아세트아미노펜 중독의 치료에 대한 최신지견
Up-to-date treatment of acetaminophen poisoning
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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.
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.
참고문헌 (40)
- Chung SP, "Acetaminophen Poisoning", J Korean Soc Clin Toxicol, 6, pp.1~8 (2008)
- 전병조, "아세트아미노펜 중독의 해독제: 아세틸시스테인", 대한의사협회지, 56(12), pp.1067~1075 (2013), 대한의사협회
- Rumack BH, "Acetaminophen and acetylcysteine dose and duration: past, present and future", Clin Toxicol(Phila), 50, pp.91~98 (2012)
- Green JL, "Oral and Intravenous Acetylcysteine for Treatment of Acetaminophen Toxicity : A Systematic Review and Meta-analysis", West J Emerg Med, 14, pp.218~226 (2013)
- Bourdeaux C, "Death from paracetamol overdose despite appropriate treatment with N-acetylcysteine", Emerg Med J, 24, pp.e31~ (2007)
- Schwartz EA, "Development of hepatic failure despite use of intravenous acetylcysteine after a massive ingestion of acetaminophen and diphenhydramine", Ann Emerg Med, 54, pp.421~423 (2009)
- Lucyk SN, "Outcomes of Patients With Premature Discontinuation of the 21-h Intravenous N-Acetylcysteine Protocol After Acute Acetaminophen Overdose", J Emerg Med, 50, pp.629~637 (2016)
- Wong 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), 54, pp.115~119 (2016)
- Chiew AL, "Updated guidelines for the management of paracetamol poisoning in Australia and New Zealand", Med J Aust, 212, pp.175~183 (2020)
- Pettie JM, "Safety and Efficacy of the SNAP 12-hour Acetylcysteine Regimen for the Treatment of Paracetamol Overdose", EClinicalMedicine, 11, pp.11~17 (2019)
- Baumgartner K, "N-acetylcysteine for acetaminophen toxicity : The one-bag regimen", Br J Clin Pharmacol, 87, pp.2399~2400 (2021)
- Marks DJB, "Outcomes from massive paracetamol overdose : a retrospective observational study", Br J Clin Pharmacol, 83, pp.1263~1272 (2017)
- Hendrickson RG, "What is the most appropriate dose of N-acetylcysteine after massive acetaminophen overdose?", Clin Toxicol (Phila), 57, pp.686~691 (2019)
- Chiew AL, "Massive paracetamol overdose : an observational study on the effect of activated charcoal and increased acetylcysteine dose(ATOM 2)", Clin Toxicol, 55, pp.1055~1065 (2017)
- Sivilotti ML, "Antidote removal during haemodialysis for massive acetaminophen overdose", Clin Toxicol(Phila), 51, pp.855~863 (2013)
- Wiegand TJ, "Massive acetaminophen ingestion with early metabolic acidosis and coma: treatment with IV NAC and continuous venovenous hemodiafiltration", Clin Toxicol(Phila), 48, pp.156~159 (2010)
- Fannin RD, "Acetaminophen dosing of humans results in blood transcriptome and metabolome changes consistent with impaired oxidative phosphorylation", Hepatology, 51, pp.227~236 (2010)
- Prill S, "Real-time monitoring of oxygen uptake in hepatic bioreactor shows CYP450-independent mitochondrial toxicity of paracetamol and amiodarone", Arch Toxicol, 90, pp.1181~1191 (2016)
- Downs JW, "Clinical outcome of massive acetaminophen overdose treated with standard-dose N-acetylcysteine", Clin Toxicol(Phila), 59, pp.932~936 (2021)
- Edwards DA, "Prediction of acetaminophen level from clinical history of overdose using a pharmacokinetic model", Ann Emerg Med, 15, pp.1314~1319 (1986)
- Chiew AL, "Acetaminophen Poisoning", Crit Care Clin, 37, pp.543~561 (2021)
- Elms AR, "Fatal myocardial infarction associated with intravenous N-acetylcysteine error", Int J Emerg Med, 4, pp.54~ (2011)
- Bailey B, "Status epilepticus after a massive intravenous N-acetylcysteine overdose leading to intracranial hypertension and death", Ann Emerg Med, 44, pp.401~406 (2004)
- Lewis JC, "Evaluation of N-acetylcysteine dose for the treatment of massive acetaminophen ingestion", Clin Toxicol(Phila), 60, pp.507~513 (2022)
- Gosselin S, "Extracorporeal treatment for acetaminophen poisoning: recommendations from the EXTRIP workgroup", Clin Toxicol(Phila), 52, pp.856~867 (2014)
- Ali M, "Haemodiafiltration as an effective treatment option for massive paracetamol overdose", BMJ Case Rep, 12, pp.e228920~ (2019)
- Gaber M, "Massive paracetamol overdose associated with mitochondrial dysfunction and pancytopenia, without hepatotoxicity", Eur J Emerg Med, 23, pp.460~462 (2016)
- Wong A, "The use of sustained low efficiency dialysis(SLED)in massive paracetamol overdose", Clin Toxicol(Phila), 56, pp.229~231 (2018)
- Mazer M, "Acetaminophen-induced nephrotoxicity : pathophysiology, clinical manifestations, and management", J Med Toxicol, 4, pp.2~6 (2008)
- Filip AB, "Fomepizole as an adjunctive therapy for acetaminophen poisoning: cases reported to the toxicology investigators consortium (ToxIC) database 2015-2020", Clin Toxicol (Phila), pp.1~6 (2022)
- Pourbagher-Shahri AM, "Use of fomepizole(4-methylpyrazole)for aceta-minophen poisoning : A scoping review", Toxicol Lett, 355, pp.47~61 (2022)
- Lee SS, "Role of CYP2E1 in the hepatotoxicity of acetaminophen", J Biol Chem, 271, pp.12063~12067 (1996)
- Kang AM, "The Effect of 4-Methylpyrazole on Oxidative Metabolism of Acetaminophen in Human Volunteers", J Med Toxicol, 16, pp.169~176 (2020)
- Akakpo JY, "Delayed Treatment With 4-Methylpyrazole Protects Against Acetaminophen Hepatotoxicity in Mice by Inhibition of c-Jun n-Terminal Kinase", Toxicol Sci, 170, pp.57~68 (2019)
- Schiødt FV, "The value of plasma acetaminophen half-life in antidote-treated acetaminophen overdosage", Clin Pharmacol Ther, 71, pp.221~225 (2002)
- Chiu MH, "Massive Acetaminophen Overdose Treated Successfully with N-Acetylcysteine, Fomepizole, and Hemodialysis", Case Rep Crit Care, 2021, pp.6695967~ (2021)
- Cuninghame S, "Massive acetaminophen overdose with metabolic acidosis refractory to N-acetylcysteine, fomepizole, and renal replacement therapy", Toxicol Rep, 8, pp.804~807 (2021)
- Ghannoum M, "Massive acetaminophen overdose: effect of hemodialysis on acetaminophen and acetylcysteine kinetics", Clin Toxicol(Phila), 54, pp.519~522 (2016)
- Kiernan EA, , Case Rep Emerg Med, 2019, pp.9301432~ (2019)
- Woolum JA, "Use of fomepizole, n-acetylcysteine, and hemodialysis for massive acetaminophen overdose", Am J Emerg Med, 38, pp.692.e5~692.e7 (2020)