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Introduction: 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., Methods: 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., Results: 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., Discussion: 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., Conclusions: 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.

Introduction: Tapentadol is an atypical opioid with mu-receptor affinity and noradrenaline reuptake inhibition approved for use in Australia in 2011. However, data on tapentadol poisoning are scarce., Objectives: To investigate tapentadol poisonings and related deaths in Australia., Methods: We performed a retrospective review of tapentadol poisonings from New South Wales Poisons Information Centre (NSWPIC) and three toxicology units in Australia. The National Coronial Information System (NCIS) database was searched to determine the number of tapentadol-related deaths., Results: Between 2016 and 2020, 220 tapentadol calls were made to NSWPIC, with a 4.5-fold increase in tapentadol exposure calls. The median dose ingested was 575 mg (IQR: 300-1163 mg). Most overdoses included co-ingestions (75%), especially benzodiazepines (26%) and opioids (25%). From Jan 2016 to Dec 2021, 107 patients presented to the three toxicology units with tapentadol poisoning. The median dose ingested was 500 mg (IQR: 200-1400 mg). Most patients took co-ingestants (84%), including benzodiazepines (40%) and opioids (32%). Naloxone was administered in 39 patients (36%), 10 (9%) were intubated and the median length of stay was 18 h (IQR: 9-30). Thirty-five tapentadol-related deaths were recorded within NCIS between Jan 2015 and Oct 2021 with a median age of 51 years (IQR: 42-61 years)., Conclusion: There are increasing tapentadol poisonings and deaths reported to the NSWPIC, three toxicology units, and NCIS in Australia. Most tapentadol poisonings were taken with benzodiazepines and/or other opioids.

Context: Inpatient toxicology services undertake remote as well as inpatient management of poisoned patients. The aim of this study is to describe the introduction of a tablet-based electronic data collection tool allowing data to be captured on inpatient and remote consultations. Methods: Retrospective review of all cases entered in the database from 1 March 2014 to 28 February 2016. Data collected included demographics (age, sex), clinical details (exposure category), presentation facility and disposition. Results: The database included 3616 cases: 59 (1.6%) were excluded due to inadequate details, 122 (3.4%) had no electronic medical record available, 1985 (54.9%) presented to the inpatient unit facility and 1450 (40.1%) were external consultations. Of these 1450, 223 (6.2%) were paediatric (aged less than 12 years), 395 (10.9%) adolescent (12-17 years) and 832 (23.0%) adults (18 years and over). The proportion of paediatric cases (median age 2 y; 45.7% females) with pharmaceutical ingestions was 122 (54.7%; 95% confidence intervals (CIs): 48.2-61.1) compared with 345 (87.3%; 95% CI: 83.7-90.3) in adolescents (median age 15 y; 79.5% females). Of the adult presentations, 659 (18.2%) were metropolitan/regional facility presentations and 173 (4.8%) rural facilities with 125 (3.4%) adults subsequently transferred to the inpatient facility. Median age was 38 years (interquartile range (IQR) 35-52) with 338 (51.4%) females in the metropolitan group and 37 years (IQR 26-48) with 51 (30.5%) females in the rural group. There were more bites and stings in the rural group, 41 (23.7%; 95% CI: 18.0-30.6) versus 54 (8.2%; 95% CI: 6.3-10.5), more recreational substance exposures 27 (15.6%; 95% CI: 11.0-21.8) versus 40 (6.1%; 95% CI: 4.5-8.2) and less pharmaceutical exposures 93 (53.8%; 95% CI: 46.3-61.0) versus 462 (70.1%; 95% CI: 66.5-73.5). Conclusions: The tablet based database provided useful information on populations of poisoned patients not accessible previously. It demonstrated important differences in the types of patients presenting to rural versus metropolitan hospitals.

Background: The assessment and management of patients with QT interval prolongation in poisoning requires an appropriate method of measuring and adjusting the QT interval for the heart rate (HR) in order to decide if the patient is at risk of life-threatening dysrhythmias, notably torsade de pointes (TdP). As the Clinical Toxicology Collaborative (CTC) workgroup reviewed the published literature on drug-induced QT interval prolongation in poisoning, it became obvious that many publications were missing essential data that were necessary to thoroughly assess and compare the evidence. The aim of this guidance document is to identify essential and ideal criteria required when reporting a case of drug-induced QT interval prolongation and/or TdP in poisoning. Methods: We employed a mixed methods approach as follows. Initially, we reviewed 188 cases of available published case reports and series in the literature regarding drug-induced QT interval prolongation and/or TdP in poisoning as the first step to another project. Common features and deficiencies were identified. Given the large gaps in reporting quality, we conducted an iterative consultative process involving all 23 members of the CTC to identify essential and ideal criteria to analyse publications of QT interval prolongation in poisoning. A priori standards were developed for acceptance or rejection of individual criteria. Results: Survey response was 100%. A minimum set of essential criteria for reporting cases of QT interval prolongation and drug-induced TdP in overdose setting are provided and a 35-item checklist is presented. Conclusions: We report a QT reporting checklist to ensure published case reports and series describing drug-induced QT interval prolongation in poisoning can contribute to the fund of knowledge of QT interval prolongation, TdP and other malignant dysrhythmias.

Context: The current 3-phase acetylcysteine infusion for paracetamol poisoning delivers half the dose over 15-60 min and frequently results in adverse reactions., Objective: We aimed to determine adverse reaction frequency with a modified 2-phase infusion protocol with a longer initial infusion., Materials and Methods: A prospective observational study of a modified 2-phase acetylcysteine protocol was undertaken at two hospitals. Acetylcysteine was commenced on admission and ceased if paracetamol concentrations were low-risk (below the nomogram line). The first infusion was 200 mg/kg over 4-9 h based on ingestion time or 4 h for staggered/chronic ingestions. The second infusion was 100 mg/kg over 16 h. Pre-defined outcomes were frequency of adverse reactions (systemic hypersensitivity reactions or gastrointestinal); proportion with alanine transaminase (ALT) > 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.

Case Report: We report a fatal case of a 37 year old gentleman who ingested a MCPA/bromoxynil co-formulation herbicide. Although clinically well on initial examination, our patient declined dramatically over his 18 h admission with increasing CO2 production, hyperthermia and metabolic derangement to eventually die from cardiac asystole 20 h post ingestion. Two hours after ingestion the MCPA concentration was 83.9 μg/mL and bromoxynil concentration was 137 μg/mL., Discussion: The patients' mechanism of death appeared to be uncoupling of oxidative phosphorylation, excess CO2 production and hyperthermia. There is limited knowledge on the acute toxicity of these herbicides, in particular bromoxynil, and this case highlights the relentless progression of severe toxicity in humans.

Context: Toxicity from recreational substances marketed for other purposes is a well-documented clinical entity. We present two cases of phenibut toxicity procured via the internet., Case Details: A 20-year-old female presented to the emergency department (ED) having used phenibut the prior day. The main finding was a decreased level of consciousness, however when roused she became delirious. Supportive care only was required with no specific intervention. The patient made a full recovery over a 24-hour period and admitted to use of phenibut purchased online. Plasma phenibut concentration was 29.7 μg/ml. A 38-year-old male presented to ED with an agitated delirium. The prior evening he had used tetrahydrocannabinol or THC, alcohol and phenibut, the latter purchased via the internet. His behavioural state had a suboptimal response to parenteral sedation. He was subsequently intubated for airway protection in the context of ongoing sedation to optimally manage his behavioural state. Post extubation the next morning he admitted using phenibut. Plasma phenibut concentration was 36.5 μg/ml., Discussion: Altered mental status was the predominant manifestation of phenibut toxicity in these cases. Clinicians to be aware of how phenibut toxicity may present as the internet has widened access to such substances.

We present a case of intravenous (IV) paracetamol overdose in a nutritionally malnourished child during hospital admission. A ten-fold IV paracetamol dosing error ocurred, with delayed recognition and treatment resulting in transient hepatotoxicity, with a peak alanine transaminase (ALT) of 1378 IU/L in a 3-year-old child. Our case suggests that hepatotoxicity may occur for lower doses of IV paracetamol compared to oral ingestion, especially in the malnourished, and that a dose less than 150 mg/kg of IV paracetamol should be used to define treatment following overdose in a child with potential nutritional deficiencies.

Objective: QT prolongation is an important complication in drug overdose, particularly with some antidepressants and antipsychotics. There are problems with the accurate measurement of the QT interval and determining for what QT interval patients should be monitored, because of the risk of torsades des pointes (TdP). We report a case of ziprasidone overdose with QT prolongation, demonstrating different methods of measuring the QT interval., Case Report: A 47-year-old female presented after taking 1.2 g of ziprasidone and 250 mg of diazepam. She was taking propranolol and venlafaxine therapeutically. She developed bradycardia and QT prolongation (540 msec). She was transferred to a telemetry bed and observed for 48 h until her QT interval returned to normal (460 msec). QT intervals were extracted from (1) 12-lead digital Holter recordings (gold standard); (2) automated measurements on standard electrocardiograms (ECGs); and (3) manual measurements on standard ECGs, and compared on a QT versus time plot. An abnormal QT was determined based on the QT nomogram. Manual QT measurements showed a clear temporal association between ziprasidone overdose and a long QT, consistent with accurate QT measurements using continuous 12-lead Holter recordings with automatic QT measurements. However, standard automated measurements did not indicate an abnormal QT., Conclusions: Manual measurement of the QT interval appeared to be similar to the more accurate measurement of the QT by automated digital Holter recordings and better than standard automated measurements. Manual QT measurements would be more appropriate in clinical assessment of patients.