Hyponatremia in children - UpToDate 15/08/18 1955 Official reprint from UpToDate® www.uptodate.com ©2018 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Hyponatremia in children Authors: Michael J Somers, MD, Avram Z Traum, MD Section Editor: Tej K Mattoo, MD, DCH, FRCP Deputy Editor: Melanie S Kim, MD All 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: Nov 11, 2016. 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 etiology, clinical findings, diagnosis, and evaluation of pediatric hyponatremia are reviewed here. Hyponatremia in adults is discussed separately. (See "Causes of hyponatremia in adults" and "Overview of the treatment of hyponatremia in adults" and "Diagnostic evaluation of adults with hyponatremia".) EPIDEMIOLOGY — The true incidence of pediatric hyponatremia is unknown, as published data are based on hospitalized children. As examples, the reported incidence of hyponatremia was 17 percent of children at the time of hospital admission in Japan, which was higher in febrile children [1]. The incidence increased to 45 percent in an Italian study in children with pneumonia [2]. This is most likely due to the release of antidiuretic hormone (ADH) associated with a number of clinical conditions that result in hospitalization. These include hypovolemia, fever, head injury, central nervous system (CNS) infections, and respiratory disorders (eg, pneumonia and respiratory syncytial virus bronchiolitis) [1,3]. In addition, in-hospital interventions, such as recent surgery (which is associated with ADH release), and the administration of hypotonic intravenous solutions, may contribute to the development of hyponatremia [4]. The effect of administered hypotonic intravenous solution on the development of hyponatremia, especially in children with persistent ADH release, was illustrated by the following studies: ● In a study from the United States of 1048 children who had normal serum sodium levels at the time of presentation, overall 35 percent of the cohort developed hyponatremia [5]. Patients who received hypotonic fluids were more likely to develop hyponatremia than those who received isotonic fluids (39 versus 28 percent). Additional identified risk factors for hyponatremia included admitting diagnoses of a cardiac or hematologic/oncologic condition, and surgical admission. ● In an observational Canadian study of 432 hospitalized children who had two or more measurements of plasma sodium, 40 patients developed hospital-acquired hyponatremia due to the administration of excessive free water as hypotonic solution [6]. PATHOPHYSIOLOGY — Hyponatremia is caused by an imbalance in the body's handling of water, resulting https://www.uptodate.com/contents/hyponatremia-in-children/print?source=bookmarks_widget Página 1 de 20 Hyponatremia in children - UpToDate 15/08/18 1955 in a relative deficit 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 (Na) salts in the extracellular space. As a result, serum or plasma sodium is used as a surrogate for assessing tonicity. In this topic, we will use plasma, but in general, serum and plasma sodium can be used interchangeably. (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 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 = 2 x [Na] + [glucose]/18 (when glucose is measured in mg/dL) ● Plasma tonicity = 2 x [Na] + [glucose] (when glucose is measured in mmol/L) 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). The 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'.) In children, the underlying pathogenesis for hyponatremia is typically due to excess free water retention that can be classified according to volume status as follows: ● Hypovolemia and appropriate ADH levels – In most pediatric cases, hyponatremia occurs in children with hypovolemia most commonly due to gastrointestinal loss, who are managed by an excess administration of free water in the setting of an elevated ADH activity. In such patients, ADH is appropriately released due to volume depletion. When hypotonic fluids are ingested or administered, free water is retained in excess of solutes resulting in a decrease in plasma sodium concentration. Less commonly, pediatric hyponatremia may be caused by loss of sodium in excess of water (eg, urinary salt wasting in obstructive uropathy, skin losses in cystic fibrosis), which results in volume depletion and a decrease in plasma sodium. ● Normovolemia and inappropriate ADH levels – In volume replete individuals, excess water intake normally suppresses ADH release allowing for free water excretion and the generation of a dilute urine. However, several pediatric conditions are associated with inappropriate ADH release that results in retention of free water with fluid intake, leading to a drop in plasma sodium. These include pulmonary and oncologic disorders, recent surgery, central nervous system (CNS) injury or infection, endocrine disorders, and certain medications. (See 'Normovolemia' below and "Pathophysiology and etiology of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)", section on 'Etiology'.) ● Hypervolemia conditions – Renal failure or edematous conditions with decreased effective circulating volume (eg, nephrotic syndrome, cirrhosis, and heart failure) result in hypervolemia with excess water retention and a drop in plasma sodium. (See 'Hypervolemia' below.) ETIOLOGY — As noted above, the etiology of hyponatremia can be categorized by volume status (low, normal, high). Within each category, the release of antidiuretic hormone (ADH) may be appropriate or https://www.uptodate.com/contents/hyponatremia-in-children/print?source=bookmarks_widget Página 2 de 20 Hyponatremia in children - UpToDate 15/08/18 1955 inappropriate. Hypovolemia — ADH release in hypovolemia is a physiologic response to maintain circulating volume (figure 2) (see "General principles of disorders of water balance (hyponatremia and hypernatremia) and sodium balance (hypovolemia and edema)", section on 'Role of ADH in volume regulation'). Most pediatric cases of hyponatremia are due to hypovolemic conditions (eg, gastroenteritis) that are associated with an appropriate elevation in ADH, which in the setting of excess free water repletion leads to water retention and a drop of plasma sodium that may result in hyponatremia. Other less common conditions associated with excess salt loss (eg, renal salt-wasting disorders) are also usually characterized by volume depletion. ● Gastrointestinal losses – The most common cause of hypovolemia in children is gastroenteritis. Other less common causes of pediatric gastrointestinal losses include secretory and osmotic diarrheas, enteric fistulas, and ostomies. Rehydration with free water in patients with significant gastrointestinal losses may lead to hyponatremia. (See "Overview of the causes of chronic diarrhea in children in resource-rich countries", section on 'Congenital secretory diarrheas' and "Overview of the causes of chronic diarrhea in children in resource-rich countries", section on 'Osmotic (malabsorptive) diarrheas' and "Overview of enteric fistulas", section on 'Fluid therapy'.) ● Diuretic-induced hyponatremia – Hyponatremia can be a complication of thiazide diuretic use, which acts in the renal cortex at the level of the distal tubule, thereby not interfering with medullarly ADH-induced water retention. Acutely, the initial volume loss can stimulate ADH release. As a result, the combination of diuretic-enhanced sodium and potassium excretion, and the resultant water retention due to ADH release from hypovolemia can result in excretion of urine with a higher solute concentration than that of plasma, leading to a drop in plasma sodium. (See "Diuretic-induced hyponatremia".) ● Renal salt wasting – Several conditions result in an inappropriate loss of urinary sodium due to impaired sodium chloride reabsorption. • Cerebral salt wasting – Cerebral salt wasting occurs in patients with central nervous system (CNS) disorders. It is characterized by hyponatremia and extracellular fluid depletion due to inappropriate renal sodium wasting. In a case series of 110 children, the most common CNS conditions associated