What drug causes grey baby syndrome?

Chloramphenicol Causes Grey Baby Syndrome

Chloramphenicol is the drug that causes grey baby syndrome, a potentially fatal toxic reaction occurring primarily in premature infants and neonates who receive excessive doses or have impaired drug metabolism. 1, 2

Mechanism and Clinical Presentation

Grey baby syndrome results from chloramphenicol toxicity due to:

• Immature hepatic glucuronyl transferase enzyme systems in neonates, leading to impaired drug metabolism and accumulation of toxic serum levels 2, 3
• Inadequate renal excretion of unconjugated chloramphenicol in premature and newborn infants 3

The syndrome typically manifests with a characteristic progression of symptoms 2:

1. Abdominal distension with or without vomiting (initial presentation)
2. Progressive pallid cyanosis (the characteristic "grey" appearance)
3. Vasomotor collapse with irregular respiration
4. Death within hours if untreated

High-Risk Populations

Grey baby syndrome occurs most commonly in 1, 2:

• Premature infants (highest risk group)
• Neonates in the first 48 hours of life when therapy is initiated
• Infants receiving doses >200 mg/day 1
• One case reported in a 3-month-old infant 2
• One case in a neonate born to a mother receiving chloramphenicol during labor 2

Toxic Serum Levels

Grey baby syndrome is associated with 4, 5:

• Peak serum concentrations of 28-180 mg/L in symptomatic patients (therapeutic range: 15-25 mg/L) 4
• Trough concentrations of 19-47 mg/L 4
• Symptoms typically appear after 3-4 days of high-dose therapy 2

Prevention Strategies

To avoid grey baby syndrome 1, 4, 5:

• Limit dosing to 25 mg/kg/day in preterm and term infants during the first week of life 5
• Use 37.5-50 mg/kg/day for older term babies 5
• Monitor serum levels at 48-hour intervals to maintain concentrations between 15-25 mg/L 4, 5
• Decrease dose when trough levels exceed 15 mg/L or peak levels exceed 30 mg/L 5
• Terminate therapy immediately upon early evidence of symptoms—this frequently reverses the process with complete recovery 2

Clinical Context for Use

Despite this serious toxicity, chloramphenicol remains indicated for specific situations 1:

• Plague meningitis in neonates (because it penetrates the blood-brain barrier) 1
• RMSF during third trimester pregnancy when other options are unavailable, though care must be taken near term 1
• Breastfeeding mothers with plague require infant monitoring for gastrointestinal distress and blood dyscrasias, though grey baby syndrome only occurs with direct infant doses >200 mg/day 1

Important Caveats

• Chloramphenicol should be avoided in neonates whenever alternatives exist 1
• The syndrome is dose-related and preventable with appropriate dosing and monitoring 4, 3
• Higher mortality occurs with accelerated symptom progression at higher doses 2
• Chloramphenicol also carries risk of dose-independent aplastic anemia (estimated 1:24,200 to 1:40,500 courses), though this has never been reported in nursing infants of treated mothers 1, 3