title: Paracetamol toxicity: What would be the implications of a change in UK treatment guidelines?
abstract: BACKGROUND
  Treatment of single-time-point ingestion acute paracetamol (acetaminophen) poisoning with N-acetylcysteine (NAC) is guided by plotting a timed plasma paracetamol concentration on established nomograms. Guidelines in the UK differ from those in the U.S. and Australasia by having two treatment lines on the nomogram. Patients deemed to be at 'normal' risk of hepatotoxicity are treated using the treatment line starting at 200 mg/L at 4 h post-ingestion; those at higher risk are treated using the 'high risk' treatment line starting at 100 mg/L at 4 h post-ingestion.
  
  
  OBJECTIVE
  To examine the effect on treatment numbers if UK guidelines were to adopt a single treatment line nomogram or lower, risk-stratified treatment lines.
  
  
  METHODS
  We undertook a retrospective analysis of a series of acute single-time-point paracetamol poisonings presenting to our inner city emergency department. Treatment numbers and effect on treatment costs were modelled for three alternative scenarios: a 150 line-a combined single treatment line starting at a 4 h concentration of 150 mg/L, a 100 line-a combined single treatment line starting at a 4 h concentration of 100 mg/L, and a 150/75 line-a double treatment line at the lower concentrations of 150 mg/L for normal risk and 75 mg/L for high risk patients.
  
  
  RESULTS
  A total of 1,214 cases were identified. Under current UK guidance, 133 (11.0%) high risk cases and 98 (8.1%) normal risk cases needed treatment (total 231, 19.0%). A 150 line would result in 87 (7.2%) high risk cases and 155 (12.8%) normal risk cases needing treatment (total 242, 19.9%). A 100 line would result in 133 (11.0%) high risk and 251 (20.7%) normal risk cases needing treatment (total 384, 31.6%). A 150/75 line would result in 153 (12.6%) high risk and 155 (12.8%) normal risk cases needing treatment (total 308, 25.4%).
  
  
  CONCLUSIONS
  Both a 100 line and a 150/75 line would result in a large increase in the number of patients being treated and an associated increase in the costs of treatment. A single 150 mg/L treatment line would simplify treatment algorithms and lead to a similar number of patients being treated with NAC overall. A potential concern however is whether any of the high risk cases that would no longer be treated might develop significant hepatotoxicity. After consideration of the evidence for dual treatment lines, we feel that these risks are small and that it is worth reconsidering a change of treatment recommendations to a single 150 line.
authors.affiliation: Emergency Department, Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: McQuade
authors.forename: Paul I
authors.initials: PI
authors.lastname: Dargan
authors.forename: Jeff
authors.initials: J
authors.lastname: Keep
authors.forename: David M
authors.initials: DM
authors.lastname: Wood
mesh_terms: D000082:Acetaminophen / Q000037:antagonists & inhibitors / Q000097:blood* / Q000493:pharmacokinetics / Q000506:poisoning*; D000111:Acetylcysteine / Q000191:economics / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000037:antagonists & inhibitors / Q000097:blood* / Q000493:pharmacokinetics / Q000506:poisoning*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000191:economics / Q000517:prevention & control* / Q000628:therapy; D015331:Cohort Studies; D016527:Drug Costs; D062787:Drug Overdose; D004636:Emergency Service, Hospital; D016166:Free Radical Scavengers / Q000191:economics / Q000627:therapeutic use*; D017048:Health Care Costs; D006786:Hospitals, Urban; D006801:Humans; D008131:London; D017410:Practice Guidelines as Topic; D012189:Retrospective Studies; D012306:Risk; D018570:Risk Assessment; D006113:United Kingdom
chemical_list: D018712:Analgesics, Non-Narcotic; D016166:Free Radical Scavengers; D000082:Acetaminophen; D000111:Acetylcysteine