https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45649 1,000 U/L), an adduct concentration ≥1.0 nmol/ml is sensitive and specific for identifying cases secondary to acetaminophen. Our aim was to characterise acetaminophen-protein adduct concentrations in patients following acetaminophen overdose and determine if they predict toxicity. Methods: We performed a multicentre prospective observational study, recruiting patients 14 years of age or older with acetaminophen overdose regardless of intent or formulation. Three serum samples were obtained within the first 24 h of presentation and analysed for acetaminophen-protein adducts. Acetaminophen-protein adduct concentrations were compared to ALT and other indicators of toxicity. Results: Of the 240 patients who participated, 204 (85%) presented following acute ingestions, with a median ingested dose of 20 g (IQR 10–40), and 228 (95%) were treated with intravenous acetylcysteine at a median time of 6 h (IQR 3.5–10.5) post-ingestion. Thirty-six (15%) patients developed hepatotoxicity, of whom 22 had an ALT ≤1,000 U/L at the time of initial acetaminophen-protein adduct measurement. Those who developed hepatotoxicity had a higher initial acetaminophen-protein adduct concentration compared to those who did not, 1.63 nmol/ml (IQR 0.76–2.02, n = 22) vs. 0.26 nmol/ml (IQR 0.15–0.41; n = 204; p <0.0001), respectively. The AUROC for hepatotoxicity was 0.98 (95% CI 0.96–1.00; n = 226; p <0.0001) with acetaminophen-protein adduct concentration and 0.89 (95% CI 0.82–0.96; n = 219; p <0.0001) with ALT. An acetaminophen-protein adduct concentration of 0.58 nmol/ml was 100% sensitive and 91% specific for identifying patients with an initial ALT ≤1,000 U/L who would develop hepatotoxicity. Adding acetaminophen-protein adduct concentrations to risk prediction models improved prediction of hepatotoxicity to a level similar to that obtained by more complex models. Conclusion: Acetaminophen-protein adduct concentration on presentation predicted which patients with acetaminophen overdose subsequently developed hepatotoxicity, regardless of time of ingestion. An adduct threshold of 0.58 nmol/L was required for optimal prediction. Lay summary: Acetaminophen poisoning is one of the most common causes of liver injury. This study examined a new biomarker of acetaminophen toxicity, which measures the amount of toxic metabolite exposure called acetaminophen-protein adduct. We found that those who developed liver injury had a higher initial level of acetaminophen-protein adducts than those who did not. Clinical Trial registration: Australian Toxicology Monitoring (ATOM) Study–Australian Paracetamol Project: ACTRN12612001240831 (ANZCTR) Date of registration: 23/11/2012.]]> Thu 23 Mar 2023 13:56:06 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:8507 Sat 24 Mar 2018 08:36:24 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23068 1000 U/L or abnormal ALT. Results: 654 paracetamol poisonings were treated with the new protocol; median age 29 y (15-98 y); 453 females; 576 acute and 78 staggered/chronic ingestions. In 420 (64%) acetylcysteine was stopped for low-risk paracetamol concentrations. An adverse reaction occurred in 229/654 admissions (35%; 95% CI: 31-39%): 173 (26.5%; 95% CI: 23-30%) only gastrointestinal, 50 (8%; 95% CI: 6-10%) skin only systemic hypersensitivity reactions; and three severe anaphylaxis (0.5%; 95% CI: 0.1-1.5%; all hypotension). Adverse reactions occurred in 111/231 (48%) receiving full treatment compared to 116/420 (28%) in whom the infusion was stopped early (absolute difference 20%; 95% CI: 13-28%; p < 0.0001). In 200 overdoses < 10 g, one had toxic paracetamol concentrations, but 53 developed reactions. Sixteen patients had an ALT > 1000 U/L and 24 an abnormal ALT attributable to paracetamol; all but one had treatment commenced >12 h post-ingestion. Conclusion: A 2-phase acetylcysteine infusion protocol results in a fewer reactions in patients with toxic paracetamol concentrations, but is not justified in patients with low-risk paracetamol concentrations.]]> Sat 24 Mar 2018 07:12:28 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44567 N-acetyl-p-benzoquinone imine in hepatocytes and enhances non-toxic sulphate conjugation. As NAC is the cornerstone of treatment in paracetamol poisoning, trials have mainly focused around optimising dose, duration, rate and route of administration, with the primary aim to decrease rates of adverse events, shorten treatment time and maintain efficacy. NAC use is not just confined to paracetamol and has been utilised for a wide variety of toxins and ingestions. These toxins range from herbicides, mushrooms, hydrocarbons and metals. NAC’s proposed mechanism of action for these toxins is as an antioxidant and/or glutathione replenishing. The evidence for its use in most other toxins is limited to animal studies, case reports and small case series, due to the uncommon occurrence of these toxin exposures. With these toxins NAC is often given in combination with other therapies, making it difficult to determine its utility for many toxins. Because of the relative safety of NAC and the high morbidity associated with many of these ingestions, NAC is often recommended.]]> Mon 17 Oct 2022 11:23:24 AEDT ]]>