Strange and Schafermeyer's Pediatric Emergency Medicine, Fourth Edition (Strange, Pediatric Emergency Medicine), 4th Ed.

CHAPTER 81. Hypo- and Hypernatremia Abnormalities

Susan A. Kecskes

HIGH-YIELD FACTS

• Sodium concentration reflects both the sodium and water contents of the body.

• Antidiuretic hormone (ADH) is one of the primary regulatory hormones for sodium concentration. It responds to the changes in osmolality and intravascular volume to restore homeostasis to the body.

• Hypernatremia may result from:

• Primary sodium excess

• Hypovolemic hypernatremia

• Hypernatremia should generally be corrected gradually to avoid the complication of cerebral edema.

• Aggressive treatment of hyponatremia may lead to the osmotic demyelination syndrome.

SODIUM

The concentration of sodium reflects the total body store of sodium and its relation to total body water (TBW). In both hypo- and hypernatremia, the total body store of sodium may be high, low, or normal. It is the amount of TBW relative to total body sodium that determines sodium concentration. Sodium is found in highest concentration in the extracellular compartment and is normally maintained between 135 and 145 mEq/L.

One of the primary regulatory mechanisms is antidiuretic hormone (ADH). ADH is secreted by the posterior pituitary gland in response to stimulation of osmoreceptors residing in the anterior hypothalamus, baroreceptors in the great vessels, and volume receptors in the left atrium. The release of ADH results in increased water absorption by the renal tubule. Osmoreceptors detect increasing osmolarity, with sodium being the primary ion responsible for extracellular osmolarity. Baroreceptors and volume receptors regulate the intravascular volume. In cases of decreasing intravascular volume and diminishing osmolarity (due to body water in excess of body sodium), the volume receptors will override the osmoreceptors, resulting in ADH secretion and water retention, despite decreasing concentrations of sodium.1

image HYPERNATREMI

Hypernatremia is defined as serum sodium >150 mEq/L. It may result from intake of sodium in excess of water or, more commonly, from loss of water in excess of sodium (Table 81-1). Primary sodium excess is usually associated with iatrogenic causes, such as inadequately diluted infant formula, excessive sodium bicarbonate administration, or intravenous hypertonic saline administration. More frequently encountered is hypovolemic hypernatremia, in which water loss exceeds sodium loss. The most common cause in pediatrics is gastroenteritis with diarrhea and vomiting. Other causes include increased insensible water loss (i.e., fever, use of radiant warming devices, burns), diabetes mellitus (solute diuresis), or inadequate access to free water.

TABLE 81-1

Causes of Hypernatremia

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Diabetes insipidus (DI) is a less common cause of hypovolemic hypernatremia. The essential feature is a functional lack of ADH, resulting in urinary water loss despite increasing osmolarity and hypovolemia. It may be caused by insufficient production and release of ADH (central DI) or end-organ unresponsiveness to ADH (nephrogenic DI). Disruption of the hypothalamic–pituitary axis by tumors, head trauma, hypoxic–ischemic brain injury, or neurosurgical procedures results in central DI. It is frequently seen in children near brain death. Nephrogenic DI is a congenital (x-linked recessive) disorder in which the ADH receptors in the renal tubules are defective and unable to respond to ADH. It is present at birth and can be life-threatening if unrecognized. Very dilute urine (osmolarity <150 mOsm/L or specific gravity <1.005), serum hyperosmolarity (osmolarity >295 mOsm/L), and hypernatremia characterize both central and nephrogenic DIs. In acute situations, they may be differentiated by their responsiveness (central DI) or lack thereof (nephrogenic DI) to vasopressin.

As the serum sodium rises, extracellular fluid (ECF) becomes relatively hyperosmolal compared to intracellular fluid (ICF). Water moves from the intracellular space to the extracellular space to equilibrate the osmolality. The assessment of decreased intravascular volume status is associated with a greater TBW deficit in hypernatremia than in isotonic or hypotonic state. The brain attempts to conserve water by an increase in glucose, electrolytes, and idiogenic osmoles.2,3 This process occurs over approximately 48 hours. Thus, although the intracellular space is relatively volume depleted in hypernatremia, the brain preserves its volume status.

Clinical manifestations of hypernatremia depend on the volume status of the patient. In primary sodium excess, the skin is often described as “doughy.” In hypovolemic hypernatremia, the signs and symptoms of dehydration are manifested. In both, the central nervous system is adversely affected. Irritability and lethargy can progress to coma and seizures. Hyperreflexia and spasticity may also occur. Concomitant laboratory findings may include hyperglycemia and hypocalcemia.

Initial therapy of hypovolemic hypernatremia is focused on correction of circulatory failure, if present (Fig. 81-1). Subsequent restoration of TBW should be gradual, for 48 hours. Fatal cases of cerebral edema have occurred with correction over 24 hours, as fluid enters the already volume-repleted brain.4 A gradual correction allows the brain to reduce the idiogenic osmoles and equilibrate with the ECF. The goal is to reduce the serum sodium at a rate of 0.5 to 1 mEq/L/h.5 The higher the serum sodium and the longer the time of accumulation, the slower the rate of correction should be. Typically, the correction is started with isotonic crystalloid for stabilization of the circulatory system and completed with hypotonic crystalloid, such as D5 0.45% NaCl. Often, combinations of intravenous fluids (i.e., one-half as 0.9% NaCl and one-half as D5 0.45% NaCl) are administered during correction to bring the sodium down in a stepwise fashion and limit the dextrose administration. Maintenance fluids and replacement of ongoing losses must be provided in addition to the deficit correction. Plasma electrolytes and osmolality should be monitored frequently and fluids adjusted accordingly.

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FIGURE 81-1. Treatment of hypernatremia.

In patients in whom DI is suspected, a trial of vasopressin should be attempted. The drug of choice is aqueous pitressin by continuous infusion beginning at 0.5 mU/kg/h and titrated every 30 minutes (maximum dose 10 mU/kg/h) to produce urine osmolality greater than serum osmolality. Alternatively, desmopressin (DDAVP) may be given via intermittent dosing. For oral administration, the initial dose is 0.05 mg po twice per day (titrate up to a maximum of 0.4 mg/dose, up to three times per day). The initial intranasal dose is 0.05 mL (5μg), once per day (titrate up to a maximum of 0.4 mL/d over 1–3 doses).6

Primary sodium excess is treated by removal of excess sodium. First, the sodium intake is curtailed. In patients with intact renal function, provision of free water via the gastrointestinal tract or hypotonic fluids parenterally will aid correction. Patients with renal failure require dialysis.

image HYPONATREMIA

Hyponatremia is defined as a serum sodium concentration <130 mEq/L and reflects excess body water relative to body sodium. Depending on etiology, total body sodium may be decreased, increased, or normal (Fig. 81-2). Hyponatremia with decreased total body sodium occurs when sodium loss exceeds water loss. These losses may be extrarenal or renal. The most common extrarenal losses in children are vomiting and diarrhea. Other causes include burns, peritonitis, and pancreatitis. Extrarenal etiologies are associated with renal sodium conservation (urine sodium <20 mEq/L).

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FIGURE 81-2. Causes of hyponatremia.

Renal losses include diuretic use, osmotic diuresis, and salt-losing renal disease. Thiazide diuretics are more common culprits in hyponatremia than loop diuretics. Osmotic diuresis may be produced iatrogenically with mannitol or excess glucose administration. It is also associated with glucosuria in diabetes mellitus. Hyperglycemia and mannitol induce urinary sodium and water loss along with osmotic water movement from ICF to ECF, further lowering serum sodium. Salt-wasting renal diseases include nephritis, obstructive uropathy, renal tubular acidosis, and adrenal insufficiency (congenital adrenal hyperplasia, Addison’s disease). Renal causes of hyponatremia with decreased total body sodium are associated with ongoing urinary sodium loss (urine sodium >20 mEq/L).

Hyponatremia with increased total body sodium occurs when the increase in TBW exceeds sodium retention. Common etiologies include congestive heart failure (CHF) and renal failure. In CHF, decreased cardiac output leads to decreased glomerular filtration rate (GFR). The kidney then conserves water and sodium in an attempt to increase intravascular volume and improve renal perfusion. Water is conserved in excess of sodium. In renal failure, decreased urine output is unable to maintain sodium balance in the face of excess water intake.

Hyponatremia with normal total body sodium is commonly associated with two etiologies in children. First, the syndrome of inappropriate antidiuretic hormone (SIADH) leads to a dilutional hyponatremia. This syndrome is associated with diverse causes including central nervous system disorders, pulmonary disease, postoperative states, malignancies, glucocorticoid deficiency, and hypothyroidism. A frequent etiology in the pediatric emergency room is meningitis. Urinary osmolarity (>200 mOsm/L) and sodium concentration (>20 mEq/L) are inappropriately elevated for the hypotonicity and sodium concentration of the serum. The second common etiology of hyponatremia with normal total body sodium is water intoxication. “WIC” syndrome (named after the Federal supplemental nutrition program for Women, Infants, and Children) occurs when small infants are fed with overly dilute formula or excess water.7 Inappropriately hypotonic replacement of fluid losses is another iatrogenic cause of water intoxication. In both, the intake of free water exceeds the ability of the body to eliminate it.

The clinical manifestations of hyponatremia depend on the volume status of the patient, the rapidity of development, and degree of hypo-osmolality. In hypovolemic hyponatremia, the symptoms of dehydration and acute circulatory failure prevail. Hyponatremia produces a decrease in the osmolarity of the ECF. Water flows into the ICF to maintain homeostasis. Rapid changes result in brain edema and CNS pathology. Symptoms range from lethargy to coma. Brain herniation may occur in the most severe cases. Hyponatremia is a common cause of afebrile seizures in children younger than 6 months.8Gradual onset of hyponatremia allows the brain to extrude electrolytes and other osmoles to prevent brain swelling and diminish the CNS pathology.

Treatment of hyponatremia begins with an assessment of the patient’s volume status and correction of hypovolemic shock, if present (Fig. 81-3). Correction of the hyponatremia requires a loss of water in excess of sodium. This must be undertaken with care, as aggressive correction may lead to the osmotic demyelination syndrome.9 Just as the brain can generate idiogenic osmoles to maintain cellular volume in hyperosmolal states, it can rid itself of osmoles in hypo-osmolal states to prevent brain edema. Once rid of these osmoles, too rapid a correction of sodium can result in cell desiccation and myelinolysis.10Gradual correction allows the brain time to equilibrate with a reduction in neurologic sequelae. In hyponatremia of acute onset (<48 hours), it appears safe to correct the sodium over 24 hours. In hyponatremia of more gradual onset, sodium correction should not exceed a rate of 0.5 mEq/L/h. Therapy can beinitiated with isotonic crystalloid at rates determined by the volume status of the patient. In euvolemic or hypervolemic patients, this may be at maintenance or fluid-restricted rates. Fluid restriction to two-thirds maintenance, or even insensible fluid loss, is the mainstay of therapy for SIADH. In hypovolemic patients, the deficit needs to be assessed and the correction timed to the desired rise in sodium concentration (approximately 10 mEq/L/24 h). Although most patients will correct gradually with isotonic crystalloid, more aggressive partial correction may be desired in patients with severe neurologic symptoms, such as seizures. A rise in serum sodium of 5 mEq/L can be produced by intravenous infusion of 6 mL/kg of 3% sodium chloride over 1 to 2 hours. A single bolus is usually sufficient to reduce acute symptoms and the remainder of the correction should be undertaken more gradually. Loop diuretics, such as furosemide, have been used as an adjunct to therapy to increase free water clearance. In all types of hyponatremia, the underlying pathology should be identified and appropriate treatment initiated.

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Figure 81-3 Treatment of hyponatremia

REFERENCES

1. Zerbe RL, Robertson GL. Osmotic and nonosmotic regulation of thirst and vasopressin secretion. In: Maxwell MH, Kleeman CR, Narins RG, eds. Clinical Disorders of Fluid and Electrolyte Metabolism.4th ed. New York, NY, McGraw-Hill; 1987:68.

2. Lee JH, Arcinue E, Ross BD. Brief report: organic osmolytes in the brain of an infant with hypernatremia. N Engl J Med. 1994;331:439.

3. Ayus JC, Armstrong DL, Arieff AI. Effects of hypernaetremia in the central nervous system and its therapy in rats and rabbits. J Physiol. 1996;492(1):243.

4. Finberg L. Hypernatremia (hypertonic) dehydration in infants. N Engl J Med. 1973;289:196.

5. Androgue HJ, Madias NE. Hypernatremia. N Engl J Med. 2000;342:1493.

6. Taketomo CK, Hodding JH, Kraus DM, eds. Pediatric Dosage Handbook. 19th ed. Hudson, OH: Lexi-Comp; 2012:494.

7. Keating JP, Schears GH, Dodge PR. Oral water intoxication in infants: an American epidemic. Am J Dis Child. 1991;145:985.

8. Farrar HC, Chande VT, Fitzpatrick DF, et al. Hyponatremia as the cause of seizures in infants: a retrospective analysis of incidence, severity and clinical predictors. Ann Emerg Med. 1995;26:42.

9. Sterns RH, Riggs JE, Schochet SS Jr. Osmotic demyelination syndrome following correction of hyponatremia. N Engl J Med. 1986;314:1535.

10. Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med. 2000;342:1581.