title: Acute liver failure in a term neonate after repeated paracetamol administration.
abstract: OBJECTIVE
  Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate.
  
  
  METHODS
  A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1 mEq/L), hypoglycemia (18 mg/dL), increased serum aminotransferase activity (AST=4,039 IU/L; ALT=1,087 IU/L) and hyperbilirubinemia (total: 9.57 mg/dL; direct: 6.18 mg/dL) after receiving oral paracetamol (10 mg/kg/dose every 4 hours) for three consecutive days (total dose around 180 mg/kg; serum concentration 36-48 hours after the last dose of 77 µg/ mL). Apart from supportive measures, the patient was successfully treated with intravenous N-acetylcysteine infusion during 11 consecutive days, and was discharged on day 34. The follow-up revealed full recovery of clinical and of laboratory findings of hepatic function.
  
  
  CONCLUSIONS
  The paracetamol pharmacokinetics and pharmacodynamics in neonates and infants differ substantially from those in older children and adults. Despite the reduced rates of metabolism by the P-450 CYP2E1 enzyme system and the increased ability to synthesize glutathione--which provides greater resistance after overdoses--, it is possible to produce hepatotoxic metabolites (N-acetyl-p-benzoquinone) that cause hepatocellular damage, if glutathione sources are depleted. Paracetamol clearance is reduced and the half-life of elimination is prolonged. Therefore, a particular dosing regimen should be followed due to the toxicity risk of cumulative doses. This report highlights the risk for severe hepatotoxicity in neonates after paracetamol multiple doses for more than two to three days.
authors.affiliation: Departamento de Pediatria, Faculdade de Ciencias Medicas, Unicamp, Campinas, SP, Brasil.
authors.forename: Fábio
authors.initials: F
authors.lastname: Bucaretchi
authors.affiliation: Centro de Controle de Intoxicacoes, Faculdade de Ciencias Medicas, Unicamp, Campinas, SP, Brasil.
authors.forename: Carla Borrasca
authors.initials: CB
authors.lastname: Fernandes
authors.affiliation: Centro de Controle de Intoxicacoes, Faculdade de Ciencias Medicas, Unicamp, Campinas, SP, Brasil.
authors.forename: Maíra Migliari
authors.initials: MM
authors.lastname: Branco
authors.affiliation: Departamento de Clinica Medica, Faculdade de Ciencias Medicas, Unicamp, Campinas, SP, Brasil.
authors.forename: Eduardo Mello
authors.initials: EM
authors.lastname: De Capitani
authors.affiliation: Departamento de Farmacologia, Faculdade de Ciencias Medicas, Unicamp, Campinas, SP, Brasil.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hyslop
authors.affiliation: Unidade de Terapia Intensiva Neonatal, Hospital da Mulher Professor Doutor Jose Aristodemo Pinotti, Unicamp, Campinas, SP, Brasil.
authors.forename: Jamil Pedro S
authors.initials: JP
authors.lastname: Caldas
authors.affiliation: Unicamp, Campinas, SP, Brasil.
authors.forename: Carolina Araújo
authors.initials: CA
authors.lastname: Moreno
authors.affiliation: Departamento de Pediatria, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil.
authors.forename: Gilda
authors.initials: G
authors.lastname: Porta
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects*; D058633:Antipyretics / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007231:Infant, Newborn; D017114:Liver Failure, Acute / Q000139:chemically induced*; D008297:Male
chemical_list: D058633:Antipyretics; D000082:Acetaminophen