grey baby syndrome
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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
- elevated levels of chloramphenicol circulating in the plasma result
from two distinct pathophysiologic processes
- 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
- 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.
Last edited 03/2019 and last reviewed 06/2022
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