What is the next best step for a 6-day-old preterm infant, born at 34 weeks of gestation, with lethargy and severe hyperbilirubinemia (bilirubin level of 380), who has failed phototherapy?

Exchange Transfusion is Indicated

For this 6-day-old preterm infant (34 weeks) with severe hyperbilirubinemia (380 µmol/L ≈ 22 mg/dL) and lethargy who has failed phototherapy, exchange transfusion (Option B) is the next step. 1, 2

Why Exchange Transfusion is Required

• Lethargy is a warning sign of acute bilirubin encephalopathy, which requires immediate exchange transfusion regardless of bilirubin level 1, 2
• The presence of altered feeding patterns, lethargy, high-pitched crying, hypotonia/hypertonia, opisthotonus, or retrocollis mandates immediate exchange transfusion 1, 2
• Phototherapy failure (bilirubin not declining despite intensive phototherapy) is a clear indication to escalate to exchange transfusion 1, 3, 2

Critical Context for This Case

• At 34 weeks gestation, this infant is at higher neurotoxicity risk with lower thresholds for intervention 1
• For sick infants or those <38 weeks gestation with TSB ≥20 mg/dL, blood type and crossmatch should already be obtained in preparation for exchange transfusion 1
• Exchange transfusion should proceed if TSB is not decreasing or continues moving closer to exchange transfusion threshold 2

Why Other Options Are Inadequate

• Phenobarbital (Option A): Not indicated for acute management of severe hyperbilirubinemia with neurological signs; this is used for chronic cholestatic conditions, not acute unconjugated hyperbilirubinemia 1
• IV fluids (Option C): While IV hydration is part of the escalation protocol for TSB ≥25 mg/dL, it is an adjunct measure, not definitive treatment when phototherapy has already failed and neurological signs are present 2
• Antibiotics (Option D): Only indicated if sepsis is suspected as an underlying cause; this does not address the immediate life-threatening hyperbilirubinemia 1

Concurrent Supportive Measures

While preparing for exchange transfusion:

• Maximize intensive phototherapy with special blue light (430-490 nm) at ≥30 μW/cm²/nm over maximum body surface area 1, 2
• Initiate IV hydration as part of escalation protocol 2
• Continue feeding every 2-3 hours with supplementation if needed to inhibit enterohepatic circulation 1, 2
• Monitor TSB every 2 hours during this critical period 2

Important Caveats

• Exchange transfusion carries a mortality risk of approximately 3 per 1,000 procedures and significant morbidity in 5% of cases, but is life-saving when acute bilirubin encephalopathy is present 1, 4
• The expected bilirubin decline with effective intensive phototherapy is at least 0.5-1 mg/dL per hour in the first 4-8 hours; failure to achieve this indicates phototherapy failure 1, 3
• Do not delay exchange transfusion when neurological signs are present—this is a medical emergency 2