Impact of revised UK paracetamol management guidelines: increasing treatment but prevention of potential missed toxicity

T Yamamoto1, M Ambler1, A Dines1, JRH Archer1,2, DM Wood1,2, PI Dargan1,2. 1Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, UK, 2King's College London, London, UK

Introduction: Paracetamol is the most common drug taken in self-poisoning cases in the UK. In September 2012 the MHRA introduced changes to the UK guidelines for the management of paracetamol overdose (1). The aim of this study was to look at the impact of these changes on the management of patients presenting with paracetamol overdose to a large inner-city hospital, specifically focusing on those who would not have received treatment if they had presented prior to the guidance changes in September 2012.

Methods: Data on all acute toxicological presentations to our hospital is collected prospectively on a purpose-designed database. This database was retrospectively interrogated to identify patients who presented with paracetamol overdose 6 months prior to and 6 months after the change in paracetamol management (1st March 2012-28th February 2013). Basic demographic data, along with information on treatment with acetylcysteine and outcome was extracted from the database and where necessary the original medical records.

Results: 314 patients presented in this study period. Pre-4th September 2012 (Group 1) there were 154 presentations; post-4th September 2012 (Group 2) there were 160 presentations. 37 were staggered overdoses (Group 1 n=19, Group 2 n=18). In Group 1, 42 patients (27%) were treated with acetylcysteine, compared to 67 patients (42%) in Group 2 (p=0.009). Of the 67 patients treated with acetylcysteine in Group 2, 21 patients (18 acute, 3 staggered) would not have been treated using pre-September 2012 guidelines. For these patients presenting after acute single overdose, 101.4±49.0 paracetamol concentration back-extrapolated to 4 hours was 123.7± 35.0 mg/L (range 65-180). In the staggered group, the preceding 24hr ingestion dose mean were 101.7mg/kg, 114.6mg/kg and 91.95mg/kg. Two patients in Group 2 who would not have been treated according to pre-September 2012 guidelines went on to develop hepatotoxicity despite early acetylcysteine therapy (see Table); this settled with extended course acetylcysteine in both cases.

Adverse reactions to acetylcysteine were documented in 12 patients (29%) from Group 1 and 3 patients (5%) from Group 2 (p=0.0009).

Discussion: This study has shown that there was a significant increase in the proportion of patients with paracetamol overdose requiring treatment with acetylcysteine in the 6 months after the introduction of the new guidelines. It will be important for larger studies to assess the impact of these new guidelines on treatment costs for paracetamol poisoning and for this assessment to include other outcomes such as adverse reactions to and efficacy of acetylcysteine therapy.

References:

(1)http://www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/CON178225 (Accessed 16th September 2013)