Gray baby syndrome
| Gray baby syndrome | |
|---|---|
| Other names | Grey baby syndrome, gray syndrome, grey syndrome |
hepatic failure, anemia, kernicterus, death | |
| Usual onset | Neonates |
| Causes | Accumulation of chloramphenicol |
| Diagnostic method | proper history taking, monitoring blood level of the drug |
Gray baby syndrome (also termed gray syndrome or grey syndrome) is a rare but serious, even fatal, side effect that occurs in newborn infants (especially
Signs and symptoms
Since the syndrome is due to the accumulation of chloramphenicol, the signs and symptoms are dose related.[10] According to Kasten's review published in the Mayo Clinic Proceedings, a serum concentration of more than 50 μg/mL is a warning sign,[10] while Hammett-Stabler and John states that the common therapeutics peak level is 10-20 μg/mL and is expected to achieve after 0.5-1.5 hours of intravenous administration in their review of antimicrobial drugs.[11] The common onset of signs and symptoms are 2 to 9 days after the initiation of the medication, which allows the serum concentration to build up to reach the toxic concentration above. Common signs and symptoms include loss of appetite, fussiness, vomiting, ashen gray color of the skin, hypotension (low blood pressure), cyanosis (blue discoloration of lips and skin), hypothermia, cardiovascular collapse, hypotonia (muscle stiffness), abdominal distension, irregular respiration, and increased blood lactate.[6]
Pathophysiology
Two pathophysiologic mechanisms are thought to play a role in the development of gray baby syndrome after exposure to chloramphenicol. This condition is due to a lack of glucuronidation reactions occurring in the baby (phase II hepatic metabolism), thus leading to an accumulation of toxic chloramphenicol metabolites:[12]
- Metabolism: The UDP-glucuronyl transferase enzyme system in infants, especially premature infants, is not fully developed and incapable of metabolizing the excessive drug load needed to excrete chloramphenicol.[6]
- Elimination: Insufficient renal excretion of the unconjugated drug.
Insufficient metabolism and excretion of chloramphenicol leads to increased blood concentrations of the drug, causing blockade of the electron transport of the liver, myocardium, and skeletal muscles. Since the electron transport is an essential part of cellular respiration, its blockade can result in cell damage. In addition, the presence of chloramphenicol weakens the binding of bilirubin and albumin, so increased levels of the drug can lead to high levels of free bilirubin in the blood, resulting in brain damage or kernicterus.[6] If left untreated, possible bleeding, renal (kidney) and/or hepatic (liver) failure, anemia, infection, confusion, weakness, blurred vision, or eventually death are expected. Additionally, chloramphenicol is significantly insoluble due to an absence of acidic and basic groups in its molecular compound. As a result, larger amounts of the medication are required to achieve the desired therapeutic effect. High volumes of a medication that can cause various toxicities is another avenue how chloramphenicol can potentially lead to grey baby syndrome.[13]
Diagnosis
Gray baby syndrome should be suspected in a new born with abdominal distension, progressive pallid cyanosis, irregular respirations, and refusal to breastfeed. The cause of gray baby syndrome can come from the direct use of intravenous or oral chloramphenicol in neonates.[6] Direct chronological relation between the use of the medication and signs and symptoms of the syndrome should be found in the previous medical history. In terms of the possible route of chloramphenicol, gray baby syndrome may not come from the mother's use of chloramphenicol during pregnancy or breastfeeding. According to the Drug and Lactation database (LactMed), it states that "milk concentrations are not sufficient to induce gray baby syndrome".[14] It is also reported that the syndrome may not develop in infants when their mothers use the medication in their late period of pregnancy.[15] According to the Oxford Review, chloramphenicol given to mothers during their pregnancy did not result in gray baby syndrome, but was caused by infants receiving supra-therapeutic doses of chloramphenicol after birth.[16] The presentation of symptoms can depend on the level of exposure of the drug to the baby, given its dose-related nature. A broad diagnosis is usually needed for babies who present with cyanosis. To support the diagnosis, blood work should be done to determine the level of serum chloramphenicol, and to further evaluate chloramphenicol toxicity, a complete blood panel including levels of serum ketones, glucose (due to the risk of hypoglycemia), metabolic panel should be completed to help determine if an infant has the syndrome.[6] Other tools used to help with diagnosis include CT scans, ultrasound, and electrocardiogram.[6]
Prevention
Since the syndrome is a side effect of chloramphenicol, the prevention is primarily related to the proper use of the medication. The WHO Model Formulary for Children 2010 recommends to reserve chloramphenicol for life-threatening infections.[15] As well as using chloramphenicol only when necessary, it should also be used in short periods of time to also prevent the potential for toxicity.[4] In particular, this medication should not be prescribed especially in neonates less than one week old due to the significant risk of toxicity. Preterm infants especially should not be administered chloramphenicol.[4] Gray baby syndrome has been noted to be dose-dependent as it typically occurs in neonates who have received a daily dose greater than 200 milligrams.[6]
When chloramphenicol is necessary, the condition can be prevented by using chloramphenicol at the recommended doses and monitoring blood levels,
Treatment
References
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- ^ Werth, Brian J (2020). "Chloramphenicol". MSD Manual Professional Edition. Retrieved 2021-07-30.
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{{cite book}}: CS1 maint: location missing publisher (link - ISBN 9780124080782.
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Further reading
- Krasinski K, Perkin R, Rutledge J (1982). "Gray baby syndrome revisited". Clinical Pediatrics. 21 (9): 571–2. S2CID 31417519.
- Feigin RD, Cherry JD, Demmler-Harrison GJ, Kaplan SL, eds. (2009). "Ch.248. Antibacterial therapeutic agents". Feigin & Cherry's textbook of pediatric infectious diseases (6th ed.). Philadelphia, PA: Saunders/Elsevier. ISBN 978-1-4160-4044-6.