AimsIn September 2012 the UK's Commission on Human Medicines (CHM) recommended changes in the management of paracetamol poisoning: use of a single ‘100 mg l−1’ nomogram treatment line, ceasing risk assessment, treating all staggered/uncertain ingestions and increasing the duration of the initial acetylcysteine (NAC) infusion from 15 to 60 min. We evaluated the effect of this on presentation, admission, treatment, adverse reactions and costs of paracetamol poisoning.MethodsData were prospectively collected from adult patients presenting to three large UK hospitals from 3 September 2011 to 3 September 2013 (year before and after change). Infusion duration effect on vomiting and anaphylactoid reactions was examined in one centre. A cost analysis from an NHS perspective was performed for 90 000 patients/annum with paracetamol overdose.ResultsThere were increases in the numbers presenting to hospital (before 1703, after 1854; increase 8.9% [95% CI 1.9, 16.2], P = 0.011); admitted (1060/1703 [62.2%] vs. 1285/1854 [69.3%]; increase 7.1% [4.0, 10.2], P < 0.001) and proportion treated (626/1703 [36.8%] vs. 926/1854 [50.0%]; increase: 13.2% [95% CI 10.0, 16.4], P < 0.001). Increasing initial NAC infusion did not change the proportion of treated patients developing adverse reactions (15 min 87/323 [26.9%], 60 min 145/514 [28.2%]; increase: 1.3% [95% CI –4.9, 7.5], P = 0.682). Across the UK the estimated cost impact is £8.3 million (6.4 million–10.2 million) annually, with a cost-per-life saved of £17.4 million (13.4 million–21.5 million).ConclusionsThe changes introduced by the CHM in September 2012 have increased the numbers of patients admitted to hospital and treated with acetylcysteine without reducing adverse reactions. A safety and cost-benefit review of the CHM guidance is warranted, including novel treatment protocols and biomarkers in the assessment of poisoning.

Background Acetylcysteine (NAC) is effective at preventing liver injury after paracetamol overdose. The Scottish and Newcastle Anti-emetic Pre-treatment for Paracetamol Poisoning (SNAP) Study demonstrated that a 12 h NAC regimen was associated with fewer adverse drug reactions compared with the standard 21 h regimen. Here, we describe the clinical effectiveness of the SNAP NAC regimen. Methods The SNAP regimen, consisting of intravenous NAC 100 mg/kg over 2 h then 200 mg/kg over 10 h, was introduced to treat all paracetamol overdose patients at the Royal Infirmary of Edinburgh, the Royal Victoria Infirmary, Newcastle and St Thomas' Hospital, London. Patient data were prospectively and systematically collected before and after the change in treatment (total patients N = 3340, 21 h N = 1488, SNAP N = 1852). Health record linkage was used to determine patient outcome after hospital discharge. Findings There was no difference in liver injury or liver synthetic dysfunction between regimens. Hepatotoxicity (peak ALT > 1000 U/L) occurred in 64 (4.3%) and 67 (3.6%) patients, respectively, in the 21 h and SNAP groups (absolute difference − 0.7%, 95% CI − 2.1 to 0.6). Multivariable logistic regression did not identify treatment regimen as an outcome-associated factor. No patients were readmitted to hospital with, or died from, liver failure within 30 days of discharge. Anti-histamine treatment (for NAC anaphylactoid drug reactions) was prescribed for 163 (11.0%) patients with the 21 h regimen and 37 (2.0%) patients with the SNAP regimen (absolute difference 9.0% (95% CI 7.3 to 10.7)). Interpretation In clinical use the SNAP regimen has similar efficacy as standard therapy for preventing liver injury and produces fewer adverse reactions.

Long delays were identified during the three-infusion acetylcysteine regimen for the treatment of paracetamol overdose. These were of clinical significance and could lead to periods of subtherapeutic plasma acetylcysteine concentrations and potentially avoidable hepatotoxicity, as well as delaying hospital discharge.

Changes to national guidelines for managing paracetamol poisoning in the UK have increased the numbers of patients with acute overdose treated with acetylcysteine, with most additional treatments occurring in patients in the 100-149 mg/L dose range, a group at low risk of hepatotoxicity and higher risk of adverse reactions.

The use of NPIS services significantly reduced ED referrals from primary healthcare services with resulting avoided healthcare costs exceeding the current annual NPIS budget. Further studies are needed to evaluate other potential benefits of accessing NPIS services.