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.

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.

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.

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.

Case series profile of olanzapine post-injection delirium/sedation syndrome.

Olanzapine pamoate is an intramuscular depot injection for the treatment of schizophrenia. Approximately 1.4% of patients develop a serious adverse event called post-injection delirium/sedation syndrome (PDSS), characterised by drowsiness, anticholinergic and extrapyramidal symptoms. The objective is to investigate olanzapine PDSS presentations including clinical features and treatment approach. This is a retrospective review of olanzapine PDSS patients from three toxicology units and the NSW Poisons Information Centre between 2017 and 2022. Adult patients were included if they had intramuscular olanzapine then developed PDSS criteria. Clinical symptoms, treatment, timing and length of symptoms were extracted into a preformatted Excel database. There were 18 patients included in the series, with a median age of 49 years (interquartile range [IQR]: 38-58) and male predominance (89%). Median onset time post injection was 30 min (IQR: 11-38). PDSS symptoms predominate with drowsiness, confusion and dysarthria. Median length of symptoms was 24 h (IQR: 20-54). Most common treatment included supportive care without any pharmacological intervention (n = 10), benzodiazepine (n = 4) and benztropine (n = 3). In one case, bromocriptine and physostigmine followed by oral rivastigmine were given to manage antidopaminergic and anticholinergic symptoms respectively. This proposed treatment combination could potentially alleviate some of the symptoms but needs further studies to validate the findings. In conclusion, this case series supports the characterisation of PDSS symptomology predominantly being anticholinergic with similar onset (<1 h) and duration (<72 h). Bromocriptine is proposed to manage PDSS if patients develop severe dopamine blockade and physostigmine followed by rivastigmine for anticholinergic delirium.

Ambulance referrals to an Australian Poisons Information Centre: a retrospective series.

INTRODUCTION: For poisoned patients, ambulance services may be the first point of contact for medical attention. With limited training in toxicology, ambulance services are encouraged to contact the Poisons Information Centre (PIC) for advice. This study aims to characterise referrals to a PIC from a state ambulance service with the purpose of improving information delivery and efficient use of these services. METHODS: This was a retrospective observational series of referrals to an Australian state PIC from ambulance staff from 1 January 2020 to 31 December 2020. Referrals were identified through the PIC Pharmhos database where the call originated from either a paramedic or emergency dispatch officer. Call reports were reviewed to extract data on patient demographics, exposure details and advice provided by the PIC. RESULTS: There were 1537 calls regarding 1420 poisoning exposures over the 12-month period, with 117 (7.6%) follow-up calls, representing 4.1% (1537/37835) of total calls to the PIC. Initial calls originated from paramedics in 999/1420 (70.4%) referrals, with dispatch officers referring 421/1420 (29.6%). Paediatric patients aged <15 years were involved in 492/1420 (34.6%) exposures with the commonest age range being 1-4 years. Most referrals involved pharmaceuticals exposures (756/1420 [53.2%]) followed by chemicals (557/1420 [39.2%]) and drugs of abuse (69/1420 [4.9%]). The commonest agents involved were paracetamol followed by quetiapine and sertraline. The PIC advised no treatment following benign exposures in 617/1420 (43.5%) calls, first aid measures in 333/1420 (23.5%) calls, supportive measures in 339/1420 (23.9%) calls and specific treatment in 32/1420 (2.3%) calls. Referral to the hospital was advised in 761/1420 (53.6%) calls, the majority of these were following deliberate self-poisonings (428/1420 [30.1%]). CONCLUSIONS: Ambulance staff commonly contact the PIC following benign exposures where no treatment is required. Ambulance referral to a PIC following suspected poisonings may have a role in preventing unnecessary transfer to hospital in poisoned patients.

Duloxetine overdose causes sympathomimetic and serotonin toxicity without major complications.

OBJECTIVE: Duloxetine is a commonly used antidepressant that is a serotonin and norepinephrine reuptake inhibitor. We aimed to investigate the frequency and severity of clinical effects following duloxetine overdose. METHODS: We undertook a retrospective review of duloxetine overdoses (>120 mg) admitted to two tertiary toxicology units between March 2007 and May 2021. Demographic information, details of ingestion (dose, co-ingestants), clinical effects, investigations (ECG parameters including QT interval), complications (coma [GCS < 9], serotonin toxicity, seizures and cardiovascular effects), length of stay [LOS] and intensive care unit [ICU] admission were extracted from a clinical database. RESULTS: There were 241 duloxetine overdoses (>120 mg), median age 37 years (interquartile range [IQR]: 25-48 years) and there were 156 females (65%). The median dose was 735 mg (IQR: 405-1200 mg). In 177 patients, other medications were co-ingested, most commonly alcohol, paracetamol, quetiapine, diazepam, ibuprofen, pregabalin and oxycodone. These patients were more likely to be admitted to ICU (12 [7%] vs. none; p = 0.040), develop coma (16 [9%] vs. none; p = 0.008) and hypotension [systolic BP < 90 mmHg] (15 [8%] vs. one; p = 0.076). Sixty four patients ingested duloxetine alone with a median dose of 840 mg (180-4200 mg). The median LOS, in the duloxetine only group, was 13 h (IQR:8.3-18 h), which was significantly shorter than those taking coingestants, 19 h (IQR:12-31 h; p = 0.004). None of these patients were intubated. Six patients developed moderate serotonin toxicity, without complications and one had a single seizure. Tachycardia occurred in 31 patients (48%) and mild hypertension (systolic BP > 140 mmHg) in 29 (45%). One patient had persistent sympathomimetic toxicity, and one had hypotension after droperidol. Two patients of 63 with an ECG recorded had an abnormal QT: one QT 500 ms, HR 46 bpm, which resolved over 3.5 h and a second with tachycardia (QT 360 ms, HR 119 bpm). None of the 64 patients had an arrhythmia. CONCLUSION: Duloxetine overdose most commonly caused sympathomimetic effects and serotonin toxicity, consistent with its pharmacology, and did not result in coma, arrhythmias or intensive care admission, when taken alone in overdose.

D-dimer testing for early detection of venom-induced consumption coagulopathy after snakebite in Australia (ASP-29).

OBJECTIVE: To assess the accuracy and marginal value of quantitative D-dimer testing for diagnosing venom-induced consumption coagulopathy (VICC) in people bitten by Australian snakes. DESIGN, SETTING: Analysis of data for suspected and confirmed cases of snakebite collected prospectively by the Australian Snakebite Project, 2005-2019, from 200 hospitals across Australia. PARTICIPANTS: 1363 patients for whom D-dimer was quantitatively assessed within 24 hours of suspected or confirmed snakebite. MAIN OUTCOME MEASURES: Diagnostic performance of quantitative D-dimer testing for detecting systemic envenoming with VICC (area under the receiver operating characteristic curve, AUC); optimal D-dimer cut-off value (maximum sum of sensitivity and specificity). RESULTS: D-dimer values exceeded 2.5 mg/L within three hours of the bite for 95% of patients who developed VICC, and were lower than 2.5 mg/L for 95% of non-envenomed patients up to six hours after snakebite. The AUC for diagnosing envenoming with VICC on the basis of quantitative D-dimer testing within six hours of snakebite was 0.97 (95% CI, 0.96-0.98; 944 patients). Diagnostic performance increased during the first three hours after snakebite; for quantitative D-dimer testing at 2-6 hours, the AUC was 0.99 (95% CI, 0.99-1.0); with a cut-off of 2.5 mg/L, sensitivity was 97.1% (95% CI, 95.0-98.3%) and specificity 99.0% (95% CI, 97.6-99.6%) for VICC. For 36 patients with normal international normalised ratio (INR) and activated partial thromboplastin time (aPTT) values 2-6 hours after snakebite, the AUC was 0.97 (95% CI, 0.93-1.0); with a cut-off of 1.4 mg/L, sensitivity was 94% (95% CI, 82-99%) and specificity 96% (95% CI, 94-97%). In all but one of 84 patients who developed VICC-related acute kidney injury, D-dimer values exceeded 4 mg/L within 24 hours of the bite. CONCLUSION: D-dimer concentrations assessed 2-6 hours after snakebite, with a cut-off value of 2.5 mg/L, could be useful for diagnosing envenoming with VICC.

Acute Opioid Withdrawal Following Intramuscular Administration of Naloxone 1.6 mg: A Prospective Out-Of-Hospital Series.

STUDY OBJECTIVE: Large doses of intramuscular (IM) naloxone are commonly used in out-of-hospital settings to reverse opioid toxicity; however, they are used less commonly in hospitals because of concerns about opioid withdrawal, particularly agitation. We aimed to determine the frequency of severe agitation following a single 1.6 mg IM naloxone dose. METHODS: We undertook a prospective study of adult (>15 years) patients treated by an Australian state ambulance service with 1.6 mg IM administration of naloxone for respiratory depression (respiratory rate <11 breaths/min and/or oxygen saturation <93% in room air) caused by presumed opioid poisoning. The primary outcome was the proportion of presentations with severe agitation (Sedation Assessment Tool score >1) within 1 hour of naloxone administration. Secondary outcomes were the proportion of presentations with acute opioid withdrawal (tachycardia [pulse rate >100 beats/min], hypertension [systolic >140 mm Hg], vomiting, agitation, seizure, myocardial infarction, arrhythmia, or pulmonary edema), and reversal of respiratory depression (respiratory rate >10 breaths/min and saturation >92% or Glasgow Coma Scale score 15). RESULTS: From October 2019 to July 2021, there were 197 presentations in 171 patients, with a median age of 41 years (range, 18 to 80 years); of the total patients, 119 were men (70%). The most common opioids were heroin (131 [66%]), oxycodone (14 [7%]), and morphine (11 [6%]). Severe agitation occurred in 14 (7% [95% confidence interval {CI} 4% to 12%]) presentations. Opioid withdrawal occurred in 76 presentations (39% [95% CI 32% to 46%]), most commonly in the form of tachycardia (18%), mild agitation/anxiety (18%) and hypertension (14%). Three presentations (1.5%) received chemical sedation for severe agitation within 1 hour of naloxone administration. A single 1.6 mg dose of naloxone reversed respiratory depression in 192 (97% [95% CI: 94% to 99%]) presentations. CONCLUSION: Severe agitation was uncommon following the administration of 1.6 mg IM naloxone and rarely required chemical sedation.

Too much of a good thing: Bicarbonate toxicity following treatment of sodium channel blocker overdose.

Although sodium bicarbonate can be a life-saving antidote for patients with overdoses resulting in sodium channel blockade, there has been a concerning rise in cases referred to the Poisons Information Centre where inappropriately large doses of bicarbonate have been used resulting in iatrogenic harm. We present a series of three clinical cases where excessive bicarbonate was used to treat poisonings and discuss our approach to managing cardiotoxicity secondary to sodium channel blockade. Serial blood gas analysis should be performed when using bicarbonate to ensure pH targets are met and severe alkalaemia, hypernatraemia and hypokalaemia are avoided. We encourage clinicians to contact the Poisons Information Centre (13 11 26) or their local clinical toxicologist when managing patients with life-threatening sodium channel blockade.

Optimising alkalinisation and its effect on QRS narrowing in tricyclic antidepressant poisoning.

AIMS: The objectives were to determine the effect of NaHCO3 and/or mechanical ventilation on the biochemical profile and serum alkalinisation in tricyclic antidepressant (TCA) poisoning and investigate the impact of effective alkalinisation therapy on the QRS interval in TCA poisoning. METHODS: This was a retrospective review of TCA poisonings from three Australian toxicology units and a poisons information centre (Jan 2013 to Jan 2019). We included patients with TCA toxicity who ingested>10 mg/kg or had clinically significant toxicities consistent with TCA poisoning, and analysed patients' clinical, electrocardiogram and biochemical data. RESULTS: Of 210 patients, 84 received NaHCO3 and ventilation (dual therapy), 12 NaHCO3 , 46 ventilation and 68 supportive care treatment. When compared with single/supportive groups, patients who received dual therapy had taken a significantly higher median dose of TCA (1.5 g vs1.3 g, P < .001), a longer median maximum QRS interval (124 ms, interquartile ranges [IQR] 108-138 vs106 ms, IQR 98-115, P < .001) and were more likely to have seizures (14% vs3%, P = .006) and arrhythmias (17% vs1%, P < .001). The dual therapy group demonstrated greater increases in serum pH (median 0.11, IQR 0.04-0.17) compared to the single/supportive therapy group (median 0.03, IQR -0.01-0.09, p < .001). A greater proportion of patients reached the target pH 7.45-7.55 in the dual therapy group (59%) compared to the single/supportive therapy group (10%) (P < .001). For each 100 mmol bolus of NaHCO3 given, the median increase in serum sodium was 2.5 mmol/L (IQR 1.5-4.0). QRS narrowing occurred twice as quickly in the dual therapy vs single/supportive therapy group. CONCLUSIONS: A combination of NaHCO3 and mechanical ventilation was most effective in achieving serum alkalinisation and was associated with a more rapid narrowing of the QRS interval. We advise that the maximal dose of NaHCO3 should be <400 mmol (6 mmol/kg).