Overview

Definition:
-Electrolyte disturbances in preterm infants, particularly sodium balance, are common due to immature renal function, increased insensible water losses, and therapeutic interventions like diuretics
-Sodium is critical for extracellular fluid volume, osmotic pressure, and acid-base balance
-Diuretics, often used for conditions like patent ductus arteriosus (PDA) or fluid overload, can significantly impact sodium homeostasis.
Epidemiology:
-Hyponatremia is the most frequent electrolyte abnormality in preterm infants, affecting up to 50% of very low birth weight (VLBW) neonates
-Hypernatremia is less common but carries higher morbidity
-Diuretic use, especially in VLBW infants for PDA or pulmonary edema, is associated with a higher incidence of both hyponatremia and hypernatremia.
Clinical Significance:
-Improper management of sodium balance and diuretic therapy in preterms can lead to serious complications, including neurological deficits (seizures, cerebral palsy), growth restriction, renal injury, and increased mortality
-Understanding these dynamics is vital for optimizing fluid and electrolyte management and improving outcomes for these vulnerable infants.

Sodium Balance In Preterms

Renal Immaturity:
-Immature renal tubules have reduced capacity for sodium reabsorption, leading to significant sodium wasting, especially in early postnatal life
-Glomerular filtration rate (GFR) and tubular function mature gradually.
High Insensible Losses:
-Preterm infants have a large surface area to volume ratio and thin stratum corneum, resulting in high transepidermal water losses
-This can lead to relative hypernatremia if fluid intake is insufficient to compensate for water losses.
Hormonal Influences:
-Antidiuretic hormone (ADH) regulation is immature, affecting water balance
-Aldosterone production is also less efficient, contributing to sodium loss.
Nutritional Factors:
-Early enteral feeds may be low in sodium
-Parenteral nutrition formulations require careful adjustment of sodium content to meet needs
-Breast milk sodium content can vary.
Therapeutic Interventions: Diuretics, fluid resuscitation, and certain medications can profoundly affect sodium levels, requiring close monitoring.

Hyponatremia In Preterms

Definition And Types:
-Hyponatremia is defined as serum sodium < 135 mEq/L
-It can be further classified as isotonic (rare), hypotonic (most common), or hypertonic
-Hypotonic hyponatremia is typically due to excessive free water retention or sodium loss.
Causes:
-Excessive free water intake
-Renal sodium wasting (immature tubules, diuretic use)
-Syndrome of Inappropriate Antidiuretic Hormone (SIADH) (rare in neonates but can be iatrogenic)
-Vomiting or nasogastric losses without adequate sodium replacement.
Clinical Presentation:
-Mild hyponatremia may be asymptomatic
-Symptoms are often non-specific: lethargy
-Irritability
-Poor feeding
-Hypotonia
-Vomiting
-Seizures (severe hyponatremia)
-Cerebral edema with rapid correction.
Diagnostic Approach:
-Review fluid intake and output
-Assess for signs of dehydration or fluid overload
-Serum electrolytes (sodium, potassium, chloride, bicarbonate)
-Urine electrolytes and osmolality
-Assess for underlying causes like PDA or infection.

Hypernatremia In Preterms

Definition And Types:
-Hypernatremia is defined as serum sodium > 145 mEq/L
-It is usually hypertonic and reflects a deficit of free water relative to sodium.
Causes:
-Insensible water losses exceeding intake (high ambient temperature, radiant warmers, phototherapy, tachypnea)
-Insufficient fluid intake
-Diuretic therapy (especially thiazides or loop diuretics)
-Osmotic diuresis (e.g., from excessive protein or glucose administration)
-Inadequate sodium supplementation in preterm formula.
Clinical Presentation:
-Irritability
-High-pitched cry
-Lethargy
-Muscle twitching
-Fever
-Dry mucous membranes
-Poor skin turgor
-Fontanelle may be sunken
-Severe hypernatremia can lead to lethargy, coma, seizures, intracranial hemorrhage, and death.
Diagnostic Approach:
-Careful assessment of fluid balance (insensible losses, intake)
-Review all fluid and electrolyte orders
-Serum electrolytes
-Urine specific gravity and osmolality
-Assess for underlying conditions contributing to water loss.

Diuretics And Sodium Balance

Common Diuretics Used:
-Furosemide (loop diuretic): inhibits Na-K-2Cl cotransporter in the thick ascending limb of Henle's loop, leading to significant sodium, potassium, and chloride excretion
-Thiazide diuretics (e.g., hydrochlorothiazide): inhibit Na-Cl cotransporter in the distal convoluted tubule
-less potent than loop diuretics but can cause significant sodium and potassium loss
-Spironolactone (potassium-sparing): acts as an aldosterone antagonist
-used cautiously due to risk of hyperkalemia and to counteract other diuretic-induced potassium losses.
Indications In Preterms:
-Management of fluid overload (pulmonary edema, ascites)
-Closure of PDA (primarily furosemide in conjunction with indomethacin/ibuprofen)
-Treatment of respiratory distress syndrome (RDS) with severe atelectasis.
Impact On Sodium:
-Furosemide and thiazides can exacerbate sodium wasting, leading to hyponatremia
-They can also impair the kidney's ability to concentrate urine, potentially contributing to water retention and hyponatremia if free water intake is not carefully controlled
-Paradoxically, in conditions of severe dehydration or excessive water intake, diuretics can unmask or worsen hypernatremia by promoting water loss.
Monitoring During Diuretic Therapy:
-Frequent monitoring of serum electrolytes (sodium, potassium), renal function (BUN, creatinine), and fluid balance is essential
-Monitor urine output and urine electrolytes
-Assess for clinical signs of hyponatremia or hypernatremia.

Management Principles

General Approach:
-Management is guided by the specific electrolyte disturbance, its severity, and the underlying cause
-Gradual correction is crucial to prevent complications like osmotic demyelination syndrome (with rapid correction of hyponatremia) or cerebral edema (with rapid correction of hypernatremia).
Hyponatremia Management:
-Mild, asymptomatic hyponatremia: Fluid restriction
-Assess and correct underlying causes (e.g., optimize fluid intake if sodium wasting is the primary issue)
-Symptomatic or severe hyponatremia: Careful, slow intravenous correction with hypertonic saline (e.g., 3% NaCl) targeting a rise of no more than 0.5 mEq/L/hr or 10-12 mEq/L over 24 hours
-Avoid rapid correction to prevent central pontine myelinolysis
-Consider oral salt supplementation if feeds are tolerated.
Hypernatremia Management:
-Gradual free water replacement is key
-Intravenous fluids with low sodium concentration (e.g., D5W or D10W) or hypotonic saline (e.g., 0.45% NaCl)
-Target a reduction of no more than 10-12 mEq/L/day to prevent cerebral edema
-Monitor neurological status closely
-If due to excessive insensible losses, address the environmental factors (e.g., humidity, temperature).
Diuretic Adjustment:
-Consider reducing the dose or discontinuing diuretics if electrolyte disturbances are severe and attributable to their use
-If diuretics are essential, use the lowest effective dose and monitor electrolytes closely
-Co-administration of potassium-sparing diuretics like spironolactone may sometimes be considered to mitigate potassium losses and potentially improve sodium retention, but requires careful monitoring for hyperkalemia.

Key Points

Exam Focus:
-Preterm infants have immature kidneys predisposing to sodium wasting
-Diuretics, particularly furosemide, are a major iatrogenic cause of electrolyte imbalances
-Hyponatremia is common
-hypernatremia is less common but more dangerous
-Gradual correction of both hyponatremia and hypernatremia is paramount to avoid neurological complications.
Clinical Pearls:
-Always calculate total fluid intake and output, including insensible losses, when assessing electrolyte status
-Monitor urine sodium concentration to differentiate renal from extra-renal sodium losses
-Consider the timing and type of fluid administration in relation to diuretic use
-Be cautious with free water boluses in hypernatremic infants, especially if there is suspicion of rapid onset.
Common Mistakes:
-Over-vigorous free water administration leading to hyponatremia or cerebral edema
-Rapid correction of severe hyponatremia leading to osmotic demyelination syndrome
-Failure to account for insensible water losses in preterm infants
-Inadequate monitoring of electrolytes and fluid balance during diuretic therapy.