Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand.
Acetaminophen
/ poisoning
Acetylcysteine
/ administration & dosage
Administration, Intravenous
Analgesics, Non-Narcotic
/ poisoning
Antidotes
/ therapeutic use
Australia
Charcoal
/ therapeutic use
Chemical and Drug Induced Liver Injury
/ drug therapy
Drug Overdose
/ therapy
Humans
New Zealand
Practice Guidelines as Topic
Chemical and drug induced liver injury
Drug overdose
Guidelines as topic
Toxicology
Journal
The Medical journal of Australia
ISSN: 1326-5377
Titre abrégé: Med J Aust
Pays: Australia
ID NLM: 0400714
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
pubmed:
2
12
2019
medline:
3
4
2020
entrez:
2
12
2019
Statut:
ppublish
Résumé
Paracetamol is a common agent taken in deliberate self-poisoning and in accidental overdose in adults and children. Paracetamol poisoning is the commonest cause of severe acute liver injury. Since the publication of the previous guidelines in 2015, several studies have changed practice. A working group of experts in the area, with representation from all Poisons Information Centres of Australia and New Zealand, were brought together to produce an updated evidence-based guidance. The optimal management of most patients with paracetamol overdose is usually straightforward. Patients who present early should be given activated charcoal. Patients at risk of hepatotoxicity should receive intravenous acetylcysteine. The paracetamol nomogram is used to assess the need for treatment in acute immediate release paracetamol ingestions with a known time of ingestion. Cases that require different management include modified release paracetamol overdoses, large or massive overdoses, accidental liquid ingestion in children, and repeated supratherapeutic ingestions. The new guidelines recommend a two-bag acetylcysteine infusion regimen (200 mg/kg over 4 h, then 100 mg/kg over 16 h). This has similar efficacy but significantly reduced adverse reactions compared with the previous three-bag regimen. Massive paracetamol overdoses that result in high paracetamol concentrations more than double the nomogram line should be managed with an increased dose of acetylcysteine. All potentially toxic modified release paracetamol ingestions (≥ 10 g or ≥ 200 mg/kg, whichever is less) should receive a full course of acetylcysteine. Patients ingesting ≥ 30 g or ≥ 500 mg/kg should receive increased doses of acetylcysteine.
Substances chimiques
Analgesics, Non-Narcotic
0
Antidotes
0
Charcoal
16291-96-6
Acetaminophen
362O9ITL9D
Acetylcysteine
WYQ7N0BPYC
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
175-183Informations de copyright
© 2019 AMPCo Pty Ltd.
Références
Fontana RJ. Acute liver failure including acetaminophen overdose. Med Clin North Am 2008; 92: 761-794.
Lancaster EM, Hiatt JR, Zarrinpar A. Acetaminophen hepatotoxicity: an updated review. Arch Toxicol 2015; 89: 193-199.
Huynh A, Cairns R, Brown JA, et al. Patterns of poisoning exposure at different ages: the 2015 annual report of the Australian Poisons Information Centres. Med J Aust 2018; 209: 74-79. https://www.mja.com.au/journal/2018/209/2/patterns-poisoning-exposure-different-ages-2015-annual-report-australian-poisons.
eTG complete. Paracetamol poisoning [website]. Melbourne: Therapeutic Guidelines. https://www.tg.org.au. In press.
Rumack BH, Bateman DN. Acetaminophen and acetylcysteine dose and duration: past, present and future. Clin Toxicol (Phila) 2012; 50: 91-98.
Chiew AL, Isbister GK, Duffull SB, Buckley NA. Evidence for the changing regimens of acetylcysteine. Br J Clin Pharmacol 2016; 81: 471-481.
Chiew AL, Gluud C, Brok J, Buckley NA. Interventions for paracetamol (acetaminophen) overdose. Cochrane Database Syst Rev 2018; (2): CD003328.
Wong A, Graudins A. Simplification of the standard three-bag intravenous acetylcysteine regimen for paracetamol poisoning results in a lower incidence of adverse drug reactions. Clin Toxicol (Phila) 2016; 54: 115-119.
McNulty R, Lim JME, Chandru P, Gunja N. Fewer adverse effects with a modified two-bag acetylcysteine protocol in paracetamol overdose. Clin Toxicol (Phila) 2018; 56: 618-621.
Schmidt LE, Rasmussen DN, Petersen TS, et al. Fewer adverse effects associated with a modified two-bag intravenous acetylcysteine protocol compared with traditional three-bag regimen in paracetamol overdose. Clin Toxicol (Phila) 2018; 56: 1128-1134.
Isbister GK, Downes MA, McNamara K, et al. A prospective observational study of a novel 2-phase infusion protocol for the administration of acetylcysteine in paracetamol poisoning. Clin Toxicol (Phila) 2016; 54: 120-126.
Wong A, Isbister GK, McNulty R, et al. Efficacy of a two bag acetylcysteine regimen to treat paracetamol overdose [Abstract], 39th International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT); 21-24 May 2019, Naples, Italy. Clin Toxicol (Phila) 2019; 57: 535.
Chiew AL, Isbister GK, Kirby KA, et al. Massive paracetamol overdose: an observational study of the effect of activated charcoal and increased acetylcysteine dose (ATOM-2). Clin Toxicol (Phila) 2017; 55: 1055-1065.
Duffull SB, Isbister GK. Predicting the requirement for N-acetylcysteine in paracetamol poisoning from reported dose. Clin Toxicol (Phila) 2013; 51: 772-776.
Buckley NA, Whyte IM, O'Connell DL, Dawson AH. Activated charcoal reduces the need for N-acetylcysteine treatment after acetaminophen (paracetamol) overdose. Clin Toxicol (Phila) 1999; 37: 753-757.
Marks DJB, Dargan PI, Archer JRH, et al. Outcomes from massive paracetamol overdose: a retrospective observational study. Br J Clin Pharmacol 2017; 83: 1263-1272.
Cairney DG, Beckwith HK, Al-Hourani K, et al. Plasma paracetamol concentration at hospital presentation has a dose-dependent relationship with liver injury despite prompt treatment with intravenous acetylcysteine. Clin Toxicol (Phila) 2016; 54: 405-410.
Hendrickson RG. What is the most appropriate dose of N-acetylcysteine after massive acetaminophen overdose? Clin Toxicol (Phila) 2019; 57: 686-691.
Rumack BH. Acetaminophen hepatotoxicity: the first 35 years. Clin Toxicol (Phila) 2002; 40: 3-20.
Doyon S, Klein-Schwartz W. Hepatotoxicity despite early administration of intravenous N-acetylcysteine for acute acetaminophen overdose. Acad Emerg Med 2009; 16: 34-39.
Chiew AL, Isbister GK, Page CB, et al. Modified release paracetamol overdose: a prospective observational study (ATOM-3). Clin Toxicol (Phila) 2018; 56: 810-819.
Graudins A, Chiew A, Chan B. Overdose with modified-release paracetamol results in delayed and prolonged absorption of paracetamol. J Intern Med 2010; 40: 72-76.
Salmonson H, Sjoberg G, Brogren J. The standard treatment protocol for paracetamol poisoning may be inadequate following overdose with modified release formulation: a pharmacokinetic and clinical analysis of 53 cases. Clin Toxicol (Phila) 2018; 56: 63-68.
Anderson BJ, Holford NH, Armishaw JC, Aicken R. Predicting concentrations in children presenting with acetaminophen overdose. J Pediatr 1999; 135: 290-295.
Prescott LF. Therapeutic misadventure with paracetamol: fact or fiction? Am J Ther 2000; 7: 99-114.
Watkins PB, Kaplowitz N, Slattery JT, et al. Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial. JAMA 2006; 296: 87-93.
Amar PJ, Schiff ER. Acetaminophen safety and hepatotoxicity - where do we go from here? Expert Opin Drug Saf 2007; 6: 341-355.
Kalsi SS, Dargan PI, Waring WS, Wood DM. A review of the evidence concerning hepatic glutathione depletion and susceptibility to hepatotoxicity after paracetamol overdose. Open Access Emerg Med 2011; 3: 87-96.
Daly FF, O'Malley GF, Heard K, et al. Prospective evaluation of repeated supratherapeutic acetaminophen (paracetamol) ingestion. Ann Emerg Med 2004; 44: 393-398.
Egan H, Isbister GK, Robinson J, et al. Retrospective evaluation of repeated supratherapeutic ingestion (RSTI) of paracetamol. Clin Toxicol (Phila) 2019; 57: 703-711.
Acheampong P, Thomas SH. Determinants of hepatotoxicity after repeated supratherapeutic paracetamol ingestion: systematic review of reported cases. Br J Clin Pharmacol 2016; 82: 923-931.
Wong A, Gunja N, McNulty R, Graudins A. Analysis of an 8-hour acetylcysteine infusion protocol for repeated supratherapeutic ingestion (RSTI) of paracetamol. Clin Toxicol (Phila) 2018; 56: 199-203.
Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med 1988; 319: 1557-1562.
Cairns R, Brown JA, Wylie CE, et al. Paracetamol poisoning in Australia, 2004-2017: an analysis of overdose frequency, overdose size, liver injury and deaths. Med J Aust 2019; 211: 218-223. https://www.mja.com.au/journal/2019/211/5/paracetamol-poisoning-related-hospital-admissions-and-deaths-australia-2004-2017
Green TJ, Sivilotti ML, Langmann C, et al. When do the aminotransferases rise after acute acetaminophen overdose? Clin Toxicol (Phila) 2010; 48: 787-792.