AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

Section 2 of 11  

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Background

Hypernatremia is an electrolyte problem that is not uncommon, especially in elderly people who are hospitalized. Poor water intake, inability to express thirst, insensible water loss, or increased urinary water loss lead to dehydration and an increased concentration of serum electrolytes relative to water.

The development of hyperosmolality from the water loss leads to neuronal cell shrinkage and resultant brain injury. Loss of volume leads to circulatory problems (eg, tachycardia, hypotension). Water replacement can lead to cerebral edema.

Pathophysiology

The fundamental problem is that hypernatremia strictly defined is hyperosmolality, ie, an overall deficit of total body water. This deficit accrues by 2 mechanisms, which are inadequate fluid intake and water loss. Because thirst is a potent mechanism in the response to hyperosmolality, hypernatremia patients either have an inadequate thirst mechanism or have an inability to respond to thirst. If the thirst response to hyperosmolality is impaired, ongoing water losses raise serum sodium concentration. Ongoing water losses include insensible (always) water in excess of solute or renal loss (with a solute diuresis such as hyperglycemia or water diuresis). Increased sodium intake (salt tablets) is a rare cause of hypernatremia in hot, humid weather. The brain cell response to hypernatremia is critical and is contained in Media file 1.

The keys to the pathophysiology of hypernatremia include the following:

1. Thirst should lead to water intake.
2. Vasopressin is critical to water reabsorption in the cortical collecting tubule.
3. The CNS is sensitive to changes in osmolality.
4. Water may be lost by renal and extrarenal mechanisms.

Frequency

United States

Overall, incidence ranges from 0.12-3.5% in hospitalized patients. Hypernatremia is most prevalent in the geriatric population.

Mortality/Morbidity

• The mortality rate across all age groups is approximately 45%.
• The mortality rate in the geriatric age group is as high as 79%.

Race

No race predilection exists.

Sex

No sex predilection exists.

Age

• The groups most commonly affected are elderly people and young people.
• People typically affected are aged 59-83 years.

CLINICAL

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History

History may uncover risks for hypernatremia, including poor oral intake, medications causing diabetes insipidus (eg, lithium), important comorbid conditions (eg, diabetes mellitus), fever, or residency in a nursing home complicated by altered mental status.

Table 1. Hypernatremia: Appropriate Historical and Physical Findings

Findings	Details
Cognitive dysfunction	Lethargy, obtundation, confusion Abnormal speech Irritability
Dehydration or volume-associated findings	Orthostatic blood pressure changes Tachycardia Oliguria High BUN-to-creatinine ratio Dry axillae
Other clinical findings	Weight loss Generalized weakness Seizures Nystagmus Myoclonic jerks

• Risk factors for hypernatremia
• • Age older than 65 years
  • Mental or physical disability
  • Hospitalization (intubation, impaired cognitive function)
  • Residence in nursing home
  • Inadequate nursing care
  • Urine concentrating defect (diabetes insipidus)
  • Solute diuresis (diabetes mellitus)
  • Diuretic therapy

Physical

For example, evaluate a 78-year-old nursing home resident for decreased mental status. The woman has diabetes mellitus and is taking diuretics for hypertension. Recent sugar levels have been greater than 300 mg/dL. She is confused and has had limited oral intake for about 4 days. A recent urinary tract infection was associated with a fever.

Her vital signs include a temperature of 100.2°F, a blood pressure and pulse supine of 150/90 mm Hg and 100 beats per minute, a blood pressure and pulse upright of 130/88 mm Hg and 118 beats per minute, and her respiration is 20 breaths per minute. She is disoriented but has no focal neurologic signs. The findings on examination of the heart are normal except for tachycardia, and her axillae are dry. No other positive findings are present.

Causes

Several risk factors exist for hypernatremia. The greatest risk factor is age older than 65 years. The worsening symptoms associated with hypernatremia may be unnoticed in elderly patients who have decreased access to water. In addition, mental or physical disability may result in impaired thirst sensation, impaired ability to express thirst, and decreased access to water.

Other situations associated with or causing hypernatremia include hospitalization, diabetes insipidus, diuretic therapy, poorly controlled diabetes mellitus, and altered mental status.

• Causes of hypernatremia
• • Poor fluid intake
  • Salt poisoning – Salt tablets, near drowning, inappropriate administration of hypertonic solutions in hospitalized patients
  • Water loss – Diuretic induced, febrile illness, osmotic diuresis, nephrogenic diabetes insipidus, central diabetes insipidus
• Ultimately, hypernatremia may be the result of several concurrent factors. The most prominent is poor fluid intake.
• • If thirst is attenuated or not responded to, sodium concentration increases and may be aggravated further by ongoing insensible water losses.
  • Normally, an increase in osmolality of just 1-2% stimulates thirst. In addition, hypovolemia and hypotension also stimulate thirst.
  • Injury to the thirst centers can occur as a result of metastatic lesions to the hypothalamus; granulomatous diseases; and vascular abnormalities, trauma, or any lesions in this specific anatomic area.
• The other significant cause of hypernatremia is inappropriate water loss. Such loss may be the result of diuretic use, febrile illnesses, or an osmotic diuresis.
• • For example, uncontrolled diabetes mellitus leads to increased solute clearance per nephron, secondarily increasing free water loss. In fact, for every 100 mg/dL that the glucose increases (eg, 100-300 mg/dL or a 200 mg increase), the serum sodium should decrease by 1.6 (eg, 1.6 x 2 = 3.2 mEq/L).
  • A serum sodium level of 145 mEq/L with a glucose level of 400 mg/dL is consistent with hypernatremia (sodium should decrease from 140-135 [3 x 1.6 = 4.8 mEq/L] with a glucose increase of 300 mg/dL above the normal level of 100 mg/dl).
• Water loss may eventuate from diabetes insipidus that is either nephrogenic (congenital or acquired) or central. Acquired nephrogenic diabetes insipidus is more common than congenital. It may be the result of medications (eg, amphotericin B, lithium), injury to the renal tubules, or electrolyte abnormalities (hypercalcemia or hypokalemia).
• Causes of nephrogenic diabetes insipidus
• Congenital
• Medications – Lithium, amphotericin B, demeclocycline
• Obstructive uropathy
• Electrolyte disorders – Hypercalcemia, hypokalemia
• Chronic tubulointerstitial diseases - Analgesic abuse nephropathy, sickle cell nephropathy, M protein disease, sarcoidosis, Sjögren syndrome, polycystic kidney disease, medullary cystic disease
• Central diabetes insipidus is the result of deficient vasopressin secretion resulting from trauma, hypophysectomy, tumors, infections, granulomatous diseases, and cerebral vascular diseases. It could also be idiopathic.
• Causes of central diabetes insipidus
• Cerebrovascular diseases – Aneurysms, cavernous sinus thrombosis, Sheehan syndrome, brain edema from massive stroke
• Granulomatous diseases – Sarcoidosis, eosinophilic granuloma, Wegener granulomatosis
• Head trauma
• Idiopathic
• Posthypophysectomy
• Tumors affecting the hypothalamus – Primary, secondary
• Infections – Tuberculosis, syphilis, mycoses, toxoplasmosis, encephalitis (basilar meningitis from tumors, Behçet syndrome, Wegener granulomatosis, or vasculitis)
• Excess salt intake also may result in hypernatremia. It may occur in infants when salt is substituted for sugar inadvertently. In hospitalized patients, it may be the result of hypertonic saline administration.
• Finally, it may be the result of near drowning with salt water or the intake of salt tablets without water in hot, humid environments.

DIFFERENTIALS

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Other Problems to be Considered

Other problems to consider include all other etiologies for metabolic or drug-induced encephalopathy (eg, cirrhosis, hyponatremia).

Metabolic encephalopathy accompanied by a history of poor oral intake, nursing home residence, certain medications, appropriate comorbid conditions, increased volume, or insensible loss and obtundation should raise the suspicion of an elevated serum sodium concentration as possible etiology for mental status changes.

WORKUP

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Lab Studies

• Diagnosis is based on an elevated serum sodium concentration. Other helpful laboratory data include urinary electrolytes and urine osmolality. In the case of hypernatremia, urine osmolality should be concentrated (often >500 mOsm/kg/H₂O). Hypernatremia is associated with a lower inappropriate urine osmolality ( <100 mOsm/kg/H₂O) when central diabetes insipidus is present and may be slightly higher (approximately 400 mOsm/kg/H₂O) when nephrogenic diabetes insipidus is responsible. The benefit of spot urine electrolytes in hypernatremia is related to interpretation of urinary sodium and/or the fractional excretion of sodium (FeNa⁺). During hypernatremia, the associated volume contraction may be mirrored in a low urine Na⁺ (usually <10 mEq/L) or a FeNa⁺ less than 1%.
• Hypokalemia and hypercalcemia may result in nephrogenic diabetes insipidus. A serum glucose level is essential because the osmotic diuresis of diabetes mellitus leads to increased water loss and hypernatremia. A urinary osmolality pre–vasopressin administration and post–vasopressin administration demonstrating an increase in osmolality may assist in the diagnosis of central diabetes insipidus.

Imaging Studies

• A CT scan of the brain may be helpful for central diabetes insipidus eventuating from head trauma or infiltrative lesions.

Histologic Findings

Histological findings usually are noncontributory (may be helpful in central diabetes insipidus).

TREATMENT

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Medical Care

The goals of management in hypernatremia are to address the underlying cause and to correct the prevailing hypertonicity. Correcting the hypertonicity requires a careful decrease in serum sodium and plasma osmolality with the replacement of free water–either oral or parenteral water (see Media file 1). The rate of sodium correction depends on the probable duration of hypernatremia. Formulas used to manage hypernatremia are outlined below.

• Equation 1: Total body water (TBW) = weight (kg) x correction factor
• • Correction factors
  • • Children = 0.6
    • Nonelderly men = 0.6
    • Nonelderly women = 0.5
    • Elderly men = 0.5
    • Elderly women = 0.45
• Equation 2: Change in serum Na⁺ = (infusate Na⁺ - serum Na⁺) ÷ (TBW + 1)
• Equation 3: Change in serum Na⁺ = ((infusate Na⁺ + infusate K⁺) – serum Na⁺) ÷ (TBW + 1)
• • Equation 2 allows for the estimation of 1 L of any infusate on serum Na⁺ concentration.
  • Equation 3 allows for the estimation of 1 L of any infusate containing Na⁺ and K⁺ on serum Na⁺.
  • Equations 2-3 are preferred over the conventional equation for water deficit because the old equation underestimates the deficit in patients with hypotonic fluid loss and is not useful in situations when sodium and potassium must be used in the infusate.
• Common infusates and their Na⁺ contents
• • 5% dextrose in water (D₅W): 0 mmol/L
  • 0.2% sodium chloride in 5% dextrose in water (D₅2NS): 34 mmol/L
  • 0.45% sodium chloride in water (0.45NS): 77 mmol/L
  • Ringer's lactate solution: 130 mmol/L
  • 0.9% sodium chloride in water (0.9NS): 154 mmol/L
• Acute hypernatremia, defined as hypernatremia occurring in a period of less than 48 hours, can be corrected rapidly (1-2 mmol/L/h). Chronic hypernatremia, however, should be corrected more slowly due to the risks of brain edema during treatment (see Media file 1). The brain adjusts to and mitigates chronic hypernatremia by increasing the intracellular content of organic osmolytes. Rapid correction can increase CNS intracellular volume significantly, and the resulting brain edema can lead to herniation, permanent neurologic deficits, and lysis of myelin.
• Chronic hypernatremia should be corrected at a rate not to exceed 0.5 mmol/L/h or a total of 10 mmol/d (eg, 160 mEq/L to 150 mEq/L in 24 h). For example, an obtunded 80-year-old man is brought to the emergency room with dry mucous membranes, fever, tachypnea, and blood pressure of 134/75. The serum sodium concentration of a 70-kg man is 165 mmol/L. This man is determined to have hypernatremia due to insensible water loss.
• 1. The man's total body water is calculated by the following: (0.5 x 70) = 35 L.
  2. To reduce the man's serum sodium, D₅W will be used. Thus, the retention of 1 L of D₅W will reduce his serum sodium by (0 - 165) ÷ (35 + 1) = -4.6 mmol. The goal is to reduce his serum sodium by no more than 10 mmol/L in a 24-hour period. Thus, (10 ÷ 4.6) = 2.17 L of solution is required. About 1-1.5 L will be added for obligatory water loss to make a total of up to 3.67 L of D₅W over 24 hours or 153 cc/h.
• If a volume deficit as well as hypernatremia is present, intravascular volume should be restored with isotonic sodium chloride prior to free water administration. A volume deficit can be identified by hypotension, orthostatic blood pressure changes, or pulse changes.
• If hypernatremia is accompanied by hyperglycemia with diabetes, take care when using a glucose-containing replacement fluid. However, appropriate use of insulin will help during correction.
• Hypernatremia in the setting of volume overload may require dialysis for correction.
• Although water can be replaced by oral and parenteral routes, an obtunded patient requires parenteral treatment. If the deficit is small and the patient alert and oriented, oral correction may be substituted.
• Once hypernatremia is corrected, efforts are directed at treating the underlying cause of the hypernatremia. Such efforts may include free access to water, better control of diabetes mellitus, and utilization of vasopressin (subcutaneous or intranasal) for central diabetes insipidus. In addition, correction of hypokalemia and hypercalcemia as etiologies for nephrogenic diabetes insipidus may be required.

Surgical Care

Surgical treatment may be required in the setting of severe CNS trauma and associated central diabetes insipidus.

Consultations

• Neurosurgeon (head trauma)
• Endocrinologist (diabetes insipidus or diabetes mellitus)
• Nephrologist (nephrogenic etiologies for hypernatremia)

Diet

Diet should be altered as applicable to diabetes mellitus and increased water intake during increased insensible loss.

Activity

Alterations in activity only are applicable as related to free access to water.

MEDICATION

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Some patients with central diabetes insipidus—particularly when it is mild or incomplete—may benefit from diuretic therapy (ie, thiazides) in an effort to increase proximal tubular reabsorption and decrease filtrate delivery to diluting segments where water may be lost. In addition, any medications that may cause nephrogenic diabetes insipidus (such as lithium) may require discontinuation. Desmopressin administered orally or intranasally may be used.

Drug Category: Diuretics

May be used to enhance sodium excretion.

Drug Category: Vasopressin analogs

May enhance sodium excretion.

FOLLOW-UP

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Further Inpatient Care

• Inpatient care is appropriate only as related to correction of underlying diseases that may lead to hypernatremia (diabetes mellitus).

Further Outpatient Care

• Outpatient care is related to water intake and medication treatment.

Transfer

• Transfer may only be necessary in the setting of severe head trauma with central diabetes insipidus.

MISCELLANEOUS

Section 9 of 11  

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Medical/Legal Pitfalls

• Failure to treat volume contraction during hypotension prior to free water replacement
• Correcting chronic hypernatremia too quickly, leading to cerebral edema or myelinolysis
• Failure to treat central diabetes insipidus with vasopressin during severe water loss

MULTIMEDIA

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Media file 1:  Figure A: Normal cell. Figure B: Cell initially responds to extracellular hypertonicity throughpassive osmosis of water extracellularly, resulting in cell shrinkage. Figure C: Cell activelyresponds to extracellular hypertonicity and cell shrinkage in order to limit water loss throughtransport of organic osmolytes across the cell membrane, as well as intracellular productionof these osmolytes. Figure D: Rapid correction of extracellular hypertonicity results in passivemovement of water molecules into the relatively hypertonic intracellular space, causing cellularswelling, damage and ultimate death.
	View Full Size Image
Media type:  Image

REFERENCES

Section 11 of 11

• Authors and Editors
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• Clinical
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• Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med. May 18 2000;342(20):1493-9. [Medline].
• Fried LF, Palevsky PM. Hyponatremia and hypernatremia. Med Clin North Am. May 1997;81(3):585-609. [Medline].
• Kumar S, Berl T. Sodium. Lancet. Jul 18 1998;352(9123):220-8. [Medline].
• Palevsky PM. Hypernatremia. Semin Nephrol. Jan 1998;18(1):20-30. [Medline].
• Sterns HR. Renal function and disorders of water and sodium balance. In: Chapter 10, Nephrology, ACP Medicine. 2005:. 10.1-10.19.

Article Last Updated: Feb 1, 2007