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15/08/18 19(54Hypernatremia in children – UpToDate
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Hypernatremia in childrenAuthors:Michael J Somers, MD, Avram Z Traum, MDSection Editor:Tej K Mattoo, MD, DCH, FRCPDeputy Editor:Melanie S Kim, MDAll topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Jul 2018. | This topic last updated: Mar 10, 2017.INTRODUCTION — Hypernatremia is typically defined as a serum or plasma sodium greater than 150mEq/L. Although pediatric hypernatremia is an uncommon electrolyte abnormality, there can be significantneurologic injury in patients with severe hypernatremia, especially those with acute and rapid changes inserum sodium.The etiology, clinical findings, diagnosis, and evaluation of pediatric hypernatremia are reviewed here.EPIDEMIOLOGY — The true incidence of pediatric hypernatremia is unknown, as published data are basedon hospitalized children.As an example, a Scottish study reported an overall incidence of hypernatremia (defined as a plasma sodium>150 mEq/L) of 0.04 percent for all pediatric hospitalizations in pediatric patients over two weeks of age overa study period from 1996 to 2006 [1]. However, the risk of hypernatremia was 10 times greater in neonatesless than two weeks of age, with an incidence of 0.4 percent. Neonatal hypernatremia was almost exclusivelyseen in breastfed infants with excessive weight (water loss). Of note, the incidence of neonatal hypernatremiain breastfed infants was higher than reported in previous studies (0.03 to 0.07 percent) (see "Initiation ofbreastfeeding", section on 'Excessive weight loss'). 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 orsystemic infection. However, in this cohort, it was more common for hypernatremia to develop duringhospitalization, particularly in patients with systemic infection or those who underwent cardiac surgery. Inaddition, 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 aserum sodium greater than 150 mEq/L) was detected in 1.4 percent of sodium values in a laboratorydatabase, but only 0.2 percent of patients were discharged with a diagnosis of hyperosmolality due tohypernatremia [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 ofhypernatremia was inadequate fluid intake.PATHOPHYSIOLOGY — Hypernatremia is caused by an imbalance in the body's handling of water, resultingin a relative excess of effective plasma osmolality (tonicity) to total body water. The plasma tonicity is definedas the concentration of solutes that do not easily cross the cell membrane, which is primarily due to sodium®

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Página 2 de 18https://www.uptodate.com/contents/hypernatremia-in-children/print?source=history_widgetsalts in the extracellular space. As a result, serum or plasma sodium is used as a surrogate for assessingtonicity. (See "General principles of disorders of water balance (hyponatremia and hypernatremia) andsodium 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 oneexception 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 pituitarypromoting water retention, and by thirst-prompting water ingestion (figure 1). These homeostatic mechanismsthat mediate plasma tonicity and water balance are similar in adults and children, resulting in a normal rangeof plasma sodium between 135 and 145 mEq/L that does not vary by age. (See "General principles ofdisorders of water balance (hyponatremia and hypernatremia) and sodium balance (hypovolemia andedema)", section on 'Regulation of plasma tonicity'.)Hypernatremia is most often caused by the failure to replace water losses, which, in children, are mostcommonly due to gastrointestinal fluid loss. In these patients, the sodium plus potassium concentration in thefluid that is lost is less than the plasma sodium concentration. As a result, water is lost in excess of sodiumplus potassium, which will tend to increase the plasma sodium concentration. In individuals with intact thirstmechanisms, the intake of free water promptly corrects any increase in plasma sodium. However, when waterlosses cannot be replaced because of a lack of free access to water, excessive loss in acute illnesses, orimpaired thirst mechanism, sodium concentration increases and may result in hypernatremia. Infants andchildren who are significantly neurodevelopmentally impaired are at particular risk for hypernatremia, as theymay be unable to communicate their thirst and are dependent on others for fluid repletion. Pediatrichypernatremia 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 tocorrect the plasma tonicity.ETIOLOGY — The causes of pediatric hypernatremia can be separated into the two previously discussedmechanisms that result in pediatric hypernatremia (see 'Pathophysiology' above):Excess water losses — Loss of body fluids with a sodium plus potassium concentration that is less thanserum or plasma sodium (hypotonic fluids) will result in an increase in sodium concentration if the waterlosses 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 normalfluid 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 hypotonicgastrointestinal losses without replacement, which result in effective water loss. In particular, gastroenteritisPlasma tonicity = 2 x [Na] + [glucose]/18 (if glucose is measured in mg/dL)●Plasma tonicity = 2 x [Na] + [glucose] (if glucose is measured in mmol/L)●
Water loss that is not replaced●Excessive salt intake relative to water ingestion●

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Página 3 de 18https://www.uptodate.com/contents/hypernatremia-in-children/print?source=history_widgetdue to rotavirus can present with profuse watery diarrhea and hypernatremia [3]. In addition, losses due tovomiting 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 urinaryconcentration (eg, diabetes insipidus [DI]) or osmotic diuresis. Without adequate water replacement, sodiumconcentration will rise and may result in hypernatremia (table 1).Urinary concentration defects — Impaired urinary concentration is typically due to antidiuretichormone (ADH) deficiency or resistance, which leads to excretion of a dilute urine (urine osmolality less thanplasma osmolality) and excessive urinary free water loss.Central DI – Central DI is caused by inadequate production or release of ADH. Central DI has multipleetiologies, including congenital central nervous system (CNS) malformations and genetic syndromes withassociated CNS anomalies, and acquired causes due to CNS tumors, infiltrative processes of thehypothalamic-pituitary stalk, and sequelae from neurosurgery and trauma. (See "Clinical manifestationsand causes of central diabetes insipidus", section on 'Causes'.)●Nephrogenic DI – Nephrogenic DI is caused by an inadequate renal tubular response to circulating ADH.The multiple causes of pediatric nephrogenic DI can be further divided into the following categories (see"Clinical manifestations and causes of nephrogenic diabetes insipidus", section on 'Causes'):●Congenital nephrogenic DI – Congenital nephrogenic DI is most often the result of mutations in thevasopressin type 2 receptor (AVPR2), found at the locus Xp28. In this X-linked disorder, maleinfants typically present in the first weeks of life with fussiness, low-grade fever, and polyuria withhypernatremia. In addition, hereditary nephrogenic DI may be caused by a mutation in theaquaporin-2 gene (AQP2) at 12q13, which encodes the ADH-sensitive water channels. Congenitalnephrogenic DI is also observed in other inherited disorders, including Bardet-Biedl and Barttersyndromes, nephronophthisis, cystinosis, and familial hypomagnesemia with hypercalciuria andnephrocalcinosis.•
Acquired nephrogenic DI – Drug toxicity is the most common cause of acquired DI. Lithium toxicityis the most frequent cause of drug-induced nephrogenic DI, and its use has increased in childrenand adolescents with mood disorders. Lithium also can cause interstitial nephritis and fibrosis,further exacerbating urinary concentrating capacity. The effects of lithium on urinary concentratingability can be permanent. (See "Renal toxicity of lithium", section on 'Nephrogenic diabetesinsipidus'.)•Other medications associated with drug-induced nephrogenic DI include amphotericin,demeclocycline, ifosfamide, foscarnet, and cidofovir.Hypercalcemia and hypokalemia also can produce functional defects in water reabsorption that areusually reversible once the electrolyte perturbation resolves. (See "Clinical manifestations andcauses of nephrogenic diabetes insipidus", section on 'Hypercalcemia' and "Hypokalemia-inducedrenal dysfunction", section on 'Impaired urinary concentrating ability'.)Renal disease – In children, impaired urinary concentration is seen in a variety of renal diseases,including obstructive uropathy, sickle cell disease, nephronophthisis, cystinosis, and acute orchronic kidney disease. In these disorders, the decline in urinary concentrating ability may be due toa number of different factors, including resistance to ADH, impairment of the renal medulla•

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Página 4 de 18https://www.uptodate.com/contents/hypernatremia-in-children/print?source=history_widgetOsmotic diuresis — Hypernatremia can also occur from urinary water losses due to renal excretion ofnonelectrolyte, nonreabsorbed solutes, such as mannitol or glucose (eg, patients with diabetic ketoacidosisand hyperglycemia). While the urine osmolality is augmented with the presence of these substances, theurinary 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 potentiallyhypernatremia. (See "Complications of mannitol therapy", section on 'Volume depletion and hypernatremia'and "Clinical features and diagnosis of diabetic ketoacidosis in children and adolescents", section on 'Serumsodium'.)Skin loss — The sodium plus potassium content of sweat is less than half that of plasma, but normalsweating 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 canbecome more substantial and can result in hypernatremia if not corrected with water intake. Increasedinsensible water losses due to burns can also lead to hypernatremia [4]. (See "Emergency care of moderateand severe thermal burns in children", 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 othersfor 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 childrenare at increased risk for hypernatremic hypovolemia because they have a higher ratio of surface area tovolume, 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 fluidlosses.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 potentiallydevastating complication [9]. (See "Initiation of breastfeeding", section on 'Excessive weight loss'.)Impaired thirst mechanism — Children with structural midline brain abnormalities may have animpaired or no thirst mechanism (adipsia or hypodipsia), which may result in chronic hypernatremia. Theselesions include congenital abnormalities, such as holoprosencephaly [10,11], acquired lesions (eg,craniopharyngioma), and infiltrative processes of the hypothalamic-pituitary stalk. These patients may haveconcomitant central DI, and careful attention to both water intake and the use of desmopressin therapymakes 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. Inchildren, excessive salt intake is generally due to iatrogenic administration of excess sodium (eg, hypertonicsaline solution), or due to salt poisoning. In either setting, patients are unable to access free water in order torestore plasma tonicity and correct hypernatremia.Iatrogenic causes — Iatrogenic causes of hypernatremia include the administration of sodiumbicarbonate infusions for metabolic acidosis or hypertonic saline, which may be used in the acutecountercurrent mechanism, and/or decrease in the number of functioning nephrons, which can leadto osmotic diuresis as the ability to reabsorb the increasing solute load is exceeded.

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Página 5 de 18https://www.uptodate.com/contents/hypernatremia-in-children/print?source=history_widgetmanagement of increased intracranial pressure. (See "Evaluation and management of elevated intracranialpressure in adults", section on 'Hypertonic saline bolus'.)In addition, the administration of isotonic saline to replete hypotonic losses can also lead to increasedsodium, and potentially hypernatremia, by net sodium gain in the following settings:
Salt poisoning — Salt poisoning has been described both from incorrect formula preparation and as anintentional form of child abuse [13-16]. Infants and young children are especially susceptible due to theirinability to communicate their thirst, and their reliance on others for access to water. A teaspoon of saltcontains 100 mEq of sodium (Na), which can increase the serum sodium concentration in a 10 kg child by 17mEq/L. The unpleasant salty taste of such preparations should limit their voluntary ingestion, but in situationsof intentional poisoning these children are often subjected to limited access to other fluids, thereby ensuringthe ingestion of the hypertonic preparations.Salt poisoning causes a rapid onset of hypernatremia, often resulting in cerebral hemorrhage and irreversibleneurologic injury. Osmotic demyelination can occur, similar to the injury caused by a rapid elevation in serumsodium in patients with chronic hyponatremia [17]. (See "Osmotic demyelination syndrome (ODS) and overlyrapid correction of hyponatremia".)Salt poisoning has a number of distinguishing features from excessive water loss, which, as noted above, isthe most common cause of hypernatremia [16,18]. (See 'Excess water losses' above.)
CLINICAL MANIFESTATIONSAcute hypernatremia — Clinical findings in acute pediatric hypernatremia are generally manifested byneurological symptoms as water moves out of brain cells leading to cerebral contraction. The presence andseverity of symptoms correlate with the degree of plasma sodium elevation and its rate of rise.Uncontrolled diabetes, in which the free water lost in an osmotic diuresis from nonreabsorbed glucose isreplaced with isotonic saline.●Recovery from acute kidney injury, in which the free water lost in an urea-induced osmotic diuresis isreplaced with isotonic saline.●Nasogastric suction, in which patients receive isotonic saline to replace hypotonic intestinal fluid losseswith 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 diuretictherapy, which impairs renal concentrating ability, resulting in inappropriately high water losses [12].●
Salt poisoning is initially associated with weight gain due to the stimulation of both thirst, which increasesfluid intake, and ADH release, which diminishes water loss. In contrast, unreplaced water losses severeenough to produce hypernatremia are usually associated with weight loss.●Total urinary sodium excretion is appropriately increased with salt poisoning, and is appropriatelyreduced 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 issuggestive of dehydration caused by water loss [1,18]. (See 'Laboratory evaluation' below.)●

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Página 6 de 18https://www.uptodate.com/contents/hypernatremia-in-children/print?source=history_widgetNonspecific initial manifestations of hypernatremia include irritability, restlessness, weakness, vomiting,muscular twitching, fever, and, in infants, high-pitched cry and tachypnea [19]. Severe symptoms areobserved 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 brainshrinkage, resulting in vascular rupture with cerebral and subarachnoid hemorrhage, demyelination, andirreversible neurologic injury [14,20].Because the most common cause of pediatric hypernatremia is excessive fluid losses, patients may alsohave manifestations of hypovolemia, including tachycardia, orthostatic blood pressure changes or decreasedblood pressure, dry mucous membranes, and decreased peripheral perfusion with a delay in capillary refill.(See "Clinical assessment and diagnosis of hypovolemia (dehydration) in children", section on 'Clinicalassessment'.)Chronic hypernatremia — It appears that patients with chronic hypernatremia (defined as hypernatremiathat is present more than one day) are asymptomatic due to cerebral adaption, which occurs within one tothree days. This process involves restoration of brain volume by water movement from the cerebrospinal fluidinto the brain, and generation and uptake of intracellular solutes (osmolytes) that promote water movementinto the brain cells. (See "Manifestations of hyponatremia and hypernatremia in adults", section on 'Cerebraladaptation to hypernatremia'.)In addition, it may be difficult to appreciate nonspecific findings, as many of these patients have underlyingneurologic 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 serumsodium level above 150 mEq/L. Clinicians need to be aware that sodium values in capillary and non-capillarywhole blood samples tend to be 2 to 3 mEq/L lower than measurements using venous samples [21,22]. Forpatients in whom ongoing monitoring of sodium is needed, this variation based on sampling technique andmethod 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/Lwithin a few minutes due to water loss into cells) can be induced by severe exercise or seizures. Sodiumreturns to normal within 5 to 15 minutes after the cessation of exercise or seizures. (See "Etiology andevaluation of hypernatremia in adults", section on 'Water loss into cells'.)In addition, spuriously falsely elevated sodium values have been observed in ill neonates withhypoalbuminemia (plasma albumin <30 g/L) in whom sodium is measured by indirect ion-selective electrodes,commonly utilized in main laboratory analyzers [23]. This artifact is circumvented by measurements usingdirect 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. Becausepediatric hypernatremia is most often due to unreplaced hypotonic fluid losses, the history focuses onwhether 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 ofthe frequency and amount, or loss from nasogastric or colostomy drainage.●

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Página 7 de 18https://www.uptodate.com/contents/hypernatremia-in-children/print?source=history_widgetLaboratory evaluation — Laboratory studies should preferably be obtained before significant fluidintervention 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 helpfulin establishing the underlying mechanism and diagnosis (algorithm 1).
Other laboratory studies that may be included:History of impaired urinary concentration based on excessive urine output (polyuria) and diluteappearance. Urinary concentrating defect is suggested in infants who regularly and frequently soakthrough 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 achild with impaired concentration typically has urine that looks like water with little or no odor (dilute), anddoes not ever have a concentrated urine typically characterized by a yellow appearance, which may beaccompanied by a strong ammonia odor.●
Neurologic impairment, particularly with midline brain defect, which is associated with impaired thirstmechanism, or inability to independently access free water.●In breastfed infants, history of intake is assessed by whether there is successful latch-on, the frequencyof feeding, mother's feeling of milk release, and whether the infant appears satiated following feeding.(See "Initiation of breastfeeding".)●
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 antidiuretichormone (ADH). Further evaluation to delineate between central and nephrogenic DI is based on thechild's urinary response to water deprivation and the subsequent administration of desmopressin, whichis discussed elsewhere. (See "Diagnosis of polyuria and diabetes insipidus", section on 'Infants andchildren'.)●Urine osmolality greater than plasma osmolality demonstrates that the secretion and response to ADH isintact. In this setting, hypernatremia is typically caused by free water loss from the gastrointestinal tractor skin and inadequate water intake, and less frequently by osmotic diuresis or excess salt intake (ie,iatrogenic causes or salt poisoning).●Serum BUN and creatinine to determine renal function. Serum creatinine is also used to calculate thefractional 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 dueto gastrointestinal losses.•In contrast, urine sodium exceeds 200 mEq/L in patients with salt poisoning [1].•Fractional excretion of sodium (FENa) may be useful, as a FENa greater than 2 percent is stronglysuggestive of salt poisoning, whereas a FENa less than 1 percent is suggestive of hypernatremiacaused by water loss [1,18]. (See "Acute kidney injury in children: Clinical features, etiology,evaluation, and diagnosis", section on 'Fractional excretion of sodium'.)•

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Página 8 de 18https://www.uptodate.com/contents/hypernatremia-in-children/print?source=history_widgetTREATMENTGeneral principles — Correction of hypernatremia requires both the administration of dilute fluids to correctthe water deficit and, when appropriate, interventions to limit further water loss. Many pediatric patients alsohave a concurrent volume isotonic deficit usually due to gastrointestinal losses. Such patients withhypernatremia will require replacement of both water and electrolyte deficits. In these patients, it is importantto assess the volume status as in the setting of significant hypovolemia, because in patients with moderate tosevere hypovolemia, fluid resuscitation with isotonic fluid to restore intravascular volume and tissue perfusiontakes precedence over correction of the hypernatremia. (See "Treatment of hypovolemia (dehydration) inchildren", section on 'Emergent fluid repletion phase'.)In cases where hypernatremia alone is the primary abnormality, therapy is aimed at correcting the plasmasodium by providing free water and determining a rate of desired correction. Issues that need to beaddressed when treating pediatric hypernatremia are:
Management also includes ongoing monitoring of the patient's fluid status with frequent clinical examinationsand follow-up laboratory evaluation, including subsequent assessment of sodium levels. Based on thesedata, the initial fluid prescription may need to be revised.Volume status and emergent fluid resuscitation — In any child with significant volume depletion, firstmanagement steps should be directed toward ensuring cardiovascular stability. In patients with moderate tosevere hypovolemia, emergent fluid resuscitation with isotonic fluid is administered to restore intravascularvolume and tissue perfusion. However, overzealous fluid resuscitation needs to be avoided to preventinadvertent volume overload, which may be associated with cerebral edema [24]. (See "Treatment ofhypovolemia (dehydration) in children", section on 'Emergent fluid repletion phase'.)Calculating the free water deficit — With the restoration of effective intra-arterial volume, or in cases wherethere is no need for urgent volume expansion, the focus turns to providing the fluid necessary to correct anyexisting 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:For this equation, estimating total body water (TBW) as 60 percent of the child's weight in kilograms (0.6 L/kg)is a reasonable starting point for the purposes of calculating fluid replacement. The exact proportion varies asa child progresses from infancy to adolescence, and is lower in obese individuals (figure 2). Thus, in a 6 kgWhat is the volume status of the patient? Is there an emergent need for fluid resuscitation to restoreintravascular 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 rapidlymay 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 beconsidered?●
Free water deficit in milliliters = Current total body water x ([current plasma Na/140] – 1)●

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Página 9 de 18https://www.uptodate.com/contents/hypernatremia-in-children/print?source=history_widgetinfant with a plasma sodium of 160, the free water deficit is: (0.6 L/kg) x (6 kg) x ([160/140] – 1) = 0.51 litersor 510 mL.This approach uses the estimate that the provision of 4 mL/kg of free water will lower plasma sodium byapproximately 1 mEq/L. For the 6 kg infant described above with plasma sodium elevated 20 mEq/L abovedesired, his or her water deficit would be: (4 mL/kg) x (6 kg) x (20 mEq/L change) = 480 mL.The variation in free water needed between the two calculations is generally clinically negligible and, in anycase, the equations are used as estimates with follow-up laboratory results and clinical exams guidingongoing changes.Prescribed fluid — Free water calculations provide for an estimate of the amount of water without sodiumneeded to return plasma sodium to a normal concentration. However, in most clinical settings, theadministered fluid typically contains sodium, but is hypotonic to the patient's plasma, thereby providing freewater. As an example, the 500 mL free water deficit in the example above could be delivered with theadministration of 1 liter of 0.45 percent saline. In addition, normal saline (0.9 percent saline) is isotonic inpatients with normal plasma sodium; however, it is a hypotonic fluid for children with hypernatremia, andaccordingly can be used as initial rehydration fluid for patients with hypernatremic hypovolemia [25]. Enteralfluids including oral rehydration therapy are also typically hypotonic fluids.Rate of correction — It is important to determine the chronicity of hypernatremia when determining the rateof correction. As mentioned previously, in patients with chronic hypernatremia, cerebral adaption tohypernatremia takes place over the first few days with restoration of brain volume. In these patients, there is arisk of cerebral edema with rapid provision of free water. Even in cases where hypernatremia is known tohave occurred acutely, similar rates of correction are generally used out of caution, especially with morepronounced aberrations in plasma sodium.For children with chronic hypernatremia (plasma sodium ≥150 mEq/L for greater than 24 hours) or those withacute severe hypernatremia (plasma sodium >160 mEq/L), we and other experts recommend that a rate ofcorrection does not exceed a fall 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:
Ongoing losses and maintenance needs — The above calculations correct free water losses that haveoccurred up to the time of presentation. Children have ongoing normal maintenance needs and may alsohave excess free water losses not accounted for by calculations for maintenance fluids (eg, continuingdiarrhea or persistent fever), and should receive replacement of these ongoing losses to prevent furtherelectrolyte derangement. Since ongoing losses can fluctuate over time, it can be challenging to try to estimatethem for inclusion in a fluid and electrolyte prescription that addresses current deficits as well. Accordingly,Free water deficit in milliliters = (4 mL/kg) x (weight in kg) x (desired change in plasma Na)●
In a retrospective case control study of 97 children with hypernatremia and dehydration with a meanbaseline serum sodium of 165 mEq/L, patients who developed cerebral edema had a significantly fasterrate of correction compared with those without complications following correction of hypernatremia (1.0versus 0.5 mEq/L per hour) [24].●Similar findings were noted in another report in which the rate of reduction in serum sodium was 1.0mEq/L per hour in the nine infants who developed seizures compared with 0.6 mEq/L per hour or less in31 infants who did not develop seizures [26].●

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Página 10 de 18https://www.uptodate.com/contents/hypernatremia-in-children/print?source=history_widgetmany clinicians will prescribe fluid orders to address current needs and desired rates of correction, and writeseparate orders to address ongoing losses. (See "Maintenance fluid therapy in children".)Treatment of specific etiologies — The initial evaluation and management of hypernatremia usually occurconcurrently. As noted above, obtaining additional laboratory studies for evaluation should not delay initiationof fluid therapy for the critically ill child. Although most young children develop hypernatremia related to acuteillness or inability to take in fluid, in cases where a chronic condition is identified, such as nephrogenic orcentral diabetes insipidus, 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 showhow the principles are applied clinically. A 10 kg child (TBW 0.6 times body weight) is estimated to have a 10percent hypovolemic loss (approximately 1 liter of fluid) and a serum/plasma sodium concentration of 156mEq/L. The following calculations can be made:During the emergent fluid phase, the patient received a 20 mL/kg bolus of normal saline (200 mL), replacingall 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 (1000mL/day of one-quarter isotonic saline in this case), and any excess ongoing loss of fluid and electrolyte. Thewater deficit should be replaced over at least 36 hours so that the sodium is lowered at a rate below 0.5mEq/L per hour. This is often accomplished by replacing two-thirds of the free water deficit over the first 24hours 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:In this case, administration of one-quarter isotonic saline at 65 mL/hour would provide adequate replacementof maintenance needs and remaining isotonic deficit, and would provide free water at a rate lower than themaximum threshold rate of 0.5 mEq/L per hour. Enteral fluids can also be used to replace free water deficitsand provide maintenance needs.SUMMARY AND RECOMMENDATIONSTotal fluid deficit – 10 percent of 10 kg = 1000 mL●Free water deficit – 6 L [(156/140 mEq/L) – 1] = 686 mL●Isotonic loss – Total fluid deficit – Water deficit = 314 mL●
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●
Hypernatremia is defined as a serum or plasma sodium greater than 150 mEq/L and is an uncommonproblem in children. Pediatric hypernatremia is most commonly seen in the newborn period due toinadequate intake in breastfeeding neonates. In older children, the most common cause ofhypernatremia is excess water loss from gastroenteritis or systemic infection. (See 'Epidemiology'above.)●

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Página 11 de 18https://www.uptodate.com/contents/hypernatremia-in-children/print?source=history_widgetUse of UpToDate is subject to the Subscription and License Agreement.Hypernatremia is due to imbalance of the body's handling of water resulting in an excess of plasmatonicity to total body water. In children, hypernatremia is usually caused by loss of body fluids with asodium plus potassium concentration that is less than serum or plasma sodium. These losses are fromthe gastrointestinal tract, urine, or skin. Less frequently, pediatric hypernatremia can be caused byexcess salt intake, including iatrogenic administration and salt poisoning. (See 'Pathophysiology' aboveand 'Etiology' above.)●Infants and small children are more vulnerable to hypernatremia than older individuals because ofgreater insensible water losses and their inability to communicate their need for fluids and access fluidsindependently. (See 'Infants and young children' above.)●Clinical findings are generally manifested by neurological symptoms in patients with acute hypernatremiaas water moves out of brain cells leading to cerebral contraction. The presence and severity ofsymptoms correlate with the degree of plasma or serum sodium elevation and its rate of rise, and rangefrom 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. Most patientswith chronic hypernatremia (defined as hypernatremia that is present more than one day) areasymptomatic as cerebral adaption restores brain volume. (See 'Clinical manifestations' above.)●
The diagnosis of hypernatremia is made by the detection of an elevated plasma or serum sodium levelabove 150 mEq/L. (See 'Diagnosis' above.)●The diagnostic evaluation of hypernatremia is focused on determining the underlying cause ofhypernatremia. However, it should be delayed in the severely ill patient who requires fluid resuscitation.In most cases, the etiology of hypernatremia is evident from the history. When the underlying diagnosisremains uncertain, comparing the urine with plasma osmolality may be helpful in identifying children withurinary concentrating defects (ie, diabetes insipidus [DI]) from those with water losses from the skin orgastrointestinal tract. In addition, urinary sodium and fractional excretion of sodium may help differentiatebetween hypernatremia due to water loss and salt ingestion/poisoning (algorithm 1 and table 1). (See'Evaluation' above.)●
Treatment of hypernatremia consists of correcting hypernatremia with both the administration of dilutefluids to correct the water deficit, and, when appropriate, interventions to limit further water loss.Management of pediatric hypernatremia includes determining the volume status of the patient, themagnitude of the water deficit, and the safe rate of sodium correction; and identifying maintenance fluidneeds, excess ongoing losses not included in maintenance fluid calculation, and the etiology ofhypernatremia. In addition, readjustment of therapy is based on data from ongoing monitoring of thepatient's fluid status based on frequent clinical examinations and follow-up laboratory evaluation,including subsequent assessment of sodium levels. (See 'Treatment' above.)●
We recommend that the rate of correction in chronic pediatric hypernatremia or severe acutehypernatremia (sodium greater than 160 mEq/L) does not exceed a fall 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 ofcerebral edema. (See 'Rate of correction' above.)•

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Página 12 de 18https://www.uptodate.com/contents/hypernatremia-in-children/print?source=history_widgetREFERENCES1. Forman S, Crofton P, Huang H, et al. The epidemiology of hypernatraemia in hospitalised children inLothian: a 10-year study showing differences between dehydration, osmoregulatory dysfunction and saltpoisoning. Arch Dis Child 2012; 97:502.2. Moritz ML, Ayus JC. The changing pattern of hypernatremia in hospitalized children. Pediatrics 1999;104:435.3. Kaiser P, Borte M, Zimmer KP, Huppertz HI. Complications in hospitalized children with acutegastroenteritis caused by rotavirus: a retrospective analysis. Eur J Pediatr 2012; 171:337.4. Namdar T, Stollwerck PL, Stang FH, et al. Transdermal fluid loss in severely burned patients. Ger MedSci 2010; 8:Doc28.5. Cooper WO, Atherton HD, Kahana M, Kotagal UR. Increased incidence of severe breastfeedingmalnutrition and hypernatremia in a metropolitan area. Pediatrics 1995; 96:957.6. Moritz ML, Manole MD, Bogen DL, Ayus JC. Breastfeeding-associated hypernatremia: are we missingthe diagnosis? Pediatrics 2005; 116:e343.7. Oddie S, Richmond S, Coulthard M. Hypernatraemic dehydration and breast feeding: a populationstudy. Arch Dis Child 2001; 85:318.8. Oddie SJ, Craven V, Deakin K, et al. Severe neonatal hypernatraemia: a population based study. ArchDis Child Fetal Neonatal Ed 2013; 98:F384.9. Iyer NP, Srinivasan R, Evans K, et al. Impact of an early weighing policy on neonatal hypernatraemicdehydration and breast feeding. Arch Dis Child 2008; 93:297.10. Schaff-Blass E, Robertson GL, Rosenfield RL. Chronic hypernatremia from a congenital defect inosmoregulation of thirst and vasopressin. J Pediatr 1983; 102:703.11. König R, Beeg T, Tariverdian G, et al. Holoprosencephaly, bilateral cleft lip and palate and ectrodactyly:another case and follow up. Clin Dysmorphol 2003; 12:221.12. Hoorn EJ, Betjes MG, Weigel J, Zietse R. Hypernatraemia in critically ill patients: too little water and toomuch salt. Nephrol Dial Transplant 2008; 23:1562.13. Paut O, André N, Fabre P, et al. The management of extreme hypernatraemia secondary to saltpoisoning in an infant. Paediatr Anaesth 1999; 9:171.14. FINBERG L, KILEY J, LUTTRELL CN. Mass accidental salt poisoning in infancy. A study of a hospitaldisaster. JAMA 1963; 184:187.15. Meadow R. Non-accidental salt poisoning. Arch Dis Child 1993; 68:448.16. Wallace D, Lichtarowicz-Krynska E, Bockenhauer D. Non-accidental salt poisoning. Arch Dis Child2017; 102:119.17. Dobato JL, Barriga FJ, Pareja JA, Vela L. [Extrapontine myelinolyses caused by iatrogenichypernatremia following rupture of a hydatid cyst of the liver with an amnesic syndrome as sequela].Rev Neurol 2000; 31:1033.18. Coulthard MG, Haycock GB. Distinguishing between salt poisoning and hypernatraemic dehydration inchildren. BMJ 2003; 326:157.19. Finberg L. Hypernatremic (hypertonic) dehydration in infants. N Engl J Med 1973; 289:196.20. FINBERG L. Pathogenesis of lesions in the nervous system in hypernatremic states. I. Clinicalovservations of infants. Pediatrics 1959; 23:40.

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Página 13 de 18https://www.uptodate.com/contents/hypernatremia-in-children/print?source=history_widget21. Levene I. Towards evidence based medicine for paediatricians. Question 1: Is measurement of sodiumfrom capillary blood accurate enough for clinical decision making? Arch Dis Child 2014; 99:481.22. Morimatsu H, Rocktäschel J, Bellomo R, et al. Comparison of point-of-care versus central laboratorymeasurement of electrolyte concentrations on calculations of the anion gap and the strong iondifference. Anesthesiology 2003; 98:1077.23. King RI, Mackay RJ, Florkowski CM, Lynn AM. Electrolytes in sick neonates – which sodium is the rightanswer? Arch Dis Child Fetal Neonatal Ed 2013; 98:F74.24. Fang C, Mao J, Dai Y, et al. Fluid management of hypernatraemic dehydration to prevent cerebraloedema: a retrospective case control study of 97 children in China. J Paediatr Child Health 2010;46:301.25. El-Bayoumi MA, Abdelkader AM, El-Assmy MM, et al. Normal saline is a safe initial rehydration fluid inchildren with diarrhea-related hypernatremia. Eur J Pediatr 2012; 171:383.26. Kahn A, Brachet E, Blum D. Controlled fall in natremia and risk of seizures in hypertonic dehydration.Intensive Care Med 1979; 5:27.Topic 14276 Version 12.0

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Página 14 de 18https://www.uptodate.com/contents/hypernatremia-in-children/print?source=history_widgetGRAPHICSOsmotic regulation of ADH release and thirst
Relation between plasma ADH concentration and plasma osmolality in normal humansin whom the plasma osmolality was changed by varying the state of hydration. Theosmotic threshold for thirst is a few mosmol/kg higher than that for ADH.ADH: antidiuretic hormone.Data from Robertson GL, Aycinena P, Zerbe RL. Neurogenic disorders of osmoregulation. Am JMed 1982; 72:339.Graphic 65195 Version 5.0

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Página 15 de 18https://www.uptodate.com/contents/hypernatremia-in-children/print?source=history_widgetPediatric causes of hypernatremia due to free urinary water lossesConditions with urinary concentration defectsCentral diabetes insipidusCongenitalCentral nervous system malformations (eg, holoprosencephaly)Genetic causesAcquiredCentral nervous system tumors (eg, craniopharyngioma)Infiltrative processesPostneurosurgeryTraumaNephrogenetic diabetes insipidusCongenitalX-linked (Xp28)Autosomal (12q13)Other inherited disorders or syndromesBardet-Biedl syndromeBartter syndromeFamilial hypomagnesemia with hypercalciuria and nephrocalcinosisAcquiredDrug inducedLithiumAmphotericinDemeclocyclineIfosfamideFoscarnetCidofovirElectrolyte abnormalitiesHypercalcemiaHypokalemiaRenal diseaseObstructive uropathySickle cell nephropathyNephronophthisisCystinosisOsmotic diuresisMannitol useHyperglycemiaGraphic 88819 Version 2.0

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Página 16 de 18https://www.uptodate.com/contents/hypernatremia-in-children/print?source=history_widgetUtility of urine and plasma osmolality in the evaluation ofpediatric hypernatremia
In cases when the cause of pediatric hypernatremia remains uncertain,comparing the urine osmolality (Uosm) with the plasma osmolality (Posm)may be helpful in establishing the underlying etiology. Uosm that is less thanPosm suggests that the child has a concentrating defect, which increases thelikelihood of excess urinary water loss. In contrast, children with Uosmgreater than Posm have an intact urinary concentrating mechanism and aremore likely to have hypernatremia due to excess gastrointestinal or skinwater loss, or excess salt intake.Graphic 88818 Version 1.0

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Página 17 de 18https://www.uptodate.com/contents/hypernatremia-in-children/print?source=history_widgetTotal body water and its major subdivisions as a function of age
Data from: Friis-Hansen B. Body water compartments in children: changes during growth andrelated changes in body composition. Pediatrics 1961; 28:169.Graphic 56512 Version 2.0

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Página 18 de 18https://www.uptodate.com/contents/hypernatremia-in-children/print?source=history_widgetContributor DisclosuresMichael J Somers, MDNothing to discloseAvram Z Traum, MDNothing to discloseTej K Mattoo, MD,DCH, FRCPNothing to discloseMelanie S Kim, MDNothing to discloseContributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these areaddressed by vetting through a multi-level review process, and through requirements for references to beprovided to support the content. Appropriately referenced content is required of all authors and mustconform to UpToDate standards of evidence.Conflict of interest policy