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Background/objectives: Previous studies have shown that a 2- bag 20-hour intravenous (IV) acetylcysteine regimen reduced the incidence of non-allergic anaphylactic reactions compared to the 3-bag 21-hour IV regimen for treatment of paracetamol overdose. We evaluated the safety and adverse reactions of the 2-bag IV acetylcysteine regimen in a larger international collaborative study. Method(s): This is a prospective cohort study of Australian centres using a 2-bag IV acetylcysteine regimen (200mg/kg over 4 hours, 100mg/kg over 16 hours) for paracetamol overdose, with data analysed from early 2014 to late 2018. Outcomes were compared with patients from the Canadian Acetaminophen Overdose Study (CAOS) treated with a 3-bag IV acetylcysteine regimen (150mg/kg over 15-60 min, 50mg/kg over 4 hours, 100mg/kg over 16 hours), 1980 to 2005. All subjects who receive acetylcysteine were included in the study. Outcomes including adverse reactions and mortality attributed to paracetamol overdose are reported. Adverse events to acetylcysteine included cutaneous (oedema, facial flushing, pruritus, urticaria) and systemic reactions (hypotension, respiratory symptoms). Result(s): Out of 15,037 paracetamol overdose presentations to 43 treatment centres, 7,663 received acetylcysteine. Study criteria were met in 1208 receiving the 2-bag and 6,455 receiving the 3- bag acetylcysteine regimen. Median years of age was 21 (IQR 17,32) vs 24 (17,37) in the 2 vs 3-bag acetylcysteine regimen, respectively. Median time to acetylcysteine was 7 hours (IQR 6,12) for the 2-bag vs 9.3 hours (6.2,19) for the 3-bag regimen. The incidence of cutaneous and systemic non-allergic anaphylactic reactions was: 22 (1.8%) with the 2-bag vs 528 (8.2%) with the 3-bag regimen (p < 0.0001, OR 0.2, 95%CI: 0.13-0.32). Mortality attributable to acetylcysteine was zero in both cohorts. Conclusion(s): In this multi-centre study, the 2-bag IV acetylcysteine regimen resulted in significantly less non-allergic anaphylactic r

Background/objectives: Previous studies of paracetamol overdose treatment show that a 2-bag, 20-hour intravenous (IV) acetylcysteine regimen decreased incidence of non-allergic anaphylactic reactions compared to the 3-bag, 21-hour IV regimen. We evaluated the efficacy and safety of the 2-bag IV acetylcysteine regimen. Method(s): This is a mixed retrospective/prospective observational study of paracetamol overdose from 2009 to mid-2019 in Australian centres currently using a 2-bag IV acetylcysteine regimen (200mg/kg over 4 hours, 100mg/kg over 16 hours). Outcomes are compared to a historical cohort treated at the same centres with a 3-bag IV acetylcysteine regimen. For the primary analysis: subjects had single, acute ingestions, a serum paracetamol-concentration performed 4 to 24-hours post-ingestion which was on or above the Rumack-Matthews treatment-nomogram line. The primary outcome was development of acute liver injury (ALI), defined as peak ALT >150 IU/L and double baseline. Result(s): Out of 6419 paracetamol overdose presentations to nine treatment centres, 2763 received acetylcysteine. For the primary analysis, 1003 received the 2-bag and 783 received the 3-bag acetylcysteine regimen. When presentation bloods were performed 8-hours post-overdose, 18 (2.6%) developed ALI with the 2-bag regimen vs 15 (2.6%) with the 3-bag regimen (p= 0.98 OR 1 95% CI: 0.50-2). When presentation bloods were performed 8 to 24-hours post-overdose, 66 (20%) developed ALI with the 2- bag regimen vs 46 (21%) with the 3-bag regimen (p= 0.51, OR 0.86, 95% CI 0.56-1.3). The incidence of hepatotoxicity (ALT >1000 IU/L) with the 2-bag regimen was: 49 (4.9%) vs 43 (5.5%) with the 3-bag regimen (p= 0.56, OR 0.88, 95% CI: 0.58-1.3)). Cutaneous and systemic non-allergic anaphylactic reactions were identified in: 20 (3%) with 2-bag vs 64 (8.1%) with 3-bag regimen (p= <0.0001, OR 0.2, 95% CI: 0.13-0.38). Conclusion(s): In this multi-centre study, the 2-bag IV acetylcysteine regimen was as effica

Objective: Previous studies have shown that a 2-bag 20-hour intravenous (IV) acetylcysteine regimen reduced the incidence of non-allergic anaphylactic (or "anaphylactoid") reactions compared to the 3-bag 21-hour IV regimen for treatment of paracetamol overdose in smaller cohort studies. We evaluated these reactions from the 2-bag IV acetylcysteine regimen in a larger international collaborative study. Method(s): This is an ongoing prospective cohort study of Australian centres using a 2-bag IV acetylcysteine regimen (200 mg/kg over 4 hours, 100 mg/kg over 16 hours) for paracetamol overdose, with data analysed from early 2014 to mid-2018. The comparison group consisted of patients from the Canadian Acetaminophen Overdose Study (CAOS) treated with a 3-bag IV acetylcysteine regimen (150 mg/kg over 15-60 minutes, 50 mg/kg over 4 hours, 100 mg/kg over 16 hours) from 1980 to 2005. Subjects all had single, acute ingestions and serum paracetamol concentration 4 to 24 hours post-ingestion that was on or above the Rumack-Matthew treatment-nomogram line. Outcomes including anaphylactoid reactions, and mortality attributed to acetylcysteine are reported. Anaphylactoid reactions to acetylcysteine included cutaneous (oedema, facial flushing, pruritus, urticaria) and systemic reactions (hypotension, respiratory symptoms). Categorical variables were compared using chisquared test. Result(s): Of 14479 paracetamol overdose presentations to 43 treatment centres, 10342 received acetylcysteine. Study criteria were met in 659 patients receiving the 2-bag and 2086 patients receiving the 3-bag acetylcysteine regimen. Median age was 21 years (IQR 17,32) versus 22 years (7,36) in the 2 versus 3-bag acetylcysteine regimen, respectively. Median time to acetylcysteine was 7 hours (IQR 6,12) for the 2-bag versus 8 hours (6,8.8) for the 3-bag regimen. The incidence of cutaneous and systemic anaphylactoid reactions was: 20 (3%) with 2-bag versus 148 (7.1%) with 3-bag regimen (p= 0.002, OR 0.41, 95

Objective: Previous studies have shown that a 2-bag 20-hour intravenous (IV) acetylcysteine regimen reduced the incidence of nonallergic anaphylactic reactions compared to the 3-bag 21-hour IV regimen for treatment of paracetamol overdose. We evaluated the efficacy and safety of the 2-bag IV acetylcysteine regimen. Method(s): This is an ongoing prospective cohort study of Australian centres using a 2-bag IV acetylcysteine regimen (200 mg/kg over 4 hours, 100 mg/kg over 16 hours) for paracetamol overdose. Outcomes were compared with historical data of patients treated with a 3-bag IV acetylcysteine regimen (150 mg/ kg over 60 minutes, 50 mg/kg over 4 hours, 100 mg/kg over 16 hours). Data was analysed from 2009 to mid-2018. Subjects all had single, acute ingestions and serum paracetamol concentration was performed 4 to 24 hours post-ingestion and was on or above the Rumack-Matthews treatment-nomogram line. The primary outcome was the development of acute liver injury (ALI), defined as peak ALT >150 IU/L and double baseline. Secondary outcomes included adverse reactions, hepatotoxicity (ALT/AST >1000), and mortality. Categorical variables were compared using chi-squared test. Result(s): Of 3996 paracetamol overdose presentations to 9 treatment centres, 1729 received acetylcysteine. Study criteria were met in 659 receiving the 2-bag and 532 receiving the 3-bag acetylcysteine regimen. Median time to acetylcysteine was 7 hours (IQR 6,12) for 2-bag versus 7 hours (5,10) for 3-bag regimens. When presentation bloods were performed <=8 hours post-overdose, 17 (3.9%) developed ALI with the 2-bag regimen versus 11 (2.7%) with the 3-bag regimen (p= 0.37 OR 1.4 95%CI: 0.66-3.07). When presentation bloods were performed 8-24 hours post-overdose, 39 (17.0%) developed ALI with the 2-bag regimen versus 28 (21.0%) with the 3-bag regimen (p= 0.34, OR 0.76, 95%CI 0.45-1.3). The incidence of hepatotoxicity with the 2-bag regimen was: 36 (5.4%) versus 23 (4.3%) with the 3-bag regimen (p=

Background: Death adders (Acanthophis spp) are found in Australia, Papua New Guinea and parts of eastern Indonesia. This study aimed to investigate the clinical syndrome of death adder envenoming and response to antivenom treatment. Methodology/Principal Findings: Definite death adder bites were recruited from the Australian Snakebite Project (ASP) as defined by expert identification or detection of death adder venom in blood. Clinical effects and laboratory results were collected prospectively, including the time course of neurotoxicity and response to treatment. Enzyme immunoassay was used to measure venom concentrations. Twenty nine patients had definite death adder bites; median age 45 yr (5-74 yr); 25 were male. Envenoming occurred in 14 patients. Two further patients had allergic reactions without envenoming, both snake handlers with previous death adder bites. Of 14 envenomed patients, 12 developed neurotoxicity characterised by ptosis (12), diplopia (9), bulbar weakness (7), intercostal muscle weakness (2) and limb weakness (2). Intubation and mechanical ventilation were required for two patients for 17 and 83 hours. The median time to onset of neurotoxicity was 4 hours (0.5-15.5 hr). One patient bitten by a northern death adder developed myotoxicity and one patient only developed systemic symptoms without neurotoxicity. No patient developed venom induced consumption coagulopathy. Antivenom was administered to 13 patients, all receiving one vial initially. The median time for resolution of neurotoxicity post-antivenom was 21 hours (5-168). The median peak venom concentration in 13 envenomed patients with blood samples was 22 ng/mL (4.4-245 ng/mL). In eight patients where post-antivenom bloods were available, no venom was detected after one vial of antivenom. Conclusions/Significance: Death adder envenoming is characterised by neurotoxicity, which is mild in most cases. One vial of death adder antivenom was sufficient to bind all circulating venom. The persis