Grey baby syndrome

Chloramphenicol reaches toxic levels more readily and less predictably in neonates, causing cardiovascular collapse. This is referred to as the grey baby syndrome.

• grey baby syndrome is a type of circulatory collapse that can occur in premature and newborn infants and is associated with excessively high serum levels of chloramphenicol
  • elevated levels of chloramphenicol circulating in the plasma result from two distinct pathophysiologic processes
    • a normally functioning liver will metabolize the chloramphenicol parent molecule (primarily by glucuronidation) - however an immature neonatal liver is unable to synthesize and recycle the UDP-glucuronyltransferase enzyme efficiently
    • neonatal kidneys are unable to excrete chloramphenicol and its metabolites efficiently
    • these two deficiencies result in elevated serum levels of chloramphenicol
    • chloramphenicol molecule displaces unconjugated bilirubin from albumin, leading to kernicterus and eventually death if untreated
      
      
• characterized by an ashen-grey color ("grey baby syndrome"), abdominal distention, vomiting, flaccidity, cyanosis, circulatory collapse, and death
  • chloramphenicol parent molecule also displaces unconjugated bilirubin from albumin, giving way to kernicterus and eventually death or permanent neurological sequelae if left untreated
    
    
• usually starts 2 to 9 days after treatment is started
  • syndrome is a result of chloramphenicol impairing myocardial contractility
  • believed to occur more often in neonates due to their diminished ability to conjugate chloramphenicol and to excrete the active form in the urine
  • also been reports in small children and adults that have had accidental overdoses of the drug

Management:

• primarily aimed towards direct removal of the parent chloramphenicol molecule
  • use of modalities such as charcoal hemoperfusion and exchange transfusion
  • also been reports of phenobarbital being used for induction of the UDP-glucuronyltransferase enzyme
  • cardiopulmonary bypass including extracorporeal membrane oxygenation may also be considered

Reference:

• Beninger P. Pharmacovigilance: An Overview. Clin Ther. 2018 Dec;40(12):1991-2004
• Ingebrigtsen SG et al. Old drug, new wrapping - A possible comeback for chloramphenicol? Int J Pharm. 2017 Jun 30;526(1-2):538-546.