Pediatric Hypernatremia

Hypernatremia is defined as a serum sodium concentration of more than 145 mEq/L. It is characterized by a deficit of total body water (TBW) relative to total body sodium levels due to either loss of free water; infrequently, the administration of hypertonic sodium solutions ^[1] ; or, even more uncommonly, administration of plasmalike isotonic fluids. ^[2]

In healthy subjects, the body's two main defense mechanisms against hypernatremia are thirst and the stimulation of vasopressin release.

Pediatric Hypernatremia. Figure A: Normal cell. Figure B: Cell initially responds to extracellular hypertonicity through passive osmosis of water extracellularly, resulting in cell shrinkage. Figure C: Cell actively responds to extracellular hypertonicity and cell shrinkage in order to limit water loss through transport of organic osmolytes across the cell membrane, as well as through intracellular production of these osmolytes. Figure D: Rapid correction of extracellular hypertonicity results in passive movement of water molecules into the relatively hypertonic intracellular space, causing cellular swelling, damage, and ultimately death.

Hypernatremia represents a deficit of water in relation to the body's sodium stores, which can result from a net water loss or a hypertonic sodium gain. Net water loss accounts for most cases of hypernatremia. Hypertonic sodium gain usually results from clinical interventions or accidental sodium loading. As a result of increased extracellular sodium concentration, plasma tonicity increases. This increase in tonicity induces the movement of water across cell membranes, causing cellular dehydration.

The following three mechanisms may lead to hypernatremia, alone or in concert:

• Pure water depletion (eg, diabetes insipidus)

• Water depletion exceeding sodium depletion (eg, diarrhea)

• Sodium excess (eg, salt poisoning)

Sustained hypernatremia can occur only when thirst or access to water is impaired. Therefore, the groups at highest risk are infants and intubated patients.

Because of certain physiologic characteristics, infants are predisposed to dehydration. They have a large surface area in relation to their height or weight compared with adults and have relatively large evaporative water losses. In infants, hypernatremia usually results from diarrhea and sometimes from improperly prepared infant formula or inadequate mother-infant interaction during breastfeeding. A retrospective study that evaluated data from 18 neonates with hypernatremic dehydration found that this condition most commonly occurs due to inadequate milk intake in breast or mixed fed babies, but only rarely as a result of feeding difficulties in infants with an acute infection. ^[3] In addition, not only was percentage weight loss at presentation strongly association with neonatal hypernatremic dehydration, but it was also the key factor for acute kidney injury in these infants. ^[3]

Hypernatremia causes decreased cellular volume as a result of water efflux from the cells to maintain equal osmolality inside and outside the cell. Brain cells are especially vulnerable to complications resulting from cell contraction. Severe hypernatremic dehydration induces brain shrinkage, which can tear cerebral blood vessels, leading to cerebral hemorrhage, seizures, paralysis, and encephalopathy.

In patients with prolonged hypernatremia, rapid rehydration with hypotonic fluids may cause cerebral edema, which can lead to coma, convulsions, and death.

A systemic review of the literature indicates that risk factors for breastfeeding-associated hypernatremia include the following ^[4] :

• Cesarean delivery

• Primiparity

• Breastfeeding difficulties

• Delayed breastfeeding

• Lack of previous breastfeeding experience

• Excessive maternal body weight

• Low maternal education level

Causes of hypovolemic hypernatremia include the following:

• Diarrhea

• Excessive perspiration

• Renal dysplasia

• Obstructive uropathy

• Osmotic diuresis

Causes of euvolemic hypernatremia include the following:

• Central diabetes insipidus causes

• Idiopathic causes

• Head trauma

• Suprasellar or infrasellar tumors (eg, craniopharyngioma, pinealoma)

• Granulomatous disease (sarcoidosis, tuberculosis, Wegener granulomatosis)

• Histiocytosis

• Sickle cell disease

• Cerebral hemorrhage

• Infection (meningitis, encephalitis)

• Associated cleft lip and palate

• Nephrogenic diabetes insipidus causes

• Congenital (familial) conditions

• Renal disease (obstructive uropathy, renal dysplasia, medullary cystic disease, reflux nephropathy, polycystic disease)

• Systemic disease with renal involvement (sickle cell disease, sarcoidosis, amyloidosis)

• Drugs (amphotericin, phenytoin, lithium, aminoglycosides, methoxyflurane)

Causes of hypervolemic hypernatremia include the following:

• Improperly mixed formula

• NaHCO₃ administration

• NaCl administration

• Primary hyperaldosteronism

United States data

Hypernatremia is primarily a hospital-acquired condition occurring in children of all ages who have restricted access to fluids, mostly due to significant underlying medical problems such as a chronic disease, neurologic impairment, a critical illness, or prematurity. The incidence is estimated to be greater than 1% in hospitalized patients. Hospital-acquired hypernatremia accounts for 60% of hypernatremia cases in children. Gastroenteritis contributes to the hypernatremia in only 20% of cases. The group most affected is intubated, critically ill patients. Most cases result from a failure to freely administer water to patients. The incidence of breastfeeding-related hypernatremia is 1-2%.

International data

In developing nations, the reported incidence is 1.5-20%.

Race-, sex-, and age-related demographics

No racial or sexual predilection for hypernatremia in children is known.

In the pediatric population, hypernatremia usually affects newborns and toddlers who depend on caretakers for water, as well patients of any age who have significant underlying medical problems such as a chronic disease, neurologic impairment, a critical illness, or prematurity.

Patients usually recover from hypernatremia. Patients with recurrent hypernatremic dehydration develop neurologic sequelae, especially infants with diabetes insipidus.

Morbidity/mortality

In children with acute hypernatremia, mortality rates are as high as 20%. Extremely low birth weight infants with sodium level fluctuations during the first week of life are particularly at risk for death. ^[5] Neurologic complications related to hypernatremia occur in 15% of patients. The neurologic sequelae consist of intellectual deficits, seizure disorders, and spastic plegias. In cases of chronic hypernatremia in children, the mortality rate is 10%.

The neurolodevelopmental effects of hypernatremia in the first week of life of preterm infants born at less than 32 weeks' gestation has a long-term impact, including lower fine motor scores at 18 months of corrected age. ^[6]

Complications

Although seizures can occur because of hypernatremia per se, this is rare. They usually occur during the treatment of hypernatremia because of a rapid decline in serum sodium levels. Therefore, slowly correcting hypernatremia is important.

Other complications include the following:

• Mental retardation

• Intracranial hemorrhage

• Intracerebral calcification

• Cerebral infarction

• Cerebral edema, especially during treatment

• Hypocalcemia

• Hyperglycemia

Parents and caregivers should avoid making oral rehydration solutions at home or adding salt to any commercial infant formula.

Parents, especially breastfeeding mothers, should watch for neonatal dehydration and perinatal care.

The breastfed infant should be routinely monitored during the first weeks of life. ^[7]

In patients with diabetes insipidus, the following is indicated:

• Monitor weight and urine output because clinically significant changes in sodium values are associated with changes in weight.

• Restrict sodium and protein intake.

• The patient should drink liberal amounts of water.

• The patient and parents should ensure thirst develops before taking or giving medications.