title: An assessment of the variation in the concentration of acetylcysteine in infusions for the treatment of paracetamol overdose.
abstract: Intravenous acetylcysteine is the treatment of choice for paracetamol poisoning. A previous UK study in 2001 found that 39% of measured acetylcysteine infusion concentrations differed by >20% from anticipated concentrations. In 2012, the UK Commission on Human Medicines made recommendations for the management of paracetamol overdose, including provision of weight-based acetylcysteine dosing tables. The aim of this study was to assess variation in acetylcysteine concentrations in administered infusions following the introduction of this guidance.
  
  
  
  A 6-month single-centre prospective study was undertaken at a UK teaching hospital. After preparation, 5-ml samples were taken from the first, second and third/any subsequent acetylcysteine infusions. Acetylcysteine was measured in diluted (1:50) samples by high-performance liquid chromatography. Comparisons between measured and expected concentrations based on prescribed weight-based dose and volume were made for each infusion.
  
  
  
  Ninety samples were collected. There was a variation of ≤10% in measured compared to expected concentration for 45 (50%) infusions, of 10-20% for 27 (30%) infusions, 20.1-50% for 14 (16%) infusions and >50% for four (4%) infusions. There was a median (interquartile range) variation in measured compared to expected concentration of -3.6 mg ml-1(-6.7 to -2.3) for the first infusion, +0.2 mg ml-1(-0.9 to +0.4) for the second infusion and -0.3 mg ml-1(-0.6 to +0.2) for third and fourth infusions.
  
  
  
  There has been a moderate improvement in the variation in acetylcysteine dose administered by infusion. Further work is required to understand the continuing variation and consideration should be given to simplification of acetylcysteine regimes to decrease the risk of administration errors.
authors: Clinical Toxicology, Guy's and St. Thomas' NHS Foundation Trust and King's Health Partners, London, UK.|Emergency Department, St. Mary's Hospital, Imperial College NHS Trust, London, UK.
authors: George P
authors: GP
authors: Bailey
authors: Clinical Toxicology, Guy's and St. Thomas' NHS Foundation Trust and King's Health Partners, London, UK.|Faculty of Life Sciences and Medicine, King's College London, London, UK.
authors: David M
authors: DM
authors: Wood
authors: Clinical Toxicology, Guy's and St. Thomas' NHS Foundation Trust and King's Health Partners, London, UK.|Faculty of Life Sciences and Medicine, King's College London, London, UK.
authors: John R H
authors: JR
authors: Archer
authors: Toxicology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
authors: Edmund
authors: E
authors: Rab
authors: Toxicology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.|Toxicology Unit, King's College Hospital NHS Foundation Trust, London, UK.
authors: Robert J
authors: RJ
authors: Flanagan
authors: Clinical Toxicology, Guy's and St. Thomas' NHS Foundation Trust and King's Health Partners, London, UK.|Faculty of Life Sciences and Medicine, King's College London, London, UK.
authors: Paul I
authors: PI
authors: Dargan
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000506:poisoning*; D000111:Acetylcysteine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000506:poisoning*; D000931:Antidotes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D062787:Drug Overdose; D006784:Hospitals, Teaching; D006801:Humans; D007262:Infusions, Intravenous; D011446:Prospective Studies; D006113:United Kingdom
chemical_list: D018712:Analgesics, Non-Narcotic; D000931:Antidotes; D000082:Acetaminophen; D000111:Acetylcysteine
keywords: acetaminophen; acetylcysteine; drug overdose; intravenous infusions; medication errors; paracetamol