Adducts Post Acetaminophen Overdose Treated with a 12-Hour vs 20-Hour Acetylcysteine Infusion
INTRODUCTION: Acetaminophen protein adducts in the circulation are a specific biomarker of acetaminophen oxidation, and may be a more sensitive measure of impending hepatic injury following overdose than alanine transaminase (ALT). We performed an exploratory analytical substudy of adducts during a clinical trial (NACSTOP) of abbreviated (12-hour) versus control (20-hour) acetylcysteine to identify any signal of diminished antidotal effectiveness with shortened therapy.
METHODS: We measured adducts at 0, 12, and 20 hours from a convenience sample of subjects enrolled in the cluster-controlled NACSTOP trial evaluating a 12-hour ("abbreviated"; 200 mg/kg over 4 hours, 50 mg/kg over 8 hours) vs 20-hour acetylcysteine regimen ("control"; 200 mg/kg over 4 hours, 100 mg/kg over 16 hours). Adducts were assayed using high-performance liquid chromatography/mass spectrometry.
RESULTS: Median ALT 20 hours after the initiation of acetylcysteine was 12 U/L (IQR 8,14) in the abbreviated 12-hour regimen group (N = 8), compared with the control group 16 U/L (IQR 11,21; N = 21) (p = 0.46). Adduct concentrations were similarly low in both groups: abbreviated [(0.005 μmol/L, IQR (0,0.14)] and control [(0.005 μmol/L, IQR (0,0.05)] (p = 0.61).
CONCLUSIONS: There were minimal to no acetaminophen protein adducts detected. These findings further support discontinuing acetylcysteine when acetaminophen concentrations are low and liver function tests normal after 12 hours of treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
Journal of medical toxicology : official journal of the American College of Medical Toxicology - 16(2020), 2 vom: 14. Apr., Seite 188-194 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wong, Anselm [VerfasserIn] |
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| Links: |
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| Themen: |
362O9ITL9D |
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| Anmerkungen: |
Date Completed 31.05.2021 Date Revised 31.05.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s13181-020-00757-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM305376012 |
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| 100 | 1 | |a Wong, Anselm |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Adducts Post Acetaminophen Overdose Treated with a 12-Hour vs 20-Hour Acetylcysteine Infusion |
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| 500 | |a Date Revised 31.05.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a INTRODUCTION: Acetaminophen protein adducts in the circulation are a specific biomarker of acetaminophen oxidation, and may be a more sensitive measure of impending hepatic injury following overdose than alanine transaminase (ALT). We performed an exploratory analytical substudy of adducts during a clinical trial (NACSTOP) of abbreviated (12-hour) versus control (20-hour) acetylcysteine to identify any signal of diminished antidotal effectiveness with shortened therapy | ||
| 520 | |a METHODS: We measured adducts at 0, 12, and 20 hours from a convenience sample of subjects enrolled in the cluster-controlled NACSTOP trial evaluating a 12-hour ("abbreviated"; 200 mg/kg over 4 hours, 50 mg/kg over 8 hours) vs 20-hour acetylcysteine regimen ("control"; 200 mg/kg over 4 hours, 100 mg/kg over 16 hours). Adducts were assayed using high-performance liquid chromatography/mass spectrometry | ||
| 520 | |a RESULTS: Median ALT 20 hours after the initiation of acetylcysteine was 12 U/L (IQR 8,14) in the abbreviated 12-hour regimen group (N = 8), compared with the control group 16 U/L (IQR 11,21; N = 21) (p = 0.46). Adduct concentrations were similarly low in both groups: abbreviated [(0.005 μmol/L, IQR (0,0.14)] and control [(0.005 μmol/L, IQR (0,0.05)] (p = 0.61) | ||
| 520 | |a CONCLUSIONS: There were minimal to no acetaminophen protein adducts detected. These findings further support discontinuing acetylcysteine when acetaminophen concentrations are low and liver function tests normal after 12 hours of treatment | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Acetaminophen | |
| 650 | 4 | |a Acetylcysteine | |
| 650 | 4 | |a NAC | |
| 650 | 4 | |a Paracetamol | |
| 650 | 4 | |a Poisoning | |
| 650 | 7 | |a Analgesics, Non-Narcotic |2 NLM | |
| 650 | 7 | |a Antidotes |2 NLM | |
| 650 | 7 | |a Acetaminophen |2 NLM | |
| 650 | 7 | |a 362O9ITL9D |2 NLM | |
| 650 | 7 | |a Acetylcysteine |2 NLM | |
| 650 | 7 | |a WYQ7N0BPYC |2 NLM | |
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| 700 | 1 | |a Graudins, Andis |e verfasserin |4 aut | |
| 700 | 1 | |a Dart, Richard |e verfasserin |4 aut | |
| 700 | 1 | |a Sivilotti, Marco L A |e verfasserin |4 aut | |
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