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Introduction Body fluid compartments Water makes up 50-75 percent of the body mass. The most important determinants of the wide range in water content are age and gender: a. the water content of a newborn, an adolescent and an elderly man are approximately 75, 60 and 50 percent; b. after puberty males generally have 2 to 10 percent higher water content than females (figure 1). The intracellular compartment contains about two-third of the total body water and the remaining is held in the extracellular compartment. The solute composition of the intracellular and extracellular fluid differs considerably because the sodium pump maintains potassium in a primarily intracellular and sodium in a primarily extracellular location. Consequently potassium largely determines the intracellular and sodium the extracellular compartment [1-3]. The extracellular compartment is further subdivided into the interstitial and the intravascular compartments (blood volume), which contain two-thirds and one-third of the extracellular fluid, respectively. Finally, the transcellular fluid compartment comprises the digestive, cerebrospinal, intraocular, pleural, peritoneal and synovial fluids but will not be further addressed in this review.

and the intravascular compartments (blood volume), which contain two-thirds and one-third of the extracellular fluid, respectively. Finally, the transcellular fluid compartment comprises the digestive, cerebrospinal, intraocular, pleural, peritoneal and synovial fluids but will not be further addressed in this review. Figure 1 Winters diagram with the subdivision of total body water, intracellular fluid and extracellular fluid as a function of age. For clinical purpose the use of "the rule of 3" is recommended: 1. total body water makes up 2/3 of the body mass; 2. the intracellular compartment contains 2/3 of the total body water and the remaining (= 1/3) is held in the extracellular compartment; 3. the extracellular compartment is further subdivided into the interstitial and the intravascular compartments (blood volume), which contain 2/3 and 1/3 of the extracellular fluid, respectively. After puberty males generally have 2 to 10 percent higher water content than females.

held in the extracellular compartment; 3. the extracellular compartment is further subdivided into the interstitial and the intravascular compartments (blood volume), which contain 2/3 and 1/3 of the extracellular fluid, respectively. After puberty males generally have 2 to 10 percent higher water content than females. The size of the intravascular compartment is determined by the overall size of the extracellular fluid compartment and by the Starling forces: they control the partition of fluids between intravascular and interstitial compartments across the capillary membrane that is crossed by salts like sodium chloride and by glucose but not by blood proteins (especially albumin). Three major forces control the distribution of fluids across the capillary membrane (figure 2): a. the hydrostatic pressure causes fluids to leave the vascular space, and; b. the higher concentration of proteins in the intravascular compartment as compared with that in interstitial fluid, which causes fluids to enter the vascular space. This force, which is called oncotic pressure, is due both to the concentration gradient of albumin (blood proteins other than albumin account for 50 percent of the weight of proteins in g in blood but only for 25 percent of the oncotic pressure) as well to the fact that albumin is anionic and therefore attracts cations (largely sodium) into the vascular compartment (Gibbs-Donnan effect; figure 3). c. Capillary permeability is a further major mechanism that modulates the distribution of fluids across the capillary membrane.

r 25 percent of the oncotic pressure) as well to the fact that albumin is anionic and therefore attracts cations (largely sodium) into the vascular compartment (Gibbs-Donnan effect; figure 3). c. Capillary permeability is a further major mechanism that modulates the distribution of fluids across the capillary membrane. Figure 2 Distribution of ultrafiltrate across the capillary membrane. The barrel-shaped structure represents a capillary. A high hydrostatic pressure or an increased capillary permeability causes fluid to leave the vascular space. On the contrary an increased intravascular albumin concentration and, therefore, an increased oncotic pressure causes fluid to enter the vascular space. Figure 3 The Gibbs-Donnan effect. There is a different concentration in the concentration of anionic albumin, which is impermeant, between the vascular (albumin approximately 40 g/L) and the interstitial (albumin approximately 10 g/L) compartments. The negative charges of albumin "attract" cations (largely Na+) into the vascular compartment and "repell" anions (Cl- and HCO3 -) out. Because the concentration of Na+exceeds that of Cl- and HCO3-, "attraction" outweighs "repulsion". Consequently the Gibbs-Donnan effect increases the vascular compartment. The dashed line represents the capillary bed separating the intravascular and interstitial spaces is freely permeable to Na+, K+, Cl-, and glucose.

Because the concentration of Na+exceeds that of Cl- and HCO3-, "attraction" outweighs "repulsion". Consequently the Gibbs-Donnan effect increases the vascular compartment. The dashed line represents the capillary bed separating the intravascular and interstitial spaces is freely permeable to Na+, K+, Cl-, and glucose. Effective circulating volume Effective circulating volume denotes the part of the intravascular compartment that is in the arterial system and is effectively perfusing the tissues. The effective circulating volume is biologically more relevant than the intravascular compartment and usually varies directly with the extracellular fluid volume [4]. As a result, the regulation of extracellular fluid balance (by alterations in urinary sodium excretion) and the maintenance of the effective circulating volume are intimately related. Sodium loading will tend to produce volume expansion, whereas sodium loss (e.g., due to vomiting, diarrhea, or drug management with diuretics) will lead to volume depletion. The body responds to changes in effective circulating volume in two steps: 1. The change is sensed by the volume receptors, which are located in the cardiopulmonary circulation, the carotid sinuses and aortic arch, and in the kidney; 2. These receptors activate effectors that restore normovolemia by varying vascular resistance, cardiac output, and renal water and salt excretion. Briefly, the extrarenal receptors primarily govern the activity of the sympathetic nervous system and natriuretic peptides. On the other side the renal receptors affect volume balance by modulating the renin-angiotensin II-aldosterone system.

ying vascular resistance, cardiac output, and renal water and salt excretion. Briefly, the extrarenal receptors primarily govern the activity of the sympathetic nervous system and natriuretic peptides. On the other side the renal receptors affect volume balance by modulating the renin-angiotensin II-aldosterone system. In some settings the effective circulating volume is independent of the extracellular fluid volume. Among patients with heart failure the extracellular fluid volume is increased but the patient is effectively volume depleted due to the low cardiac output. Blood osmolality - measurement of sodium Osmolality is the concentration of all of the solutes in a given weight of water. The total (or true) blood osmolality is equal to the sum of the osmolalities of the individual solutes in blood. Most of the osmoles in blood are sodium salts, with lesser contributions from other ions, glucose, and urea. However, under normal circumstances, the osmotic effect of the ions in blood can usually be estimated from two times the sodium concentration. Blood osmolality (in mosm/kg H20) can be measured directly (via determination of freezing point depression) or estimated from circulating sodium, glucose and urea (in mmol/L [To obtain glucose in mmol/L divide glucose in mg/dL by 18. To obtain urea in mmol/L divide urea nitrogen in mg/dL by 2.8 or urea in mg/dL by 6.0.]) as [5-9]:

lity (in mosm/kg H20) can be measured directly (via determination of freezing point depression) or estimated from circulating sodium, glucose and urea (in mmol/L [To obtain glucose in mmol/L divide glucose in mg/dL by 18. To obtain urea in mmol/L divide urea nitrogen in mg/dL by 2.8 or urea in mg/dL by 6.0.]) as [5-9]: The effective blood osmolality, known colloquially as blood tonicity, is a further clinically significant entity, which denotes the concentration of solutes impermeable to cell membranes (sodium, glucose [Glucose is a unique solute because, at normal concentrations in blood, it is actively taken up by cells and therefore acts as an ineffective solute, but under conditions of impaired cellular uptake (like diabetes mellitus) it becomes an effective extracellular solute.], mannitol) and are therefore restricted to the extracellular compartment (osmoreceptors sense effective blood osmolality rather than the total blood osmolality). These solutes are effective because they create osmotic pressure gradients across cell membranes leading to movement of water from the intracellular to the extracellular compartment. Solutes that are permeable to cell membranes (urea, ethanol, methanol) are ineffective solutes because they do not create osmotic pressure gradients across cell membranes and therefore are not associated with such water shifts. Since no direct measurement of effective blood osmolality (which is biologically more important than the total or true blood osmolality) is possible, following equations are used to calculate this entity:

ot create osmotic pressure gradients across cell membranes and therefore are not associated with such water shifts. Since no direct measurement of effective blood osmolality (which is biologically more important than the total or true blood osmolality) is possible, following equations are used to calculate this entity: Flame photometry, the traditional assay for circulating sodium, measures the concentration of sodium per unit volume of solution, with a normal range between 135 and 145 mmol/L. In fact, sodium is dissolved in plasma water, which normally accounts for 93% of the total volume of plasma, the remaining 7% consisting of protein and lipid. Ion selective electrodes, that have replaced flame photometry in most laboratories, determine the activity of sodium in plasma water, which ranges between 145 and 155 mmol/L. For convenience, laboratories routinely apply a correction factor so that the reported values still correspond to the traditional normal range of 135-145 mmol/L [5-9]. A kind of "pseudohyponatraemia" caused by expansion of the non-aqueous phase of plasma - for example, due to hyperlipidaemia or paraproteinemia - is no longer seen because determination by selective electrodes in undiluted serum, plasma or whole blood is unaffected by this [The recommended name for this quantity is ionized sodium.] [9]. Although, strictly speaking, a sodium concentration outside the range of 135-145 mmol/L denotes dysnatremia, clinically relevant hypo- or hypernatremia is mostly defined as a sodium concentration outside the extended normal range of 130-150 mmol/L [5-9].

[The recommended name for this quantity is ionized sodium.] [9]. Although, strictly speaking, a sodium concentration outside the range of 135-145 mmol/L denotes dysnatremia, clinically relevant hypo- or hypernatremia is mostly defined as a sodium concentration outside the extended normal range of 130-150 mmol/L [5-9]. Dehydration and extracellular fluid volume depletion The terms extracellular fluid volume depletion and dehydration are mostly used interchangeably. However, these terms denote conditions resulting from different types of fluid losses. Volume depletion refers to any condition in which the effective circulating volume is reduced. It is produced by salt and water loss (as with vomiting, diarrhea, diuretics, bleeding, or third space sequestration). Strict sense dehydration refers to water loss alone. The consequence of strict sense dehydration is hypernatremia. The elevation in serum sodium concentration, and therefore effective blood osmolality, pulls water out of the cells into the extracellular fluid. However, much of the literature does not distinguish between the two terms. Although dehydration in general usage means loss of water, in physiology and medicine, the word means both a loss of water and salt. Depending on the type of pathophysiologic process, water and sodium may be lost in physiologic proportion or lost disparately, with each type producing a somewhat different clinical picture, designated as normotonic (mostly isonatremic), hypertonic (mostly hypernatremic), or hypotonic (always hyponatremic) dehydration. Dehydration develops when fluids are lost from the extracellular space at a rate exceeding intake. The most common sites for fluid loss are 1. the intestinal tract (diarrhea, vomiting, or bleeding), 2. the skin (fever, burns, or cystic fibrosis) and 3. the urine (osmotic diuresis, diuretic therapy, or diabetes insipidus). More rarely, dehydration results from prolonged inadequate intake without excessive losses [1-3,10].

ost common sites for fluid loss are 1. the intestinal tract (diarrhea, vomiting, or bleeding), 2. the skin (fever, burns, or cystic fibrosis) and 3. the urine (osmotic diuresis, diuretic therapy, or diabetes insipidus). More rarely, dehydration results from prolonged inadequate intake without excessive losses [1-3,10]. Children and especially infants are more susceptible to dehydration than adults. The risk is high for the following causes: a. infants and children are more susceptible to infectious diarrhea and vomiting than adults; b. there is a higher proportional turnover of body fluid in infants compared to adults (it is estimated that the daily fluid intake and outgo, as a propotion of extracellular fluid, is in infancy twice that of an adult); c. young children do not communicate their need for fluids or do not independently access fluids to replenish volume losses [1-3,10]. Dehydration reduces the effective circulating volume, therefore impairing tissue perfusion. If not rapidly corrected, ischemic end-organ damage occurs, leading to serious morbidity. Three groups of symptoms and signs occur in dehydration [1-3,5-10]: a. those related to the manner in which fluids loss occurs (including diarrhea, vomiting or polyuria); b. those related to the electrolyte and acid-base imbalances that sometimes accompany dehydration; and c. those directly due to dehydration. The following discussion will focus the third group.

dehydration [1-3,5-10]: a. those related to the manner in which fluids loss occurs (including diarrhea, vomiting or polyuria); b. those related to the electrolyte and acid-base imbalances that sometimes accompany dehydration; and c. those directly due to dehydration. The following discussion will focus the third group. When assessing a child with a tendency towards dehydration, the clinician needs to address the degree of extracellular fluid volume depletion. More rarely the clinician will address the laboratory testing and the type of fluid lost (extracellular or intracellular fluid). Degree of dehydration It is imperative to accurately assess the degree of dehydration since severe extracellular fluid volume depletion calls for rapid fluid resuscitation [10,11]. Dehydration is most objectively measured as a change in weight from baseline (acute loss of body weight reflects the loss of fluid, not lean or fat body mass; thus, a 1.2 kg weight loss should reflect the loss of 1.2 liters of fluid). In most cases, however, a previous recent weight is unavailable.

suscitation [10,11]. Dehydration is most objectively measured as a change in weight from baseline (acute loss of body weight reflects the loss of fluid, not lean or fat body mass; thus, a 1.2 kg weight loss should reflect the loss of 1.2 liters of fluid). In most cases, however, a previous recent weight is unavailable. As a result, a pertinent history and a number of findings on physical examination are used to help assess dehydration. Skin turgor, sometimes referred to as skin elasticity, is a sign commonly used to assess the degree of hydration. The skin on the back of the hand, lower arm, or abdomen is grasped between two fingers, is held for a few seconds then released: skin with normal turgor snaps rapidly back to its normal position but skin with decreased turgor remains elevated and returns slowly to its normal position. However, decreased skin turgor is a late sign in dehydration that is associated with moderate or, more frequently, severe dehydration. Like decreased skin turgor, arterial hypotension is a late sign in hypovolemia that is rapidly followed by cardiac arrest (in children with minimal to mild dehydration blood pressure is often slightly increased). Symptoms and signs of dehydration include dry mucous membranes, sunken eyes, reduced urine output, a sunken open fontanelle, delayed capillary refill, deep respiration with or without increased respiratory rate, and tachycardia. Several attempts have been made to determine a measure of dehydration by using combinations of clinical findings. Very recently, in children < 4 years of age with a diagnosis of acute gastroenteritis, 4 clinical items (a. general appearance, b. eyes, c. mucous membranes, and d. tears), which may be summed for a total score ranging from 0 to 8 [12], were found to significantly estimate dehydration (table 1).

s of clinical findings. Very recently, in children < 4 years of age with a diagnosis of acute gastroenteritis, 4 clinical items (a. general appearance, b. eyes, c. mucous membranes, and d. tears), which may be summed for a total score ranging from 0 to 8 [12], were found to significantly estimate dehydration (table 1). Table 1 "4-item 8-point rating scale" clinical dehydration scale [12]. Score Characteristic 0 1 2 General appearance Normal Thirsty, restless or lethargic but irritable when touched Drowsy, limp, cold, or sweathy; comatose or not Eyes Normal Slightly sunken Very sunken Mucous membranes (tongue) Moist Sticky Dry Tears Tears Decreased tears Absent tears The score consists of 4 clinical items, which may be summed for a total score ranging from 0 to 8. The final 3 categories are no or minimal dehydration (< 3%; score of 0), mild dehydration (3% to < 6% dehydration; score of 1--4), and moderate to severe dehydration (≥ 10% dehydration; score of 5--8). Laboratory testing and the type of fluid lost Laboratory testing can confirm the presence of dehydration [13]. The fractional excretion of sodium (which measures the amount of filtered sodium that is excreted in the urine): is < 0.5 × 10-2 (< 0.5 percent) and the urine spot sodium concentration < 30 mmol/L (unless the source of dehydration is renal).

Laboratory testing and the type of fluid lost Laboratory testing can confirm the presence of dehydration [13]. The fractional excretion of sodium (which measures the amount of filtered sodium that is excreted in the urine): is < 0.5 × 10-2 (< 0.5 percent) and the urine spot sodium concentration < 30 mmol/L (unless the source of dehydration is renal). Furthermore, in dehydration, the urine is concentrated with an osmolality > 450 mosm/kg H2O. The urinary concentration can be measured with an osmometer or fairly estimated, in the absence of proteinuria and glucosuria, from the specific gravity, as determined by refractometry, as follows: Dipstick measurement of specific gravity is very popular but unfortunately unreliable [14]. Furthermore, laboratory testing can detect associated electrolyte and acid-base disturbances but determination of circulating electrolytes and acid-base balance is typically limited to children requiring intravenous fluids. These children are more severely volume depleted and are therefore at greater risk for dyselectrolytemias. Laboratory testing is less useful for assessing the degree of volume depletion.

es but determination of circulating electrolytes and acid-base balance is typically limited to children requiring intravenous fluids. These children are more severely volume depleted and are therefore at greater risk for dyselectrolytemias. Laboratory testing is less useful for assessing the degree of volume depletion. - Bicarbonatemia ≤ 17.0 mmol/L might be the most useful laboratory test to assess dehydration. The blood urea level reflects the severity of dehydration, the decreased glomerular filtration rate and the increased sodium and water reabsorption in the proximal tubule [11]. Unfortunately the clinical usefulness of this test is limited, since this blood parameter can be increased by other factors such as bleeding or tissue breakdown (on the other side the rise can be minimized by a concurrent decrease in protein intake). - The sodium concentration varies with the relative loss of solute to water. Changes in sodium concentration play a pivotal role in deciding the type of fluid depletion (figure 4):

- Bicarbonatemia ≤ 17.0 mmol/L might be the most useful laboratory test to assess dehydration. The blood urea level reflects the severity of dehydration, the decreased glomerular filtration rate and the increased sodium and water reabsorption in the proximal tubule [11]. Unfortunately the clinical usefulness of this test is limited, since this blood parameter can be increased by other factors such as bleeding or tissue breakdown (on the other side the rise can be minimized by a concurrent decrease in protein intake). - The sodium concentration varies with the relative loss of solute to water. Changes in sodium concentration play a pivotal role in deciding the type of fluid depletion (figure 4): Figure 4 Extracellular and intracellular compartments in children with dehydration. Normally the extracellular compartment makes up approximately 20 percent and the intracellular 40 percent of the body weight (upper panel of the figure). The second, third and fourth panels depict the relationship between extracellular and intracellular compartment in three children with dehydration in the context of an acute diarrheal disease: dehydration is normotonic-normonatremic in the first, hypotonic-hyponatremic (mainly extracellular fluid losses) in the second, and hypernatremic (mainly intracellular fluid losses) in the third child. The lower panel depicts the relationship between extracellular and intracellular compartment (mainly intracellular fluid losses) in a child with dehydration in the context of diabetic ketoacidosis (hypertonic-"normonatremic" dehydration; in this context the concentration of circulating sodium is normal or even reduced). In each panel the solid circles denote sodium and open circles impermeable solutes that do not move freely across cell membranes (in the present example glucose). For reasons of simplicity, no symbols are given for potassium, the main intracellular cation.

concentration of circulating sodium is normal or even reduced). In each panel the solid circles denote sodium and open circles impermeable solutes that do not move freely across cell membranes (in the present example glucose). For reasons of simplicity, no symbols are given for potassium, the main intracellular cation. Hyponatremic and hypotonic dehydration [5,6]: The development of hyponatremia reflects net solute loss in excess of water loss. This does not occur directly, as fluid losses such as diarrhea are not hypertonic. Usually solute and water are lost in proportion, but water is taken in and retained in the context of hypovolemia-induced secretion of antidiuretic hormone. Since body water shifts from extracellular fluid to cells under these circumstances, signs of dehydration easily become profound. Normonatremic and isotonic dehydration: In this setting, solute is lost in proportion to water loss. Hypernatremic and hypertonic dehydration [7,8]: This setting reflects water loss in excess of solute loss. Since body water shifts from intracellular to extracellular fluid under these circumstances, these children have less signs of dehydration for any given amount of fluid loss than do children with normonatremic (or normotonic) dehydration and especially those with hyponatremic dehydration.

loss in excess of solute loss. Since body water shifts from intracellular to extracellular fluid under these circumstances, these children have less signs of dehydration for any given amount of fluid loss than do children with normonatremic (or normotonic) dehydration and especially those with hyponatremic dehydration. Conclusion Clinical assessment of dehydration may be difficult, especially in young infants. A large body of evidence suggests the use of a recently developped and validated "4-item 8-point rating scale". Mainly extracellular fluid losses occur in hypotonic dehydration, where signs of dehydration easily become profound; on the contrary, mainly intracellular fluid losses occur in hypertonic dehydration, where signs of dehydration tend to be less evident. Competing interests The authors declare that they have no competing interests. Authors' contributions MGB and AB wrote the first version of the manuscript. GDS revised the manuscript and prepared the figures. All authors have read and approved the paper, have met the criteria for authorship as established by the International Committee of Medical Journals Editors, believe that the paper represents honest work, and are able to verify the validity of the results reported.

Introduction The first part of this review, published some months ago, outlined the physiology of the body fluid compartments, dehydration and extracellular fluid volume depletion [1]. The second part will focus the causes underlying dysnatremia and, more importantly, both the parenteral hydration and the management of dysnatremia. Dysnatremia Under normal conditions, blood sodium concentrations are maintained within the narrow range of 135-145 mmol/L despite great variations in water and salt intake. Sodium and its accompanying anions, principally chloride and bicarbonate, account for 90% of the extracellular effective osmolality. The main determinant of the sodium concentration is the plasma water content, itself determined by water intake (thirst or habit), "insensible" losses, and urinary dilution. The last of these is under most circumstances crucial and predominantly determined by vasopressin. In response to this hormone, concentrated urine is produced by water reabsorption across the renal tubules. Dysnatremias produce signs and symptoms secondary to central nervous system dysfunction. While hyponatremia may induce brain swelling, hypernatremia may induce brain shrinkage, yet the clinical features elicited by opposite changes in tonicity are remarkably similar [2-7].

y water reabsorption across the renal tubules. Dysnatremias produce signs and symptoms secondary to central nervous system dysfunction. While hyponatremia may induce brain swelling, hypernatremia may induce brain shrinkage, yet the clinical features elicited by opposite changes in tonicity are remarkably similar [2-7]. Hyponatremia Introduction Hyoponatremia [4,6] is classified (Figure 1 left and middle panel) according to the extracellular fluid volume status, as either hypovolemic (= depletional) or normo- hypervolemic (= dilutional). Vasopressin is released both in children with low effective arterial blood volume, by far the most common cause of hyponatremia in everyday clinical practice, as well as in those with normo-hypervolemic hyponatremia [8]. In hypovolemic hyponatremia vasopressin release is triggered by the low effective arterial blood volume (this condition has been called by some syndrome of appropriate anti-diuresis). In dilutional hyponatremia [8] the primary defect is euvolemic, inappropriate increase in circulating vasopressin levels (this condition is also termed syndrome of inappropriate anti-diuresis).

red by the low effective arterial blood volume (this condition has been called by some syndrome of appropriate anti-diuresis). In dilutional hyponatremia [8] the primary defect is euvolemic, inappropriate increase in circulating vasopressin levels (this condition is also termed syndrome of inappropriate anti-diuresis). Figure 1 Mechanisms underlying hypotonic hyponatremia. In most cases (middle panel) hyotonic hyponatemia results from a low effective arterial blood volume and is termed hypovolemic (or depletional) hyponatremia. The term syndrome of appropriate anti-diuresis has also been used to denote this condition. In childhood diarrhea, vomiting and febrile infections are the most common cause of hypovolemic hyponatremia. Persistently high levels of vasopressin or, exceptionally, an increased renal response to vasopressin cause the syndrome of inappropriate anti-diuresis (left panel), which is less frequent than the syndrome of appropriate anti-diuresis (hypovolemic or depletional hyponatremia). A peculiar form of depletional hyponatremia sometimes develops in patients with cerebral disease that mimics all of the findings in the syndrome of inappropriate anti-diuresis, except that renal salt-wasting is the primary defect with the ensuing volume depletion leading to a secondary rise in release of antidiuretic hormone (right panel). The ultimate causes of the three different conditions are "bordered".

sease that mimics all of the findings in the syndrome of inappropriate anti-diuresis, except that renal salt-wasting is the primary defect with the ensuing volume depletion leading to a secondary rise in release of antidiuretic hormone (right panel). The ultimate causes of the three different conditions are "bordered". Assessing the cause of hyponatremia may be straightforward if an obvious cause is present (for example in the setting of vomiting or diarrhea) or in the presence of a clinical evident extracellular fluid volume depletion. Sometimes, however, distinguishing hypovolemic from normo- hypervolemic hyponatremia may not be straightforward. In such cases, further laboratory investigations are warranted [4,6,8]: a) the urine spot sodium and the fractional sodium clearance are helpful in patients in whom volume status is difficult to assess, as patients with dilutional hyponatremia have a urinary sodium > 30 mmol/L (and fractional sodium clearance > 0.5 × 10-2), whereas those with extracellular fluid volume depletion (unless the source is renal) will have a urinary sodium < 30 mmol/L (and fractional sodium clearance < 0.5 × 10-2). Since effective blood osmolality is mostly low in hyponatremia, and urine is less than maximally dilute (inappropriately concentrated), blood and urine osmolalities, although usually measured, are rarely discriminant.

ource is renal) will have a urinary sodium < 30 mmol/L (and fractional sodium clearance < 0.5 × 10-2). Since effective blood osmolality is mostly low in hyponatremia, and urine is less than maximally dilute (inappropriately concentrated), blood and urine osmolalities, although usually measured, are rarely discriminant. b) in hypovolemic hyponatremia the urine spot sodium concentration and the fractional sodium clearance allow the distinction between extrarenal (sodium < 30 mmol/L; fractional sodium clearance < 0.5 × 10-2) and renal (sodium > 30 mmol/L; fractional sodium clearance > 0.5 × 10-2) salt loss. A decrease in sodium concentration and effective blood osmolality causes movement of water into brain cells and results in cellular swelling and raised intracranial pressure. Nausea and malaise are typically seen when sodium level acutely falls below 125-130 mmol/L. Headache, lethargy, restlessness, and disorientation follow, as the sodium concentration falls below 115-120 mmol/L. With severe and rapidly evolving hyponatremia, seizure, coma, permanent brain damage, respiratory arrest, brain stem herniation, and death may occur. In more gradually evolving hyponatremia, the brain self regulates to prevent swelling over hours to days by transport of, firstly, sodium, chloride, and potassium and, later, solutes like glutamate, taurine, myoinositol, and glutamine from intracellular to extracellular compartments. This induces water loss and ameliorates brain swelling, and hence leads to few symptoms in subacute and chronic hyponatremia [4,6,8].

level, low blood urea level and normal acid-base and potassium balance. The longstanding assumption that hypontremia [8-11] associated with meningitis and respiratory infectious diseases is caused by inappropriate anti-diuresis has not been substantiated by reports that adequately assessed the volume status (Figure 2). Figure 2 Hypotetical diagrams depicting the relationship between initial state of hydration and plasma sodium in acute meningitis (and respiratory infectious diseases). It has been traditionally assumed that hyponatremia is due to inappropriate anti-diuresis (left panel). On the contrary, most recent data indicate that hyponatremia is due to appropriate, volume-dependent anti-diuresis (right panel). Postoperative hyponatremia is a serious problem in children, which sometimes is caused by a combination of nonosmotic stimuli for release of antidiuretic hormone, such as pain, nausea, stress, narcotics, and edema-forming conditions [4,6,8]. However, subclinical depletion of the effective arterial blood volume and administration of hypotonic fluids are the most important causes of postoperative hyponatremia.

o days by transport of, firstly, sodium, chloride, and potassium and, later, solutes like glutamate, taurine, myoinositol, and glutamine from intracellular to extracellular compartments. This induces water loss and ameliorates brain swelling, and hence leads to few symptoms in subacute and chronic hyponatremia [4,6,8]. Evaluating the cause In normovolemic subjects, the primary defense against developing hyponatremia is the ability to dilute urine and excrete free-water. Rarely is excess ingestion of free-water alone the cause of hyponatremia. It is also rare to develop hyponatremia from excess urinary sodium losses in the absence of free-water ingestion. In order for hyponatremia to develop it typically requires a relative excess of free-water in conjunction with an underlying condition that impairs the ability to excrete free-water. Renal water handling is primarily under the control of vasopressin, which is released from the posterior pituitary and impairs water diuresis by increasing the permeability to water in the collecting tubule. There are osmotic, hemodynamic and non-hemodynamic stimuli for release of vasopressin. In most cases, hyponatremia develops when the body attempts to preserve the extracellular fluid volume at the expense of circulating sodium (therefore, a hemodynamic stimulus for vasopressin production overrides an inhibitory effect of hyponatremia). However, there are further stimuli for production of vasopressin in hospitalized children that make virtually any hospitalized patient at risk for hyponatremia (Table 1).

e at the expense of circulating sodium (therefore, a hemodynamic stimulus for vasopressin production overrides an inhibitory effect of hyponatremia). However, there are further stimuli for production of vasopressin in hospitalized children that make virtually any hospitalized patient at risk for hyponatremia (Table 1). Table 1 Causes of hypotonic hyponatremia in childhood.

e at the expense of circulating sodium (therefore, a hemodynamic stimulus for vasopressin production overrides an inhibitory effect of hyponatremia). However, there are further stimuli for production of vasopressin in hospitalized children that make virtually any hospitalized patient at risk for hyponatremia (Table 1). Table 1 Causes of hypotonic hyponatremia in childhood. Hypovolemic Normovolemic (or hypervolemic) Intestinal salt loss Increased body water - Diarrheal dehydration  - Parenteral hypotonic solutions - Vomiting, gastric suction  - Exercise-associated hyponatermia - Fistulae  - Habitual (and psychogenic) polydipsia - Laxative abuse Transcutaneous salt loss Non osmolar release of antidiuretic hormones* - Cystic fibrosis  - Cardiac failure - Endurance sport  - Sever liver disease (mostly cirrhosis) - Nephrotic syndrome - Glucocorticoid deficiency - Drugs causing renal water retention - HyopthyroidismΔ Renal sodium loss Syndrome of inappropriate anti-diuresis - Mineralocorticoid deficiency (or resistance)  - Classic syndrome of inappropriate secretion of antidiuretic hormone - Diuretics  - Hereditary nephrogenic syndrome of inappropriate anti-dieresis - Salt wasting renal failure - Salt wasting tubulopathies (including Bartter syndromes, Gitelman syndrome, and De Toni-Debré-Fanconi syndrome) - Cerebral salt wasting Perioperative (e.g.: preoperative fasting, vomiting, third space losses) Reduced renal water loss - Chronic renal failure - Oliguric acute renal failure Third space losses (e.g.: burns, major septic shock, surgery) * Effective arterial blood volume mostly reduced; Δ evidence supporting this association rather poor.

ing Perioperative (e.g.: preoperative fasting, vomiting, third space losses) Reduced renal water loss - Chronic renal failure - Oliguric acute renal failure Third space losses (e.g.: burns, major septic shock, surgery) * Effective arterial blood volume mostly reduced; Δ evidence supporting this association rather poor. Some special causes of hypotonic hyponatremia deserve some further discussion.

ing Perioperative (e.g.: preoperative fasting, vomiting, third space losses) Reduced renal water loss - Chronic renal failure - Oliguric acute renal failure Third space losses (e.g.: burns, major septic shock, surgery) * Effective arterial blood volume mostly reduced; Δ evidence supporting this association rather poor. Some special causes of hypotonic hyponatremia deserve some further discussion. • Hospital-acquired hyponatremia is most often seen in the postoperative period or in association with a reduced effective circulating volume [4,6]. More rarely hospital-acquired hyponatremia is seen in association with the syndrome of inappropriate anti-diuresis [8], which is caused either by elevated activity of vasopressin (80-90 percent of the cases) or by hyperfunction of its renal (= V2) receptor (10-20 pecent of the cases), independently of increased effective blood osmolality and hemodynamic stimulus (i.e.: reduced effective circulating volume). It is currently assumed that this condition results not only from dilution of the blood by free-water but also from inappropriate natriuresis [8]. The syndrome of inappropriate anti-diuresis (Figure 1 middle panel) should be suspected in any child with hyponatremic hypotonia, a urine osmolality above 100 mosmol/kg H20, a normal fractional clearance of sodium (> 0.5 × 10-2), low normal or reduced uric acid level, low blood urea level and normal acid-base and potassium balance. The longstanding assumption that hypontremia [8-11] associated with meningitis and respiratory infectious diseases is caused by inappropriate anti-diuresis has not been substantiated by reports that adequately assessed the volume status (Figure 2).

combination of nonosmotic stimuli for release of antidiuretic hormone, such as pain, nausea, stress, narcotics, and edema-forming conditions [4,6,8]. However, subclinical depletion of the effective arterial blood volume and administration of hypotonic fluids are the most important causes of postoperative hyponatremia. • Desmopressin, a synthetic analogue of the natural antidiuretic hormone, is used in central diabetes insipidus, in some bleeding disorders, in diagnostic urine concentration testing and especially in primary nocturnal enuresis with nocturnal polyuria. Desmopressin is generally regarded as a safe drug and adverse effects due to treatment are uncommon. Nonetheless, hyponatremic water intoxication leading to covulsions has been reported as a rare but potentially life threatening side effect of desmopressin therapy in enuretic children with high fluid intake during the day [12]. • Male infants have been recently described with hyponatremia and laboratory features consistent with release of vasopressin but who had no measurable circulating levels of this hormone. Genetic testing revealed gain-of-function mutations of the X-linked receptor gene that mediates the renal response to vasopressin, resulting in persistent activation of the receptor [8,13]. This very rare disease has been termed hereditary nephrogenic syndrome of inappropriate anti-diuresis: it represents a kind of mirror image of the X-linked nephrogenic diabetes insipidus, which results from loss-of-function genetic defects in the aforementioned renal receptor [8,13].

activation of the receptor [8,13]. This very rare disease has been termed hereditary nephrogenic syndrome of inappropriate anti-diuresis: it represents a kind of mirror image of the X-linked nephrogenic diabetes insipidus, which results from loss-of-function genetic defects in the aforementioned renal receptor [8,13]. • Cerebral salt wasting syndrome is a peculiar form of depletional hyponatremia that sometimes occurs in patients with cerebral disease (Figure 1 right panel). It mimics the findings in the syndrome of inappropriate anti-diuresis, except that salt-wasting is the primary defect with the ensuing volume depletion leading to a secondary release of vasopressin [8,14]. It has been suggested that renal salt wasting of central origin results from increased secretion of a natriuretic peptide with subsequent suppression of aldosterone synthesis. The clinical distinction between cerebral salt wasting and inappropriate activity of vasopressin is not always simple to make since the true volume status is sometimes difficult to ascertain [8,14]. • Endurance athletes sometimes replace their dilute but sodium-containing sweat losses with excessive amounts of severely hypotonic solutions: the net effect is a reduction in the circulating sodium level (the effect is likely compounded by a reduced renal blood flow and glomerular filtration rate during exercise). Such individuals may also be taking non-steroidal anti-inflammatory drugs, which can impair the excretion of free water [4,6].

ypotonic solutions: the net effect is a reduction in the circulating sodium level (the effect is likely compounded by a reduced renal blood flow and glomerular filtration rate during exercise). Such individuals may also be taking non-steroidal anti-inflammatory drugs, which can impair the excretion of free water [4,6]. • A tendency towards low normal plasma sodium level is sometimes seen in children who drink excessively and present with polyuria and polydipsia [15]. Usually the problem is simply one of habit, particularly in infants who are attached to a bottle (= habitual polydipsia). Rarely, in childhood, polydispia is a symptom of significant psychopathology (= psychogenic polydipsia). • Diuretics, mostly thiazides, and drugs that block the renin-angiotensin-aldosterone system, either converting enzyme inhibitors or sartans, make up a common cause of hyponatremia (Additional file 1: Table S1). More rarely, other drugs sometimes cause renal retention of fluids and therefore dilutional hyponatremia [16]. Hypernatremia Introduction Hypernatremia reflects a net water loss or a hypertonic sodium gain, with inevitable hypertonicity [3,5]. Severe symptoms are usually evident only with acute and large increases in sodium concentrations to above 160 mmol/L. Importantly, the sensation of thirst protecting against the tendency towards hypernatemia is absent or reduced in patients with altered mental status or with hypothalamic lesions and in infancy.

[3,5]. Severe symptoms are usually evident only with acute and large increases in sodium concentrations to above 160 mmol/L. Importantly, the sensation of thirst protecting against the tendency towards hypernatemia is absent or reduced in patients with altered mental status or with hypothalamic lesions and in infancy. The cause of hypernatremia is almost always evident from the history. Determination of urine osmolality in relation to the effective blood osmolality and the urine sodium concentration helps if the cause is unclear. Patients with diabetes insipidus present with polyuria and polydipsia (and not hypernatremia unless thirst sensation is impaired). Central diabetes insipidus and nephrogenic diabetes insipidus may be differentiated by the response to water deprivation (failure to concentrate urine) followed by desmopressin, causing concentration of urine in patients with central diabetes insipidus. Non-specific symptoms such as anorexia, muscle weakness, restlessness, nausea, and vomiting tend to occur early. More serious signs follow, with altered mental status, lethargy, irritability, stupor, or coma. Acute brain shrinkage can induce vascular rupture, with cerebral bleeding and subarachnoid hemorrhage [3].

The cause of hypernatremia is almost always evident from the history. Determination of urine osmolality in relation to the effective blood osmolality and the urine sodium concentration helps if the cause is unclear. Patients with diabetes insipidus present with polyuria and polydipsia (and not hypernatremia unless thirst sensation is impaired). Central diabetes insipidus and nephrogenic diabetes insipidus may be differentiated by the response to water deprivation (failure to concentrate urine) followed by desmopressin, causing concentration of urine in patients with central diabetes insipidus. Non-specific symptoms such as anorexia, muscle weakness, restlessness, nausea, and vomiting tend to occur early. More serious signs follow, with altered mental status, lethargy, irritability, stupor, or coma. Acute brain shrinkage can induce vascular rupture, with cerebral bleeding and subarachnoid hemorrhage [3]. Evaluating the cause Two mechanisms protect against developing hypernatremia (sodium 145 mmol/L or more) or increased effective blood osmolality: the ability to release vasopressin (and therefore to concentrate urine) and a powerful thirst mechanism. Release of vasopressin occurs when the effective blood osmolality exceeds 275-280 mosmol/kg H2O and results in maximally concentrated urine when the effective blood osmolality exceeds 290-295 mosmol/kg H2O [3,5]. Thirst, the second line of defense, provides a further protection against hypernatremia and increased effective osmolality. If the thirst mechanism is intact and there is unrestricted access to free-water, it is rare to develop sustained hypernatremia from either excess sodium ingestion or a renal concentrating defect (Table 2). Hypernatremia is primarily a hospital-acquired condition occurring in children who have restricted access to fluids. Most children with hypernatremia are debilitated by an acute or chronic disease, have neurological impairment, are critically ill or are born premature. Hypernatremia in the intensive care setting is common as these children are typically either intubated or moribund, and often are fluid restricted, receive large amounts of sodium as blood products or have renal concentrating defects from diuretics or renal dysfunction. The majority of hypernatremia results from the failure to administer sufficient free-water to children who are unable to care for themselves and have restricted access to fluids [2,3,5].

estricted, receive large amounts of sodium as blood products or have renal concentrating defects from diuretics or renal dysfunction. The majority of hypernatremia results from the failure to administer sufficient free-water to children who are unable to care for themselves and have restricted access to fluids [2,3,5]. Table 2 Causes of hypernatremia in childhood. Hypovolemic Normovolemic Hypervolemic Inadequate Intake - Breast feeding hypernatremia Hypodypsia (essential hypernatremia) Inappropriate intravenous fluids (e.g.: hypertonic saline, NaHCO3) - Poor access to water Hyperventilation Salt poisoning (accidental, deliberate) - Altered thirst perception (uncosciousness, mental impairment) Fever Primary aldosteronism (and other conditions that cause low-renin hypertension) Intestinal salt loss (diarrheal dehydration) Renal water and salt loss - Postobstructive polyuria - Diuretics - Diabetes insipidus - Medullary renal damage Two special causes of hypernatremia deserve some further discussion.

Hypovolemic Normovolemic Hypervolemic Inadequate Intake - Breast feeding hypernatremia Hypodypsia (essential hypernatremia) Inappropriate intravenous fluids (e.g.: hypertonic saline, NaHCO3) - Poor access to water Hyperventilation Salt poisoning (accidental, deliberate) - Altered thirst perception (uncosciousness, mental impairment) Fever Primary aldosteronism (and other conditions that cause low-renin hypertension) Intestinal salt loss (diarrheal dehydration) Renal water and salt loss - Postobstructive polyuria - Diuretics - Diabetes insipidus - Medullary renal damage Two special causes of hypernatremia deserve some further discussion. • A frequent cause of hypernatremia in the outpatient setting is currently breastfeeding-associated hypernatremia, which should more properly be labeled "not-enough-breastfeeding-associated hypernatremia" [17]. This condition occurs between days 7 and 15 in otherwise healthy term or near-term newborns of first-time mothers who are exclusively breast-fed. In all cases feeding had been difficult to establish and the volume of milk ingested was likely to have been low. The underlying problem is water deficiency: sodium concentration raises predominantly as a result of low volume intake and a loss of water, demonstrating that inadequate feeding is the cause of hypernatremic dehydration. Monitoring postnatal weight loss provides an objective assessment of the adequacy of nutritional intake allowing targeted support to those infants who fail to thrive or demonstrate excessive weight loss (10 percent or more of birth weight).

emonstrating that inadequate feeding is the cause of hypernatremic dehydration. Monitoring postnatal weight loss provides an objective assessment of the adequacy of nutritional intake allowing targeted support to those infants who fail to thrive or demonstrate excessive weight loss (10 percent or more of birth weight). • Diarrhea or vomiting are a further reason of hypernatremia in the outpatient setting, but are much less common than in the past, presumably due to the advent of low solute infant formulas and the increased use and availability of oral rehydration solutions [2,3,5,18]. Management The discussion will exclusively focus some points of parenteral hydration and the management of hyponatremia with either V2 antidiuretic hormone receptor antagonists or urea.

• Diarrhea or vomiting are a further reason of hypernatremia in the outpatient setting, but are much less common than in the past, presumably due to the advent of low solute infant formulas and the increased use and availability of oral rehydration solutions [2,3,5,18]. Management The discussion will exclusively focus some points of parenteral hydration and the management of hyponatremia with either V2 antidiuretic hormone receptor antagonists or urea. Parenteral hydration • Maintenance and perioperative fluids Intravenous maintenance fluids are designed to provide water and electrolyte requirements in a fasting patient. The prescription for intravenous maintenance fluids was originally described by Holliday more than 50 years ago [19], who rationalized a daily H20 requirement of 1700-1800 ml/m2 body surface area and the addition of 3 and 2 mmol/kg body weight of Na+ and K+ respectively (as it approximates the electrolyte requirements and urinary excretion in healthy infants). This is the basis for the traditional recommendation that hypotonic intravenous maintenance solutions are ideal for children [19]. In clinical practice the daily parenteral water requirement is calculated as given in Table 3 (left panel). This approach has been recently questioned considering the potential of these hypotonic solutions in determining hyponatremia and subsequently severe neurological sequelae [20-22]. Surgical patients appear the subgroup of pediatric patients with the highest risk to develop severe hyponatremia with the use of hypotonic intravenous solutions, likely because they tend to be hypovolemic. Furthermore, traditional maintenance fluid recommendations might be largely greater than actual water needs in children at risk of hyponatremia.

ubgroup of pediatric patients with the highest risk to develop severe hyponatremia with the use of hypotonic intravenous solutions, likely because they tend to be hypovolemic. Furthermore, traditional maintenance fluid recommendations might be largely greater than actual water needs in children at risk of hyponatremia. Table 3 Intravenous maintenance fluids designed to provide water and electrolyte requirements in a fasting patient. Holliday's recommendation Current suggestion Solution 5 percent dextrose in water supplemented with NaCl 3 mmol/kg body weight daily Isotonic saline in 5 percent dextrose in water Amount (ml/m2 body surface area* daily) 1700-1800 1400-1500 Clinical practice 100 mL/kg body weight for a child weighing less than 10 kg◇ + 50 mL/kg for each additional kg up to 20 kg + 20-[25] mL/kg for each kg in excess of 20 kg 80 mL/kg body weight for a child weighing less than 10 kg◇ + 40 mL/kg for each additional kg up to 20 kg + 15-[20] mL/kg for each kg in excess of 20 kg * the Mosteller's formula may be used to calculated the body surface area (in m2): height (cm)×body wight (kg)3600; ◇ in children weighing ≤5.0 kg the daily parenteral water requirement is 120 mL/kg body weight. Both the recommendation originally described by Holliday and the most recent recommendation are given. The addition of KCl 2 mmol/kg body weight is also recommended.

Holliday's recommendation Current suggestion Solution 5 percent dextrose in water supplemented with NaCl 3 mmol/kg body weight daily Isotonic saline in 5 percent dextrose in water Amount (ml/m2 body surface area* daily) 1700-1800 1400-1500 Clinical practice 100 mL/kg body weight for a child weighing less than 10 kg◇ + 50 mL/kg for each additional kg up to 20 kg + 20-[25] mL/kg for each kg in excess of 20 kg 80 mL/kg body weight for a child weighing less than 10 kg◇ + 40 mL/kg for each additional kg up to 20 kg + 15-[20] mL/kg for each kg in excess of 20 kg * the Mosteller's formula may be used to calculated the body surface area (in m2): height (cm)×body wight (kg)3600; ◇ in children weighing ≤5.0 kg the daily parenteral water requirement is 120 mL/kg body weight. Both the recommendation originally described by Holliday and the most recent recommendation are given. The addition of KCl 2 mmol/kg body weight is also recommended. More recente data [20-22] suggest that the prevention of hyponatremia should be obtained both by using isotonic (usually normal saline, which contains NaCl 9 g/L) or near-isotonic (usually lactate Ringer) solutions (Table 3 right panel) and by reducing the volume of maintenance fluid (approximately by 20 percent). Considering the potential of hypoglycemia in infancy, isotonic saline in 5 percent glucose in water (which contains approximately glucose 50 g/L and NaCl 9 g/L) seems to be the safest fluid composition in most children [20-22]. On the other side, we refrain from the uncritical, generalized adoption of this new standard care until rigorous trials confirming this suggestion have been made.

in 5 percent glucose in water (which contains approximately glucose 50 g/L and NaCl 9 g/L) seems to be the safest fluid composition in most children [20-22]. On the other side, we refrain from the uncritical, generalized adoption of this new standard care until rigorous trials confirming this suggestion have been made. • Dehydration Oral rehydration therapy is currently the treatment of choice for children with minimal, mild or moderate dehydration due to diarrheal diseases. However, in the practice of pediatric emergency medicine, intravenous rehydration is a commonly used intervention for these children [21,23].

in 5 percent glucose in water (which contains approximately glucose 50 g/L and NaCl 9 g/L) seems to be the safest fluid composition in most children [20-22]. On the other side, we refrain from the uncritical, generalized adoption of this new standard care until rigorous trials confirming this suggestion have been made. • Dehydration Oral rehydration therapy is currently the treatment of choice for children with minimal, mild or moderate dehydration due to diarrheal diseases. However, in the practice of pediatric emergency medicine, intravenous rehydration is a commonly used intervention for these children [21,23]. Treatment approaches to parenteral rehydration in the hospitalized child vary. There are numerous ways to estimate the degree of dehydration (the "4-item 8-point rating scale" is currently widely recommended [1]) and especially to calculate fluid and electrolyte deficits, and to deliver the deficits to the patient. For many years, the traditional teaching was that 100 percent (or even less) replacement of the volume deficit should be accomplished during the first 24 hours of treatment. In recent years, the aim of treatment has generally been to accomplish a more rapid full repletion within 6 hours or less [21,23]. In many children with mild to moderate dehydration, especially those resistant to initial oral rehydration therapy, and in children with severe dehydration, we currently administer intravenous isotonic (or near isotonic) crystalloid solutions such as normal saline or lactate Ringer as repeated boluses of [10]-20 mL/kg body weight (administered over 20 to 60 minutes).

n, especially those resistant to initial oral rehydration therapy, and in children with severe dehydration, we currently administer intravenous isotonic (or near isotonic) crystalloid solutions such as normal saline or lactate Ringer as repeated boluses of [10]-20 mL/kg body weight (administered over 20 to 60 minutes). In children with diarrhea and vomiting reduced carbohydrate intake leads to free fatty acid breakdown, excess ketones, and an increased likelihood for continued nausea and vomiting. Consequently, some authorities have suggested (but so far not proven) that the use of a glucose containing isotonic solution (mostly the aforementioned isotonic saline in 5 percent glucose in water), which will stimulate insulin release, reduce free fatty acid breakdown, and therefore reduce treatment failure due to persisting nausea and vomiting [24].

e suggested (but so far not proven) that the use of a glucose containing isotonic solution (mostly the aforementioned isotonic saline in 5 percent glucose in water), which will stimulate insulin release, reduce free fatty acid breakdown, and therefore reduce treatment failure due to persisting nausea and vomiting [24]. The child with circulatory shock presents with a) increased heart rate and weak peripheral pulses, b) cold, pale and diaphoretic skin, and c) delayed capillary refill. The initial management recommended by the American Academy of Pediatrics includes the administration of a high concentration of oxygen (ensuring that 100 percent of the available arterial hemoglobin is oxygenated) and the fluid resuscitation with a 20 mL/kg body weight bolus of an isotonic crystalloid over 5-20 minutes (if the child fails to improve, at least 2 further boluses for a total of 60 mL/kg body weight are rapidly given). The most common error in the child with circulatory shock secondary to a diarrheal disease is the delayed or inadequate (i.e. with hypotonic crystalloid solution) fluid resuscitation.

oid over 5-20 minutes (if the child fails to improve, at least 2 further boluses for a total of 60 mL/kg body weight are rapidly given). The most common error in the child with circulatory shock secondary to a diarrheal disease is the delayed or inadequate (i.e. with hypotonic crystalloid solution) fluid resuscitation. Children with hypernatremic dehydration are also hydrated parenterally with isotonic crystalloid solutions until diagnosis of the dyselectrolytemia, followed by slightly hypotonic solutions (e.g.: half-saline) in order to slowly correct circulating sodium level (abruptly correcting hypernatremia using a sodium free glucose solution creates an increased risk for the development of brain edema; Figure 3). In acute dysnatremic dehydration, sodium should be corrected slowly at a rate not exceeding 0.5 mmol/L per hour and no more than by 12 mmol/L per day. Subacute or chronic hypernatremia should be corrected even more slowly [3].

ree glucose solution creates an increased risk for the development of brain edema; Figure 3). In acute dysnatremic dehydration, sodium should be corrected slowly at a rate not exceeding 0.5 mmol/L per hour and no more than by 12 mmol/L per day. Subacute or chronic hypernatremia should be corrected even more slowly [3]. Figure 3 Cell volume in acute or subacute hypernatremia and following rapid correction of hypernatremia. When hypernatemia develops acutely, all cells are reduced in size (the degree of cell volume reduction reflects the degree of hypernatremia). When hypernatremia is present for 36-48 hours or more (= subacute hypernatremia), cell volume reduction persists in most cells, including muscle cells (upper panel). However, brain cells (and red blood cells) tend to restore their normal cell volume (lower panel). An abrupt normalization of sodium level in children with subacute or chronic hypernatremia pathologically increases the volume of brain cells (and red blood cells). Swelling of cells, which does not have serious consequences when it occurs in most organs, may have devastating consequences when it occurs in the brain (lower panel, right).

tion of sodium level in children with subacute or chronic hypernatremia pathologically increases the volume of brain cells (and red blood cells). Swelling of cells, which does not have serious consequences when it occurs in most organs, may have devastating consequences when it occurs in the brain (lower panel, right). • Hydration in infectious diseases associated with a tendency towards hyponatremia Fluid restriction has been widely advocated in the initial management of infectious diseases such as meningitis, pneumonia or bronchiolitis, which are often associated with a low sodium level. However, there is no evidence that fluid restriction is useful. Furthermore, hyponatremia results from appropriate, volume-dependent anti-diuresis in these disease conditions. In clinical practice, initial restoration of the intravascular space with an isotonic crystalloid followed by isotonic maintenance fluids 1400-1500 mL/m2 body surface area daily (Table 3 right panel) are currently advised [8]. In cases presenting with overt hyponatremia frequent monitoring of electrolytes is also required with adjustments made as warranted by laboratory findings.

space with an isotonic crystalloid followed by isotonic maintenance fluids 1400-1500 mL/m2 body surface area daily (Table 3 right panel) are currently advised [8]. In cases presenting with overt hyponatremia frequent monitoring of electrolytes is also required with adjustments made as warranted by laboratory findings. • Chronic hyponatremia Chronic normovolemic (or hypervolemic) hyponatremia has been traditionally managed either by restricting water intake or by giving salt. An alternative may be the use of nonpeptide vasopressin receptor antagonists [25]. There are multiple receptors for vasopressin: the V1a receptors that mediate vasoconstriction, the V1b receptors that mediate adrenocorticotropin release, and the V2 receptors that mediate the antidiuretic response. Vaptans, oral V2 receptor antagonists, have been recently approved for the management of normovolemic and hypervolemic hyponatremia: these agents produce a selective water diuresis (without affecting sodium and potassium excretion) that raises the circulating sodium level [25]. No information is currently available with these agents in childhood. Vaptans do not correct hyponatremia in patients affected with nephrogenic syndrome of inappropriate childhood anti-diuresis [8,13]. In these patients, a way to enhance water excretion is the oral administration of urea (dosage in adulthood: 30 g per day). This regimen, which may be effective because it causes simultaneously water diuresis and renal sodium retention, is well tolerated, and has been used chronically in ambulatory pediatric patients [8,26].

se patients, a way to enhance water excretion is the oral administration of urea (dosage in adulthood: 30 g per day). This regimen, which may be effective because it causes simultaneously water diuresis and renal sodium retention, is well tolerated, and has been used chronically in ambulatory pediatric patients [8,26]. Conclusions In conclusion pediatricians must be aware of the changing epidemiology of dysnatremia in children with diarrhea (and vomiting) and in those hydrated parenterally with the hypotonic solutions recommended by Holliday. We recommend that clinicians consider more frequently the use of isotonic or near-isotonic crystalloid solutions both for replacement, i.e. to expand the extracellular fluid compartment, as well as for maintenance. Finally, recent data indicate that in meningitis and respiratory infections hyponatremia results from appropriate, volume-dependent anti-diuresis. Competing interests The authors declare that they have no competing interests. Authors' contributions MGB, AB and GDS wrote the first version of the manuscript. MP, GPM, LL and LG consistently revised the manuscript and prepared both the figures as well as the references. EFF revised the final version of the manuscript. All authors have read and approved the paper, have met the criteria for authorship as established by the International Committee of Medical Journals Editors, believe that the paper represents honest work, and are able to verify the validity of the content. Supplementary Material Additional file 1 Table S1. Click here for file