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Serotonin syndrome (toxicity), resulting from an excessive accumulation of serotonin in the central nervous system, it can occur due to various factors such as the initiation of medication, overdose or drug interactions. Diagnosing serotonin toxicity presents challenges as there are no definitive criteria. This review delves into the pathophysiology, incidence, clinical assessment and management of serotonin toxicity, stressing the significance of promptly recognizing and managing severe cases. Diagnosis relies primarily relies on clinical assessment due to the absence of specific laboratory tests. The Hunter Serotonin Toxicity criteria are commonly utilized but have only been validated in the overdose setting. Assessing the severity of toxicity is crucial for guiding management decisions. Supportive care, discontinuation of causative agents and symptomatic treatment are prioritized in management. Mild toxicity often requires withdrawal or reduction of the serotonergic agent, while more severe toxicity requires more aggressive resuscitative and supportive care. Severe serotonin toxicity characterized by hyperthermia and rigidity requires aggressive supportive measures, including benzodiazepines, intubation, paralysis and active cooling. Animal studies suggest potential benefits of 5‐HT2A receptor antagonists in preventing hyperthermia and fatalities, but only at high doses. Their clinical effectiveness remains uncertain, and evidence is predominately from case series and case reports. Although commonly used, serotonin antagonists like cyproheptadine lack conclusive evidence of efficacy. Other serotonin antagonists such as chlorpromazine and olanzapine have been explored but evidence is limited to case reports. Hence, the cornerstone of treating severe cases does not lie in ‘antidote’ administration or even diagnosis but in effective early resuscitative and supportive care. [ABSTRACT FROM AUTHOR]

Antivenom is first line treatment for snake envenomation worldwide, despite few placebo controlled clinical trials demonstrating effectiveness. We aimed to investigate whether early antivenom in red-bellied black snake (Pseudechis porphyriacus) bites would prevent systemic myotoxicity. We undertook a multicentre randomized placebo-controlled trial of antivenom for red-bellied black snake bites with patients recruited from the Australian Snakebite Project (July 2014 to June 2020). In addition, we report all patients with red-bellied black snake bites during the same period, comparing the same outcomes. Patients over 2 years of age with definite red-bellied black snake bites and early systemic effects were randomized to receive 50 per cent glucose (placebo) or tiger snake antivenom within 6 hours post-bite, or in the cohort group received antivenom determined by the treating clinician. The primary outcome was the proportion of patients with myotoxicity (peak creatine kinase activity >1,000 U/L). Secondary outcomes were: area under the curve of total creatine kinase elevation over 48 hours, presence of venom post-antivenom, and adverse reactions. We analyzed both the randomized control trial patients and the combination of randomized control trial and cohort patients. Fifteen patients were recruited to the randomized controlled trial, and a cohort of 68 patients who were not randomized were included in the analysis. After treatment, two of seven patients given placebo had a peak creatine kinase activity >1,000 U/L versus none of the eight given antivenom (difference in favour of antivenom; 29 per cent; 95 per cent confidence interval:-18 per cent to +70 per cent; P = 0.2). The median area under the curve of total creatine kinase elevation over 48 hours in patients given placebo was 0 U/L*h (interquartile range: 0–124 U/L*h), which was not significantly different to those given antivenom: 197 U/L*h (interquartile range: 0–66,353 U/L*h; P = 0.26). Venom was not detected post-antivenom in six patients with measured venom concentrations given antivenom. Two patients given antivenom had immediate hypersensitivity reactions, one severe anaphylaxis, and another had serum sickness. Combining randomized and not randomized patients, three of 36 (8 per cent) administered antivenom less than 6 hours post-bite had a peak creatine kinase activity >1,000 U/L versus 17/47 (36 per cent) patients not receiving antivenom less than 6 hours post-bite (difference in favour of antivenom 29 per cent; 95 per cent confidence interval: 8 per cent to 44 per cent; P < 0.004). Overall, 13/36 (36 per cent) patients administered antivenom within 6 hours had hypersensitivity reactions, six severe anaphylaxis (17 per cent). We found that early antivenom was effective in red-bellied black snake bites, and only three patients need to be given antivenom within 6 hours to prevent myotoxicity in one (number needed to treat = 3). However, one in three patients administered antivenom developed a hypersensitivity reaction, and one in six had severe anaphylaxis. The major limitation of this study was the small number of patients recruited to the randomized controlled trial. Administration of antivenom in red-bellied black snake envenomation within 6 hours post-bite appeared to decrease the proportion of patients with myotoxicity, but a third of patients had adverse reactions. [ABSTRACT FROM AUTHOR]

Chlorpromazine, one of the oldest antipsychotic medications, remains widely available and is still taken in overdose. We aimed to investigate the clinical effects of chlorpromazine overdose and determine if there is a relationship between the reported dose ingested and intensive care unit admission or endotracheal intubation. We performed a retrospective analysis of patients admitted to our toxicology tertiary referral hospital with chlorpromazine overdose (reported dose ingested greater than 300 mg) between 1987 and 2023. We extracted demographic information, details of ingestion, clinical effects and complications (Glasgow Coma Scale, hypotension [systolic blood pressure less than 90 mmHg], delirium, dysrhythmias), length of stay, intensive care unit admission, and endotracheal intubation. There were 218 chlorpromazine overdose cases, with presentations decreasing in frequency over the 36 years. The median age at presentation was 32 years (interquartile range: 25–40 years) and 143 (61 per cent) were female. The median reported dose ingested was 1,250 mg (interquartile range; 700–2,500 mg). The majority of presentations (135; 62 per cent) involved reported co-ingestion of other medications, typically benzodiazepines, paracetamol or antipsychotics. There were 76 (35 per cent) chlorpromazine alone ingestions in which there was a slightly higher median reported dose ingested of 1,650 mg (interquartile range: 763–3,000 mg) compared to the reported co-ingestion group, median reported dose ingested of 1,200 mg (interquartile range: 700–2,100 mg). Of all presentations, 36 (27 per cent) had a Glasgow Coma Scale less than 9, 50 (23 per cent) were admitted to the intensive care unit, and 32 (15 per cent) were endotracheally intubated. There was a significant difference in the median reported dose ingested between patients intubated (2,000 mg; interquartile range: 1,388–3,375 mg) and those not intubated (1,200 mg; interquartile range: 644–2,050mg; P < 0.001), and between those admitted to the intensive care unit and not admitted to the intensive care unit (P < 0.0001). The median reported dose ingested in seven chlorpromazine alone presentations who were intubated was 2,500 mg (interquartile range: 2,000–8,000 mg, range: 1,800–20,000 mg). Eighteen (8 per cent) patients developed delirium, eight (4 per cent) had hypotension, three had seizures, and there was one death. Almost one quarter of cases were admitted to the intensive care unit and over half of these were intubated. Whist the decision to admit to an intensive care unit or intubate a patient is based on clinical need, there was a significant association between reported dose ingested and requirement for endotracheal intubation. Both the frequency of presentation and reported dose ingested declined after 2013. The major limitations of the study were a retrospective design and no analytical confirmation of ingestion. We found that the most common effect of chlorpromazine overdose was central nervous system depression and that endotracheal intubation was associated with larger reported doses ingested, particularly in single chlorpromazine ingestions. [ABSTRACT FROM AUTHOR]

Antivenom is widely accepted as an effective treatment for snake envenomation. This is despite very limited evidence supporting clinical effectiveness for major envenomation syndromes, and is mainly based on pre-clinical studies and observational studies without control groups. Although antivenom exhibits efficacy by binding to snake toxins and preventing toxic injury in animals if pre-mixed with venom, this efficacy does not always translate to clinical effectiveness. There are many irreversible venom mediated effects that antivenom cannot neutralise or reverse, such as pre-synaptic neurotoxicity and myotoxicity. Fortunately, early antivenom appears to prevent some of these. With good evidence that early antivenom prevents some envenomation syndromes, the time between bite and antivenom administration must be reduced. This requires improving the initial assessment of snakebite patients, and improving early decision making based on clinical effects. Until there are improved, simplified, easy to use, rapid and inexpensive tests, whether available in the laboratory or preferably at the bedside that identify systemic envenomation, the key to early antivenom administration is early assessment and decision making based on systemic symptoms, including nausea, vomiting, headache and abdominal pain. [ABSTRACT FROM AUTHOR]

Methotrexate toxicity following intravenous (IV) methotrexate is well reported, but there is less information on accidental daily dosing of a prescribed weekly dose of oral methotrexate. A 70 year old female presented following accidentally taking 20 mg methotrexate for five days, with multiple oral ulcers, thrombocytopenia (platelets 80 x 109/L [reference range[RR]:150-400 x 109/L]) and an alanine aminotransferase 820 U/L [RR:10-35 U/L]. Methotrexate was undetectable [<0.04 µmol/L]. She was treated with folinic acid, 15 mg orally and then 15 mg IV every six hours. She became progressively pancytopenic, with the lowest counts occurring days 3-6: Hb, 87 g/L, platelets, 22 x 109/L, neutrophils, 0.0 x 109/L [RR:2-8 x 109/L] and white cell count, 0.6 x 109/L [RR:4-11 x 109/L]. She received 2 units of platelets, filgrastim 300 mcg daily for days 3-7 and IV ceftazidime/gentamicin for a fever. On day 6, her platelet and neutrophil counts began to recover, and her ALT was almost normal on discharge day 9. She had alopecia in the 3 months post-discharge. Our patient developed severe toxicity, consistent with complete absorption and cellular uptake of methotrexate, with slow cellular elimination. She was treated with folinic acid, granulocyte-colony stimulating factor and blood product transfusions. [ABSTRACT FROM AUTHOR]

Objective: Opioid‐related harm has risen in recent decades, but limited research describes the clinical burden of opioid poisoning to Australian EDs. We aimed to investigate hospital presentations with opioid poisoning over three decades. Methods: This is an observational series of prospectively collected data investigating presentations of opioid poisoning to an ED in Newcastle (1990–2021). Type of opioid, naloxone administration, intubation, intensive care unit (ICU) admission, length of stay and death were extracted from the unit's database. Results: There were 4492 presentations in 3574 patients (median age 36, 57.7% female), increasing from an average of 93 presentations annually in the first decade to 199 in the third decade. Deliberate self‐poisonings accounted for 3694 presentations (82.2%). Heroin dominated the 1990s, peaking in 1999 before decreasing. Prescription opioids then rose, with codeine (usually in paracetamol combination) predominating until 2018, after which oxycodone presentations exceeded them. Methadone consistently increased from six presentations annually in the first decade to 16 in the last decade. Naloxone was administered in 990 (22.0%) presentations and 266 (5.9%) were intubated, most frequently following methadone and heroin exposures. ICU admissions increased from 5% in 1990 to 16% in 2021. Codeine exposures resulted in less severe effects, whereas methadone had more severe effects overall. The median length of stay was 17 h (interquartile range 9–27 h). There were 28 deaths (0.6%). Conclusion: Opioid presentations increased in number and severity over three decades as the type of opioid changed. Oxycodone is currently the main opioid of concern. Methadone poisoning was the most severe. [ABSTRACT FROM AUTHOR]