title: Early predictors of severe acetaminophen-induced hepatotoxicity in a paediatric population referred to a tertiary paediatric department.
abstract: OBJECTIVE
  The data on severe acetaminophen-induced hepatotoxicity in children are very limited. This study explored the dose-response relationship between ingested acetaminophen and hepatotoxicity, the early biochemical and clinical predictors of hepatotoxicity, the impact of early N-acetylcysteine treatment on hepatotoxicity and the incidence of nephrotoxicity.
  
  
  METHODS
  We carried out a retrospective case study on 25 children aged 11-16 years with severe acetaminophen poisoning.
  
  
  RESULTS
  Initial biochemical parameters predicted hepatotoxicity, defined as the maximum levels of the international normalised ratio (INR) and alanine aminotransferase (ALT). Significant relationships were found between: (1) the maximal INR and, for example, the initial bilirubin (p = 0.0003) and initial phosphate (p = 0.003), (2) the maximal ALT and, for example, the initial INR (p = 0.0003) and initial creatinine (p = 0.002), (3) the number of prehospital vomiting episodes and, for example, the maximal INR (p = 0.013) and maximum ALT (p = 0.0005) and (4) the time of N-acetylcysteine initiation and, for example, maximum ALT (p = 0.001) and maximum gamma-glutamyl transferase (GGT) (p = 0.007). The incidence of nephrotoxicity was 12%. There was no significant relationship between the amount of ingested acetaminophen and the degree of hepatotoxicity.
  
  
  CONCLUSIONS
  Paediatric patients at increased risk of severe hepatotoxicity were identified by early biochemical parameters, prehospital vomiting episodes and latency time before N-acetylcysteine initiation.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Nordsjaellands Hospital, Hillerød, Denmark.
authors.forename: Rikke Lindgaard
authors.initials: RL
authors.lastname: Hedeland
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Nordsjaellands Hospital, Hillerød, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Andersen
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Nordsjaellands Hospital, Hillerød, Denmark.
authors.forename: Natasha
authors.initials: N
authors.lastname: Askbo
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Nordsjaellands Hospital, Hillerød, Denmark.
authors.forename: Amne
authors.initials: A
authors.lastname: Iskandar
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Marianne Hørby
authors.initials: MH
authors.lastname: Jørgensen
mesh_terms: D000082:Acetaminophen / Q000506:poisoning*; D000111:Acetylcysteine / Q000627:therapeutic use; D000293:Adolescent; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000209:etiology*; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D006748:Hospital Departments; D006801:Humans; D008297:Male; D010372:Pediatrics; D012017:Referral and Consultation; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013406:Suicide, Attempted; D062606:Tertiary Care Centers; D013997:Time Factors
chemical_list: D000082:Acetaminophen; D000111:Acetylcysteine
keywords: Acetaminophen; Hepatotoxicity; Liver failure; N-acetylcysteine; Nephrotoxicity