Browse > Article
http://dx.doi.org/10.22537/jksct.2022.20.2.39

Up-to-date treatment of acetaminophen poisoning  

Sung Phil Chung (Department of Emergency Medicine, Yonsei University College of Medical)
Jeongmi Moon (Department of Emergency Medicine, Chonnam National University Medical School)
Byeongjo Chun (Department of Emergency Medicine, Chonnam National University Medical School)
Publication Information
Journal of The Korean Society of Clinical Toxicology / v.20, no.2, 2022 , pp. 39-44 More about this Journal
Abstract
N-Acetylcysteine (NAC) is the standard antidote treatment for preventing hepatotoxicity caused by acetaminophen (AAP) poisoning. This review summarizes the recent evidence for the treatment of AAP poisoning. Several alternative intravenous regimens of NAC have been suggested to improve patient safety by reducing adverse drug reactions and medication errors. A two-bag NAC infusion regimen (200 mg/kg over 4 h, followed by 100 mg/kg over 16 h) is reported to have similar efficacy with significantly reduced adverse reactions compared to the traditional 3-bag regimen. Massive AAP poisoning due to high concentrations (more than 300-lines in the nomogram) needs to be managed with an increased maintenance dose of NAC. In addition to NAC, the combination therapy of hemodialysis and fomepizole is advocated for severe AAP poisoning cases. In the case of a patient presenting with an altered mental status, metabolic acidosis, elevated lactate, and an AAP concentration greater than 900 mg/L, hemodialysis is recommended even if NAC is used. Fomepizole decreases the generation of toxic metabolites by inhibiting CYP2E1 and may be considered an off-label use by experienced clinicians. Since the nomogram cannot be applied to sustained-release AAP formulations, all potentially toxic sustained-release AAP overdoses should receive a full course of NAC regimen. In case of ingesting less than the toxic dose, the AAP concentration is tested twice at an interval of 4 h or more; NAC should be administered if either value is above the 150-line of the nomogram.
Keywords
Acetaminophen; Poisoning; N-Acetylcysteine; Hemodialysis; Fomepizole;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Wong A, Tong RLK, Ryan L, Crozier T, Graudins A. The use of sustained low efficiency dialysis (SLED) in massive paracetamol overdose. Clin Toxicol (Phila) 2018;56:229-31.   DOI
2 Mazer M, Perrone J. Acetaminophen-induced nephrotoxicity: pathophysiology, clinical manifestations, and management. J Med Toxicol 2008;4:2-6.   DOI
3 Filip AB, Berg SE, Mullins ME, Schwarz ES; Toxicology Investigators Consortium (ToxIC). Fomepizole as an adjunctive therapy for acetaminophen poisoning: cases reported to the toxicology investigators consortium (ToxIC) database 2015-2020. Clin Toxicol (Phila) 2022:1-6.
4 Woolum JA, Hays WB, Patel KH. Use of fomepizole, n-acetylcysteine, and hemodialysis for massive acetaminophen overdose. Am J Emerg Med 2020;38:692.e5-692.e7.
5 Chung SP, Kim SH, Lee HS. Acetaminophen Poisoning. J Korean Soc Clin Toxicol 2008;6:1-8.
6 Chun BJ, Moon JM, Kim SH. Antidote for acetaminophen poisoning: N-acetylcysteine. J Korean Med Assoc 2013;56:1067-75.   DOI
7 Rumack BH, Bateman DN. Acetaminophen and acetylcysteine dose and duration: past, present and future. Clin Toxicol (Phila) 2012;50:91-8.   DOI
8 Green JL, Heard KJ, Reynolds KM, Albert D. Oral and Intravenous Acetylcysteine for Treatment of Acetaminophen Toxicity: A Systematic Review and Meta-analysis. West J Emerg Med 2013;14:218-26.   DOI
9 Chiew AL, Isbister GK, Kirby KA, et al. Massive paracetamol overdose: an observational study on the effect of activated charcoal and increased acetylcysteine dose (ATOM 2). Clin Toxicol 2017;55:1055-65.
10 Sivilotti ML, Juurlink DN, Garland JS, Lenga I, Poley R, Hanly LN, et al. Antidote removal during haemodialysis for massive acetaminophen overdose. Clin Toxicol (Phila) 2013;51:855-63.   DOI
11 Wiegand TJ, Margaretten M, Olson KR. Massive acetaminophen ingestion with early metabolic acidosis and coma: treatment with IV NAC and continuous venovenous hemodiafiltration. Clin Toxicol (Phila) 2010;48:156-9.   DOI
12 Fannin RD, Russo M, O'Connell TM, Gerrish K, Winnike JH, Macdonald J, et al. Acetaminophen dosing of humans results in blood transcriptome and metabolome changes consistent with impaired oxidative phosphorylation. Hepatology 2010;51:227-36.   DOI
13 Bourdeaux C, Bewley J. Death from paracetamol overdose despite appropriate treatment with N-acetylcysteine. Emerg Med J 2007;24:e31.
14 Schwartz EA, Hayes BD, Sarmiento KF. Development of hepatic failure despite use of intravenous acetylcysteine after a massive ingestion of acetaminophen and diphenhydramine. Ann Emerg Med 2009;54:421-3.
15 Lucyk SN, Yarema MC, Sivilotti ML, Johnson DW, NettelAguirre A, Victorino C, et al. Outcomes of Patients With Premature Discontinuation of the 21-h Intravenous N-Acetylcysteine Protocol After Acute Acetaminophen Overdose. J Emerg Med 2016;50:629-37.   DOI
16 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;54:115-9.   DOI
17 Chiew AL, Reith D, Pomerleau A, Wong A, Isoardi KZ, Soderstrom J, et al. Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand. Med J Aust 2020;212:175-83.
18 Pettie JM, Caparrotta TM, Hunter RW, Morrison EE, Wood DM, Dargan PI, et al. Safety and Efficacy of the SNAP 12-hour Acetylcysteine Regimen for the Treatment of Paracetamol Overdose. EClinicalMedicine 2019;11:11-7.   DOI
19 Baumgartner K, Filip A, Liss D, Devgun J, Schwarz E, Mullins M. N-acetylcysteine for acetaminophen toxicity: The one-bag regimen. Br J Clin Pharmacol 2021;87:2399-400.   DOI
20 Marks DJB, Dargan PI, Archer JRH, et al. Outcomes from massive paracetamol overdose: a retrospective observational study. Br J Clin Pharmacol 2017;83:1263-72.   DOI
21 Hendrickson RG. What is the most appropriate dose of N-acetylcysteine after massive acetaminophen overdose? Clin Toxicol (Phila) 2019;57:686-91.   DOI
22 Kang AM, Padilla-Jones A, Fisher ES, Akakpo JY, Jaeschke H, Rumack BH, et al. The Effect of 4-Methylpyrazole on Oxidative Metabolism of Acetaminophen in Human Volunteers. J Med Toxicol 2020;16:169-76.   DOI
23 Prill S, Bavli D, Levy G, Ezra E, Schmalzlin E, Jaeger MS, et al. Real-time monitoring of oxygen uptake in hepatic bioreactor shows CYP450-independent mitochondrial toxicity of paracetamol and amiodarone. Arch Toxicol 2016; 90:1181-91.   DOI
24 Pourbagher-Shahri AM, Schimmel J, Shirazi FM, Nakhaee S, Mehrpour O. Use of fomepizole (4-methylpyrazole) for acetaminophen poisoning: A scoping review. Toxicol Lett 2022;355:47-61.   DOI
25 Lee SS, Buters JT, Pineau T, Fernandez-Salguero P, Gonzalez FJ. Role of CYP2E1 in the hepatotoxicity of acetaminophen. J Biol Chem 1996;271:12063-7.   DOI
26 Akakpo JY, Ramachandran A, Duan L, Schaich MA, Jaeschke MW, Freudenthal BD, et al. Delayed Treatment With 4-Methylpyrazole Protects Against Acetaminophen Hepatotoxicity in Mice by Inhibition of c-Jun n-Terminal Kinase. Toxicol Sci 2019;170:57-68.   DOI
27 Schiodt FV, Ott P, Christensen E, Bondesen S. The value of plasma acetaminophen half-life in antidote-treated acetaminophen overdosage. Clin Pharmacol Ther 2002;71:221-5.   DOI
28 Chiu MH, Jaworska N, Li NL, Yarema M. Massive Acetaminophen Overdose Treated Successfully with N-Acetylcysteine, Fomepizole, and Hemodialysis. Case Rep Crit Care 2021;2021:6695967.
29 Cuninghame S, Lotfy K, Cameron P. Massive acetaminophen overdose with metabolic acidosis refractory to N-acetylcysteine, fomepizole, and renal replacement therapy. Toxicol Rep 2021;8:804-7.   DOI
30 Ghannoum M, Kazim S, Grunbaum AM, Villeneuve E, Gosselin S. Massive acetaminophen overdose: effect of hemodialysis on acetaminophen and acetylcysteine kinetics. Clin Toxicol (Phila) 2016;54:519-22.   DOI
31 Chiew AL, Buckley NA. Acetaminophen Poisoning. Crit Care Clin 2021;37:543-61.
32 Downs JW, Cumpston KL, Kershner EK, Troendle MM, Rose SR, Wills BK. Clinical outcome of massive acetaminophen overdose treated with standard-dose N-acetylcysteine. Clin Toxicol (Phila) 2021;59:932-6.   DOI
33 Kiernan EA, Fritzges JA, Henry KA, Katz KD. Case Rep Emerg Med 2019;2019:9301432.
34 Edwards DA, Fish SF, Lamson MJ, et al. Prediction of acetaminophen level from clinical history of overdose using a pharmacokinetic model. Ann Emerg Med 1986;15:1314-9.   DOI
35 Elms AR, Owen KP, Albertson TE, Sutter ME. Fatal myocardial infarction associated with intravenous N-acetylcysteine error. Int J Emerg Med 2011;4:54.
36 Bailey B, Blais R, Letarte A. Status epilepticus after a massive intravenous N-acetylcysteine overdose leading to intracranial hypertension and death. Ann Emerg Med 2004;44:401-6.   DOI
37 Lewis JC, Lim M, Lai L, Mendoza E, Albertson TE, Chenoweth JA. Evaluation of N-acetylcysteine dose for the treatment of massive acetaminophen ingestion. Clin Toxicol (Phila) 2022;60:507-13.   DOI
38 Gosselin S, Juurlink DN, Kielstein JT, Ghannoum M, Lavergne V, Nolin TD, et al. Extracorporeal treatment for acetaminophen poisoning: recommendations from the EXTRIP workgroup. Clin Toxicol (Phila) 2014;52:856-67.   DOI
39 Ali M, Misurati M, Rodgers R, Pooni J. Haemodiafiltration as an effective treatment option for massive paracetamol overdose. BMJ Case Rep 2019;12:e228920.
40 Gaber M, Wong A, Koutsogiannis Z, Greene SL. Massive paracetamol overdose associated with mitochondrial dysfunction and pancytopenia, without hepatotoxicity. Eur J Emerg Med 2016;23:460-2.   DOI