Assessment of high-dose acetylcysteine in acute high-risk paracetamol (acetaminophen) ingestion.

Autor:	Moss MJ; UT Poison Control Center, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.; Department of Emergency Medicine, University of Utah, Salt Lake City, UT, USA., Hinchman B; UT Poison Control Center, College of Pharmacy, University of Utah, Salt Lake City, UT, USA., Lambson JE; NM Poison and Drug Information Center, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA., Scott JW; UT Poison Control Center, College of Pharmacy, University of Utah, Salt Lake City, UT, USA., Hinckley P; UT Poison Control Center, College of Pharmacy, University of Utah, Salt Lake City, UT, USA., Wylie SJ; UT Poison Control Center, College of Pharmacy, University of Utah, Salt Lake City, UT, USA., Dorey A; UT Poison Control Center, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.; Department of Emergency Medicine, University of Utah, Salt Lake City, UT, USA.
Jazyk:	angličtina
Zdroj:	Clinical toxicology (Philadelphia, Pa.) [Clin Toxicol (Phila)] 2024 Aug; Vol. 62 (8), pp. 519-525. Date of Electronic Publication: 2024 Jul 25.
DOI:	10.1080/15563650.2024.2377268
Abstrakt:	Background: Prompt acetylcysteine treatment with standard doses (300 mg/kg over 21 h in divided doses) is almost universally effective in preventing hepatotoxicity after paracetamol (acetaminophen) overdose. However, hepatotoxicity is reported despite early treatment when paracetamol concentrations exceed 300 mg/L (1,985 μmol/L) at 4 h. Prior studies evaluating high-dose acetylcysteine to treat high-risk ingestions have shown mixed results. We compared outcomes in patients with high-risk ingestions receiving standard or high-dose acetylcysteine. Methods: Records from a single poison center were reviewed from 1 January 2017 to 31 December 2022. We included cases of acute paracetamol ingestion treated with intravenous acetylcysteine with an initial paracetamol concentration above the "300 mg/L" (1,985 μmol/L) line on the Rumack-Matthew nomogram. We compared standard and high-dose acetylcysteine groups by odds ratios and multivariable logistic regression. We defined hepatotoxicity as aminotransferase activity >1,000 U/L. Results: We included 190 cases. Fifty-six percent received standard-dose acetylcysteine while 44% received high-dose acetylcysteine. Treatment within 8 h yielded no difference in hepatotoxicity between groups (odds ratio 1.67, 95% CI 0.067-42.3). Among patients treated after 8 h, hepatoxicity was more common in the high-dose group (odds ratio 3.39, 95% CI 1.25-9.2) though odds of liver failure were similar (odds ratio 2.78, 95% CI 0.89-8.69). Eighty-eight percent of patients with hepatotoxicity had elevated aminotransferase activity at presentation. No patient died or received a liver transplant. Discussion: Rates of hepatotoxicity were low in patients treated within 8 h regardless of acetylcysteine dose. Unexpectedly, high-dose acetylcysteine treatment was associated with an increased odds of hepatoxicity in those treated after 8 h, but most had abnormal aminotransferase activities at presentation and there was no difference in rates of liver failure. Limitations include the use of retrospective, voluntarily reported poison center data. Conclusions: Prompt treatment with acetylcysteine, regardless of dose, prevented hepatotoxicity in high-risk paracetamol ingestion.
Databáze:	MEDLINE
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