Hypernatremia in children

INTRODUCTION — Hypernatremia is typically defined as a serum or plasma sodium greater than 150 mEq/L. Although pediatric hypernatremia is an uncommon electrolyte abnormality, there can be significant neurologic injury in patients with severe hypernatremia, especially those with acute and rapid changes in serum sodium.

The etiology, clinical findings, diagnosis, and evaluation of pediatric hypernatremia are reviewed here.

EPIDEMIOLOGY — Most data on the incidence of pediatric hypernatremia are based on hospitalized children. In a study from Scotland, the incidence of hypernatremia (defined as a plasma sodium >150 mEq/L) was 0.04 percent for all hospitalized children over a study period from 1996 to 2006 [1]. The risk of hypernatremia was 10 times greater in neonates less than two weeks of age, with an incidence of 0.4 percent. Neonatal hypernatremia was almost exclusively seen in breastfed infants with excessive weight loss (water loss). Of note, the incidence of neonatal hypernatremia in breastfed infants was higher than reported in previous studies (0.03 to 0.07 percent) (see "Initiation of breastfeeding", section on 'Assessment of intake'). In older patients between two weeks and 17 years of age, the most common cause of hypernatremia on admission was excess water loss due to gastroenteritis or systemic infection. However, in this cohort, it was more common for hypernatremia to develop during hospitalization, particularly in patients with systemic infection or those who underwent cardiac surgery. In addition, approximately one-third of the patients had an underlying neurologic condition.

In an earlier study from a tertiary children's hospital in Texas from 1992 to 1994, hypernatremia (defined as a serum sodium greater than 150 mEq/L) was detected in 1.4 percent of sodium values in a laboratory database, but only 0.2 percent of patients were discharged with a diagnosis of hyperosmolality due to hypernatremia [2]. Of the 68 children with a final discharge diagnosis of hyperosmolality/hypernatremia, two-thirds of the children developed hypernatremia during hospitalization, and the most common cause of hypernatremia was inadequate fluid intake.

PATHOPHYSIOLOGY — Hypernatremia is caused by an imbalance in the body's handling of water, resulting in a relative excess of effective plasma osmolality (tonicity) to total body water. The plasma tonicity is defined as the concentration of solutes that do not easily cross the cell membrane, which is primarily due to sodium salts in the extracellular space. As a result, serum or plasma sodium is used as a surrogate for assessing tonicity. (See "General principles of disorders of water balance (hyponatremia and hypernatremia) and sodium balance (hypovolemia and edema)", section on 'Plasma tonicity'.)

The formulas used to estimate plasma tonicity are similar to those for the plasma osmolality, with the one exception that the contribution of urea (an ineffective osmole) is not included. The multiplier factor of "2" accounts for the osmotic contributions of the anions that accompany sodium, the primary extracellular cation:

Plasma tonicity is tightly regulated by the release of antidiuretic hormone (ADH) from the posterior pituitary promoting water retention, and by thirst-prompting water ingestion (figure 1). These homeostatic mechanisms that mediate plasma tonicity and water balance are similar in adults and children, resulting in a normal range of plasma sodium between 135 and 145 mEq/L that does not vary by age. (See "General principles of disorders of water balance (hyponatremia and hypernatremia) and sodium balance (hypovolemia and edema)", section on 'Regulation of plasma tonicity'.)

Hypernatremia is most often caused by the failure to replace water losses, which, in children, is most commonly due to gastrointestinal fluid loss. In these patients, the sodium plus potassium concentration in the fluid that is lost is less than the plasma sodium concentration. As a result, water is lost in excess of sodium plus potassium, which will tend to increase the plasma sodium concentration. In individuals with intact thirst mechanisms, the intake of free water promptly corrects any increase in plasma sodium. However, when water losses cannot be replaced because of a lack of free access to water, excessive loss in acute illnesses, or impaired thirst mechanism, sodium concentration increases and may result in hypernatremia. Infants and children who are significantly neurodevelopmentally impaired are at particular risk for hypernatremia, as they may be unable to communicate their thirst and are dependent on others for nutrition and fluid repletion. Pediatric hypernatremia also may result from urinary or skin loss of free water without adequate water replacement.

Less commonly, pediatric hypernatremia may be caused by intake of sodium in excess of water (eg, administration of a hypertonic salt solution). In this setting, patients also are unable to access free water to correct the plasma tonicity.

ETIOLOGY — The causes of pediatric hypernatremia can be separated into the two previously discussed mechanisms that result in pediatric hypernatremia (see 'Pathophysiology' above):

●Water loss that is not replaced

●Excessive salt intake relative to water ingestion

Excess water losses — Loss of body fluids with a sodium plus potassium concentration that is less than serum or plasma sodium (hypotonic fluids) will result in an increase in sodium concentration if the water losses are not replaced. Sources of hypotonic body fluid losses include gastrointestinal fluids, dilute urine, and skin loss due to sweat or burns. In addition, inadequate water intake that fails to replace ongoing normal fluid losses will result in excess water loss and increases in serum or plasma sodium.

Gastrointestinal loss — In children, the most common cause of hypernatremia is hypotonic gastrointestinal losses without replacement, which result in effective water loss. In particular, gastroenteritis due to rotavirus can present with profuse watery diarrhea and hypernatremia [3]. In addition, losses due to vomiting or nasogastric drainage can lead to excess free water loss and hypernatremia.

Urinary water loss — Excessive urinary free water loss may be caused by disorders with impaired urinary concentration or osmotic diuresis. Without adequate water replacement, sodium concentration will rise and may result in hypernatremia (table 1).

Urinary concentration defects — Impaired urinary concentration is typically due to antidiuretic hormone (ADH) deficiency or resistance, which leads to excretion of a dilute urine (urine osmolality less than plasma osmolality) and excessive urinary free water loss.

●Arginine vasopressin deficiency (AVP-D, previously called central diabetes insipidus) – AVP-D is caused by inadequate production or release of ADH. AVP-D has multiple etiologies, including congenital central nervous system (CNS) malformations and genetic syndromes with associated CNS anomalies, and acquired causes due to CNS tumors, infiltrative processes of the hypothalamic-pituitary stalk, and sequelae from neurosurgery and trauma. (See "Arginine vasopressin deficiency (central diabetes insipidus): Etiology, clinical manifestations, and postdiagnostic evaluation".)

●Arginine vasopressin resistance (AVP-R, previously called nephrogenic diabetes insipidus) – AVP-R is caused by an inadequate renal tubular response to circulating ADH. The multiple causes of pediatric AVP-R can be further divided into the following categories (see "Arginine vasopressin resistance (nephrogenic diabetes insipidus): Clinical manifestations and causes", section on 'Causes'):

•Congenital AVP-R – Congenital AVP-R is most often the result of mutations in the vasopressin type 2 receptor (AVPR2), found at the locus Xp28. In this X-linked disorder, male infants typically present in the first weeks of life with fussiness, low-grade fever, and polyuria with hypernatremia. In addition, hereditary AVP-R may be caused by a mutation in the aquaporin-2 gene (AQP2) at 12q13, which encodes the ADH-sensitive water channels. Congenital AVP-R is also observed in other inherited disorders, including Bardet-Biedl and Bartter syndromes, nephronophthisis, cystinosis, and familial hypomagnesemia with hypercalciuria and nephrocalcinosis.

•Acquired AVP-R – Drug toxicity is the most common cause of acquired DI. Lithium toxicity is the most frequent cause of drug-induced AVP-R, and its use has increased in children and adolescents with mood disorders. Lithium also can cause interstitial nephritis and fibrosis, further exacerbating urinary concentrating capacity. The effects of lithium on urinary concentrating ability can be permanent. (See "Renal toxicity of lithium", section on 'Arginine vasopressin resistance (nephrogenic diabetes insipidus)'.)

Other medications associated with drug-induced AVP-R include amphotericin, demeclocycline, ifosfamide, foscarnet, and cidofovir.

Hypercalcemia and hypokalemia also can produce functional defects in water reabsorption that are usually reversible once the electrolyte perturbation resolves. (See "Hypokalemia-induced kidney dysfunction", section on 'Impaired urinary concentrating ability' and "Arginine vasopressin resistance (nephrogenic diabetes insipidus): Clinical manifestations and causes".)

•Kidney disease – In children, impaired urinary concentration is seen in a variety of kidney diseases, including obstructive uropathy, sickle cell disease, nephronophthisis, cystinosis, and acute or chronic kidney disease. In these disorders, the decline in urinary concentrating ability may be due to a number of different factors, including resistance to ADH, impairment of the renal medullary countercurrent mechanism, and/or decrease in the number of functioning nephrons, which can lead to osmotic diuresis as the ability to reabsorb the increasing solute load is exceeded.

Osmotic diuresis — Hypernatremia can also occur from urinary water losses due to excretion of nonelectrolyte, nonreabsorbed solutes, such as mannitol or glucose (eg, patients with diabetic ketoacidosis and hyperglycemia). While the urine osmolality is augmented with the presence of these substances, the urinary concentration of sodium plus potassium is below plasma levels. If there is inadequate water repletion, the enhanced urinary free water loss leads to an increase in sodium concentration, and potentially hypernatremia. (See "Complications of mannitol therapy", section on 'Volume depletion and hypernatremia' and "Diabetic ketoacidosis in children: Clinical features and diagnosis", section on 'Serum sodium'.)

Skin loss — The sodium plus potassium content of sweat is less than half that of plasma, but normal sweating causes only modest overall free water losses and does not typically lead to hypernatremia. However, with vigorous or sustained exercise, or significant febrile illness, water losses from sweat can become more substantial and can result in hypernatremia if not corrected with water intake. Increased insensible water losses due to burns can also lead to hypernatremia [4]. (See "Moderate and severe thermal burns in children: Emergency management", section on 'Fluid resuscitation'.)

Inadequate water intake — Hypernatremia can develop if normal free water losses are not replaced, either because of lack of access to water or lack of thirst. Infants and children who are dependent on others for fluid intake or who have an impaired thirst mechanism are more vulnerable to hypernatremic hypovolemia.

Infants and young children — Compared with older children and adults, infants and young children are at increased risk for hypernatremic hypovolemia because they have a higher ratio of surface area to volume, resulting in greater insensible water losses from the skin; and, while their thirst mechanism is intact, they are unable to communicate their need for fluids and cannot independently access fluids to replenish fluid losses.

In neonates, the most common cause of hypernatremia is inadequate intake in infants who are breastfed [1,5-8]. Careful attention to weight loss and breastfeeding adequacy has been shown to prevent this potentially devastating complication [9]. (See "Initiation of breastfeeding", section on 'Assessment of intake'.)

Impaired thirst mechanism — Children with structural midline brain abnormalities may have an impaired or no thirst mechanism (adipsia or hypodipsia), which may result in chronic hypernatremia. These lesions include congenital abnormalities, such as holoprosencephaly [10,11], acquired lesions (eg, craniopharyngioma), and infiltrative processes of the hypothalamic-pituitary stalk. These patients may have concomitant AVP-D, and careful attention to both water intake and the use of desmopressin therapy makes their management especially challenging. (See "Etiology and evaluation of hypernatremia in adults", section on 'Hypothalamic lesions affecting thirst or osmoreceptor function'.)

Excess salt intake — Hypernatremia can be a consequence of salt intake out of proportion to water. In children, excessive salt intake is generally due to iatrogenic administration of excess sodium (eg, hypertonic saline solution), or due to salt poisoning. In either setting, patients are unable to access free water in order to restore plasma tonicity and correct hypernatremia.

Iatrogenic causes — Iatrogenic causes of hypernatremia include the administration of sodium bicarbonate infusions for metabolic acidosis or hypertonic saline, which may be used in the acute management of increased intracranial pressure. (See "Evaluation and management of elevated intracranial pressure in adults", section on 'Hypertonic saline bolus'.)

In addition, the administration of isotonic saline to replete hypotonic losses can also lead to increased sodium, and potentially hypernatremia, by net sodium gain in the following settings:

●Uncontrolled diabetes, in which the free water lost in an osmotic diuresis from nonreabsorbed glucose is replaced with isotonic saline.

●Recovery from acute kidney injury, in which the free water lost in a urea-induced osmotic diuresis is replaced with isotonic saline.

●Nasogastric suction, in which patients receive isotonic saline to replace hypotonic intestinal fluid losses with a sodium plus potassium concentration well below that of plasma.

●Edematous, critically ill patients who have received large volumes of saline and then receive loop diuretic therapy, which impairs renal concentrating ability, resulting in inappropriately high water losses [12].

Salt poisoning — Salt poisoning has been described both from incorrect formula preparation and as an intentional form of child abuse [13-17]. Infants, young children, and individuals with significant developmental delay are especially susceptible due to their inability to communicate their thirst, their reliance on others for access to water, and smaller volume of distribution. A teaspoon of salt contains 100 mEq of sodium (Na), which can increase the serum sodium concentration in a 10 kg child by 15 mEq/L. The unpleasant salty taste of such preparations should limit their voluntary ingestion, but in situations of intentional poisoning these individuals are often subjected to limited access to other fluids, thereby ensuring the ingestion of the hypertonic preparations.

Salt poisoning causes a rapid onset of hypernatremia and tonicity, often resulting in cerebral hemorrhage and irreversible neurologic injury. Osmotic demyelination can occur, similar to the injury caused by a rapid elevation in serum sodium in patients with chronic hyponatremia [18]. (See "Osmotic demyelination syndrome (ODS) and overly rapid correction of hyponatremia".)

Salt poisoning has a number of distinguishing features from excessive water loss, which, as noted above, is the most common cause of hypernatremia [16,19]. (See 'Excess water losses' above.)

●Salt poisoning is initially associated with weight gain due to the stimulation of both thirst, which increases fluid intake, and ADH release, which diminishes water loss. In contrast, unreplaced water losses severe enough to produce hypernatremia are usually associated with weight loss.

●Total urinary sodium excretion is appropriately increased with salt poisoning, and is appropriately reduced with hypovolemia due to unreplaced water losses. The fractional excretion of sodium (FENa) may be useful in a patient with hypernatremia, as a FENa greater than 2 percent in a volume-replete (well hydrated) patient is strongly suggestive of salt poisoning, whereas a FENa less than 1 percent is suggestive of dehydration caused by water loss [1,19]. (See 'Laboratory evaluation' below.)

More rapid correction has been safely reported for patients with acute salt poisoning who present within 24 hours of ingestion than for those with hypernatremia due to other causes [17].

CLINICAL MANIFESTATIONS

Acute hypernatremia — Clinical findings in acute pediatric hypernatremia are generally manifested by neurologic symptoms as water moves out of brain cells leading to cerebral contraction. The presence and severity of symptoms correlate with the degree of plasma sodium elevation and its rate of rise.

Nonspecific initial manifestations of hypernatremia include irritability, restlessness, weakness, vomiting, muscular twitching, fever, and, in infants, high-pitched cry and tachypnea [20]. Severe symptoms are observed with an acute rise of sodium above 160 mEq/L and include altered mental status, lethargy, coma, and seizures. In the most severe cases, such as salt poisoning, the rapid rise in sodium leads to acute brain shrinkage, resulting in vascular rupture with cerebral and subarachnoid hemorrhage, demyelination, and irreversible neurologic injury [14,21].

Because the most common cause of pediatric hypernatremia is excessive fluid losses, patients may also have manifestations of hypovolemia, including tachycardia, orthostatic blood pressure changes or decreased blood pressure, dry mucous membranes, and decreased peripheral perfusion with a delay in capillary refill. (See "Clinical assessment of hypovolemia (dehydration) in children", section on 'Clinical assessment'.)

Chronic hypernatremia — It appears that patients with chronic hypernatremia (defined as hypernatremia that is present more than one day) are asymptomatic due to cerebral adaption, which occurs within one to three days. This process involves restoration of brain volume by water movement from the cerebrospinal fluid into the brain, and generation and uptake of intracellular solutes (osmolytes) that promote water movement into the brain cells. (See "Manifestations of hyponatremia and hypernatremia in adults", section on 'Cerebral adaptation to hypernatremia'.)

In addition, it may be difficult to appreciate nonspecific findings, as many of these patients have underlying neurologic conditions (midline brain abnormalities) [10,11]. (See 'Inadequate water intake' above.)

DIAGNOSIS — The diagnosis of hypernatremia is made by the detection of an elevated plasma or serum sodium level above 150 mEq/L. Clinicians need to be aware that sodium values in capillary and non-capillary whole blood samples tend to be 2 to 3 mEq/L lower than measurements using venous samples [22,23]. Measurements obtained via blood gas analyzers may be even lower [24], necessitating familiarity with the technique used in a clinical setting. For patients in whom ongoing monitoring of sodium is needed, this variation based on sampling technique and method of analysis should be kept in mind while managing patients with abnormal sodium values.

Transient hypernatremia (in which the serum sodium concentration can rise by as much as 10 to 15 mEq/L within a few minutes due to water loss into cells) can be induced by severe exercise or seizures. Sodium returns to normal within 5 to 15 minutes after the cessation of exercise or seizures. (See "Etiology and evaluation of hypernatremia in adults", section on 'Water loss into cells'.)

In addition, spuriously falsely elevated sodium values have been observed in ill neonates with hypoalbuminemia (plasma albumin <30 g/L) in whom sodium is measured by indirect ion-selective electrodes, commonly utilized in main laboratory analyzers [25]. This artifact is circumvented by measurements using direct ion-selective electrodes found in point-of-care blood analyzers.

EVALUATION — The evaluation in pediatric hypernatremia is focused on determining the underlying etiology. However, evaluation should be delayed in the severely ill patient who requires fluid resuscitation.

Clinical evaluation — The underlying etiology of hypernatremia is usually evident from the history. Because pediatric hypernatremia is most often due to unreplaced hypotonic fluid losses, the history focuses on whether there are increased body fluid losses (eg, diarrhea) or inadequate fluid intake.

●History of excess gastrointestinal losses because of the presence of watery stools with documentation of the frequency and amount, or loss from nasogastric or colostomy drainage.

●History of impaired urinary concentration based on excessive urine output (polyuria) and dilute appearance. Urinary concentrating defect is suggested in infants who regularly and frequently soak through their diapers every few hours, and in older children with increased frequency of voiding, including nighttime voiding. In addition, questions about the appearance of the urine may be helpful, as a child with impaired concentration typically has urine that looks like water with little or no odor (dilute), and does not ever have a concentrated urine typically characterized by a yellow appearance, which may be accompanied by a strong ammonia odor.

●Neurologic impairment, particularly with midline brain defect, which is associated with impaired thirst mechanism, or inability to independently access free water.

●In breastfed infants, history of intake is assessed by whether there is successful latch-on, the frequency of feeding, mother's feeling of milk release, and whether the infant appears satiated following feeding. (See "Initiation of breastfeeding".)

Laboratory evaluation — Laboratory studies should preferably be obtained before significant fluid intervention has taken place, although fluid therapy should never be delayed in the severely ill patient.

When the underlying diagnosis remains uncertain, comparing the urine with plasma osmolality may be helpful in establishing the underlying mechanism and diagnosis (algorithm 1).

●Urine osmolality less than plasma osmolality is consistent with a urinary concentrating defect (ie, diabetes insipidus [DI]), which is usually due to a defect in either the release or response to antidiuretic hormone (ADH). Further evaluation to delineate between arginine vasopressin deficiency (AVP-D) and arginine vasopressin resistance (AVP-R) is based on the child's urinary response to water deprivation and the subsequent administration of desmopressin, which is discussed elsewhere. (See "Evaluation of patients with polyuria", section on 'Protocol in infants and children'.)

●Urine osmolality greater than plasma osmolality demonstrates that the secretion and response to ADH is intact. In this setting, hypernatremia is typically caused by free water loss from the gastrointestinal tract or skin and inadequate water intake, and less frequently by osmotic diuresis or excess salt intake (ie, iatrogenic causes or salt poisoning).

Other laboratory studies that may be included:

●Serum BUN and creatinine to determine kidney function. Serum creatinine is also used to calculate the fractional excretion of sodium (FENa).

●Serum/plasma and urine measurements of sodium and creatinine.

•Urine sodium is typically low (<25 mEq/L) in patients with hypernatremic hypovolemia, generally due to gastrointestinal losses and an increased proximal renal tubular sodium reabsorption.

•In contrast, urine sodium exceeds 200 mEq/L in patients with salt poisoning without hypovolemia [1].

•Fractional excretion of sodium (FENa) may be useful. FENa greater than 2 percent in a volume-replete (well-hydrated) patient is strongly suggestive of salt poisoning, whereas an FENa less than 1 percent is suggestive of hypernatremia caused by water loss [1,19]. (See "Acute kidney injury in children: Clinical features, etiology, evaluation, and diagnosis", section on 'Fractional excretion of sodium'.)

TREATMENT

General principles — Correction of hypernatremia requires both the administration of dilute fluids to correct the water deficit and, when appropriate, interventions to limit further water loss. Many pediatric patients also have a concurrent volume isotonic deficit usually due to gastrointestinal losses. Such patients with hypernatremia will require replacement of both water and electrolyte deficits. In these patients, it is important to assess the volume status as in the setting of significant hypovolemia because in patients with moderate to severe hypovolemia, fluid resuscitation with isotonic fluid to restore intravascular volume and tissue perfusion takes precedence over correction of the hypernatremia. (See "Treatment of hypovolemia (dehydration) in children in resource-abundant settings", section on 'Emergency fluid repletion phase'.)

In cases where hypernatremia alone is the primary abnormality, therapy is aimed at correcting the plasma sodium by providing free water and determining a rate of desired correction. Issues that need to be addressed when treating pediatric hypernatremia are:

●What is the volume status of the patient? Is there an emergent need for fluid resuscitation to restore intravascular volume and tissue perfusion?

●What is the magnitude of the water deficit that needs to be restored?

●At what rate should the hypernatremia be corrected (as lowering the sodium concentration too rapidly may lead to neurologic injury)?

●Is there a concurrent ongoing fluid loss that needs to be addressed?

●What is the underlying cause of hypernatremia and are there specific interventions that need to be considered?

Management also includes ongoing monitoring of the patient's fluid status with frequent clinical examinations and follow-up laboratory evaluation, including subsequent assessment of sodium levels. Based on these data, the initial fluid prescription may need to be revised.

Volume status and emergent fluid resuscitation — In any child with significant volume depletion, first management steps should be directed toward ensuring cardiovascular stability. In patients with moderate to severe hypovolemia, emergent fluid resuscitation with isotonic fluid is administered to restore intravascular volume and tissue perfusion. However, overzealous fluid resuscitation needs to be avoided to prevent inadvertent volume overload, which may be associated with cerebral edema [26]. (See "Treatment of hypovolemia (dehydration) in children in resource-abundant settings", section on 'Emergency fluid repletion phase'.)

Calculating the free water deficit — With the restoration of effective intra-arterial volume, or in cases where there is no need for urgent volume expansion, the focus turns to providing the fluid necessary to correct any existing hypovolemia, and enough free water to correct the hypernatremia.

The volume of free water to be provided can be calculated using one of two common approaches.

The first approach employs the estimate that total body water (TBW) is approximately 60 percent of the child's weight in kilograms (0.6 L/kg). The exact proportion varies as a child progresses from infancy to adolescence and is lower in individuals with obesity (figure 2):

Using this equation for a 14-kg child with a plasma sodium of 160, the free water deficit is: (0.6 L/kg) × (14 kg) × ([160/140] – 1) = 1.2 liters or 1200 mL.

The second approach uses the estimate that infusing 4 mL/kg of free water will lower plasma sodium by approximately 1 mEq/L:

Using this equation for the 14-kg child described above with plasma sodium elevated 20 mEq/L above desired, the water deficit would be: (4 mL/kg) × (14 kg) × (20 mEq/L change) = 1120 mL.

The variation in free water needed between the two calculations is generally clinically negligible and, in any case, the equations are used as estimates with follow-up laboratory results and clinical exams guiding ongoing changes.

Prescribed fluid — In most clinical settings, the administered fluid typically contains sodium, but is hypotonic compared with the patient's plasma, thereby providing free water. Although normal saline (0.9% saline) is isotonic in patients with normal plasma sodium, it is a hypotonic fluid for children with hypernatremia, and accordingly can be used as initial rehydration fluid for patients with hypernatremic hypovolemia [27]. Free water calculations provide for an estimate of the amount of water without sodium needed to return plasma sodium to a normal concentration. As an example, the 500 mL free water deficit in the example above could be delivered with the administration of 1 liter of 0.45% saline. Enteral fluids including oral rehydration therapy are also typically hypotonic fluids.

Rate of correction — It is important to determine the chronicity of hypernatremia when determining the rate of correction. As mentioned previously, in patients with chronic hypernatremia, cerebral adaption to hypernatremia takes place over the first few days with restoration of brain volume. In these patients, there is a risk of cerebral edema with rapid provision of free water. Even in cases where hypernatremia is known to have occurred acutely, similar rates of correction are generally used out of caution, especially with more pronounced aberrations in plasma sodium.

For children with chronic hypernatremia (plasma sodium ≥150 mEq/L for greater than 24 hours) or those with acute severe hypernatremia (plasma sodium >160 mEq/L), we and other experts recommend that a rate of correction does not exceed a decline of sodium greater than 0.5 mEq/L per hour (ie, 10 to 12 mEq/L per day). The following studies provide support for this recommendation:

●In a retrospective case control study of 97 children with hypernatremia and dehydration with a mean baseline serum sodium of 165 mEq/L, patients who developed cerebral edema had a significantly faster rate of correction compared with those without complications following correction of hypernatremia (1.0 versus 0.5 mEq/L per hour) [26].

●Similar findings were noted in another report in which the rate of reduction in serum sodium was 1.0 mEq/L per hour in the nine infants who developed seizures compared with 0.6 mEq/L per hour or less in 31 infants who did not develop seizures [28].

Slow correction of serum sodium remains the mainstay of therapy for children with hypernatremia, but the evidence to support this practice is limited. One retrospective study of the rate of serum sodium correction in hypernatremic children did not detect a difference in neurologic complications or mortality [29]. These observations highlight the need for a prospective study to address this question.

Ongoing losses and maintenance needs — The above calculations correct free water losses that have occurred up to the time of presentation. Children have ongoing normal maintenance needs and may also have excess free water losses not accounted for by calculations for maintenance fluids (eg, continuing diarrhea or persistent fever), and should receive replacement of these ongoing losses to prevent further electrolyte derangement. Since ongoing losses can fluctuate over time, it can be challenging to try to estimate them for inclusion in a fluid and electrolyte prescription that addresses current deficits as well. Accordingly, many clinicians will prescribe fluid orders to address current needs and desired rates of correction, and write separate orders to address ongoing losses. (See "Maintenance intravenous fluid therapy in children".)

Treatment of specific etiologies — The initial evaluation and management of hypernatremia usually occur concurrently. As noted above, obtaining additional laboratory studies for evaluation should not delay initiation of fluid therapy for the critically ill child. Although most young children develop hypernatremia related to acute illness or inability to take in fluid, in cases where a chronic condition is identified, such as arginine vasopressin resistance (AVP-R) or arginine vasopressin deficiency (AVP-D), therapy directed to the underlying condition (eg, administration of desmopressin) should be initiated in addition to providing free water replacement.

Clinical example — The following case synthesizes the information presented above in an attempt to show how the principles are applied clinically. A 10 kg child (TBW 0.6 times body weight) is estimated to have a 10 percent hypovolemic loss (approximately 1 liter of fluid) and a serum/plasma sodium concentration of 156 mEq/L. The following calculations can be made:

●Total fluid deficit: 10 percent of 10 kg = 1 L (1000 mL)

●Free water deficit: 6 L [(156/140 mEq/L) – 1] = 0.686 L (686 mL)

●Isotonic loss: Total fluid deficit – Water deficit = 1000 mL – 686 mL = 314 mL

During the emergent fluid phase, the patient received a 20 mL/kg bolus of normal saline (200 mL), replacing all but 114 mL of the isotonic fluid loss. Subsequent therapy includes replacement of the free water deficit (686 mL) and remaining isotonic loss (114 mL), maintenance of usual daily sodium and fluid needs (1000 mL per day of one-quarter isotonic saline in this case), and any excess ongoing loss of fluid and electrolyte. The water deficit should be replaced over at least 36 hours so that the sodium is lowered at a rate below 0.5 mEq/L per hour. This is often accomplished by replacing two-thirds of the free water deficit over the first 24 hours and the remainder over the next 12 or more hours.

Over the first 24 hours, the fluid regimen, which does not include replacement of excess ongoing losses, would entail:

●Free water deficit (two-thirds of total water deficit) = 460 mL

●Remaining isotonic deficit = 114 mL of water and 17 mEq of sodium

●Maintenance needs = 1000 mL of water and 30 mEq of sodium

In this case, administration of one-quarter isotonic saline at 65 mL per hour would provide adequate replacement of maintenance needs and remaining isotonic deficit, and would provide free water at a rate lower than the maximum threshold rate of 0.5 mEq/L per hour. Enteral fluids can also be used to replace free water deficits and provide maintenance needs.

SUMMARY AND RECOMMENDATIONS

●Definition and epidemiology – Hypernatremia is defined as a serum or plasma sodium greater than 150 mEq/L and is an uncommon problem in children. Pediatric hypernatremia is most commonly seen in the newborn period due to inadequate intake in breastfeeding neonates. In older children, the most common cause of hypernatremia is excess water loss from gastroenteritis or systemic infection. (See 'Epidemiology' above.)

●Pathophysiology – Hypernatremia is due to imbalance of the body's handling of water resulting in an excess of plasma tonicity to total body water. (See 'Pathophysiology' above.)

●Causes – In children, hypernatremia is usually caused by loss of body fluids with a sodium plus potassium concentration that is less than serum or plasma sodium. These losses are from the gastrointestinal tract, urine, or skin. Infants and small children are more vulnerable to hypernatremia than are older individuals because of greater insensible water losses and their inability to communicate their need for fluids and access fluids independently. Less frequently, pediatric hypernatremia can be caused by excess salt intake, including iatrogenic administration and salt poisoning. (See 'Etiology' above and 'Infants and young children' above.)

●Clinical manifestations – When hypernatremia develops acutely, neurologic symptoms can develop as water moves out of brain cells, leading to cerebral contraction. The presence and severity of symptoms correlate with the degree of plasma or serum sodium elevation and its rate of rise and range from nonspecific findings (eg, irritability, restlessness, weakness, vomiting, muscular twitching, fever, and, in infants, high-pitched cry and tachypnea) to severe neurologic findings of altered mental status, lethargy, coma, seizures, intracerebral and subarachnoid hemorrhage, and demyelination. (See 'Acute hypernatremia' above.)

Most patients with chronic hypernatremia (defined as hypernatremia that is present more than one day) are asymptomatic because cerebral adaption restores brain volume. (See 'Chronic hypernatremia' above.)

●Diagnosis – The diagnosis of hypernatremia is made by the detection of an elevated plasma or serum sodium level above 150 mEq/L. (See 'Diagnosis' above.)

●Evaluation – The diagnostic evaluation of hypernatremia is focused on determining the underlying cause of hypernatremia. However, in the severely ill patient, the first priority is fluid resuscitation. In most cases, the etiology of hypernatremia is evident from the history. When the underlying diagnosis remains uncertain, comparing the urine with plasma osmolality may be helpful in distinguishing children with urinary concentrating defects (ie, diabetes insipidus [DI]) from those with water losses from the skin or gastrointestinal tract. In addition, urinary sodium and fractional excretion of sodium may help differentiate between hypernatremia due to water loss and salt ingestion/poisoning (algorithm 1 and table 1). (See 'Evaluation' above.)

●Treatment – Treatment of hypernatremia consists of correcting hypernatremia by administering dilute fluids to correct the water deficit and, when appropriate, interventions to limit further water loss.

•Steps include determining the volume status of the patient, magnitude of the water deficit, and safe rate of sodium correction and calculating maintenance fluid needs and excess ongoing losses. (See 'Treatment' above.)

•For children with chronic hypernatremia or severe acute hypernatremia (sodium greater than 160 mEq/L), we recommend that the rate of serum sodium correction not exceed a decline of 0.5 mEq/L per hour (ie, 10 to 12 mEq/L per day) (Grade 1B). Faster rates of correction are associated with a higher risk of cerebral edema. (See 'Rate of correction' above.)

•The therapy should be readjusted as needed based on frequent clinical examinations and follow-up laboratory evaluation, including subsequent assessment of sodium levels.