Paracetamol poisoning: beyond the nomogram

Abstract

Paracetamol poisoning is the commonest overdose seen in the UK. The management of patients with paracetamol poisoning has been little changed for the past 40 years, with a weight related dose of antidote (acetylcysteine) and treatment based on nomograms relating paracetamol concentration to time from ingestion. In 2012 the UK Commission on Human Medicines recommended a revision of the nomogram, following the death of a young woman, lowering the treatment threshold for all patients. As a result many more patients were treated. This has resulted in a large increase in admissions and in the proportion suffering adverse reactions to the antidote acetylcysteine since, interestingly, higher paracetamol concentrations inhibit anaphylactoid reactions to the antidote. New approaches to assessing the toxicity of paracetamol are now emerging using new biomarkers in blood. This article discusses new approaches to risk assessment and treatment for paracetamol overdose based on recent research in this area.

Outcomes from massive paracetamol overdose: a retrospective observational study

“…The standard acetylcysteine protocol was 150 mg kg −1 over 15 min, followed by 50 mg kg −1 over 4 h, and finally 100 mg kg −1 over 16 h. From 2012, UK guidelines changed such that everyone was treated according to the 100 mg l −1 at 4 h nomogram threshold line, with the duration of the first dose of acetylcysteine extended to 1 h . With both of these regimens, after completion of the third infusion, renal function, liver function and coagulation parameters are rechecked, and a further 16 h acetylcysteine infusion instituted in the event of any significant derangement .…”

N‐Acetyl cysteine does not prevent liver toxicity from chronic low‐dose plus subacute high‐dose paracetamol exposure in young or old mice

“…This finding of a lack of protection from NAC against sub-acute paracetamol dosing, confirms the clinical observations of, and provides pre-clinical evidence that, for those who have taken staggered doses of paracetamol over several days, NAC may not be effective at preventing paracetamol hepatotoxicity. The high rate of side-effects associated with NAC (31) emphasises the importance of optimising NAC treatment and not using it in patients for whom it will be ineffective or unnecessary (32). This finding has important clinical implications in treating different types of paracetamol exposures, and is particularly important for older patients, as they are more likely to have the type of exposures, as explored here, against which NAC does not protect.…”

Medicamentos isentos de prescrição: perfil de consumo e os riscos tóxicos do paracetamol

“…Para inferir o dano hepático ainda no seu início, alguns marcadores podem ser utilizados, como os produtos metabólicos de proteína-paracetamol (3-(cisteína-S-yl)-paracetamol), o aminoácido taurina, liberado na corrente sanguínea pelos hepatócitos quando ocorre lesão hepática e biomarcadores circulantes do fígado, tais como micro RNA específico miR-122 e a proteína relacionada a necrose HMGB1 (BATEMAN, 2015;TERRES, 2015;BUCARETCHI et al, 2014;BARBOSA, 2013;FERNER et al, 2011).…”

“…Por via oral, sintomas gastrointestinais (náuseas, vômitos e diarreia) são frequentes. Na administração venosa, ocorrem reações alérgicas, do tipo anafilática (com broncoespasmo, erupção cutânea e hipotensão) (BATEMAN, 2015;HODGMAN;GARRARD, 2012;FERNER et al, 2011). O uso da substância N-Acetil-Cisteína-EtilÉster (NACET) vem sendo utilizado; por via oral, apresenta rápida absorção e excelente biodisponibilidade e área sob a curva concentração plasmática versus tempo (ASC), atingindo rapidamente os tecidos, devido a sua alta lipofilicidade, quando comparada com a NAC.…”