https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 Retrospective evaluation of repeated supratherapeutic ingestion (RSTI) of paracetamol https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47721 1000 U/L). Method: Retrospective review of paracetamol RSTI presentations to two toxicology services over a four-year period. Patients were included if they ingested >4 g per 24 h of paracetamol for a period >8 h, regardless of intent. Data collected included demographics, ingestion history, pathology results, treatments and outcomes. Results: 266 patients were identified with median ingested dose of 9 g per 24 h (IQR: 6–12 g) over a median of 2 days (IQR: 1–5 days). On presentation, paracetamol was detected in 192 (72%), with median concentration of 14 mg/L (IQR: 7–27 mg/L). Median ALT on admission in those developing hepatotoxicity was significantly higher, 1182 U/L (IQR: 598–4251 U/L), compared to 30 U/L (IQR: 18–59 U/L; p < .0001) in those who did not. All 17 who developed hepatotoxicity had an ALT ≥50 U/L on presentation. Five patients presenting with an ALT <50 U/L developed a peak ALT between 50 and 1000 U/L, of which three had a paracetamol concentration <20 mg/L. 139 (52%) received acetylcysteine, of which 64 received an abbreviated course (<20 h), with a median length of infusion of 11 h (IQR: 7–14 h). 127 (48%) patients were not treated with acetylcysteine, none of these patients returned to hospital. Conclusions: Our results confirm that those developing hepatotoxicity from RSTI of paracetamol have an elevated ALT on presentation. Presenting ALT <50 U/L appears to be a safe threshold not to administer acetylcysteine, provided the paracetamol concentration is low.]]> Wed 25 Jan 2023 13:37:11 AEDT ]]> Authors' reply to Thomas and colleagues https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23169 150 mg/kg is ingested. However, 75 mg/kg is used in many UK sources, including a flow chart on the Royal College of Emergency Medicine website, NHS trust guidelines and a 2015 BMJ Best Practice monograph.]]> Wed 24 Aug 2016 16:12:42 AEST ]]> Predicting the requirement for N-acetylcysteine in paracetamol poisoning from reported dose https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14405 1000 U/L) and treatment (single dose-activated charcoal [SDAC] and NAC) were analysed. Data were analysed within a repeated measures logistic regression framework using NONMEM (ver 7.2). The primary outcome was administration of NAC, which was determined based on a serum paracetamol concentration greater than the nomogram line. Result.: There were 1571 admissions in 1303 patients, with a median age of 27 years (12–96 years) and 1140 (73%) were females. The median dose was 10 g (1–100 g). The paracetamol concentration was above the nomogram line in 337 of 1571 (22%) patients. Patients presenting later (first paracetamol concentration between 7 and 16 h post-overdose) compared to those presenting earlier (4–7 h post-overdose) were more likely to have hepatotoxicity (5.5% vs. 0.4%; p < 0.0001), have a toxic paracetamol concentration (34% vs. 18%; p  0.0001) and receive NAC (48% vs. 23%; p < 0.0001). SDAC reduced the probability of the paracetamol concentration being above the nomogram. Based on SDAC not being administered there was a 5% probability of requiring NAC at a dose of 6–9 g, a 10% chance of requiring NAC at a dose of 13–16 g, a 50% chance of requiring NAC at a dose of 30–34 g and a 90% chance for needing NAC at 48–50 g. Conclusion. Reported dose was a good predictor of a toxic paracetamol concentration and SDAC reduced the probability of the concentration being above the nomogram. These predictions may assist in determining which patients could be started on NAC immediately.]]> Sat 24 Mar 2018 08:24:53 AEDT ]]> Design and rationale of a 16-week adjunctive randomized placebo-controlled trial of mitochondrial agents for the treatment of bipolar depression https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26171 Sat 24 Mar 2018 07:30:06 AEDT ]]> Evidence for the changing regimens of acetylcysteine https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26190 Sat 24 Mar 2018 07:24:09 AEDT ]]> A prospective observational study of a novel 2-phase infusion protocol for the administration of acetylcysteine in paracetamol poisoning https://nova.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 ]]> Massive paracetamol overdose: an observational study of the effect of activated charcoal and increased acetylcysteine dose (ATOM-2) https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34253 1000 U/L). Results: Two hundred paracetamol overdoses were analysed, reported median dose ingested was 50 g (interquartile range (IQR): 45-60 g) and median paracetamol ratio 1.9 (IQR: 1.4-2.9, n = 173). One hundred and ninety-three received acetylcysteine at median time of 6.3 h (IQR: 4-9.3 h) post-ingestion. Twenty-eight (14%) developed hepatotoxicity, including six treated within 8 h of ingestion. Activated charcoal was administered to 49(25%), at median of 2 h post-ingestion (IQR:1.5-5 h). Those receiving activated charcoal (within 4 h of ingestion), had significantly lower paracetamol ratio versus those who did not: 1.4 (n = 33, IQR: 1.1-1.6) versus 2.2 (n = 140, IQR: 1.5-3.0) (p < .0001) (paracetamol concentration measured ≥ 1 h after charcoal). Furthermore, they had lower rates of hepatotoxicity [unadjusted OR: 0.12 (95% CI: < 0.001-0.91); adjusted for time to acetylcysteine OR: 0.20 (95%CI: 0.002-1.74)]. Seventy-nine had a paracetamol ratio ≥2, 43 received an increased dose of acetylcysteine in the first 21 h; most commonly a double dose in the last bag (100 to 200 mg/kg/16 h). Those receiving increased acetylcysteine had a significant decrease risk of hepatotoxicity [OR:0.27 (95% CI: 0.08-0.94)] . The OR remained similar after adjustment for time to acetylcysteine and paracetamol ratio. Conclusion: Massive paracetamol overdose can result in hepatotoxicity despite early treatment. Paracetamol concentrations were markedly reduced in those receiving activated charcoal within 4 h. In those with high paracetamol concentrations, treatment with increased acetylcysteine dose within 21 h was associated with a significant reduction in hepatotoxicity.]]> Fri 22 Feb 2019 16:55:23 AEDT ]]> Mixed Methods Thematic Analysis of a Randomised Controlled Trial of Adjunctive Mitochondrial Agents for Bipolar Depression https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51362 Fri 01 Sep 2023 13:44:30 AEST ]]>