Isoardi Katherine (Orcid ID: 0000-0002-1176-7923) Abstract Objective: There is little recent published data characterising methamphetamine intoxication. This study aims to describe the clinical effects, management, complications and disposition of patients with methamphetamine exposure. Methods: This is a retrospective review of patients presenting with methamphetamine intoxication to an Emergency Department in 2016. All presentations were extracted from a relational database and each medical record reviewed. Demographics, clinical features, complications and disposition were extracted. Results: There were 378 presentations of 329 patients (234 males [71%]), median age 31 years (range 16-68 years). The commonest clinical effect was acute behavioural disturbance, occurring in 295 (78%) presentations. This was successfully managed with oral sedation alone in 180 (61%) patients with the remainder receiving parenteral sedation. Other effects included tachycardia in 212 (56%), hypertension in 160 (42%) and hyperthermia in 17 (4%) presentations. No antihypertensives were given. One patient was actively cooled. Complications included 21 (30%) presentations with rhabdomyolysis and 43 (11%) presentations with acute kidney injury. There were two seizures, three intracranial bleeds and one myocardial infarction. The majority of This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/1742-6723.13219 This article is protected by copyright. All rights reserved. patients (310 [82%]) were managed solely within the emergency department. The median length of stay was 14 hours. There were 41(11%) mental health admissions. Two deaths occurred; one following an out of hospital cardiac arrest, the other a subarachnoid haemorrhage. Conclusions: The main toxicity seen with methamphetamines is acute behavioural disturbance, which is managed well with sedation. Complications, apart from rhabdomyolysis and acute kidney injury, are rare. Most patients are managed within the Emergency Department and discharged home. Introduction Methamphetamine is a highly addictive methylated derivate of amphetamine.1 It is available in three main forms of increasing purity; powdered “speed”, a yellow paste “base” and crystalline “ice”.2 Methamphetamine potentiates the release and blocks the reuptake of catecholamines, stimulating the sympathetic and central nervous systems.3 Acute poisoning is associated with a sympathomimetic toxidrome, which can vary from mild psychomotor agitation through to severe toxicity with hyperthermic crisis, myocardial ischaemia, arrhythmia and intracerebral haemorrhage.1 Chronic use is associated with dependence, mental health conditions including anxiety, depression and psychosis and societal dysfunction. 4 This article is protected by copyright. All rights reserved. Methamphetamine use in South East Queensland, Australia, has increased over the last decade. Wastewater analysis in urban southeast Queensland has demonstrated a five-fold increase in methamphetamine usage over the period of 2009 to 2015.5 This increase in usage, coupled with a shift in the Australian market to a higher purity product,4 has translated into increasing methamphetamine-related hospital presentations and specialist drug treatment episodes.6 There is little published data that characterises methamphetamine intoxication in patients presenting to an emergency department (ED).3, 7, 8 There is even less in the last 10 years, 9, 10 during which time higher purity methamphetamine has dominated. Most research however, focuses on the severe medical complications of methamphetamine intoxication including myocardial ischaemia,11 stroke 12 and hyperthermic crises.13 These serious complications happen infrequently whereas agitation and aggression (acute behavioural disturbance) appear to be more commonplace.7 A prospective series of 100 methamphetamine intoxicated patients presenting to an Australian inner-city ED in 2006 found acute behavioural disturbance was present in 41% of cases.7 Similarly another Australian prospective case series also found acute behavioural disturbance was the most common presenting complaint in amphetamine related ED presentations.3 There is variation in the management of methamphetamine related acute behavioural disturbance. Chemical restraint using titrated intravenous benzodiazepines is This article is protected by copyright. All rights reserved. typically recommended.14-16 However antipsychotics, such as droperidol, have been shown to be as effective but safer than benzodiazepines17-19 for the management of all forms of acute behavioural disturbance including stimulant toxicity. Complications of chemical restraint include over-sedation, aspiration, respiratory depression and hypotension. Given the risks of sedation, many departments have protocols to guide clinicians in the management of acute behavioural disturbance.20-22 The effectiveness of these guidelines in managing methamphetamine related acute behavioural disturbance has not been specifically examined. The aim of this study is to describe the clinical effects of methamphetamine intoxication in patients presenting to the ED and report its management and complications, including the treatment of methamphetamine related acute behavioural disturbance. Methods Study Design and Setting This is a retrospective observational study of patients presenting with methamphetamine intoxication to the ED at the Princess Alexandra Hospital (PAH) in Brisbane, Australia. The PAH is a tertiary referral adult (>15 years of age) hospital This article is protected by copyright. All rights reserved. with an ED that has approximately 60 000 presentations per year. The use of chemical sedation in the PAH ED is standardised, following a local area guideline that details the management of acute behavioural disturbance.20 The Sedation Assessment Tool (SAT)23 scoring system (Figure 1) is used routinely in the PAH ED to assess the degree of patient agitation. The Clinical Toxicology Unit manages all patients presenting to the PAH with drug intoxication, overdose, poisoning or envenomation. In 2016 there were 2133 toxicological presentations to the PAH resulting in 1567 inpatient admissions under the Clinical Toxicology Unit. All toxicological presentations are entered into a purpose built relational database by the unit’s medical staff that undergoes weekly audit. The Clinical Toxicology Unit has approval from the Metro South Human Research Ethics Committee to use their database and patient medical records for research. Patient selection All patients presenting to the PAH during the 2016 calendar year with an exposure to methamphetamine were included in the study. This was determined by a patient admitting to methamphetamine use or when this was not provided, through clinical examination findings consistent with a sympathomimetic toxidrome and a collateral history suggestive of methamphetamine exposure. Cases were identified through the toxicology database using the search term ‘methamphetamine’ with date limits of the 1st January 2016 through to the 31st December 2016. This article is protected by copyright. All rights reserved. Data Collection Methamphetamine presentations were extracted from the toxicology unit’s relational database, and each patient’s electronic medical record was subsequently reviewed. A data collection sheet was designed and piloted by two of the authors (CP and KI) prior to the formal data extraction. The data collection sheet included baseline characteristics (age, sex, ethnicity, employment status), presentation details (arrival method, ingested drug, presenting complaint, intention, co-ingested agents, mental health considerations), clinical features (vital signs, laboratory results, management), complications (rhabdomyolysis, acute kidney injury, seizure, intracranial haemorrhage, myocardial infarction, cardiac arrest) and disposition details (admission location, length of stay, discharge location). Double data extraction (SA and KI) was performed on the first 10% of records extracted, of which there was excellent agreement with only a very small number of discrepancies that were identified and corrected for the remaining extraction. Data extraction was performed on the remaining 90% of cases by a single extractor (SA). Outcomes The following outcomes were predefined to describe the clinical effects and complications of methamphetamine intoxication and included tachycardia (heart rate > 100 beats per minute), hypertension (systolic blood pressure > 140mmHg), severe hypertension (systolic blood pressure >180mmHg), hyperthermia (temperature > 38 degrees Celsius), rhabdomyolysis (creatine kinase [CK] > 1000 IU/L) and acute This article is protected by copyright. All rights reserved. kidney injury (AKI) was defined in accordance with the KDIGO Clinical Practice Guideline for Acute Kidney Injury.24 Analysis Continuous variables are reported as medians, interquartile ranges (IQR) and ranges. All analysis was performed in GraphPad Prism 7.0d for Mac OS X (GraphPad Software, La Jolla California CA, USA; www.graphpad.com) This article is protected by copyright. All rights reserved. Results Baseline Characteristics There were 378 presentations of 329 patients (234 males [71%]), median age 31 years (IQR 25-37 years, range 16-68 years). There were 156 (41%)