The management of paracetamol poisoning Khairun Nain Bin Nor Aripin Imti Choonara Abstract Paracetamol poisoning is a common presentation in paediatrics. Toxicity may cause hepatocellular injury, in certain cases progressing to fulminant liver failure. Young children appear less at risk of hepatotoxicity due to an increased metabolic capacity for paracetamol. A single dose of 150 mg/kg can cause hepatocellular damage. Children who ingest multiple supra- therapeutic doses can accumulate significant concentrations and may suffer worse outcomes. Older children who intentionally overdose may also suffer worse outcomes, especially those who present late. The risk of hepatotoxicity after a single overdose can be predicted using a widely used nomogram, although it was derived from adult data. The corner- stone of management is administering the antidote N-acetylcysteine when hepatotoxicity is likely to occur. The National Poisons Information Service is available to be consulted at all hours. When severe poisoning is suspected, the child may require referral to a liver unit in view of possible liver transplantation. Keywords children; drug metabolism; paracetamol; toxicity Introduction The analgesic and antipyretic properties of paracetamol were first described in 1893. It was shown to be an effective antipyretic in children in 1956 and since the 1960s, it has been widely available as a non-prescription drug, with a therapeutic profile that reflects widespread safety and efficacy. Following the discovery of an association between aspirin and Reye’s syndrome in the 1980s, paracetamol became the most widely used analgesic and anti- pyretic in children. It is the most frequently used over-the- counter medicine in young children and is nearly universally used in infants. The drug is used by millions of children every day. Epidemiology On the other hand, paracetamol is one of the most common causes of poisoning in the developed world. Paracetamol poisoning is the leading subject of inquiries to poison centres in the US, UK and Australasia. It is the single most commonly taken drug in overdose in the UK, accounting for half of all admissions for poisoning and an estimated 100e200 deaths per year. In the US, the FDA reports that there are about 112,000 poisoning calls, 56,000 emergency department (ED) visits, 26,000 hospitalisations and over 450 deaths annually associated with paracetamol poisoning. FDA statistics also show that children aged 16 years or younger account for about 33% of ED visits, 24% of hospitalisations but only between 1e3% of mortality related to paracetamol overdose. Paracetamol toxicity primarily manifests in the liver, and paracetamol overdose is the most common apparent cause of acute liver failure in the UK and Western countries. Paracetamol poisoning in the paediatric age group can be divided into three major groups with differing demographic and clinical characteristics. These are intentional self-poisoning, accidental paediatric ingestion and poisoning due to repeated supratherapeutic dosings of paracetamol. Rumack and Matthew’s landmark review in 1975 brought attention to paracetamol poisoning in children. In 1984, Rumack described a cohort of 417 children, aged 5 years or younger, who had ingested potentially toxic amounts of paracetamol. Only three children had altered liver enzymes and all recovered with treatment with no fatalities in the cohort. Thus, it was accepted that in general, young children with accidental single exposures to paracetamol overdoses were less at risk of developing toxic reactions and subsequent morbidity and mortality than adoles- cents or adults. A study of 140 children admitted to a hospital in Scotland reported only one case (a 13 year old girl) of hepatotoxicity. The majority of the children were less than 5 years old (Table 1). Following early case reports, there has been growing concern regarding children developing toxicity after receiving repeated supratherapeutic doses of paracetamol. A Californian case series of 73 overdoses included 63 cases of intentional poisoning. The remaining 10 cases where the overdoses were unintentional were in children under 10 years of age who had been given multiple supratherapeutic doses. Eight out of the 10 developed hepato- toxicity and encephalopathy resulting in one death and three liver transplants. Another American study of children under the age of 10 years described 24 deaths occurring in a cohort of 47 young children. The vast majority of these children experienced repeated para- cetamol overdoses and these findings are in contrast to the cohort originally described by Rumack in the same country. In an Australian review of 18 children with fulminant hepatic failure, unintentional recurrent overdose was presumed to have caused the liver failure in 11 children, aged below 11 years of age. Alander et al. reviewed all presentations of paracetamol poisoning to two regional children’s hospitals in the US over a 10 year period. They found that out of 322 paediatric para- cetamol overdoses, intentional and unintentional overdoses occurred with a similar frequency. Intentional overdoses occurred in older children and adolescents ranging between 11 to 17 years old (median age, 14 years), while unintentional overdoses occurred in children with a median age of 2 years old. Only one out of the 172 young children who unintentionally ingested an overdose of paracetamol developed hepatotoxicity. 10 children presented after ingesting repeated supratherapeutic doses and one of the 10 developed hepatotoxicity. In this case series, all four cases of liver failure and one death occurred in older children who intentionally overdosed on paracetamol. Khairun Nain Bin Nor Aripin MBChB MSc is Postgraduate Student at University of Nottingham, Derbyshire Children’s Hospital, Derby, UK. Imti Choonara MBChB MD is Professor of Child Health at University of Nottingham, Derbyshire Children’s Hospital, Derby, UK. SYMPOSIUM: ACCIDENTS AND POISONING PAEDIATRICS AND CHILD HEALTH 19:11 492 Ó 2009 Elsevier Ltd. All rights reserved.