipidus (DI) describes impaired ADH synthesis that manifests as polyuria and defects in the ability to concentrate urine. The kidneys cannot produce/maintain the hypertonic medullary interstitium that is required to concentrate urine; this results in a solute (osmotic) diuresis and excessive free water loss. Central DI may be seen after pituitary surgery, severe head trauma (damage to the neurohypophyseal stalk), or basilar skull fracture.
Nephrogenic diabetic insipidus describes renal resistance to ADH; it manifests similarly to central DI (polyuria and an inability to concentrate urine). Hereditary nephrogenic DI can result from a gene mutation of the ADH receptor or the AQP-2 water channel. Acquired nephrogenic DI is commonly due to lithium toxicity or metabolic abnormalities, particularly hypokalemia and hypercalcemia.
Mineralocorticoid excesses will increase aldosterone levels, leading to potassium depletion and sodium retention (increase in total body sodium). Aldosterone acts on the distal collecting ducts to increase tubular reabsorption of sodium and potassium excretion.

Prevantative Measures

Free water loss via the GI, respiratory, and urinary tract should be replaced in critically ill patients.

Pediatric Considerations

Symptoms include hyperpnea, muscle weakness, restlessness, a characteristic high pitched cry, insomnia, lethargy, and coma.

Signs and symptoms

Lethargy, mental status changes, irritability
Thirst, shock, peripheral edema, ascites, and myoclonus
Muscular tremor, rigidity, hyperactive reflexes, and spasticity
Serum [Na⁺] >145 mEq/L
If the urine output is >100 mL/hour with hypernatremia, the patient should be evaluated for DI. A urine osmolality <300 mOsm/L and serum sodium >150 mEq/L makes the diagnosis of DI likely.

Differential Diagnosis

Must make a distinction between the three types:

Low total body sodium (loss of water >sodium); also referred to as hypovolemic hypernatremia
- Renal: Osmotic diuresis from hyperglycemia or mannitol. Urine [Na⁺] >20 mOsm/L
- Extrarenal: Diarrhea, insensible fluid losses, vomiting. Urine [Na⁺] <10–20 mOsm/L
Normal total body sodium (water loss); also referred to as euvolemic hypernatremia
- Renal: Central and renal DI. Urine osmolality: Low. Urine [Na⁺]: Variable.
- Extrarenal: Impaired water intake. Urine osmolality: High Urine [Na⁺] >20 mOsm/L.
High total body sodium (gain of sodium >water) and includes hypertonic saline; also referred to as hypervolemic hypernatremia. Urine [Na⁺] >20 mOsm/L

Depends on the underlying cause and course of development
- In chronic hypernatremia, brain cells accumulate organic osmoles when intracellular water is lost, thus minimizing cell shrinkage. If corrected too fast, cerebral edema will occur as a result of rapid uptake of water into brain cells that outpaces the extrusion of organic osmoles and electrolytes from the brain cells. To that extent, a reduction in serum [Na⁺] by <10 mEq/day, or 0.5 mEq/hour in chronic hypernatremia, is recommended.
- In acute hypernatremia, rapid correction (e.g., 1 mEq/hour) may not increase the risk of cerebral edema.
High total body sodium/hypervolemic hypernatremia. Excessive salt and water can be corrected with a potent diuretic (e.g., furosemide) combined with a hypotonic solution such as D5%W. Alternatively, hemodialysis may be utilized.
Normal total body sodium/euvolemic hypernatremia.
- Central DI. Intranasal DDAVP 5–10 µg once or twice daily or aqueous vasopressin SC 5–10 U twice daily. In an emergency, IV DDAVP 1–2 µm BID or TID.
- Nephrogenic DI. Thiazide diuretics with or without prostaglandin synthetase inhibitors (e.g., indomethacin or amiloride) and modest sodium restriction.
Low total body sodium/hypovolemic hyponatremia. Correct hypovolemia using 0.9% normal saline followed by correction of the water deficit with a hypotonic solution. The free water deficit can be estimated as follows: Total body water (TBW) × [(serum Na⁺/140) – 1]. The TBW for males and females are 0.6 and 0.5 multiplied by the lean body weight, respectively. In elderly patients and those with significant dehydration, a more conservative estimate is needed (0.5 for males and 0.4 for females).
- for example, a male patient with a body weight of 70 kg presenting with a serum sodium of 160 mEq/L would have a free water deficit = 70 × 0.6 × [(160/140) – 1]; this is equal to 42 × 0.143 or 6 L.
- Correction of the water deficit can occur with oral intake, a G tube, or IV replacement using D5%W or 0.45% NaCl.

Adrogue HJ , Madias NE. Hypernatremia. N Engl J Med. 2000;342(20):1493–1499.
Wakil A , Atkin SL. Serum sodium disorders: Safe management. Clin Med. 2010;10(1):79–82.
Prough DS. Physiologic acid-base and electrolyte changes in acute and chronic renal failure patients. Anesthesiol Clin North America. 2000;18(4):809–833.
Robertson G , Carrihill M , Hatherill M , et al. Relationship between fluid management, changes in serum sodium and outcome in hypernatraemia associated with gastroenteritis. J Paediatr Child Health. 2007;43(4):291–296.
Leung C , Chang WC , Yeh SJ. Hypernatremic dehydration due to concentrated infant formula: Report of two cases. Pediatr Neonatol. 2009;50(2):70–73.

Prough DS , Funston JS , Svensen CH , et al. Fluids, electrolytes, and acid-base physiology. In Barash PG et al. (Eds.), Clinical Anesthesia, 6th edn.Philadelphia: Lippincott Williams & Wilkins, 2009, p. 309.

See Also (Topic, Algorithm, Electronic Media Element)

ICD9

276.0 Hyperosmolality and/or hypernatremia

ICD10

E87.0 Hyperosmolality and hypernatremia

Hypernatremia increases the minimum alveolar concentration of inhaled anesthetic agents, possibly because of enhanced sodium conductance during depolarization of excitatory membranes.
Common errors in the correction include underestimation of fluid deficit, ongoing fluid losses, and maintenance fluid requirement.

Michael S. Green , DO

Poovendran Saththasivam , MD

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Basics ⬇

Incidence

Prevalence

Morbidity

Mortality

Diagnosis ⬆ ⬇

Treatment ⬆ ⬇

References ⬆ ⬇

Additional Reading ⬆ ⬇

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Clinical Pearls ⬆ ⬇

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