64: Hyponatremia

An infant has a serum sodium of 127 mEq/L, below the normal accepted value of 135 mEq/L. The incidence of hyponatremia is greater than hypernatremia in premature infants. Evidence now shows it is a serious condition in very preterm infants (<33 weeks' gestation), who have large variations of the serum sodium concentration, as they are at risk for poor neuromotor outcome at 2 years. Preterm infants with an increased risk of hyponatremia from sodium restriction show impaired growth and worse neurodevelopment at 10–13 years of age. Hyponatremia is also a risk factor for sensorineural hearing loss, intracranial hemorrhage, and cerebral palsy. Hyponatremia in infants who experienced perinatal birth asphyxia are at risk for an increased mortality.

1. Is there any seizure activity? Seizure activity can be seen in patients with extremely low serum sodium levels (usually <120 mEq/L). This is a medical emergency, and urgent intravenous (IV) sodium correction is needed.

2. How much sodium and free water is the patient receiving? Is weight gain or loss occurring? Be certain that an adequate amount of sodium is being given and that free water intake is not excessive. The normal amount of sodium intake is 2–4 mEq/kg/d. Weight gain with low serum sodium levels is most likely a result of volume overload, especially in the first day or two of life, when weight loss is expected.

3. What is the urine output? With syndrome of inappropriate secretion of antidiuretic hormone (SIADH), urine output is decreased. If the urine output is increased (>4 mL/kg/h), perform a spot check of urine sodium to determine whether urinary sodium losses are high.

4. What medications is the infant receiving? Are renal salt-wasting medications being given? Diuretics such as furosemide may cause hypovolemic hyponatremia. Other medications that cause hyponatremia include theophylline, carbamazepine, chlorpromazine, indapamide, amiodarone, and selective serotonin reuptake inhibitors. Most of these cause SIADH (euvolemic hyponatremia). Morphine and barbiturates can also cause hyponatremia.

5. Did the mother receive hypotonic IV fluids or an excessive amount of oxytocin? Was the mother hyponatremic in the intrapartum period? If so, the infant can have hyponatremia at birth. Infants of mothers with hyponatremia can have low levels of sodium after delivery.

6. Is the infant <1 week old (early-onset hyponatremia) or is the infant in the third to fourth week of life (late-onset hyponatremia)? Early-onset hyponatremia may be due to free water excess from either increased maternal free water in labor or perinatal nonosmotic release of vasopressin (occurs in perinatal asphyxia, respiratory distress syndrome, bilateral pneumothoraces, intraventricular hemorrhage [IVH], and with certain medications). It can also occur from too much free water given or not enough sodium intake in fluids. Late-onset hyponatremia is usually from inadequate sodium intake or excessive renal losses. Late onset can also be from excessive antidiuretic hormone (ADH) release, renal failure, or edema causing retention of free water, but it is less common. Preterm infants >28 weeks have a high fractional excretion of sodium.

When considering the differential, determine whether the value is real. Certain conditions can cause pseudohyponatremia. Is the amount of sodium given adequate? Then you need to decide whether the hyponatremia is caused by deficit of total body sodium or an excess of free water. Is there an inability to excrete water? Is there an excessive sodium loss? Have medications caused the hyponatremia? The cause dictates the form of treatment. The most frequent cause of hyponatremia in the neonate is hypotonic hyponatremia (dilutional) caused by excessive fluid administration or retention of free water.

1. Pseudohyponatremia. This can be caused by hyperlipidemia, hyperproteinemia, or hyperglycemia. In hyperglycemia, for every 100 mg/dL the glucose is above 100, the sodium falls 1.6 mEq/L. A spurious result can also occur from a diluted sample drawn from an indwelling catheter with a low sodium fluid.

2. Inadequate sodium intake. Maintenance sodium is usually 2–4 mEq/kg/d.

3. Hyponatremia with extracellular fluid (ECF) excess (hypervolemia). This occurs with excess of ECF. There is a positive water balance. The total body sodium and total body water are increased. ECF is very increased, resulting in edema and weight gain. Causes include the following:

   1. Congestive heart failure

   2. Sepsis with decreasing cardiac output

   3. Neuromuscular paralysis with fluid retention (eg, pancuronium)

   4. Renal failure

   5. Liver failure (cirrhosis)

   6. Nephrotic syndrome

   7. Necrotizing enterocolitis (late)

   8. Indomethacin therapy (can cause water retention)

4. Hyponatremia with hypovolemia (ECF deficit). This occurs with a deficit of ECF and can be caused by either renal losses or extrarenal losses. The total body sodium and total body water and ECF are all decreased.

   1. Renal losses (spot urinary Na >20 mEq/L)

      1. Diuretics

      2. Renal disorders

         1. Renal immaturity. Neonates can have immature kidneys. Preterm infants are prone to hyponatremia because of a lower glomerular filtration rate, lower proximal tubular reabsorption of sodium, and an increase arginine vasopressin level when sick. Often very low birthweight infants show increased renal tubular sodium and water loss causing hyponatremia.

         2. Salt-losing nephropathy.

         3. Acute/chronic renal failure.

         4. Renal tubular acidosis.

         5. Obstructive uropathy. This can cause high urinary losses of sodium.

         6. Bartter and Fanconi syndromes.

         7. Hypertension-hyponatremia syndrome in neonates caused by renovascular pathology. Renal ischemia from renal microthrombi can be the cause. Suspect if umbilical artery catheter has been placed and unilateral renal arterial stenosis is present.

      3. Mineralocorticoid deficiency (adrenal salt-wasting disorders)

         1. Addison disease

         2. Hypoaldosteronism

         3. Congenital adrenal hyperplasia

         4. Pseudohypoaldosteronism

         5. Hypopituitarism

      4. Cerebral salt-wasting syndrome. Occurs when there is loss of sodium in the urine and is secondary to acute or chronic damage to the central nervous system (hemorrhage, increased intracranial pressure). Extracellular volume is decreased and blood urea nitrogen, albumin, and hematocrit are increased.

      5. Osmotic diuresis from hyperglycemia (rare in neonates), hyperosmolality.

   2. Extrarenal losses (urinary Na <20 mEq/L)

      1. Gastrointestinal (GI) losses such as vomiting, diarrhea, nasogastric tubes.

      2. Third spacing of fluids. Ascites, pleural effusion, ileus, necrotizing enterocolitis, sloughing of skin.

      3. Radiant warmer skin loss.

5. Hyponatremia with normal ECF. Total body water is increased, total sodium is normal or a slightly decreased, ECF is minimally increased but no edema.

   1. Excessive IV fluids, free water, or using diluted (hypotonic) formulas. A common cause of the hyponatremia in a neonate. Maternal fluid overload (with glucose- only sodium-free solutions) or maternal water intoxication is also a cause of hyponatremia in a newborn. This is associated with a low urine-specific gravity and high urine output.

   2. SIADH. Occurs more commonly in CNS disorders such as IVH, hydrocephalus, birth asphyxia, and meningitis, but may also be seen with lung disease (pneumothorax and positive pressure ventilation). SIADH is often seen in critically ill premature and term neonates. It can also be seen in association with pain and with medications such as opiates, carbamazepine, barbiturates, theophylline, and thiazides.

   3. Endocrine related. Hypothyroidism or hypoadrenalism.

6. Drug-induced hyponatremia. Diuretics (used frequently with bronchopulmonary dysplasia/chronic lung disease [BPD/CLD]) can lead to sodium losses. Indomethacin causes water retention (dilutional hyponatremia). SIADH can be due to medications, as noted previously. Infusion of mannitol or hypertonic glucose can cause hyperosmolality with salt wasting. Maternal medication use (diuretics, infusion of oxytocin and glucose) can cause hyponatremia in the infant.

1. Evaluate the bedside chart

   1. Check for weight loss or gain. Weight gain is more likely to be associated with dilutional hyponatremia. Weight loss is seen with hyponatremia with decreased ECF.

   2. Check fluid intake and output over a 24-hour period. Normally, infants retain two-thirds of the fluid administered, and the rest is lost in the urine or by insensible loss. If the input is much greater than the output, the patient may be retaining fluid, and dilutional hyponatremia should be considered.

   3. Assess the urine output and specific gravity. A low urine output with a high specific gravity is more commonly seen with SIADH. In excessive fluid, one sees a low urine-specific gravity and a high urine output.

2. History and physical examination. Are there maternal factors present (hypotonic IV fluids or an excessive amount of oxytocin) or was there maternal hyponatremia in the intrapartum period? Note signs of seizure activity (abnormal eye movements, jerking of the extremities, and tongue thrusting). Is there a bulging fontanel, any lethargy? Check for edema, a sign of volume overload (renal failure, congestive heart failure). Decreased skin turgor and dry mucous membranes are seen in dehydration. Is the infant in shock? Does the infant have genital hyperpigmentation (congenital adrenal hyperplasia)? Is there virilization or ambiguous genitalia in a female infant or hypospadias in a male (3-β-hydroxysteroid dehydrogenase deficiency)?

3. Laboratory studies

   1. Specific tests

      1. Serum sodium and osmolality

      2. Urine spot sodium, osmolality, and specific gravity

      3. Serum electrolytes, creatinine, and total protein to assess renal function

   2. See Table 64–1 for diagnosis specific laboratory results

      1. Volume overload (dilutional hyponatremia)

         1. Excess IV fluids. Increased urine output and decreased urine osmolality and (decreased) low specific gravity.

         2. Other (congestive heart failure or paralysis with fluid retention). Decreased urine output and increased urine specific gravity.

      2. Increased sodium losses

         1. Renal losses, with diuretics and adrenal insufficiency. Increased urine output and urine Na+ and decreased urine osmolality and specific gravity.

         2. Skin and GI losses and with third spacing. Decreased urine output and sodium and increased urine osmolality and specific gravity.

      3. SIADH. The diagnosis is made by documenting the following on simultaneous laboratory studies: low urine output, urine osmolality greater than serum osmolality, low serum sodium level and low serum osmolality, and high urinary sodium level and high specific gravity. A plasma ADH concentration and a plasma concentration of atrial natriuretic peptide can be obtained. If they show a high ADH concentration in the presence of low serum osmolality and elevated urinary osmolality, the diagnosis is confirmed.

4. Imaging and other studies. None usually needed. Ultrasound of the head or brain magnetic resonance imaging (MRI) may reveal IVH as a cause of hyponatremia secondary to SIADH.

Treatment is essential, and effort should be made to keep sodium in the normal range especially in the preterm infant, as hyponatremia can cause future problems.

1. Emergency measures. If the infant is having hyponatremia-induced seizures as a result of low sodium (usually <120 mEq/dL), hypertonic saline solution (3% sodium chloride) should be given. Hyponatremic seizures usually stop with a correction of only 3–5 mEq/L. Rapid corrections (especially in chronic hyponatremia or a >8 mEq/L increase in serum sodium over 24 hours) can cause brain damage (central pontine myelinolysis). Suspect this in a neonate who, in the course of the correction, develops cranial nerve dysfunction and quadriparesis. MRI shows a round lesion in the central pontine area. Once symptoms resolve and the serum sodium is >120 mEq/dL, a slow correction can be given over 24 hours (not to exceed 8 mEq/L/d). There is controversy regarding the rate and how it should be given. Follow institutional guidelines.

   1. IV push over 15 minutes (1–3 mL/kg of 3% NaCl [513 mEq of sodium/L]). This method should be reserved for those patients who have seizures, those with repeated apnea requiring intubation, or refractory status epilepticus from hyponatremia (controversial).

   2. Hourly correction. 2 mL/kg/h of 3% NaCl can be given (should raise the sodium concentration by 2 mmol/L/h) until the sodium is >120 mmol/L.

   3. 24-hour correction. The total body deficit can be calculated (see below) and half of that is given over 12–24 hours.

   4. Anticonvulsant therapy. Medication should be considered if seizures persist after 3% normal saline is given. Note: Use of anticonvulsants may not be effective and can be associated with apnea.

2. General management. Always treat the underlying disorder.

   1. Hyponatremia with hypervolemia. Sodium and water restriction.

   2. Hyponatremia with hypovolemia. Volume expansion with sodium and water to replace losses.

   3. Hyponatremia with normal ECF. Water restriction.

3. Specific management

   1. Volume overload (dilutional hyponatremia). Treated with fluid restriction. The total maintenance fluids can be decreased by 20 mL/kg/d, and serum sodium levels should be monitored every 6–8 hours. The underlying cause must be investigated and treated.

   2. Inadequate sodium intake

      1. The maintenance sodium requirement for term infants is 2–4 mEq/kg/d and higher in premature infants. Calculate the amount of sodium the patient is receiving, using the equations in Chapter 9. Readjust the IV sodium intake if it is the cause of hyponatremia.

      2. If the infant is receiving oral formula only, check the formula being used. Low-sodium formulas such as Similac PM 60/40 or breast milk (which is low in sodium) may contribute to hyponatremia. Use of supplemental sodium chloride or a formula with higher sodium content may be necessary.

      3. Calculate the total sodium deficit using the following equation. The result will be the amount of sodium needed to correct the hyponatremia. Usually, only half of this amount is given over 12–24 hours.

         (Desired sodium [130–135 mEq/L] – Infant's sodium value) × (Weight [kg] × 0.6) = Total sodium deficit

   3. Increased sodium losses. Treat the underlying cause and increase the sodium administered to replace the losses.

   4. Drug-induced hyponatremia. If a renal salt-wasting medication such as furosemide is being given, serum sodium levels will be low even though an adequate amount of sodium is being given in the diet. An increase in sodium intake may be required, as is often the case in infants with BPD/CLD who are receiving diuretics. Most are also receiving oral feedings, so an oral sodium chloride supplement can be used. Start with 1 mEq 3 times per day with feedings and adjust as needed. Some infants may require 12–15 mEq/d. Sodium levels should be kept in the low 130s because higher levels may result in fluid retention when diuretics are used. Indomethacin-induced hyponatremia is treated with fluid restriction.

   5. SIADH. The cause of SIADH is usually obvious; if it is not, further investigation is needed (eg, ultrasonography of the head or chest radiograph to rule out lung disease). During treatment, monitor the serum sodium, osmolality, and urine output to determine whether the patient is responding.

      1. Seizures present or serum sodium is <120 mEq/L

         1. Hypertonic saline solution (3% sodium chloride). See Section V.A.

         2. Lasix. 1 mg/kg IV every 6 hours.

         3. Anticonvulsant therapy can be considered (controversial). A case report successfully used phenytoin for a neonate with SIADH and refractory hyponatremic seizures.

         4. Fluid restriction. Usually 40–60 mL/kg/d free water.

      2. Serum sodium is >120 mEq/L without seizures:

         1. Fluid restriction. Usually 40–60 mL/kg/d. This regimen does not allow for fluid loss that accompanies the use of a radiant warmer or phototherapy.

         2. Lasix can also be used.