Hyponatremia in children: Evaluation and management

INTRODUCTION — Hyponatremia is defined as a serum or plasma sodium less than 135 mEq/L. Hyponatremia is among the most common electrolyte abnormalities in children. Drops in sodium level can lead to neurologic findings and, in severe cases, significant morbidity and mortality, especially in those with acute and rapid changes in plasma or serum sodium.

The diagnostic evaluation, prevention, and treatment of pediatric hyponatremia are reviewed here. Causes and clinical manifestations of pediatric hyponatremia and hyponatremia in adults are discussed separately. (See "Hyponatremia in children: Etiology and clinical manifestations" and "Causes of hypotonic hyponatremia in adults" and "Overview of the treatment of hyponatremia in adults" and "Diagnostic evaluation of adults with hyponatremia".)

TERMINOLOGY AND DEFINITIONS

Serum versus plasma — Serum and plasma sodium levels are typically interchangeable, except for the uncommon cases of pseudohyponatremia. Because most laboratory testing of blood sodium (clotted blood samples) is based on the serum sodium, this topic preferentially uses serum sodium, except if a study specifies the use of plasma sodium. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Pseudohyponatremia'.)

Severity of hyponatremia — Severity of hyponatremia is defined by the serum sodium level as follows:

●Mild hyponatremia – Serum concentration between 130 and 134 mEq/L

●Moderate hyponatremia – Serum concentration between 120 to 129 mEq/L

●Severe hyponatremia – Serum concentration <120 mEq/L

Acute versus chronic hyponatremia — The durations of hyponatremia are defined as:

●Acute hyponatremia develops over a period of less than 48 hours

●Chronic hyponatremia is defined as hyponatremia that has been present for more than 48 hours

DETECTION — Hyponatremia is detected when serum sodium level is below 135 mEq/L. In many instances, hyponatremia is found incidentally when serum electrolytes are obtained during clinical evaluation for an acute illness, especially in children with levels between 125 and 135 mEq/L. Levels below 125 mEq/L are more often associated with clinical signs and symptoms, or conditions that are associated with low sodium values (eg, chronic kidney disease). (See "Hyponatremia in children: Etiology and clinical manifestations".)

Clinicians should be aware that sodium levels vary by measurement technique. Normal values are typically based on measurements from central hospital automated blood biochemistry autoanalyzers with ion-selective electrodes using indirect potentiometry. Whole blood sodium measurements obtained via point-of-care blood chemistry analyzers (eg, iSTAT) tend to be 2 to 3 mEq/L lower than central laboratory-based measurements [1-3]. 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, especially if measurements are performed using different techniques.

DIAGNOSTIC EVALUATION

Overview — Once hyponatremia is detected, the evaluation is focused on determining the underlying etiology. The cause of the child's hyponatremia is often evident from the initial clinical assessment (history, physical examination, and basic laboratory testing). For example, most pediatric cases are seen in patients with hypovolemia due to gastrointestinal loss when they receive hypotonic fluids for repletion. Physical findings of edema and/or ascites are suggestive of fluid retention, which may be associated with depleted effective circulating volume, as seen in children with heart failure, cirrhosis, or nephrotic syndrome.

Further laboratory testing is performed for children with either persistent or severe hyponatremia when no etiology is confirmed by the initial assessment.

Initial assessment — The initial assessment consists of history, physical examination, and basic laboratory testing.

History and physical examination — History and clues from the physical examination can help delineate the underlying cause of hyponatremia:

●Fluid loss (eg, vomiting, diarrhea, diuretic therapy) and repletion with hypotonic fluids and signs of extracellular volume depletion (eg, decreased skin turgor, tachycardia, or orthostatic or persistent hypotension) are indicative of conditions associated with hypovolemia. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Hypovolemia'.)

●Anuria or oliguria may be indicative of severe kidney function impairment with an inability to excrete free water. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Kidney dysfunction and inability to excrete water load'.)

●Conditions or medications associated with unsuppressed antidiuretic hormone (ADH) secretion (syndrome of inappropriate ADH [SIADH]) including brain injury or infection, pulmonary disease, or immobilization (table 1). (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Syndrome of inappropriate ADH secretion'.)

●Excess water intake, especially in a child with psychiatric disease suggestive of primary polydipsia. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Primary polydipsia'.)

●Excess sodium loss can be seen in disorders with increased sodium loss from the kidney (eg, cerebral salt wasting or primary tubular disorder [Bartter or Gitelman syndromes]) or skin (eg, cystic fibrosis). (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Conditions with excess salt loss'.)

●Edema and ascites with signs of reduced effective circulating volume (eg, tachycardia, gallop) suggests a condition with hypervolemia, such as heart failure, nephrotic syndrome, and cirrhosis. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Reduced effective circulating volume'.)

●Administration of lipid emulsions may result in pseudohyponatremia due to a lipemic blood sample that may impede the true measurement of sodium concentration, depending on the method used. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Pseudohyponatremia'.)

●Hyperglycemia or addition of exogenous osmoles such as mannitol or intravenous immunoglobulin.

●Review medications and identify those that are associated with hyponatremia (table 2).

Basic laboratory testing — In most cases, initial concomitant laboratory testing has been obtained. These studies should include the following:

●Blood glucose – Hyperglycemia decreases serum sodium values. The measured serum sodium is reduced by 1.6 mmol/L for every 100 mg/dL (5.5 mmol/L) increase above the normal blood glucose concentration of 100 mg/dL. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Hyperglycemia'.)

●Serum blood urea nitrogen (BUN) and creatinine – Elevation of BUN and creatinine indicate kidney dysfunction.

●Plasma/serum potassium – Hyperkalemia may be a sign of adrenal insufficiency including 21-hydroxylase deficiency and hypoaldosteronism. (See "Hyponatremia and hyperkalemia in adrenal insufficiency" and "Clinical manifestations and diagnosis of adrenal insufficiency in children", section on 'Primary adrenal insufficiency'.)

●Urine dipstick – A urine dipstick provides a quick measure of specific gravity, which provides information on the release of ADH. Most pediatric patients with hyponatremia will also be hypotonic, in which case, the urine should be dilute due to the absence of ADH. The urine-specific gravity varies with the osmolality, rising by approximately 0.001 for every 35 to 40 mosmol/kg increase in urine osmolality (figure 1). Thus, a urine osmolality of 280 mosmol/kg (which is isosmotic to normal plasma) is usually associated with a urine-specific gravity of 1.008 or 1.009. Release of ADH is associated with a urine-specific gravity ≥1.008.

However, specific gravity can be affected when there are other large molecules in the urine that are not normally present, such as glucose or radiocontrast material. The urine dipstick will also detect glycosuria.

Further evaluation — Generally, the initial assessment of history, physical examination, and basic laboratory testing is sufficient to determine the cause of hyponatremia. However, in some cases, further evaluation is needed to determine or confirm the underlying etiology of hyponatremia.

Lipemic plasma and serum — Patients with lipemic serum/plasma may have inaccurate sodium measurements in the routine laboratory. In these patients at risk for pseudohyponatremia, the sodium concentration should preferably be measured with a direct sodium-selective electrode to obtain a more accurate measurement. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Pseudohyponatremia'.)

Detection of disorders of water and sodium handling — Testing of serum and urine osmolality and urine sodium can identify disorders of water and sodium handling in children (table 3). They should be obtained in children with persistent hyponatremia if the initial assessment does not identify an underlying etiology.

Serum osmolality and tonicity — Serum osmolality is obtained when a diagnosis cannot be confirmed with the initial assessment and hyponatremia remains persistent. Since serum sodium is the principal determinant of serum osmolality, hyponatremic children typically are hypotonic, with an osmolality lower than the normal range of 275 to 290 mosmol/kg. (See "General principles of disorders of water balance (hyponatremia and hypernatremia) and sodium balance (hypovolemia and edema)", section on 'Regulation of plasma tonicity' and "Hyponatremia in children: Etiology and clinical manifestations", section on 'Hypotonic hyponatremia'.)

However, if there is a relative elevation of the serum osmolality to serum sodium, causes of hyponatremia with increased tonicity due to the presence of another osmole must be considered. In children, most of these cases will be due to hyperglycemia or azotemia, which would be identified by the initial laboratory assessment. Other causes of hyponatremia with increased tonicity are due to exogenous sources of osmoles such as sorbitol and mannitol, which are uncommon in children. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Hyponatremia without hypotonicity'.)

Urine osmolality and water excretion — Urine osmolality can help identify conditions associated with impaired water excretion from those that are able to produce maximally dilute urine (table 3):

●For children with hyponatremia and hypotonicity, a urine osmolality >100 mosmol/kg is indicative of impaired water excretion:

•SIADH – Persistent (inappropriate) ADH release is the most common cause of pediatric hyponatremia (table 1). SIADH is characterized by persistently high urine osmolality (>100 mosmol/kg), in contrast with the normal response to serum hypotonicity, which is to produce dilute urine. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Syndrome of inappropriate ADH secretion'.)

•Kidney function impairment – Depending on the underlying etiology, the kidney's ability to excrete free water may decrease. As a result, patients with chronic kidney disease are at risk for retaining ingested water (increased total body volume), resulting in hyponatremia. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Kidney dysfunction and inability to excrete water load'.)

•Chronic thiazide diuretics – Prolonged administration of a thiazide diuretic results in volume loss (urine), which stimulates ADH release, leading to water retention and excretion of reduced urine volume with a high solute concentration (eg, urine osmolality >100 mosmol/kg). These combined processes result in hyponatremia.

●For children with increased total body water, a urine osmolality >100 mosmol/kg is indicative of reduced effective circulating volume, leading to ADH release seen in children with nephrotic syndrome, heart failure, and cirrhosis. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Reduced effective circulating volume'.)

●For children with hyponatremia and maximally dilute urine (urine osmolality <100 mosmol/kg), the differential diagnosis includes:

•Psychogenic polydipsia – In this disorder, patients drink excessively large volumes of water that exceed renal excretory capacity, resulting in lower serum sodium levels despite suppression of ADH release. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Primary polydipsia'.)

•Reset osmostat – Patients with reset osmostat have a lower-than-normal threshold for ADH release. As a result, they are able to generate a dilute urine (urine osmolality below 100 mosmol/kg) when serum osmolality is below their lower-than-normal reset threshold for ADH in response to a water load. These patients can present with recurrent episodes of hyponatremia. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Reset osmostat'.)

•Salt-losing nephropathy – Children with salt-losing nephropathy may also have dilute urine as a result of impaired tubular urinary concentration.

•Excessive administration of hypotonic fluids.

Urine osmolality measurement — The urine osmolality (Uosm) can be measured directly with an osmometer, or, in the absence of marked glycosuria or metabolic acidosis, Uosm can be calculated from the urine concentrations of sodium (Na), potassium (K), and urea.

If urea is reported in mg/dL, the formula is:

If urea is reported in mmol/L, the formula is:

Urine sodium and renal sodium reabsorption — Urine sodium concentration is a measure of the renal response (sodium reabsorption) to the patient's volume status. It can help determine if reduced effective circulating volume, renal salt wasting, and SIADH are underlying contributors to hyponatremia (table 3):

●In patients with reduced effective circulating volume, urine sodium concentration should be <25 mEq/L because the decrease in effective kidney perfusion leads to avid sodium resorption, resulting in a low urine sodium. This is seen in children with heart failure, cirrhosis, and nephrotic syndrome. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Reduced effective circulating volume'.)

However, in children with metabolic alkalosis, most commonly seen with ongoing vomiting, there are obligate sodium losses in the urine accompanying the bicarbonaturia. In this setting, despite reduced effective circulating volume, urine sodium can exceed 25 mEq/L. Urine chloride concentrations, which generally parallel urinary sodium in volume depletion, will be <25 mEq/L and can be used to more accurately assess volume status in the setting of metabolic alkalosis.

●In hypovolemic patients with hypoaldosteronism or cerebral salt wasting, or who are treated with thiazide diuretics, the urine sodium typically is >40 mEq/L, reflecting renal salt wasting. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Hypovolemia'.)

●In patients with SIADH who are euvolemic, the urine sodium is usually >40 mEq/L and reflects ongoing sodium intake similar to in other euvolemic children. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Syndrome of inappropriate ADH secretion'.)

PREVENTION — As noted above, a significant number of children who are hospitalized develop hyponatremia as a result of excessive free water administration. In particular, children who are postoperative or have central nervous system (CNS) illness (eg, meningitis, encephalitis, or brain trauma) or respiratory disorders (eg, pneumonia or bronchiolitis) are likely to have antidiuretic hormone (ADH) release, which is independent of effective volume contraction. This pediatric population is at risk for developing acute hyponatremia if unrestricted hypotonic fluids, either intravenously or by mouth, are provided [4]. As a result, fluid and electrolyte therapy need to be tailored to prevent the administration of excessive free water.

In our centers, isotonic fluid is typically given to hospitalized or postoperative euvolemic children requiring parenteral therapy. The goal of this approach is to prevent hyponatremia because these patients are at risk for inappropriately increased ADH secretion, with associated hyponatremia (table 1). (See "Maintenance intravenous fluid therapy in children", section on 'Composition of initial fluid' and "Hyponatremia in children: Etiology and clinical manifestations", section on 'Syndrome of inappropriate ADH secretion'.)

Other management approaches may be warranted for children with neurosurgical disorders, cardiac or hepatic disease, cancer, kidney dysfunction, and diabetes insipidus. These patients are at risk for fluid imbalance and require close monitoring of fluid status and electrolytes, with individualized decisions about the volume and composition of intravenous fluid therapy.

TREATMENT

Goals — The goals of therapy encompass the following:

●Relieve the symptoms of hyponatremia

●Avoid too rapid correction to prevent central nervous system (CNS) complications

●Prevent a further decline in sodium concentration

General principles — Our approach to the management of hyponatremia depends on:

●Duration of hyponatremia – Acute versus chronic hyponatremia

●Severity of hyponatremia based on the presence and severity of symptoms

●Determining and treating the underlying cause in a timely manner, if possible

●Readjustment of therapy based on data from ongoing monitoring of the patient's fluid status from frequent clinical examinations and follow-up laboratory evaluation, including subsequent assessment of sodium levels

Duration and symptoms — Cerebral adaptation begins within a day of sustained hyponatremia, and management decisions are based on whether the duration of hyponatremia is less than 48 hours' duration (acute hyponatremia) and the presence and severity of symptoms. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Underlying pathogenesis of symptoms'.)

Acute — Acute hyponatremia develops over a period of less than 48 hours. Children with acute hyponatremia are more likely to be symptomatic and are at risk for complications as there has not been sufficient time for cerebral adaption to occur. In this setting, saline therapy is given to all symptomatic patients.

●Severe symptoms include seizures, obtundation, and coma and are more commonly seen in children with severe hyponatremia defined as a serum sodium concentration of <120 mEq/L. These patients require aggressive therapy to raise sodium concentration, typically requiring hypertonic saline (3 percent saline). (See 'Acute symptomatic hyponatremia' below.)

●Mild to moderate symptoms are seen in children with moderate acute hyponatremia, defined as a serum sodium concentration of 120 to 129 mEq/L. They are nonspecific, may overlap with the underlying acute illness, include nausea and malaise, and progress to headache and lethargy as sodium levels fall. In these patients, therapy is also directed toward raising the sodium concentration.

●Asymptomatic – Patients with mild acute hyponatremia, defined as a serum sodium concentration of 130 to 134 mEq/L, are typically asymptomatic. In these patients, treating the underlying cause may be an option if correction can occur in a timely manner. Otherwise or concomitantly, fluid and electrolyte management can be used to correct the serum sodium level.

Chronic — In patients with chronic hyponatremia (duration greater than 48 hours), cerebral cell volume adaptation has likely occurred. As a result, these patients are less likely to be symptomatic and, more importantly, are at risk for osmotic demyelination if hyponatremia is corrected too quickly. In patients who are asymptomatic or have mild symptoms, management is focused on correcting the underlying cause. However, if patients are symptomatic, especially if they are severe in nature, directed therapy to increase serum sodium levels is provided.

Unknown — If the duration of hyponatremia is unclear, patients are treated as if they have chronic hyponatremia. However, if patients are symptomatic, especially with severe symptoms, treatment directed toward increasing serum sodium levels is provided.

Treatment choices — Serum sodium can be raised by one or more of the following methods:

●Administration of oral or intravenous sodium chloride. Hypertonic saline (3 percent) is typically reserved for symptomatic children. (See 'Acute symptomatic hyponatremia' below.)

●Fluid restriction in patients with antidiuretic hormone (ADH) release.

●Treatment of the underlying disease, if possible. For example, treatment of pediatric diseases (eg, pneumonia and meningitis) associated with the syndrome of inappropriate ADH (SIADH) will lead to correcting the inappropriate ADH release and excessive free water retention.

Rate of correction — The rate of correction depends on the following factors:

●Chronicity of hyponatremia – As discussed above, patients with chronic hyponatremia (duration greater than 48 hours) are more likely than those with acute hyponatremia to have cerebral adaption, which protects them from cerebral edema but makes them more susceptible to osmotic demyelination with overly rapid correction. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Clinical manifestations'.)

●Acute hyponatremia and severe symptoms – Severe neurologic symptoms (eg, seizures and altered mental status) are most likely to occur with acute hyponatremia, which is accompanied by a rapidly decreasing sodium concentration. In these patients, there has been no time for cerebral adaption and a more rapid approach using hypertonic saline is used for correction. (See 'Acute symptomatic hyponatremia' below.)

●Severe hyponatremia – Overly rapid correction of severe hyponatremia (serum sodium concentration less than 120 mEq/L and usually less than 115 mEq/L) can lead to a severe and sometimes irreversible osmotic demyelination syndrome (ODS), resulting in diffuse demyelination in the brain and the development of profound irreversible neurologic symptoms (dysarthria, confusion, obtundation, and coma). Symptoms of ODS can present several days after the sodium has been acutely corrected. Most reported cases have occurred when the serum sodium corrections exceeded 10 mEq/L in a 24-hour period, especially in patients with chronic hyponatremia. (See "Osmotic demyelination syndrome (ODS) and overly rapid correction of hyponatremia", section on 'Risk factors for ODS'.)

Patients with chronic hyponatremia are more susceptible to ODS, and, therefore, we recommend a targeted daily correction rate in serum sodium of 4 to 6 mEq/L in patients with chronic hyponatremia (see "Osmotic demyelination syndrome (ODS) and overly rapid correction of hyponatremia", section on 'Duration of hyponatremia'). In most patients, this targeted rate appears to be sufficient for any symptom resolution [5,6].

In otherwise healthy patients with acute hyponatremia, rapid correction has not been associated with adverse CNS effect, but there is no specific benefit in most for a more rapid correction than the above targeted rate, as symptoms typically are alleviated with this targeted goal [7-9].

Initial therapy — As discussed above, initial treatment depends on the presence and severity of any symptoms related to the hyponatremia and the chronicity of hyponatremia, as demonstrated by the following clinical settings.

Acute symptomatic hyponatremia — Acute symptomatic hyponatremia is one of the rare clinical settings in children in which hypertonic (3 percent) saline is used (sodium concentration of 513 mEq/L compared with 154 mEq/L in 0.9 percent or isotonic saline). In the child with seizures or altered mental status, correction of acute hyponatremia should not be delayed. In these patients, 3 to 5 mL/kg of 3 percent saline is the suggested initial therapy, administered within 10 to 15 minutes [10]. This will raise the serum sodium approximately 2.5 to 4 mEq/L. After the initial hypertonic saline infusion, serum sodium should be measured and, if seizures are ongoing, the infusion should be repeated.

Evolving cerebral edema may be a complication of symptomatic hyponatremia with seizures. In these patients, the risk of morbidity from delayed therapy is greater than the risk of complication from too rapid correction and osmotic demyelination. As a result, aggressive initial correction, including 3 percent saline, repeated two times if needed, is indicated until the seizures resolve. Often, an initial goal is to raise the serum sodium by 5 mEq/L over the first several hours as seizures seem to resolve with this therapeutic approach [11].

A report of 56 children who received 3 to 5 mL/kg of 3 percent saline demonstrated that such doses administered over a median time interval of only 17 minutes raised serum sodium effectively and without adverse effect [10]. Nearly 90 percent received hypertonic saline via peripheral intravenous catheter, simplifying management by avoiding central venous access. A study at a large children's hospital found that, among 826 children receiving 3 percent saline, there were no incidents of infiltrations or extravasations, supporting the use of peripheral venous access for hypertonic saline administration [12].

For these acutely symptomatic patients, 3 percent saline is provided at a rate of 1 to 2 mL/kg per hour. As symptoms abate, the child's clinical status and ongoing degree of hyponatremia guide adjustments for the rate and the tonicity of the replacement fluid (transition to more isotonic fluid), with the targeted goal of raising serum sodium to less than 8 to 9 mEq/L over the initial 24 hours [13-16].

Of note, seizures due to hyponatremia may be refractory to anticonvulsant therapy.

Acute asymptomatic hyponatremia — In a child with asymptomatic hyponatremia, there is no need for hypertonic saline provision. These children require ongoing monitoring for newly emerging CNS symptoms, but their treatment is guided more by treatment of the underlying condition that caused the sodium to drop than attention to their volume status or need for sodium supplementation. The targeted rate of correction in this setting is 6 to 8 mEq/L over 24 hours.

Chronic hyponatremia with severe symptoms — In patients with suspected chronic hyponatremia but severe symptoms (seizures, obtundation, coma), hypertonic (3 percent) saline is used. In these patients, 3 to 5 mL/kg of 3 percent saline is the suggested initial therapy to increase serum sodium acutely by 2.5 to 4 mEq/L. Subsequent provision of additional sodium should be adjusted to keep total daily correction in the 6 to 8 mEq/L per day range.

Chronic hyponatremia with mild to moderate symptoms — In patients with suspected chronic hyponatremia but nonurgent symptoms (nausea, malaise), there is no indication for 3 percent saline. Provision of sodium should be adjusted to keep total daily correction at 6 to 8 mEq/L. Especially in cases of severe hyponatremia (serum sodium <120 mEq/L), there needs to be close monitoring for newly emerging CNS symptoms that would prompt treatment with 3 percent saline, as with a presentation with severe symptoms.

Chronic asymptomatic hyponatremia — In patients with suspected chronic hyponatremia who do not have associated symptoms, daily serum sodium correction should not exceed 6 to 8 mEq/L. Correction can be with either oral or intravenous sodium chloride. Patients need to be monitored during correction for the development of any urgent symptoms, though these are less likely to develop in the asymptomatic patient.

Symptomatic hyponatremia of unknown duration — Children with symptomatic hyponatremia but the duration of hyponatremia is unknown are managed in a similar manner to those with chronic hyponatremia with severe symptoms. In this setting, 3 percent saline is the suggested initial therapy to increase serum sodium by 2.5 to 4 mEq/L. Subsequent provision of additional sodium should be adjusted to keep total daily correction in the 6 to 8 mEq/L per day range.

Fluid management — In addition to the administration of saline to correct hyponatremia, fluid management interventions are initiated based on the clinical setting:

●In the hyponatremic child with normal or increased effective circulating volume due to excess ADH release (SIADH), water restriction to 60 percent of usual daily maintenance fluid provision will correct volume imbalance and contribute to the normalization of serum sodium as excess free water is excreted. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Syndrome of inappropriate ADH secretion'.)

●In patients with fluid retention and decreased effective circulating volume due to heart failure, nephrotic syndrome, or cirrhosis, additional measures include treating the underlying conditions and fluid restriction. In these patients, the retained free water by the kidney moves from the vascular into interstitial spaces, resulting in edema and ascites. Fluid restriction allows slow restoration in the balance between the preexisting total body sodium and water overload and prevents further exacerbation of clinical symptoms. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Reduced effective circulating volume'.)

●In patients with hypovolemia and reduced effective circulating volume, as seen with gastroenteritis, there is often both a loss of total body salt and water. Provision of isotonic fluid will restore the circulating volume and improve kidney perfusion. Since the administered fluid will remain in the effective circulating volume, it will inhibit activation of the renin-angiotensin-aldosterone axis and ADH release and limit the free water reabsorption that has mediated the hyponatremia. The child can then receive sufficient sodium and water to replace losses and restore fluid and sodium balance. (See "Treatment of hypovolemia (dehydration) in children in resource-abundant settings", section on 'Hyponatremia'.)

Subsequent therapy — Subsequent therapy is directed at monitoring serum sodium levels to determine whether additional intervention is required and treatment of the underlying etiology.

Monitoring — The frequency of monitoring depends on the child's clinical condition, the severity of the hyponatremia, and the ongoing treatment plan. In the setting of severe hyponatremia or symptomatic hyponatremia, serum sodium should be assayed at least every two to four hours. Once there is stability to the rate of rise of serum sodium and reassurance that the rate of rise is consistent with a daily target of 6 to 8 mEq/L, and any clinical symptoms have started to abate, laboratory assessment can be decreased in frequency. Generally, if serum sodium values exceed 130 mEq/L and the child is asymptomatic, laboratory assessment can be transitioned to daily testing if there is ongoing provision of intravenous fluid therapy and, even less frequently, if intake is now following a normal enteral pattern.

SUMMARY AND RECOMMENDATIONS

●Definition and clinical presentation – Hyponatremia is defined as a serum or plasma sodium less than 135 mEq/L and is among the most common electrolyte abnormalities in children. It is often detected incidentally, especially in asymptomatic cases of mild or moderate hyponatremia (serum sodium between 125 and 134 mEq/L). (See 'Detection' above.)

●Evaluation – The goal of diagnostic evaluation of hyponatremia is to determine the underlying etiology, which is often evident from the initial clinical assessment:

•Most cases of hyponatremia in children are related to gastrointestinal fluid loss that was replaced with hypotonic fluids. Other children have physical findings of edema and/or ascites, which may be associated with depleted effective circulating volume, and can be seen in children with heart failure, cirrhosis, or nephrotic syndrome. (See 'History and physical examination' above.)

•Initial laboratory testing may detect kidney dysfunction noted by elevated blood urea nitrogen (BUN), creatinine, or serum potassium; hyperglycemia; or evidence of antidiuretic hormone (ADH) stimulation based on an inappropriately high specific gravity. (See 'Basic laboratory testing' above.)

•Further laboratory testing is performed when the diagnosis remains uncertain for children with either persistent or severe hyponatremia after initial assessment. Studies include measuring plasma and urine osmolality and urine sodium, which may identify disorders of water and sodium handling. (See 'Further evaluation' above.)

●Prevention – Prevention of hyponatremia includes avoiding hypotonic fluid infusions in hospitalized children; these children are at risk for developing hyponatremia due to inappropriate ADH release. Children with conditions predisposing to fluid imbalance, such as neurosurgical disorders or cardiac disease, also may require fluid restriction. (See 'Prevention' above.)

●Principles of management – The goals of pediatric hyponatremia treatment consists of relief of symptoms caused by hyponatremia, avoidance of too rapid correction that may mediate central nervous complications, and prevention of further decline in sodium concentration. (See 'Goals' above.)

Management decisions regarding intervention are based on the duration of hyponatremia, the severity of hyponatremia, and if the underlying cause can be treated in a timely manner. Treatment options include administration of sodium chloride, fluid restriction, and treatment of the underlying etiology. (See 'General principles' above.)

●Symptomatic hyponatremia – We recommend intravenous sodium chloride administration for all symptomatic children with hyponatremia regardless of chronicity (Grade 1C). (See 'Initial therapy' above.)

Initial therapy is with intravenous administration of 3 to 5 mL/kg of hypertonic (3 percent) saline, repeated if needed, as guided by laboratory monitoring of serum sodium. The targeted rate of serum sodium correction depends on whether the condition is acute or chronic:

•Acute hyponatremia – For children with acute hyponatremia (develops over a period of less than 48 hours), aggressive initial correction is indicated for the first three to four hours (or until the symptoms resolve). To reduce the risk of cerebral edema, the rate of rise in serum sodium should be <8 mEq/L over 24 hours. The primary problem with symptomatic hyponatremia is evolving cerebral edema, and the risk of morbidity from delayed therapy is greater than the risk of complication from too rapid correction and osmotic demyelination. (See 'Acute symptomatic hyponatremia' above.)

•Chronic hyponatremia – For children with chronic hyponatremia with severe symptoms (eg, seizures, obtundation, coma), the rate of rise in serum sodium should be 4 to 6 mEq/L over 24 hours. This target should alleviate the symptoms and also avoid too rapid correction that may trigger osmotic demyelination syndrome (ODS). (See 'Chronic hyponatremia with severe symptoms' above.)

●Asymptomatic patients – Hypertonic saline is not used for asymptomatic patients or those with chronic hyponatremia with mild to moderate symptoms. Treatment is guided toward correcting the underlying etiology and monitoring serum sodium levels to ensure that there is no further drop in the sodium concentration. Sodium supplementation can be provided, with a targeted rate of correction not to exceed 6 to 8 mEq/kg over 24 hours. (See 'Acute asymptomatic hyponatremia' above and 'Chronic hyponatremia with mild to moderate symptoms' above and 'Chronic asymptomatic hyponatremia' above.)

●Fluid management – Fluid management interventions are based on the clinical setting. For children with inappropriate ADH release, fluid restriction will correct the underlying problem of excess free water retention. (See 'Fluid management' above.)

●Subsequent steps – Subsequent therapy includes providing additional sodium if needed and treating the underlying cause. Frequency of monitoring sodium levels depends on the severity of hyponatremia and the presence of symptoms. (See 'Subsequent therapy' above and 'Monitoring' above.)