How should metabolic acidosis in a preterm infant be evaluated and managed?

Metabolic Acidosis in Preterm Infants: Evaluation and Management

In preterm infants with metabolic acidosis, immediately identify and address the underlying cause—particularly excessive chloride intake from parenteral nutrition, inadequate ventilation, or tissue hypoperfusion—before considering any bicarbonate therapy, which should be reserved only for severe cases (pH <7.2, base deficit >10 mmol/L) after effective ventilation is established. 1, 2

Define Severe Metabolic Acidosis

Severe metabolic acidosis in preterm infants on parenteral nutrition is defined as: 1

• pH < 7.2 with base deficit > 10 mmol/L, OR
• Bicarbonate < 12 mmol/L

Identify the Underlying Cause

Iatrogenic Hyperchloremic Acidosis (Most Common in Preterm Infants on PN)

Excessive chloride intake is the primary iatrogenic cause of metabolic acidosis in preterm infants receiving parenteral nutrition. 1

• High-risk infants include those with large PDA, weight loss >15%, and ELBW 1
• Cumulative chloride intake thresholds that induce acidosis: 1
  • >10 mmol/kg during first 3 days (average 3.3 mmol/kg/day)
  • >45 mmol/kg during first 10 days (average 4.5 mmol/kg/day)

Nutritional Factors

Early aggressive parenteral nutrition with high amino acid and lipid intake increases risk of metabolic acidosis, particularly in the most immature infants (24-26 weeks gestation). 3

• Higher amino acid intake (mean 3.3 g/kg/day) and lipid intake (mean 2.8 g/kg/day) correlate with more severe acidosis (mean BE -8.7) 3
• Gestational age is a significant independent risk factor—smaller infants display greater acidotic disequilibrium 3

Other Causes to Evaluate

• Tissue hypoperfusion/shock: Check for tachycardia, prolonged capillary refill >2 seconds, decreased urine output <1 ml/kg/hour, hypotension 1
• Inadequate ventilation: Ensure effective gas exchange before any other intervention 2, 4
• Hyperkalemia: Non-oliguric hyperkalemia (NOHK) occurs with systemic acidosis, birth asphyxia, lack of antenatal corticosteroids 1
• Renal dysfunction: Distinguish oliguric (urinary K <20 mmol/L) from non-oliguric hyperkalemia (urinary K >20 mmol/L) 1

Management Algorithm

Step 1: Ensure Adequate Ventilation FIRST

Effective ventilation must be established before considering any bicarbonate administration, as sodium bicarbonate produces CO2 that requires adequate ventilation for elimination. 2

• Assess respiratory effort and oxygenation immediately 2
• Provide positive pressure ventilation if needed 2
• Maintain SaO₂ >90% 4

Step 2: Address the Underlying Cause

For Hyperchloremic Acidosis from PN:

Use "chloride-free" sodium and potassium solutions (acetate-based) in preterm infants on PN to reduce the risk of hyperchloremia and metabolic acidosis. 1

• Sodium acetate is efficient and practical for maintaining normal acid-base balance 5
• Acetate in parenteral nutrition provides slow correction to stabilize acid-base status 6
• Alternative: oral citrate for slow correction 6

For Tissue Hypoperfusion/Shock:

• Volume resuscitation with 20 ml/kg bolus of lactated Ringer's solution (preferred over saline) 6
• Lactated Ringer's provides base equivalents while addressing hypovolemia 6

For Nutritional Intolerance:

• Consider reducing amino acid and lipid intake if severe acidosis develops, particularly in extremely preterm infants (24-26 weeks) 3
• Balance nutritional goals against acid-base homeostasis 3

Step 3: Bicarbonate Therapy (Reserved for Severe Cases Only)

Bicarbonate should only be administered for severe metabolic acidosis (pH <7.2, base deficit >10 mmol/L, bicarbonate <12 mmol/L) that persists AFTER adequate ventilation is established and underlying causes are addressed. 1, 2, 4

Dosing:

• 1-2 mEq/kg IV/IO given slowly 2, 4
• Use only 0.5 mEq/mL concentration for newborn infants 2

Critical Caveats:

• Bicarbonate produces CO2, worsening intracellular acidosis without adequate ventilation 2, 4
• No improvement in survival when used during resuscitation 6
• Concerns exist regarding fluctuations in cerebral blood flow and osmolar load with rapid infusions 6

Monitoring

• Monitor arterial blood gases every 2-4 hours during active treatment 4
• Monitor electrolytes (sodium, potassium, ionized calcium) every 2-4 hours during bicarbonate therapy to avoid hypernatremia or hypokalemia 4
• Daily monitoring of serum electrolytes and weight for first days of PN, then adjust based on clinical stability 1
• Calculate chloride-sodium difference (Diff[NaCl]) and Cl-Na ratio as simple bedside tools to identify raised unmeasured anions 7

Common Pitfalls to Avoid

• Never give bicarbonate before ensuring adequate ventilation—this is the most critical error 2, 4
• Don't overlook iatrogenic chloride overload from standard PN formulations—this is preventable 1
• Don't assume all acidosis requires bicarbonate—most cases resolve by addressing the underlying cause 6
• Don't use normal saline for volume boluses—lactated Ringer's is preferred 6
• Don't advance amino acids/lipids too aggressively in the most immature infants without monitoring acid-base status 3