Re: Treatments for paracetamol poisoning
We were very interested to read the perspective on the 2012 UK changes to risk assessment provided by Thomas et al, internationally recognised British experts on paracetamol poisoning. We agree that from evidence to date this appears to have been a very expensive decision with no demonstrable benefit. Further it is possible that even if the two deaths that were predicted to have been prevented in the last four years were indeed prevented, that more deaths than that have occurred due to acetylcysteine dosing errors and infusion reactions among the tens of thousands of extra people that have been treated. The UK has generally been a leader in advances in the management of poisoning. However, while it's been widely discussed worldwide, we believe only one country (Ireland) has followed the UK on this particular strategy.
The change has also caused a great deal of confusion about threshold doses for initiating treatment. We accept their correction that the current Toxbase advice is to treat an acute overdose above 150mg/kg (when a level cannot be used for guidance). Our misapprehension that 75mg/kg was being used arose from several UK based sources. For example the Royal College of Emergency Medicine website links to a flowchart (1) that specifically states that 75mg/kg is the threshold dose for administration of acetylcysteine in late presenters. Similar advice that doses >75mg/kg are potentially hepatotoxic appear on NHS Trust guidelines (2) and in a 2015 BMJ Best Practice article (3). According to Bateman et al 2014 (4), the British National Formulary (BNF) stated in 2012 that 75mg/kg is the threshold dose for acetylcysteine administration in 'high risk' patients, and the UK Commission on Human Medicines (CHM) 2012 advice was that doctors should no longer categorise patients as to whether they were high risk or not (5). They suggested adopting the 'high risk patient' nomogram line that starts at 100mg/L at 4 hours to interpret paracetamol concentrations. It appears that the Royal College of Emergency Medicine and others may have assumed the high risk patient dose threshold of 75mg/kg/24 hours should also be adopted (although this was not specifically in the CHM advice).
We can only agree with Thomas et al that this was an unwarranted extension of the risk mitigation strategy. Indeed one of us (NB) has deliberately taken two overdoses larger than 75 mg/kg without acetylcysteine in the name of science (6). Even 150mg/kg is very conservative. In Australia, we have adopted 200mg/kg or 10 grams for many years (7) and are unaware of any serious problems arising from waiting for the results of blood tests before treating asymptomatic patients ingesting less than this amount.
1. Paracetamol poisoning proforma to guide ED management of ORAL ingestions in adults. Link from Royal College of Emergency Medicine statement - Paracetamol overdose: new guidance on the use of intravenous acetylcysteine. [25/1/2013 [cited 2016 Jun. 9]; Available from: URL: http://secure.rcem.ac.uk/code/document.asp?ID=6692
2. Barts Health NHS Trust ED & CDU Guidelines: Paracetamol Overdose in Adults. 2012 [cited 2016 Jun. 9]; Available from: URL: http://www.rcem.ac.uk/CEM/document?id=6066
3. Paracetamol Overdose. BMJ Best Practice 5/8/2015 [cited 2016 Jun. 9]; Available from: URL: http://bestpractice.bmj.com/best-practice/monograph/337/treatment/step-b...
4. Bateman DN, Carroll R, Pettie J, Yamamoto T, Elamin ME, Peart L et al. Effect of the UK's revised paracetamol poisoning management guidelines on admissions, adverse reactions and costs of treatment. Br J Clin Pharmacol 2014; 78(3):610-618.
5. Medicines and Healthcare products Regulatory Agency. Treating paracetamol overdose with intravenous acetylcysteine: new guidance. MHRA [ 2016 [cited 2016 Jan. 28]; Available from: URL:https://www.gov.uk/drug-safety-update/treating-paracetamol-overdose-with...
6. James LP, Chiew A, Abdel-Rahman SM, Letzig L, Graudins A, Day P, Roberts D.
Acetaminophen protein adduct formation following low-dose acetaminophen exposure: comparison of immediate-release vs extended-release formulations. Eur J Clin Pharmacol. 2013 Apr;69(4):851-7. doi: 10.1007/s00228-012-1410-7.
7. Chiew A, Graudins A, Fountain J, Isbister GK, Reith D, Buckley NA. Consensus Statement: New guidelines for the Management of Paracetamol Poisoning in Australia and New Zealand. Medical Journal of Australia 2015;203(5):215-218
Competing interests: No competing interests