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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.

Baclofen toxicity results from intentional self-poisoning (acute baclofen poisoning) or accumulation of therapeutic dose in the setting of impaired kidney function. Standard care includes baclofen discontinuation, respiratory support and seizure treatment. Use of extracorporeal treatments (ECTRs) is controversial. To clarify this, a comprehensive review of the literature on the effect of ECTRs in baclofen toxicity was performed and recommendations following EXTRIP methods were formulated based on 43 studies (1 comparative cohort, 1 aggregate results cohort, 1 pharmacokinetic modeling, and 40 patient reports or series). Toxicokinetic data were available for 20 patients. Baclofen's dialyzability is limited by a high endogenous clearance and a short half-life in patients with normal kidney function. The workgroup assessed baclofen as "Moderately dialyzable" by intermittent hemodialysis for patients with normal kidney function (quality of evidence C) and "Dialyzable" for patients with impaired kidney function (quality of evidence C). Clinical data were available for 25 patients with acute baclofen poisoning and 46 patients with toxicity from therapeutic baclofen in kidney impairment. No deaths or sequelae were reported. Mortality in historical controls was rare. No benefit of ECTR was identified in patients with acute baclofen poisoning. Indirect evidence suggests a benefit of ECTR in reducing the duration of toxic encephalopathy from therapeutic baclofen in kidney impairment. These potential benefits were balanced against added costs and harms related to the insertion of a catheter, the procedure itself, and the potential of baclofen withdrawal. Thus, the EXTRIP workgroup suggests against performing ECTR in addition to standard care for acute baclofen poisoning and suggests performing ECTR in toxicity from therapeutic baclofen in kidney impairment, especially in the presence of coma requiring mechanical ventilation., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

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.

Aims: Morbidity and mortality from drug overdose has decreased over three decades. This is credited to safer drugs and therefore better outcomes in overdose. We aimed to investigate changing prescriptions of antipsychotic medications and associated changes in antipsychotic overdoses over a 26-year period., Methods: All antipsychotic poisoning presentations to a tertiary referral toxicology unit between 1987 and 2012 were reviewed. Data were collected prospectively on demographics, ingestion information, clinical effects, complications and treatment. Rates of antipsychotic drug use in Australia were obtained from Australian government publications for 1990-2011 and linked to overdose admissions by postcode., Results: There were 3180 antipsychotic overdoses: 1235 first generation antipsychotics, 1695 'atypical' second generation antipsychotics and 250 lithium overdoses. Over 26 years, antipsychotic overdoses increased 1.8-fold, with first generation antipsychotics decreasing to one-fifth of their peak (≈80/year to 16) and second generation antipsychotics increasing to double this (≈160/year), olanzapine and quetiapine accounting for 78%. All antipsychotic overdoses had a median length of stay of 18.6 h, 15.7% admitted to intensive care unit, 10.4% ventilated and 0.13% died in hospital, which was the same for first generation compared to second generation antipsychotics. There was a 2.3-fold increase in antipsychotic prescriptions over the same period; first generation antipsychotics declined whereas there was a dramatic rise in second generation antipsychotics, mainly olanzapine, quetiapine and risperidone (79%)., Conclusion: Over 26 years there was an increase in antipsychotic prescribing associated with an increase in antipsychotic overdoses. Although the type of antipsychotics changed, the morbidity and mortality remained the same, so that antipsychotics are an increasing proportion of overdose admissions., (© 2016 The British Pharmacological Society.)

Study Objective: Antipsychotic drugs are frequently reported to cause QT prolongation and torsade de pointes. We aim to investigate the potential risk of torsade de pointes in antipsychotic overdose by assessing the QT interval with the QT nomogram., Methods: All presentations to a toxicology service between January 1987 and May 2013 were reviewed. Admissions with single ingestions of an antipsychotic greater than maximum daily dose were extracted. Demographics, dose, ECG, and outcomes (arrhythmias and death) were obtained. QT intervals in multiple leads were manually measured and the median taken. QT-heart rate (QT-HR) pairs were plotted on the QT nomogram and defined as prolonged if above the abnormal line. The QTcF (Fridericia's HR correction) was calculated and compared with dose., Results: From 2,356 antipsychotic overdoses, 494 were included. There were no abnormal QT-HR pairs in 4 aripiprazole, 31 pericyazine, 14 trifluoperazine, and 7 haloperidol overdoses. Abnormal QT intervals occurred in 9 of 16 amisulpride overdoses (56%; 95% confidence interval [CI] 31% to 79%), 16 of 57 thioridazine overdoses (28%; 95% CI 17% to 42%), and 5 of 29 chlorpromazine overdoses (17%; 95% CI 7% to 36%). Abnormal QT intervals occurred in 5 of 41 risperidone overdoses (12%; 95% CI 5% to 27%), 10 of 202 quetiapine overdoses (5%; 95% CI 3% to 9%), and 2 of 76 olanzapine overdoses (3%; 95% CI 0.5% to 10%), but there was no correlation between dose and QTcF, and most abnormal QT intervals were at fast HR. An additional 186 single antipsychotic ingestions with noncardiotoxic coingestants had similar proportions of abnormal QT. There was 1 case of torsade de pointes in a thioridazine overdose., Conclusion: There appeared to be significant risk of QT prolongation with amisulpride and thioridazine overdoses. Although there were abnormal QT intervals for quetiapine, olanzapine, and risperidone overdoses, they were associated with tachycardia and not dose dependent, and so were unlikely to be associated with increased torsade de pointes risk., (Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

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. To investigate tapentadol poisonings and related deaths in Australia. 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. 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). 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

For instance, associating shock or myocardial injury, as evidenced by troponin elevation, to a delayed QT interval does not reflect the underlying mechanisms of risk associated with the QT interval prolongation. Likewise, linking a drug that is unlikely to cause QT interval prolongation to delayed ECG changes that have presumably been caused by other factors may create a misunderstanding and could result in drugs being labelled at risk of causing QT interval prolongation when they do not. Drug induced QT prolongation: the measurement and assessment of the QT interval in clinical practice. [Extracted from the article]

Background: Intentional poisoning with warfarin is not the same as over-anticoagulation, for which guidelines exist. The coagulopathy resulting from a warfarin overdose is reversed with vitamin K1, the dose and timing of which is often guided by experience with the management of over-anticoagulation with warfarin therapy, rather than acute overdose.Case Report: We report a case of a 50-year-old man who ingested an unknown amount of his warfarin, venlafaxine, and paracetamol. He presented with an international normalized ratio (INR) of 2.5, which steadily increased over 24 h to 7, despite receiving an initial 1 mg of vitamin K1. He was then treated with 5 mg vitamin K1, and once the INR returned to 4.5, 40 h post ingestion, he was discharged home. He was also treated with a full course of acetylcysteine for the paracetamol overdose. The following day his INR rebounded to 8.5 and he suffered a spontaneous epistaxis requiring readmission; he was treated with low titrated doses of vitamin K1. The warfarin concentration was 74.6 μg/mL 26 h post ingestion and decreased to 3.7 μg/mL over 72 h. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case highlights the risk of a rebound elevated INR even 3 days after acute warfarin overdose despite treatment with vitamin K1. Understanding the pharmacokinetics of vitamin K1 in comparison with warfarin, repeat INR testing, and continued treatment with oral vitamin K1 may help avoid complications of rebound coagulopathy in warfarin overdose. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]