Suggested guide to using lactate gap as a surrogate marker in the diagnosis of ethylene glycol overdose.

BBACKGROUND: Ethylene glycol (EG) poisoning, if not diagnosed rapidly, can lead to poor patient outcomes. Gas Chromatography (GC) is primarily used for EG quantitation which is rarely available, and the turn-around time may be prolonged. Most lactate results from point-of care (POCT) methods are falsely elevated in EG poisoning compared with automated chemistry analyser results. In combination the lactate gap (POCT-Automated chemistry) can be used as surrogate marker in just about all laboratories to indicate likely EG toxicity and guide treatment. CASE REPORT: A male presented by ambulance to hospital with severe agitation requiring mechanical ventilation to facilitate ongoing management. Venous blood gas analysis confirmed a high anion gap metabolic acidosis (HAGMA) with an elevated lactate. The lactate and osmolarity measured in the laboratory showed a normal lactate and high osmolarity, giving a large osmolar gap. The patient was immediately commenced on renal replacement therapy for presumed EG poisoning to minimize kidney injury, and the treatment continued for 19 hours. A very high EG concentration was confirmed by GC the next day. CONCLUSION: An elevated lactate gap along with a HAGMA and osmolar gap can provide rapid surrogate laboratory data indicating EG poisoning enabling timely treatment and better patient outcomes.

Effectiveness of intramuscular naloxone 1,600 µg in addition to titrated intravenous naloxone 100 µg for opioid poisoning: a randomised controlled trial.

INTRODUCTION: Naloxone is an effective antidote, but its short half-life means repeated doses, and infusions are often required. We investigated the effectiveness of adding intramuscular naloxone to titrated intravenous naloxone in opioid overdose in preventing recurrence of respiratory depression. METHODS: This double-blinded randomised placebo-controlled trial was conducted in patients with suspected opioid poisoning and respiratory depression (respiratory rate <10 breaths/min or oxygen saturation <93%). Patients were randomised to receive either intramuscular naloxone 1,600 µg or saline placebo. All patients received titrated intravenous naloxone 100 µg and were managed on an opioid poisoning care pathway. The primary outcome was recurrence of respiratory depression within 4 h. Secondary outcomes were the proportion receiving naloxone infusions, number of naloxone boluses administered, reversal of respiratory depression at 10 min, and precipitation of opioid withdrawal (any symptom). RESULTS: Recurrence of respiratory depression within 4 h was less common in 28/69 (41%) patients receiving intramuscular naloxone versus 48/67 (72%) patients receiving placebo (difference 31%, 95% CI: 13-46%; P < 0.001). Fewer naloxone infusions (5/69; 7% versus 25/67; 37%, difference 30%, 95% CI: 15 to 55%; P < 0.001) and fewer naloxone doses were administered (median 2, IQR: 1 to 5, versus median 5, IQR: 2 to 8; P = 0.001) in the intramuscular group. Reversal of respiratory depression at 10 min was similar between groups (51/69; 74% intramuscular naloxone versus 47/67; 70% placebo; P = 0.703). Opioid withdrawal occurred in 35/69 (51%) given intramuscular naloxone compared to 28/67 (42%) in the placebo group (difference 9%; 95% CI: -8 to 27%; P = 0.308). DISCUSSION: The favourable pharmacokinetics of intramuscular naloxone, particularly its longer duration of activity, likely explains the improved effectiveness with lower recurrence of respiratory depression. CONCLUSION: The addition of intramuscular naloxone 1,600 µg to titrated intravenous naloxone prolonged effective reversal of respiratory depression, with fewer naloxone doses and infusions given, and no significant difference in patients developing withdrawal.

Calcium channel blocker overdose: Not all the same toxicity.

AIMS: Calcium channel blocker (CCB) overdose remains an important poisoning, with increasing availability of dihydropyridines. We aimed to compare the severity and treatment of CCB overdoses. METHODS: We reviewed CCB overdoses presenting to two toxicology services from 2014 to 2023. We extracted prospectively collected data from a clinical database, including demographics, dose, co-ingestants, complications, treatments and outcomes, to compare different CCBs. RESULTS: There were 236 overdoses; median age 55 years (interquartile range [IQR]: 41-65 years); 130 (55%) were females. Dihydropyridine overdoses increased significantly: median of nine cases annually (IQR: 8.8-12.3) during the study compared to a median of three cases annually (IQR: 1-4.3; P < 0.001) in the 10 years prior. The commonest agent was amlodipine (147), then lercanidipine (28), diltiazem (27), verapamil (23) and felodipine (11). Median defined daily dose ingested was higher for dihydropyridines, and cardiac co-ingestants were common except verapamil. Median length of stay was 21 h (IQR: 13-43 h), which was similar except longer for diltiazem (median, 39 h). Fifty-six patients (24%) were admitted to intensive care, more often for diltiazem (14; 52%) and verapamil (7; 30%). Dysrhythmias occurred in 19 patients (diltiazem [9], verapamil [8], amlodipine [2]), and included 13 junctional dysrhythmias. Hypotension occurred in 91 patients (39%), 62 (26%) received inotropes/vasopressors (adrenaline 32 [52%], noradrenaline 48 [77%]), 21 (9%) high-dose insulin and 44 (19%) calcium. Adrenaline and high-dose insulin were more commonly given in diltiazem and verapamil overdoses, compared to vasopressors in dihydropyridine overdoses. Acute kidney injury occurred in 39 patients. Seven (3%) patients died. CONCLUSIONS: Dihydropyridines were the commonest CCB overdoses, with amlodipine making up half. More severe toxicity occurred with diltiazem and verapamil.

Rationalising the dose threshold for severe carbamazepine toxicity: a retrospective series.

INTRODUCTION: Carbamazepine causes dose-dependent toxicity in overdose. Resources commonly state that severe toxicity occurs with ingestions >50 mg/kg without supporting evidence. We aimed to compare ingested dose with clinical toxicity. METHODS: This was a retrospective series of patients reportedly ingesting carbamazepine >2,000 mg referred to a clinical toxicology unit and state poisons information centre. Medical records were reviewed to extract patient demographics, ingestion details, clinical effects and management. Severe toxicity was defined as the presence of coma (Glasgow Coma Scale <9), seizure, or hypotension (systolic blood pressure <90 mmHg). RESULTS: There were 69 presentations in 42 patients with a median ingested carbamazepine dose of 113 mg/kg (IQR: 71-151 mg/kg). Coma occurred in 10 cases, eight having ingested >200 mg/kg and the remaining two ingesting 113 mg/kg and 151 mg/kg, respectively. Seizures occurred in four cases (lowest ingested dose 143 mg/kg). Hypotension occurred in five cases (lowest ingested dose 113 mg/kg). DISCUSSION: Severe carbamazepine toxicity did not occur with reported ingestions <100 mg/kg and was uncommon in ingestions <200 mg/kg. CONCLUSION: Severe toxicity was common in ingestions >200 mg/kg. Using the suggested threshold of severe toxicity of >50 mg/kg appeared overly conservative in this series.

Growing burden of gamma-hydroxybutyrate intoxication on emergency department resource utilisation.

OBJECTIVE: Recreational gamma-hydroxybutyrate (GHB) use is rising in Australia. We aimed to describe ED presentation patterns related to GHB over time and the impact this has on ED resource use. METHODS: Retrospective review of prospective data collection from two clinical toxicology units based in Queensland and New South Wales. RESULTS: There were 751 GHB-related presentations to the two units (Newcastle, 127; Princess Alexandria, 624), with marked increases in presentations occurring in 2019 and 2023. The major intervention was intubation, with 95 (13%) patients intubated. CONCLUSION: GHB presentations to ED are rising and the impact on acute bed space and clinical resources is significant.

Virtual Toxicology Service decreases the average length of stay of poisoned patients and saves bed days.

OBJECTIVE: We aimed to assess the impact a Virtual Toxicology Service had on the ALOS of poisoned patients. METHODS: This single-centre before-after study compares the ALOS of poisoned patients (diagnosis-related group X62, poisoning/toxic effects of drugs and other substances) following the introduction of a Virtual Toxicology Service in 2020. RESULTS: The ALOS decreased from 0.89 days in the 2-year pre-intervention period to 0.62 days in the 3-year post-intervention period, with a potential bed saving of 703 days. CONCLUSION: The introduction of a Virtual Toxicology Service appeared to be associated with a decreased ALOS of poisoned patients.

Bedside urine testing for fentanyl in self-reported heroin users in a tertiary Brisbane emergency department.

OBJECTIVE: To determine if patients presenting to our toxicology unit following self-reported heroin use had positive urine immunoassay testing for fentanyl or its analogues. METHODS: Urine samples from consenting patients were tested at the bedside for the presence of opiates or fentanyl and its analogues. RESULTS: Over a 30-month period, 58 patients were recruited. All samples tested positive for opiates, but none tested positive for fentanyl or its analogues. CONCLUSION: In patients presenting to our toxicology unit in Brisbane, we did not find any cases where the urine of patients self-reporting heroin exposure tested positive for fentanyl or its analogues.

Rivastigmine for the management of anticholinergic delirium.

INTRODUCTION: Anticholinergic agents are commonly taken in overdose, often causing delirium. The spectrum of anticholinergic delirium ranges from mild agitation to severe behavioural disturbance. Physostigmine is an effective treatment for anticholinergic delirium, but its availability is limited. As rivastigmine is readily available, it has been used to manage anticholinergic delirium; however, there is limited research investigating its use. METHOD: This was a retrospective review of patients with anticholinergic delirium treated in two toxicology units with rivastigmine (oral capsule or transdermal patch) from January 2019 to June 2023. The primary outcome was the use of further parenteral treatment (sedation or physostigmine) for delirium post rivastigmine administration. RESULTS: Fifty patients were administered rivastigmine for the management of anticholinergic delirium. The median age was 36 years (interquartile range: 25-49 years) and 27 (54 per cent) were females. Features consistent with anticholinergic toxicity included tachycardia in 44 (88 per cent) and urinary retention requiring catheterisation in 40 (80 per cent). Forty-three patients (86 per cent) were treated with physostigmine before rivastigmine administration. Twenty-two were managed with transdermal rivastigmine (most commonly 9.5 mg/24 hour patch), and 28 with oral rivastigmine 6 mg. Further parenteral sedation and/or physostigmine treatment were required more often in patients given transdermal than oral rivastigmine [16/22 (73 per cent) versus 9/28 (32 per cent), P = 0.010)]. No patients had bradycardia or gastrointestinal symptoms following rivastigmine administration. One patient with a history of epilepsy had a seizure, 1.5 hours post physostigmine administration and 7 hours post transdermal rivastigmine. DISCUSSION: Rivastigmine has been increasingly used for the management of patients with anticholinergic delirium, due to the lack of availability of physostigmine. In this case series, rivastigmine transdermal patch appeared to be less effective than oral rivastigmine capsules, likely due to its slow onset of action and/or insufficient dose. CONCLUSION: Rivastigmine can be used to treat anticholinergic delirium. In our case series oral rivastigmine appeared more effective than transdermal rivastigmine.

Psychosis in acute methamphetamine intoxication is usually self-limiting and can be managed in the emergency department: A retrospective series.

OBJECTIVES: There is little recent published data characterising acute psychosis associated with methamphetamine intoxication. We aim to describe the clinical features of psychosis, management of acute behavioural disturbance and disposition of patients with psychosis associated with acute methamphetamine intoxication. METHODS: This is a retrospective review of patients presenting with acute (use within 24 h) methamphetamine intoxication, with features of psychosis (presence of delusions, hallucinations or formal thought disorder), to an ED over 4 months in 2020. All presentations were extracted from a toxicology unit database and each medical record reviewed. Demographics, past mental health diagnoses, clinical features and disposition were extracted. RESULTS: There were 287 presentations of methamphetamine intoxication over the period. Of these 287 presentations, 205 (71%) had features of acute psychosis, occurring in 171 patients (111 males [65%], median age 36, range 16-57 years). Paranoid delusion occurred in 134 of 205 (65%) presentations and was the most common feature of psychosis. Chemical sedation was given to 194 (95%), with 143 (70%) receiving parenteral sedation to manage acute behavioural disturbance. Complete resolution of psychotic symptoms occurred in 170 of 205 (83%) of exposures. There were 9 of 205 (4%) presentations that resulted in a mental health admission. Most presentations - 200 of 205 (98%) - were managed within the ED, primarily the short-stay unit. The median length of stay was 15 h (interquartile range 11-20 h). CONCLUSIONS: In this series of patients presenting to ED with acute methamphetamine intoxication, psychosis appeared to occur commonly and was mostly short-lived, resolving within 24 h in the majority of patients.

Impact of pharmacists during in-hospital resuscitation or medical emergency response events: A systematic review.

BACKGROUND: We sought to determine the impact of the presence of a pharmacist on medication and patient related outcomes during the emergency management of critically ill patients requiring resuscitation or medical emergency response team care in a hospital setting. METHODS: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A literature search of databases from January 1995 to April 2023 was conducted to identify studies of contemporary pharmacist practice. Results were extracted and analysed for included studies, those evaluating the impact of the presence of a pharmacist on medication and patient related outcomes during the emergency management of critically ill hospitalised patients requiring resuscitation or medical emergency response team care. To determine risk of bias, the Newcastle-Ottowa Quality Assessment scale was used for non-randomised studies and the Revised Cochrane risk-of-bias tool for randomised trials. RESULTS: Of 1345 studies identified, 54 were selected for full text review, and 30 were included in the final analysis. There were 29 cohort studies and one randomised controlled trial. The studies reported the impact of a pharmacist for a variety of patient presentations. The study team assigned each study to one of eight patient cohorts: acute stroke, cardiac arrest, rapid response calls, S-T segment elevation myocardial infarction, acute haemorrhage, major trauma resuscitation, sepsis and status epilepticus. The most frequently reported outcome, associated with a statistically significant benefit in 23 studies, was time to medication administration. Few studies reported a significant difference in patient outcome measures such as mortality. Only 8 of the 30 studies were assessed to have a low risk of bias. CONCLUSIONS: The results of this systematic review provide support for a beneficial impact of a pharmacist presence and intervention during resuscitation or medical emergency response team care, with significant improvements in outcomes such as time to initiation of time-critical medications, medication appropriateness and guideline compliance. However, studies were predominantly small and retrospective and were not powered to detect differences in patient related measures such as length of stay and mortality. Future research should investigate the clinical impacts of the pharmacist in ED resuscitation settings in controlled, prospective studies with robust sampling methods.

Suspected stonefish envenomation in Queensland over eight years: a retrospective series.

INTRODUCTION: Stonefish envenomation results in localized severe pain and swelling and systemic features, including vomiting, arrhythmia, pulmonary oedema, and possibly death. There are limited data regarding the effectiveness of the available antivenom. The aim of this series is to characterize presentations of patients with suspected stonefish envenomation and investigate treatment, including antivenom. METHODS: This is a retrospective observational series of suspected stonefish envenomation as reported to the Queensland Poisons Information Centre or Princess Alexandra Hospital Clinical Toxicology Unit from July 2015 to January 2023. Patients were identified through the databases held by both the Centre and Unit, and data on clinical features and investigations were collected from the patient's electronic medical record. RESULTS: There were 87 suspected stonefish envenomations from July 2015 to January 2023. The median age was 26 (range: 5-69) years, and 69 (79 per cent) patients were male. Pain was reported in 85 (98 per cent) with a median peak pain score of 10 (range 4-12; three rated their pain greater than 10/10). A clear wound was documented in 64 (74 per cent), with local swelling in 63 (72 per cent). A foreign body was retained in eight (9 per cent) presentations. Systemic symptoms were rare, with vomiting in four (5 per cent) and dizziness in two (2 per cent) presentations. There were no instances of hypotension, arrhythmia, or pulmonary oedema. Hot water was administered in 72 (83 per cent) presentations. Oral analgesia was given in 55 (63 per cent). Parenteral analgesia was given in 53 (61 per cent), most commonly opioids. Local anaesthetic block was performed in 19 presentations (22 per cent), with effectiveness documented in 16/19 (84 per cent). Five patients received antivenom for intractable pain, and all received subsequent parenteral analgesia or local anaesthetic block. CONCLUSIONS: Stonefish envenomation is characterized by severe pain. Systemic symptoms were rare and not severe in this series. Local anaesthetic block appeared to be the most effective intervention for severe pain when performed. Antivenom appeared to be ineffective in managing pain.

Epidemiology and survival outcomes of out-of-hospital cardiac arrest following volatile substance use in Queensland, Australia.

INTRODUCTION: The deliberate inhalation of volatile substances for their psychotropic properties is a recognised public health issue that can precipitate sudden death. This study aimed to describe the epidemiological characteristics and survival outcomes of patients with out-of-hospital cardiac arrests following volatile substance use. METHODS: We conducted a retrospective cohort analysis of all out-of-hospital cardiac arrest attended by the Queensland Ambulance Service over a ten-year period (2012-2021). Incidents were extracted from the Queensland Ambulance Service cardiac arrest registry, which collects clinical information using the Utstein-style guidelines and linked hospital data. RESULTS: During the study period, 52,102 out-of-hospital cardiac arrests were attended, with 22 (0.04%) occurring following volatile substance use. The incidence rate was 0.04 per 100,000 population, with no temporal trends identified. The most commonly used product was deodorant cans (19/22), followed by butane canisters (2/22), and nitrous oxide canisters (1/22). The median age of patients was 15 years (interquartile range 13-23), with 14/22 male and 8/22 Indigenous Australians. Overall, 16/22 patients received a resuscitation attempt by paramedics. Of these, 12/16 were bystander witnessed, 10/16 presented in an initial shockable rhythm, and 9/16 received bystander chest compressions. The rates of event survival, survival to hospital discharge, and survival with good neurological outcome (Cerebral Performance Category 1-2) were 69% (11/16, 95% CI 41-89%), 38% (6/16, 95% CI 15-65%) and 31% (5/16, 11-59%), respectively. Eight patients in the paramedic-treated cohort that used hydrocarbon-based products were administered epinephrine during resuscitation. Of these, none subsequently survived to hospital discharge. In contrast, all six patients that did not receive epinephrine survived to hospital discharge, with 5/6 having a good neurological outcome. CONCLUSION: Out-of-hospital cardiac arrest following volatile substance use is rare and associated with relatively favourable survival rates. Patients were predominately aged in their adolescence with Indigenous Australians disproportionately represented.

A cluster of acute thebaine poisonings from non-food grade poppy seeds in the Australian food supply.

INTRODUCTION: Poppy seed tea is used for its opioid effects and contains multiple opium alkaloids, including morphine, codeine, papaverine, and thebaine. Animal studies indicate thebaine has strychnine-like properties, but there is limited literature describing human thebaine poisoning. We describe a cluster of acute thebaine poisoning in people ingesting tea made using poppy seeds with high thebaine content that entered the Australian food supply chain. METHODS: This is an observational study of patients poisoned after drinking poppy seed tea. Cases were identified by three prospective toxicovigilance systems: the Emerging Drug Network of Australia collaboration, the New South Wales Prescription, Recreational and Illicit Substance Evaluation program, and the Emerging Drugs Network of Australia Victoria study. We report characteristics of clinical toxicity in cases with reported ingestion of poppy seed tea and analytical confirmation of thebaine exposure. RESULTS: Forty cases presenting with multi-system toxicity following poppy seed tea ingestion were identified across seven Australian states/territories from November 2022 to January 2023. Blood testing in 23 cases confirmed high thebaine concentrations. All 23 were male (median age 35, range 16-71 years). All patients experienced muscle spasms. Rigidity was described in nine, convulsions in six, while rhabdomyolysis, acute kidney injury, and metabolic acidosis occurred in five patients. There were two cardiac arrests. The thebaine median admission blood concentration was 1.6 mg/L, with a range of 0.1-5.6 mg/L, and was the dominant opium alkaloid in all samples. Convulsions, acute kidney injury, metabolic acidosis, and cardiac arrest were associated with increasing median thebaine concentrations. Four patients were managed in the Intensive Care Unit, with two receiving continuous kidney replacement therapy (one also received intermittent haemodialysis) for kidney injury. There was one death. CONCLUSIONS: Thebaine toxicity, like strychnine poisoning, resulted in neuromuscular excitation characterized by muscle spasm, rigidity, and convulsions. Severe toxicity, including acute kidney injury, metabolic acidosis, and cardiac arrest, appears dose-dependent.

Introduction of QScript real-time prescription monitoring system was associated with a fall in pregabalin poisoning presentations to a clinical toxicology unit.

OBJECTIVE: To investigate the impact of QScript implementation on pregabalin-related poisoning presentations to the ED. METHODS: This is a retrospective review of pregabalin-related poisoning presentations to a tertiary Australian ED in the 4 years prior to, and 1 year following the introduction of QScript real-time prescription monitoring system. RESULTS: Pregabalin-related poisoning presentations fell by 28% from an average of 98 presentations annually over the 4 years prior to QScript implementation to 71 in 2022. The severity of poisonings was similar over the periods. CONCLUSIONS: The introduction of QScript was associated with a reduction in pregabalin-related poisoning presentations.

Opioid poisoning in Newcastle over the last three decades: From heroin to prescription opioids.

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.

Intubation for patients with overdose: Time to move on from the Glasgow Coma Scale.

Patients frequently present to the ED with drug overdose and reduced conscious level leading to coma. There is considerable practice variation around which patients require intubation. Indications include: (i) respiratory failure (including airway obstruction); (ii) to facilitate specific therapies or intubation as a therapy in itself; and (iii) for airway protection in the unprotected airway. We argue that intubating a patient purely for (iii) is outdated and that most patients can be safely observed. There is a paucity of good quality research in the area of drug overdose with reduced consciousness. Teaching may be outdated and based on the use of the Glasgow Coma Scale in head trauma. Current low quality research suggests observation is safe. We recommend that patients undergo an individualised risk assessment of the need for intubation. We propose a flow diagram to aid clinicians in safely observing comatose overdose patients. This can be applied if the drug is unknown, or there are multiple drugs involved.

Acetaminophen Metabolites on Presentation Following an Acute Acetaminophen Overdose (ATOM-7).

Acetaminophen (APAP) is commonly taken in overdose and can cause acute liver injury via the toxic metabolite NAPQI formed by cytochrome (CYP) P450 pathway. We aimed to evaluate the concentrations of APAP metabolites on presentation following an acute APAP poisoning and whether these predicted the subsequent onset of hepatotoxicity (peak alanine aminotransferase > 1,000 U/L). The Australian Toxicology Monitoring (ATOM) study is a prospective observational study, recruiting via two poison information centers and four toxicology units. Patients following an acute APAP ingestion presenting < 24 hours post-ingestion were recruited. Initial samples were analyzed for APAP metabolites, those measured were the nontoxic glucuronide (APAP-Glu) and sulfate (APAP-Sul) conjugates and NAPQI (toxic metabolite) conjugates APAP-cysteine (APAP-Cys) and APAP-mercapturate (APAP-Mer). The primary outcome was hepatotoxicity. In this study, 200 patients were included, with a median ingested dose of 20 g, 191 received acetylcysteine at median time of 5.8 hours post-ingestion. Twenty-six patients developed hepatotoxicity, one had hepatotoxicity on arrival (excluded from analysis). Those who developed hepatotoxicity had significantly higher total CYP metabolite concentrations: (36.8 µmol/L interquartile range (IQR): 27.8-51.7 vs. 10.8 µmol/L IQR: 6.9-19.5) and these were a greater proportion of total metabolites (5.4%, IQR: 3.8-7.7) vs. 1.7%, IQR: 1.3-2.6, P < 0.001)]. Furthermore, those who developed hepatotoxicity had lower APAP-Sul concentrations (49.1 µmol/L, IQR: 24.7-72.2 vs. 78.7 µmol/L, IQR: 53.6-116.4) and lower percentage of APAP-Sul (6.3%, IQR: 4.6-10.9 vs. 13.1%, IQR, 9.1-20.8, P < 0.001)]. This study found that those who developed hepatotoxicity had higher APAP metabolites derived from CYP pathway and lower sulfation metabolite on presentation. APAP metabolites may be utilized in the future to identify patients who could benefit from increased acetylcysteine or newer adjunct or research therapies.

Overdose and off-label psychotropic prescribing in patients with borderline personality disorder: A retrospective series.

OBJECTIVE: Borderline personality disorder (BPD) is common and poses many clinical challenges. Despite limited evidence of effectiveness, psychotropic medications are often prescribed. We aimed to characterise overdose presentations in patients with BPD. METHOD: This is a retrospective observational series of patients with BPD presenting to a tertiary hospital following an overdose from January 2019 to December 2020. Medical records were reviewed to determine baseline characteristics, overdose details, clinical features, treatment, and disposition. RESULTS: There were 608 presentations in 370 people (76% female), median age 28 years (range 16-75 years). The majority (331[89%]) of patients were prescribed at least one psychotropic medication, with 129 (35%) being prescribed three or more different psychotropic agents. Of the total prescribed psychotropics, 520/1459 (36%) were for off-label indications. The majority of agents (860/1487[58%]) taken in overdose were prescribed. The commonest drug classes taken in overdose were benzodiazepines (241[16%]) and antipsychotics (229[15%]). Severe toxicity occurred in 99 (16%) cases with either coma (GCS<9) or hypotension (systolic BP <90 mmHg). The commonest agent associated with severe toxicity was quetiapine 39/99 (39%). CONCLUSIONS: Psychotropic polypharmacy is common in BPD, often with off-label indications. Prescribed medications are commonly taken in overdose. Quetiapine is over-represented both in off-label prescribing and associated harm.