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In clinical toxicology, gastric endoscopic decontamination is rarely used, and only a few cases of pharmacobezoar removal after intentional ingestion of slow-release drugs have been described. Our case describes the use of gastric endoscopic decontamination to remove potential pharmacobezoar in an adolescent after ingestion of a lethal dose of isoniazid and rifampin, even long after gastric lavage. This technique allowed the removal of pharmacobezoars still present in the stomach while preventing further deterioration of the patient.

Hemoperfusion (HP) is an extracorporeal blood purification therapy that is used to remove poisons or drugs from the body. This chapter provides a brief overview of the technical aspects and the potential indications and limitations of HP, with the focus being on the use of HP for acute poisoning cases reported from January 1, 2000, to April 30, 2022., (© 2023 S. Karger AG, Basel.)

Opioid use and associated morbidity and mortality have increased in several countries during the past 20 years. We performed a study whose objective was to assess the frequency and causes of opioid-related emergency division (ED) visits in an adult tertiary Swiss University Hospital over 9 weeks in 2018. We primarily assessed opioid-related adverse drug reactions (ADR), secondary overdose, misuse, abuse, and insufficient pain relief. Current opioid use was identified in 1037 (8.3%) of the 12 470 included ED visits. In 64 opioid users, an ADR was identified as a contributing cause of the ED visit, representing 6.2% of opioid users, and 0.5% of the total ED visits. Moreover, we identified an overdose in 16 opioid users, misuse or abuse in 19 opioid users, and compatible withdrawal symptoms in 7 opioid users. After pooling all these events, we conclude that the ED visits could be related to opioid use in 10.2% of opioid users. Finally, in 201 opioid users, insufficient pain relief (pain not responding to the current pharmacological treatment) was identified as a contributing cause of ED visits. In these cases, other factors than simply pharmacological nonresponse may have been involved. In the context of an ever-increasing opioid use to better control chronic pain situations, these results should reinforce emergency network epidemiological surveillance studies at a national level., (© 2022 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Calcium-channel blocker overdose can result in profound vasoplegia and cardiogenic shock, which can quickly spiral into multi-organ failure and death. In this case report, we discuss two separate cases of massive amlodipine overdose with polydrug intoxication (Patient A: amlodipine and quetiapine; Patient B: amlodipine, fluoxetine and zopiclone), both of which were complicated by life-threatening vasoplegic shock refractory to supportive therapy (endotracheal intubation, fluid resuscitation, activated charcoal, vasopressors and inotropes), multimodal antidotes (calcium and hyper-insulinemic euglycemic therapy) and even second-line treatment (methylene blue and therapeutic plasma exchange). Despite exhausting all therapeutic options, resuscitation remained futile with no clinical response elicited until veno-arterial extracorporeal membrane oxygenation (ECMO) salvage therapy was initiated in both cases as a bridge-to-recovery. Albumin dialysis was also commenced to further enhance elimination of amlodipine given its high plasma protein-binding properties. Both patients improved drastically once perfusion to vital organs was maintained by ECMO and eventually survived with good neurological outcomes and preserved cardiac contractility on discharge. This case report supports the growing evidence that although ECMO support represents a potentially life-saving salvage therapy for refractory poisoning-induced shock, escalation to ECMO must be considered and instituted early before irreversible multi-organ failure sets in to ensure good clinical outcomes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Context: For more than a decade, the state of Ohio has been an epicenter of the opioid crisis. Multiple interventions have been deployed to address this crisis and reduce opioid overdoses and overdose deaths in the state. The Hamilton County Addiction Response Coalition (HC ARC) and its strategic, countywide prearrest diversion (LEAD) and deflection (QRT) programs have been at the forefront of this effort in Cincinnati, Ohio. Operating since April 2018, these programs have continued to grow and improve and have been successful in connecting hundreds of citizens to needed treatment and other social services., Program: HC ARC combats overdoses and overdose deaths by utilizing cross-sector planning and collaboration to operate 2 countywide programs: Quick Response Team (QRT) and Law Enforcement Assisted Diversion (LEAD)., Implementation: The QRT and LEAD programs leverage partnerships with law enforcement, public health, addiction and mental health services, reentry services, and trained peer supporters. The QRT emphasizes triage, assessment, and connection to appropriate services for people with recent nonfatal drug overdoses and provides outreach and education in hot spot communities. LEAD provides diversion from the criminal justice system into long-term case management for nonviolent individuals with low-level offenses who also struggle with substance use disorder, mental health, homelessness, and/or poverty., Evaluation: QRT and LEAD team members routinely track and record client contacts and outcomes using a centralized electronic case management platform. Data are extracted and analyzed by the evaluation team to examine indices of program success and provide ongoing feedback to the QRT and LEAD teams., Discussion: HC ARC has implemented, tested, expanded, and now standardized its prearrest diversion programming. It has built a sustainable model to improve health and health equity for marginalized individuals whose needs intersect across health care, public health, community-based social services, and the criminal-legal system. Collectively, this work offers a guide for implementation and best practices for the following: detailed planning, policy, and procedure development; identification of key leaders and community partners; and methods to evaluate program operations to make data-driven decisions and real-time program adjustments., Competing Interests: The authors declare that they have no potential conflicts of interest to disclose., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

Aim: To differentiate the severity of acute opioid toxicity and describe both the clinical and physiological features associated with heroin overdose in a cohort of witnessed overdose cases., Methods: Witnessed heroin overdose cases over a 12-month period (30 June 2018 - 30 June 2019) at the Medically Supervised Injecting Room (MSIR) in Melbourne, Australia were examined. The severity of acute opioid toxicity was classified according to the level of clinical intervention required to manage the overdose cases where an escalating level of care was provided. Heroin overdose cases were classified into one of three graded severity categories and a fourth complicated heroin overdose category., Results: A total of 1218 heroin overdose cases were identified from 60,693 supervised injecting visits over the study period. On the spectrum of toxicity, 78% ( n  = 955) of overdose cases were classified as Grade 1 severity, 7% ( n  = 83) as Grade 2 severity, and 13% ( n  = 161) as Grade 3 acute opioid toxicity severity cases, as well as 2% ( n  = 19) classified as complicated heroin overdose cases. The median onset time for heroin overdose cases was 17 min (IQR 11-28 min) from the time the individual was ready to prepare and inject heroin until clinical intervention was initiated., Conclusion: We demonstrated that heroin overdose is a dynamic illness and cases differ in the severity of acute opioid toxicity. The risk of airway occlusion including positional asphyxia was an early and consistent feature across all levels of toxicity, while exaggerated respiratory depression together with exaggerated depression of consciousness was increasingly observed with greater levels of toxicity. We also demonstrated the importance of early intervention in overdose cases, where in a large cohort of heroin overdose cases there were no fatal outcomes, a very low hospitalisation rate and most cases were able to be managed to clinical resolution on-site.

Background: Individuals involved in the criminal legal system face unique challenges to accessing substance use disorder (SUD) treatment, yet state-level variation in referrals for treatment remains largely unknown. To address disparities in the overdose crisis among individuals with criminal legal involvement, it is important to understand variation in SUD treatment across states., Methods: We conducted a retrospective comparison of substance use treatment referrals from the criminal legal system and other sources across participating states. Using data from the 2018-2019 Treatment Episode Dataset-Admissions, we characterized treatment referral rates from the criminal legal system, the substances most commonly leading to treatment, and rates of treatment with medication for opioid use disorder (MOUD) across states., Results: Across all states, criminal legal referral rates were higher than non-criminal legal rates. Criminal-legal referral rates, adjusted for state overdose deaths, were highest in the Northeast and Midwest. Methamphetamine use was the most common substance leading to treatment referral from the criminal legal system in 24 states while opioid use was the most common reason for non-criminal legal referrals in 34 states. In over half the states analyzed, fewer than 10% of opioid treatment referrals from the criminal legal system received MOUD. In almost all states, MOUD was more common in treatment referred from non-criminal legal settings., Conclusion: State-specific policies and practices shape drug policy and the SUD treatment landscape for people with criminal legal involvement. Standards and ongoing monitoring for substance use treatment referrals from the criminal-legal system should be considered by federal agencies charged with addressing the ongoing overdose crisis., Competing Interests: Conflict of Interest No conflict declared., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: There is a lack of US population-based research on healthcare utilization differences caused by opioid misuse., Objective: The aim of this study was to explore disparities in healthcare utilization by type of opioid use disorder, race, region, and other patient factors for a more targeted prevention and treatment program., Methods: The National Inpatient Sample of the United States was used to identify patients with opioid use disorder (n = 101,231, weighted n = 506,155) from 2016 to 2019. Type of opioid use disorder was defined as opioid dependence/unspecified use, adverse effects of opioids, opioid misuse, and opioid poisoning (also known as overdose). We examined the sample characteristics and the association between type of disorder, racial and regional variables, and healthcare utilization, measured by hospital charges and length of stay. The multivariate survey linear regression model was used., Results: Among 506,155 patients, most were categorized as opioid dependence/unspecified use (56.3%) and opioid poisoning (42.7%). The number of opioid use disorder patients during the study decreased; however, overall total charges and length of stay continuously increased. Survey linear results showed that opioid poisoning, adverse effects, and abuse were associated with higher hospital charges than opioid dependence; however, length of stay was significantly lower for these groups. White patients compared with minorities, and West, Northeast, and South regions were associated with higher hospital charges and length of stay., Conclusion: Significant differences in healthcare utilization exist between type of disorder, race, and region. Such findings illustrate that tailored treatment regimens are required to bridge the gaps in care and combat the opioid crisis. Minorities with opioid use disorder utilize healthcare the least, possibly because of affordability, and need culturally sensitive and financially feasible treatment options., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Recent reports indicate that stimulant-related deaths are increasing dramatically. People who die from acute stimulant toxicity have high rates of pre-existing cardiovascular disease (CVD), much of which is undiagnosed. Moreover, people who use stimulants with CVD often remain asymptomatic until presenting to an emergency department with an acute event. Prior research shows that symptoms of stimulant toxicity may occur on a regular basis, and that people who die from stimulant toxicity are older than those who die of opioid toxicity. Taken collectively, the existing evidence suggests that death from acute stimulant toxicity is often an outcome of long-term, cumulative exposure leading to cardiovascular dysfunction rather than acute intoxication. Strategies tailored to the distinct etiology of stimulant overdose are needed. We propose a three-part approach including (1) implementing stimulant use interventions that promote not only abstinence, but also use reduction, (2) treating ongoing stimulant use as a chronic cardiovascular condition, and (3) making stimulant toxicity interventions relevant to the populations most affected, which includes people outside of the traditional health-care system. In short, to reduce stimulant-related fatality, we need to transform our approach in ways that are tailored to address its natural history., (© 2022. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Introduction: Benzonatate is a local anesthetic-like sodium channel antagonist that is widely prescribed as an antitussive. While it may be reasonable to assume that patients would present with a prolonged QRS interval following benzonatate overdose, the published literature does not support this. We report a case of a patient presenting following a benzonatate overdose with a prolonged QRS on her initial electrocardiograph (ECG) rhythm strip with rapid normalization of QRS duration., Case Report: A 14-year-old girl presented in cardiac arrest following a benzonatate overdose. The patient was found in cardiac arrest within minutes of last being known well. Bystanders immediately provided cardiopulmonary resuscitation (CPR), and she was in asystole on emergency medical services (EMS) arrival. Return of spontaneous circulation (ROSC) was obtained following administration of intraosseous epinephrine and naloxone. EMS obtained an ECG rhythm strip following ROSC demonstrating a sinus rhythm with a QRS duration of 160 ms. Over the ensuing 30 minutes, there was progressive narrowing of the QRS. A 12-lead ECG obtained on arrival in the emergency department (ED) 44 minutes later demonstrated a QRS duration of 94 ms. Initially, EMS ECG rhythm strips were unavailable and an isolated benzonatate ingestion was considered less likely as ECG intervals were normal. Benzonatate exposure was later confirmed with a urine benzonatate concentration, which was 8.5 mcg/mL. The patient made a full recovery., Discussion: Cases of pediatric benzonatate overdose with rapid development of cardiac arrest and full recovery have been previously reported. In this case, evidence of cardiac sodium channel blockade was demonstrated with a prolonged QRS interval on initial ECG rhythm strip analysis. However, unlike previous cases, rapid resolution of QRS prolongation occurred in this case. While transient QRS prolongation may be observed, finding a normal QRS interval should not discount the possibility of benzonatate overdose., (© 2022. American College of Medical Toxicology.)

The Toxicology Investigators Consortium (ToxIC) Core Registry was established by the American College of Medical Toxicology in 2010. The Core Registry collects data from participating sites with the agreement that all bedside and telehealth medical toxicology consultations will be entered. This twelfth annual report summarizes the registry's 2021 data and activity with its additional 8552 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from January 1 to December 31, 2021. Detailed data was collected from these cases and aggregated to provide information, which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. Gender distribution included 50.4% of cases in females, 48.2% of cases in males, and 1.4% of cases in transgender or gender non-conforming individuals. Non-opioid analgesics were the most commonly reported agent class (14.9%), followed by opioids (13.1%). Acetaminophen was the most common agent reported. Fentanyl was the most common opioid reported and was responsible for the greatest number of fatalities. There were 120 fatalities, comprising 1.4% of all cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe new demographic characteristics, including marital status, housing status and military service, the continued COVID-19 pandemic and related toxicologic exposures, and novel substances of exposure., (© 2022. American College of Medical Toxicology.)

Importance: Federal emergency authorities were invoked during the COVID-19 pandemic to expand use of telehealth for new and continued care, including provision of medications for opioid use disorder (MOUD)., Objective: To examine receipt of telehealth services, MOUD (methadone, buprenorphine, and extended-release [ER] naltrexone) receipt and retention, and medically treated overdose before and during the COVID-19 pandemic., Design, Setting, and Participants: This exploratory longitudinal cohort study used data from the US Centers for Medicare & Medicaid Services from September 2018 to February 2021. Two cohorts (before COVID-19 pandemic from September 2018 to February 2020 and during COVID-19 pandemic from September 2019 to February 2021) of Medicare fee-for-service beneficiaries 18 years and older with an International Statistical Classification of Diseases, Tenth Revision, Clinical Modification OUD diagnosis., Exposures: Pre-COVID-19 pandemic vs COVID-19 pandemic cohort demographic characteristics, medical and substance use, and psychiatric comorbidities., Main Outcomes and Measures: Receipt and retention of MOUD, receipt of OUD and behavioral health-related telehealth services, and experiencing medically treated overdose., Results: The pre-COVID-19 pandemic cohort comprised 105 240 beneficiaries; of these, 61 152 (58.1%) were female, 71 152 (67.6%) were aged 45 to 74 years, and 82 822 (79.5%) non-Hispanic White. The COVID-19 pandemic cohort comprised 70 538 beneficiaries; of these, 40 257 (57.1%) were female, 46 793 (66.3%) were aged 45 to 74 years, and 55 510 (79.7%) were non-Hispanic White. During the study period, a larger percentage of beneficiaries in the pandemic cohort compared with the prepandemic cohort received OUD-related telehealth services (13 829 [19.6%] vs 593 [0.6%]; P < .001), behavioral health-related telehealth services (28 902 [41.0%] vs 1967 [1.9%]; P < .001), and MOUD (8854 [12.6%] vs 11 360 [10.8%]; P < .001). The percentage experiencing a medically treated overdose during the study period was similar (18.5% [19 491 of 105 240] in the prepandemic cohort vs 18.4% [13 004 of 70 538] in the pandemic cohort; P = .65). Receipt of OUD-related telehealth services in the pandemic cohort was associated with increased odds of MOUD retention (adjusted odds ratio [aOR], 1.27; 95% CI, 1.14-1.41) and lower odds of medically treated overdose (aOR, 0.67; 95% CI, 0.63-0.71). Among beneficiaries in the pandemic cohort, those receiving MOUD from opioid treatment programs only (aOR, 0.54; 95% CI, 0.47-0.63) and those receiving buprenorphine from pharmacies only (aOR, 0.91; 95% CI, 0.84-0.98) had lower odds of medically treated overdose compared with beneficiaries who did not receive MOUD., Conclusions and Relevance: Emergency authorities to expand use of telehealth and provide flexibilities for MOUD provision during the pandemic were used by Medicare beneficiaries initiating an episode of OUD-related care and were associated with improved retention in care and reduced odds of medically treated overdose. Strategies to expand provision of MOUD and increase retention in care are urgently needed.

A woman in her 30s presented to our emergency department with vomiting and lethargy after an intentional ingestion of unknown antimicrobial pills which was later found to be dapsone. The patient developed cyanosis, hypoxia and tachycardia due to acute methaemoglobinaemia (level of 30.9% on venous blood gas analysis). As dapsone is notorious for prolonged and rebound methaemoglobinaemia, she was managed with repeated doses of intravenous methylene blue and oral multidose activated charcoal which warranted elective intubation and intensive care unit admission. Subsequent drug-induced hepatitis and delayed dapsone-induced haemolysis were managed conservatively. She was discharged in a stable condition with outpatient follow-ups. Physician familiarity with the nuances of this rare condition and its complications contributes to better patient care., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: There are conflicting recommendations for lay rescuer management of patients who are unresponsive and apneic due to opioid overdose. We evaluated the management of such patients at an urban supervised consumption site., Methods: At a single urban supervised consumption site in Vancouver, BC, we conducted a retrospective chart review and administrative database linkage of consecutive patients who were unresponsive and apneic following witnessed opioid overdose between January 1, 2012 and December 31, 2017. We linked these visits with regional hospital records to define the entire care episode, which concluded when the patient was discharged from the supervised consumption site, ED, or hospital, or died. The primary outcome was successful resuscitation, defined as alive and neurologically intact (ambulatory and speaking coherently, or alert and oriented, or Glasgow Coma Scale 15) at the conclusion of the care episode. Secondary outcomes included mortality and predefined complications of resuscitation., Results: We collected 767 patients, with a median age of 43 and 81.6% male, with complete follow-up on 763 patients (99.5%). All patients were managed with oxygen and ventilation (100%, 95% CI 0.995-1.0); 715 (93.2%, 95% CI 0.911-0.949) received naloxone; no patients underwent chest compressions (0%, 95% CI 0-0.005). All patients with complete follow-up were alive and neurologically intact at the end of their care episode (100%, 95% CI 0.994-1.0). Overall, 191 (24.9%) patients were transported to hospital, and 15 (2.0%) patients required additional naloxone after leaving the supervised consumption site; 16 (2.1%) developed complications, and 1 patient was admitted to hospital., Conclusions: At an urban supervised consumption site, all unresponsive, apneic patients with witnessed opioid overdose were successfully resuscitated with oxygen and/or naloxone. No patients required chest compressions., (© 2022. The Author(s), under exclusive licence to Canadian Association of Emergency Physicians (CAEP)/ Association Canadienne de Médecine d'Urgence (ACMU).)

Background: Therapeutic plasma exchange (TPE) is gaining popularity for the management of nonsteroidal anti-inflammatory drug (NSAID) overdose in dogs., Hypothesis/objectives: Describe a population of dogs treated with TPE for NSAID overdose., Animals: Sixty-two dogs with NSAID overdose treated with TPE., Methods: Multicenter retrospective study of dogs treated with TPE for ibuprofen, carprofen, or naproxen overdose., Results: The median dose of ibuprofen, carprofen or naproxen ingested was 533 mg/kg (range, 36-4857 mg/kg), 217 mg/kg (range, 88-625 mg/kg) and 138 mg/kg (range, 26-3000 mg/kg), respectively. Based on previously established toxic ranges for each NSAID, 2 (3.2%), 14 (22.6%), and 46 (74.2%) dogs ingested a gastrointestinal, renal, and neurological toxic dose, respectively. The median time between ingestion and presentation was 4 hours (range, 1-20 hours). The median number of plasma volumes processed was 1.6 (range, 0.4-2.2). The median TPE session duration was 2 hours (range, 1-4.5 hours). Circuit clotting developed during 8 (12.9%) sessions. Patient adverse events reported during 21 (33.8%) sessions consisted of urticaria (12.9%), asymptomatic hypocalcemia (9.6%), and hypotension (9.6%). The median duration of hospitalization was 2.25 days (range, 1-11 days). Sixty-one (98.4%) dogs survived to discharge, and none were rehospitalized. Thirty-one (91.1%) of the 34 dogs with at least 1 follow-up visit were not azotemic at the time of reevaluation., Conclusions and Clinical Importance: This population of dogs managed with TPE had excellent outcomes, even in cases of high NSAID dose ingestion. When TPE is available and the time frame is appropriate, this extracorporeal modality should be considered for the management of NSAID overdose., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: To describe the prevalence of incarceration among survivors of non-fatal overdose addressed through an emergency medical services (EMS) response, and compare incarceration by whether the emergency was for opioid-involved or stimulant-involved overdose., Methods: Administrative records on 192,113 EMS incidents and 70,409 jail booking events occurring between January 1, 2019 and December 31, 2020 in Indianapolis, Indiana were record-linked at the event level. Incarceration taking place within 6-hours of an EMS incident was associated with that incident. Logistic regression was used to calculate adjusted odds ratios (AOR) of incarceration after an overdose., Results: Among all EMS incidents, 2.6% were followed by incarceration. For overdose EMS incidents, the prevalence of incarceration was 10.0%. Overdose incidents had higher odds than non-overdose incidents of leading to a charge of felony, booked on a warrant, and transferred to another law enforcement agency upon release. Prevalence of incarceration following a stimulant-involved overdose was 21.3%, compared to 9.3% for opioid-involved overdose survivors. Compared to persons from other EMS incidents, overdose survivors had greater odds of incarceration (AOR=3.48, 95% confidence interval (CI)= 3.22, 3.75, p < .001), with opioid-involved overdoses (AOR=3.03, 95% CI=2.76, 3.33, p < .001) and stimulant-involved overdoses (AOR=6.70, 95% CI=5.26, 8.55, p < .001) leading to higher odds of incarceration., Conclusion: Incarceration in county jail followed one in ten overdose-involved EMS responses. As illicit drug consumption increasingly involves stimulants, the frequency of incarceration following these events is likely to increase. Policy changes and interventions are needed to reduce incarceration after overdose emergencies., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The number of nonfatal opioid-involved overdoses treated by health care providers has risen in the United States; the median number of emergency department (ED) visits for these overdoses was significantly higher during 2020 than during 2019 (1). ED visit data can underestimate nonfatal opioid-involved overdose incidence because, increasingly, persons experiencing a nonfatal opioid overdose are refusing transport to EDs by emergency medical services (EMS) (2). A study in Kentucky found that during a 6-month period, 19.8% of persons treated by EMS for an opioid overdose refused transport to an ED (2). Thus, EMS encounter data involving suspected nonfatal opioid-involved overdoses complement ED data and also allow for near real-time analysis (3). This report describes trends in rates of EMS encounters for nonfatal opioid-involved overdoses per 10,000 total EMS encounters (rates) by selected patient- and county-level characteristics during January 2018–March 2022 in 491 counties from 21 states using data from biospatial, Inc.* During this period, the nonfatal opioid-involved overdose rate increased, on average, 4.0% quarterly. Rates increased for both sexes and for most age groups. Rates were highest among non-Hispanic White (White) and non-Hispanic Native Hawaiian or other Pacific Islander (NH/OPI) persons, and increases were largest among non-Hispanic Black (Black), followed by Hispanic or Latino (Hispanic) persons. Rates increased in both urban and rural counties and for all quartiles of county-level characteristics (i.e., unemployment, education, and uninsured), except in counties with the lowest percentage of uninsured persons. Rates were highest and rate increases were largest in urban counties and counties with higher unemployment rates. This analysis of nonfatal opioid-involved overdose trends in EMS data highlights the utility of these data and the importance of addressing inequities that contribute to disproportionate overdose risk, such as through focused outreach to racial and ethnic minority groups, who disproportionately experience these inequities, and communities with higher levels of unemployment. EMS providers are in a unique position to engage in postoverdose response protocols and promote evidence-based overdose education and facilitate linkage to care and harm reduction services.†,§, Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Josh Walters reports that he owns employee stock options in biospatial, Inc. No other potential conflicts of interest were disclosed.

The opioid crisis is a growing public health emergency and increasing resources are being directed towards overdose education. Simulation has emerged as a novel strategy for training overdose response, yet little is known about training non-clinicians in bystander resuscitation. Understanding the perspectives of individuals who are likely to experience or witness opioid overdose is critical to ensure that emergency response is effective. The Surviving Opioid Overdose with Naloxone Education and Resuscitation (SOONER) study evaluates the effectiveness of a novel naloxone education and distribution tool among people who are non-clinicians and likely to witness opioid overdose. Participants' resuscitation skills are evaluated using a realistic overdose simulation as the primary outcome of the trial. The purpose of our study is to describe the experience of participants with the simulation process in the SOONER study. We employed a semi-structured debriefing interview and a follow up qualitative interview to understand the experience of participants with simulation. A qualitative content analysis was performed using data from 21 participants who participated in the SOONER study. Our qualitative analysis identified 5 themes and 17 subthemes which described the experience of participants within the simulation process. These themes included realism, valuing practical experience, improving self-efficacy, gaining new perspective and bidirectional learning. Our analysis found that simulation was a positive and empowering experience for participants in the SOONER trial, most of whom are marginalized in society. Our study supports the notion that expanding simulation-based education to non-clinicians may offer an acceptable and effective way of supplementing current opioid overdose education strategies. Increasing the accessibility of simulation-based education may represent a paradigm shift whereby simulation is transformed from a primarily academic practice into a patient-based community resource., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Extracorporeal Treatment (ECTR) is an essential component in management of severe lithium toxicity. The Extracorporeal Treatments in Poisoning (EXTRIP) group's suggested indications for ECTR include "if the expected time to obtain a [Li+] < 1.0mEq/L with optimal management is >36h". Buckley et al. developed a lithium nomogram which could help predict the fall in lithium concentrations for chronic poisoning. Our aim is to externally validate the lithium nomogram in a cohort of cases with chronic accumulation and acute on chronic lithium poisoning., Methods: A retrospective analysis of suspected cases of chronic accumulation and acute on chronic lithium poisoning referred to our Toxicology Unit from May 2013 to 2020 was performed., Results: Out of 51 cases, 29 cases of chronic accumulation and eight cases of acute on chronic poisoning were analysed after excluding 14 cases who required haemodialysis. In chronic accumulation cases, the nomogram correctly identified 10 out of 14 patients whose [Li+] failed to drop below 1.0 mmol/L by 36 h (sensitivity 71.4% [95% CI 42 - 92%]), and 8 out of 15 patients whose [Li+] dropped below 1.0 mmol/L by 36 h (specificity 53.3% [95% CI 27 - 78%]), resulting in the positive predictive value (PPV) of 58.8%, negative predictive value (NPV) of 66.7% and accuracy of 62.1%., Conclusions: Our study shows that the lithium nomogram is moderately sensitive at identifying patients with chronic lithium accumulation who will have a serum lithium concentration >1 mmol/L at 36 h without ECTR.

Context: Prior studies have observed shorter lengths of stay when practitioners consult a US poison control center (PCC) regarding hospitalized toxicology patients, but the most recent study used data from 2010. Since then, the implementation of the Affordable Care Act, a trend toward shorter hospitalizations and substantial adjustments in hospital charges have occurred., Methods: This is a retrospective study of administrative hospital data and poison center data obtained from the Wisconsin Hospital Association and Wisconsin Poison Center for patients treated from 2010 to 2017. Stratified analysis was used to investigate the potential effects of PCC consultation on hospitalization. Univariate and multivariable regression analysis was used to characterize which factors were associated with an increased rate of PCC consultation., Discussion: 127,224 hospitalized cases were found, of which 44,628 were entered into a stratified hospital charge and length of stay analysis. PCC consultation was associated with an 11.6 h (95% CI 10.4-13.0 h) shorter mean length of stay overall, with children aged 0-6 having a larger reduction of 1.18 days. While total charges were higher by $600 in PCC consultation cases in the overall analysis (95% CI $390-$777), mean charges in patients aged 0-6 were $6695 lower when the PCC was consulted. PCC consultation was more likely to occur in cases involving children and adolescents, intentional overdoses (versus accidental or unknown intent), and women., Conclusions: Our findings suggest that PCC consultation should be encouraged to potentially shorten hospitalizations of poisoned patients, and for pediatric patients in particular. Intentionality and demographic factors affect the rate of PCC consultation for overdose, but the nature of these relationships is unclear.

Introduction: Valproic acid (VPA) toxicity commonly results in a self-limited state of CNS depression that is managed with supportive care and levocarnitine. In massive overdose, patients can develop toxic encephalopathy, shock, multisystem organ failure, and death. We present a case with relevant toxicokinetics of a patient presenting with a profoundly elevated VPA concentration resulting in survival, treated with supportive care including high-dose continuous venovenous hemodiafiltration (CVVHDF)., Case Report: A 17-year-old female presented to an emergency department after being found unresponsive at home with concern for massive VPA ingestion. She arrived obtunded and hypotensive with initial VPA concentration of 2226 mg/L, estimated 9 h post-ingestion. Her early hospital course was marked by hypotension requiring multiple vasopressors, and her workup was notable for multiple severe metabolic derangements. High-dose CVVHDF was initiated upon transfer to a tertiary children's hospital with the aim to enhance VPA removal and normalize metabolic derangements. At that time, her VPA concentration was 1071 mg/L. Apparent half-life of VPA improved modestly with extracorporeal treatment, but her metabolic derangements and hemodynamic instability corrected rapidly. Her clinical course was complicated by necrotizing pancreatitis, pancytopenia requiring transfusions of multiple cell lines, coma, and seizures. She ultimately recovered with normal neurological function., (© 2022. American College of Medical Toxicology.)

In 2019, 65.8 million U.S. adults reported past-month binge drinking and 35.8 million reported illicit drug use or prescription pain reliever misuse during the past month; 20.4 million met diagnostic criteria for a substance use disorder during the past year (1). Approximately 81,000 persons died of a drug overdose* during May 2019-May 2020; excessive alcohol use contributes to an estimated 95,000 deaths per year (2). Persons with a substance use disorder are at elevated risk for overdose and associated harms (3). To examine the prevalence of past 30-day substance use patterns and the severity of problems experienced across seven biopsychosocial domains (alcohol, drug, employment, family, legal, medical, and psychiatric), CDC used 2019 data from the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO) Addiction Severity Index-Multimedia Version (ASI-MV) tool (4); these data are collected from adults aged ≥18 years who seek substance use treatment in the United States. Alcohol was the most commonly reported substance used during the past 30 days (35.8%), followed by cannabis (24.9%), prescription opioids (misuse) (18.5%), illicit stimulants (14.0%), heroin (10.2%), prescription sedatives or tranquilizers (misuse) (8.5%), cocaine (7.4%), illicit fentanyl (4.9%), and prescription stimulants (misuse) (1.8%). † Polysubstance use (use of two or more substances) during the past 30 days was reported by 32.6% of respondents. Among the biopsychosocial domains measured, 45.4% of assessments reported more severe problems with drugs; others reported psychiatric (35.2%), legal (28.8%), medical (27.4%), employment (25.0%), alcohol (24.2%), and family problems (22.8%). These findings highlight the complex nature of substance use in the United States, the interplay between substance use and mental illness, and the complex challenges that persons with substance use disorder face when seeking treatment. Actions to enhance comprehensive substance use programs that incorporate polysubstance use and co-occurring mental health problems into strategies for prevention, treatment, and response are needed, as is expanded linkage to services. CDC provides data and resources to equip and inform states, territories, and local jurisdictions to help improve opioid prescribing practices, improve linkage to care for the treatment of opioid use disorder, and prevent and reverse overdoses. § ., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Poisoning is a common problem in the United States. Acid-base disturbances, electrolyte derangements, or acute kidney injury result from severe poisoning from toxic alcohols, salicylates, metformin, and acetaminophen. Lithium is highly sensitive to small changes in kidney function. These poisonings and drug overdoses often require the nephrologist's expertise in diagnosis and treatment, which may require correction of acidosis, administration of selective enzyme inhibitors, or timely hemodialysis. The clinical and laboratory abnormalities associated with the poisonings and drug overdoses can develop rapidly and lead to severe cellular dysfunction and death. Understanding the pathophysiology of the disturbances and their clinical and laboratory findings is essential for the nephrologist to rapidly recognize the poisonings and establish an effective treatment plan. This installment of AJKD's Core Curriculum in Nephrology presents illustrative cases of individual poisonings and drug overdoses and summarizes up to date information on their prevalence, clinical and laboratory findings, pathophysiology, diagnosis, and treatment., (Published by Elsevier Inc.)

Numerous drugs and toxins can cause metabolic acidosis. The treating clinician should be aware of the many compounds that can produce metabolic acidosis following an accidental exposure, an overdose, or with therapeutic use. Awareness and comprehension of those substances associated with metabolic acidosis will facilitate the diagnosis and treatment of poisoned patients., Competing Interests: Disclosure The author has no conflicts of interest, financial or otherwise, to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Accidental acetaminophen overdoses are associated with substantial morbidity and health care costs. In Canada, updated labelling standards were implemented in October 2009 and September 2016, with the intent of communicating risks of overdose and facilitating product identification and safe use, respectively. Full compliance with the 2016 standards was expected by March 2018. We sought to explore whether these changes affected rates of hospital admission for accidental acetaminophen overdose., Methods: We conducted a population-based study of hospital admissions for accidental acetaminophen overdose in 9 Canadian provinces and 3 Canadian territories between Apr. 1, 2014, and Mar. 31, 2020. We used interventional autoregressive integrated moving average (ARIMA) models to evaluate the impact of the updated labelling standards on rates of hospital admission for accidental acetaminophen overdose. In secondary analyses, we studied intensive care unit (ICU) admissions and hospital admissions for accidental acetaminophen overdose involving opioids., Results: Monthly rates of hospital admission for accidental acetaminophen overdose were essentially unchanged over the study period (0.21 and 0.22 cases per 100 000 population in April 2004 and March 2020, respectively). We found no association between changing labelling standards and trends in rates of hospital admission for accidental acetaminophen overdose (October 2009 p = 0.2, September 2016 p = 0.7 and March 2018 p = 0.2). Similarly, labelling changes did not have an impact on admissions involving ICU admission and concomitant opioid poisoning., Interpretation: Modifications to product labels did not reduce the rate of acetaminophen-related harm. Additional measures to reduce the burden of accidental acetaminophen overdose are required., Competing Interests: Competing interests: Tara Gomes reports funding from the Canadian Institutes of Health Research and support for committee attendance from Indigenous Services Canada, outside the submitted work. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

A 25-year-old woman presented with cardiogenic shock following intentional overdose of Common Yew ( Taxus baccata ). The pharmacological mechanisms underlying yew toxicity resulted in failure of multiple treatment modalities including inotropes, vasopressors and attempted pacing. Resuscitation was ultimately unsuccessful. The limited literature available on this kind of overdose suggests that early extracorporeal membrane oxygenation (ECMO) is the mainstay of treatment in severe cases presenting with hypotension and arrhythmias. However, there may be a role for digoxin antibody fragments in maintaining patients presenting to remote sites, to allow transfer to a specialist centre., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Bupropion is an antidepressant with unique mechanisms of action leading to a narrow therapeutic window. Parallel to increasing indications, there is an increasing number of overdoses and fatalities attributable to bupropion overdose. Due to the serious effects of a bupropion overdose including arrhythmias and early or delayed seizures, these patients necessitate prolonged monitoring with high levels of medical care. In the setting of a tertiary care center with a medical toxicology consult service, our institution is heavily relied upon to manage these patients. This study was performed to provide clarity on the resources used, lengths-of-stay, and treatments provided for these patients., Methods: All patients at a tertiary care center with an oral bupropion overdose and a medical toxicology consult less than 24 h after the ingestion were included between July 15, 2017 and October 14, 2021. Chart review was performed to determine lengths-of-stay, the unit of disposition, treatments provided, and outcomes., Results: A total of 73 cases were identified with 36 bupropion-only ingestions. Most cases were transferred from outside facilities, developed seizures, had QRS prolongation; and almost a third required intubation. The vast majority were admitted to an ICU and received GABA-A agonists. A median of 1.47 days per case was spent in the ED or ICU. There was an average of 41.9 ED or ICU bed-days per year and 68.5 non-psychiatric bed-days per year occupied by a patient after a bupropion overdose at a single center., Conclusions: Bupropion overdose necessitates high resource utilization which we believe will increase with the expanding indications for its use., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: COBRA was developed as a decision rule to predict which patients visiting the emergency department (ED) following intentional drug overdose will not require intensive care unit (ICU) interventions. COBRA uses parameters from five vital systems (cardiac conduction, oxygenation, blood pressure, respiration, and awareness) that are readily available in the ED. COBRA recommends against ICU admission when all these parameters are normal., Objective: The primary aim of this study was to determine the negative predictive value (NPV) of COBRA in predicting ICU interventions. Secondary outcomes were the sensitivity, specificity and positive predictive value (PPV), and the observation time required for a reliable prediction., Design: Observational cohort study., Settings and Participants: Patients with a reported intentional overdose with drugs having potential acute effects on neurological, circulatory or ventilatory function were included, and data necessary to complete the decision rule was collected. The attending physician in the ED made the actual admission decision, on the basis of clinical judgement. COBRA was measured 0, 3 and 6 h after arrival at the ED., Outcome Measures: Need for ICU interventions (treatment of convulsion; defibrillation; mechanical or noninvasive ventilation; intravenous administration of vasopressive agents, antiarrhythmics, atropine, calcium, magnesium or sedation; continuous hemofiltration or administration of antagonist/antidote and fluid resuscitation)., Main Results: Of 230 new cases (144 unique patients), 59 were immediately referred to the psychiatric services and/or sent home by the attending physician, 27 went to a regular ward, and 144 were admitted to the ICU. Of these 144 cases, 40 required one or more ICU interventions. By the time the first parameters were collected, the NPV of COBRA was 95.6%. After 3 h of observation, NPV was 100%, while sensitivity, specificity and PPV were 100, 61.1 and 35.1%, respectively. None of these values improved by prolonging the observation time to 6 h., Conclusion: In patients with a reported intentional overdose with drugs having potential acute effects on neurological, circulatory or ventilatory function, the COBRA decision rule showed good performances in predicting the need for intensive care interventions, with a NPV of 100% after 3 h of observation., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Methamphetamine use is rising globally and we have limited treatments for this. Subgroups within the diverse methamphetamine-using population may have distinct treatment needs. Among a community-recruited sample of people who use crystal methamphetamine, we aimed to identify subgroups and characterize their overdose risk and access to addiction care., Methods: Data from prospective cohorts of people who use drugs in Vancouver, Canada from 2014 to 2018 were used to conduct a repeated measures latent class analysis among participants who used crystal methamphetamine. Multivariable generalized estimating equations models were fit to determine the associated factors., Results: Among 824 eligible participants, a five-class model was identified as the best fit: (1) primary stimulant use (15.7%); (2) women engaged in sex work and opioid use (21.4%); (3) street income generation and opioid use (31.6%); (4) opioid agonist therapy (OAT) patients (22.3%); and (5) men who have sex with men (9.0%). In multivariable analyses, compared to the primary stimulant use group, non-fatal overdose was positively associated with street income generation (adjusted odds ratio [AOR] = 1.49, 95% confidence interval [95% CI]=1.30-1.71), sex work (AOR = 1.38, 95% CI=1.20-1.59) and OAT (AOR = 1.22, 95% CI=1.06-1.41) subgroups; engagement in non-OAT addiction care was negatively associated with street income generation (AOR = 0.81, 95% CI=0.68-0.97) and sex work (AOR = 0.78, 95% CI=0.63-0.98) subgroups., Discussion: Socioeconomically marginalized subgroups with opioid and crystal methamphetamine co-use were at highest risk of non-fatal overdose and had poorer access to addiction care, highlighting the need for tailored interventions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Valproic acid (VPA) and derivatives are effective anticonvulsants that are also used for numerous mood disorders. VPA toxicity can cause central nervous system (CNS) depression, dose related hyperammonemia, and eventually hepatotoxicity. While traditional treatment of VPA toxicity often includes l-carnitine, activated charcoal, and hemodialysis; an interaction with carbapenem class antibiotics has been well established in literature and may offer a different avenue of treatment. This case describes a 38 year-old female with a past medical history of epilepsy effectively treated with meropenem to rapidly and safely lower toxic VPA levels after an acute ingestion. A review of four VPA poisoning case reports and the interaction with carbapenem class antibiotics is also included., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Quetiapine is a psychotropic drug. Excessive use of quetiapine may lead to drowsiness, blurred vision, respiratory depression, hypotension and extrapyramidal reactions. Acute respiratory distress syndrome (ARDS) is rare due to overdose of quetiapine. On 14 February 2020, a patients with coma, respiratory arrest and hypotension due to overdose of quetiapine were admitted to our hospital. After receiving mechanical ventilation、plasma adsorption and anti-inflammatory treatment, the patient's consciousness turned clear, the machine was successfully removed and extubated, and the patient's condition was improved and discharged from hospital. We analyzed the clinical data of the patient with quetiapine poisoning, and discussed the clinical symptoms and chest CT characteristics of ARDS caused by quetiapine poisoning, in order to improve the understanding of quetiapine poisoning and improve the success rate of rescue.

A 17-year-old man was admitted to the paediatric intensive care unit 2 hours following an intentional ingestion of unknown substances. In the first 23 hours of hospitalisation, lactate levels remained elevated at 2-4 mmol/L, during the 24th hour, he developed lactic acidosis with lactate levels increasing from 4 to 16 mmol/L. His neurological status declined, requiring orotracheal intubation. Central and arterial access were obtained, and vasoactive infusions were initiated for haemodynamic support. Due to increasing lactate levels (maximum level >24 mmol/L) and haemodynamic instability, a dialysis line was inserted, and continuous renal replacement therapy (CRRT) was initiated. The lactic acidosis resolved over 10 hours. Serum ibuprofen level subsequently resulted at 841 µg/mL (reference range 10-50). Few reported cases discuss the sequela of large quantity ibuprofen ingestion leading to severe lactic acidosis and multiorgan system failure. Early intervention with CRRT may reverse acidosis, stabilise haemodynamics and halt secondary organ failure., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Perampanel is indicated for partial onset seizures in children and adults. The mechanism is unique among antiepileptic agents as it inhibits glutamate activity on AMPA receptors. Currently, there are few published case reports describing overdose., Methods: This is a retrospective observational study of all single substance perampanel ingestions from January 2014 to December 2019 reported to the national poison data system (NPDS). The primary outcome is to describe the clinical effects of perampanel exposures. Secondary outcomes include evaluation of management and investigation of a dose-effect relationship for the purpose of triaging acute unintentional exposures., Results: A total of 138 exposures were reported to NPDS since the release of the agent. Median age was 20 years (IQR 10-38) with 68 (49.3%) males. The reason for exposure was most commonly therapeutic error (80, 58.0%), followed by exploratory ingestion (24, 17.4%), and suicidal ingestion (14, 10.1%). A total of six (4.3%) patients developed major effects, 20 (14.5%) moderate, 32 (23.2%) minor effects and 22 (15.9%) no effect. An additional 54 (39.1%) cases were not followed. Almost half of cases were managed at home. Of those that were in a healthcare facility (HCF) ( n  = 72), most were treated/evaluated and released (31, 43.1%), followed by admission to a non-critical care unit (20, 27.8%), and critical care unit (13, 18.1%). Most frequently reported symptoms were drowsiness (27, 19.6%), agitation (20, 14.5%), ataxia (13, 9.4%), and confusion (12, 8.7%). The most common therapies provided in a HCF were intravenous fluids (22,30.6%), followed by benzodiazepines (14, 19.4%), then other types of sedation (9, 12.5%). There were too few cases to determine a dose cut off for triaging., Conclusions: While drowsiness, agitation, ataxia, and confusion were the most often reported symptoms, close to 19% developed moderate/major effects and almost 4% of patients received potentially life-saving interventions.

Calcium channel blocker ingestions remain one of the leading causes of death related to cardiovascular medication ingestion in both adults and pediatric patients. We report a case of a 17-year-old, 103 kg female presenting after an intentional polypharmacy ingestion, including 500 to 550 mg of amlodipine. She presented with profound vasoplegia and cardiovascular collapse requiring high-dose inotropes and eventual life support with extracorporeal membrane oxygenation (ECMO). Current available treatments, designed for adults, including lipid emulsion and methylene blue, provided no sustained clinical improvement. This resulted in the initiation of single-pass albumin dialysis (SPAD). We aim to describe the clinical implications, amlodipine toxic dose effects, and clinical challenges associated with large pediatric patients and high-dose medications. We also discuss several challenges encountered related to dosing and concentration of medications, which led to fluid overload. Given the ongoing obesity epidemic, we routinely see pediatric patients of adult size. This will continue to challenge pediatric use of adult dosing and concentrations to avoid excessive fluid administration for high-dose medications, such as insulin and vasoactive agents. To our knowledge, this is the first successful case of using SPAD in conjunction with ECMO for salvage therapy after refractory life-threatening calcium channel blocker toxicity.

Background: The COVID-19 pandemic can exacerbate underlying substance use disorder and has impacted this vulnerable population in a variety of ways. There are limited data regarding how this pandemic has impacted emergency department (ED) patient presentations., Methods: We extracted data on ED visits from the electronic health record (EHR) of a large healthcare system in the Washington, DC/Baltimore, MD metropolitan area. The dataset includes data from 7 hospitals on ED visits between 11/1/2019-6/30/2020. The health system utilizes a validated screening program for substance use, Screening, Brief Intervention, and Referral to Treatment (SBIRT), for ED patients who are clinically stable and willing to complete screening. We evaluated trends in patients with a positive SBIRT screen and those presenting with a clinical diagnosis of acute alcohol or substance intoxication/overdose before (11/1/19-2/29/2020-pre) and during the first wave of the COVID pandemic (3/1/2020-6/30/2020-post). Data were described using descriptive statistics. Bivariate analyses were conducted using chi-square test and two-sample t-tests. Interrupted time series analysis was used to evaluate the changes in the weekly trends with the start of the pandemic., Results: There were 107,930 screens performed in the EDs during the study period (61,961 pre, 45,969 post). The population was primarily African American (64.7%) and female (57.1%). Positive SBIRT screens increased from 12.5% to 15.8% during COVID (p < 0.001). Alcohol intoxication presentations increased as a proportion of positive screens from 12.6% to 14.4% (p = 0.001). A higher percentage of screened patients reported problem drinking (AUDIT score ≥ 7) during the pandemic (2.4% pre vs 3.2% post, p < 0.001). Substance intoxication/overdoses among all screened increased from 2.1% to 3.1% (p < 0.001) and as a percentage of positive screens during the pandemic (16.8% to 20%, p < 0.001). The proportion of opioid vs. non-opioid overdoses remained unchanged before (67%) and during the pandemic (64%, p = 0.33)., Discussion: There was an increase in the proportion of positive SBIRT screens and visits for acute overdoses and intoxication during the first wave of the COVID-19 pandemic. Additional research should focus on mitigation strategies to address substance use during this vulnerable time., Competing Interests: Declaration of Competing Interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent- licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. Kira Chandran, Maryann Mazer-Amirshahi, Nikash Shankar, Sameer Desale, Lewis Nelson, Mihriye Mete., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Adulteration, substitution or contamination of illicit substances can have clinically significant implications when other illicit substances are included. Such circumstances can present as clusters of poisonings, including severe toxicity and death following exposure to unexpected illicit substances. We report a cluster of laboratory-confirmed lysergic acid diethylamide (LSD) in a powder that was sold as cocaine and used recreationally., Methods: The Prescription, Recreational and Illicit Substance Evaluation (PRISE) program established by the New South Wales Ministry of Health includes State-based hospital toxicology services, Poisons Information Centre, Forensic & Analytical Science Service and emergency services to identify clusters of severe and unusual toxicity associated with substance use. PRISE criteria include a known cluster (geographically or situationally related) of people with acute severe toxicity, especially when accompanied by a toxidrome that is inconsistent with the history of exposure. A timely comprehensive drug screen and quantification is performed in eligible cases and the results are related to the clinical features. The need for a public health response is then considered. Four individuals inhaled a white powder that was sold as cocaine and developed severe toxicity that was not consistent with cocaine which prompted transfer to hospital for further management., Results: LSD was confirmed in four subjects, and the concentrations in 3 of the individuals were 0.04-0.06 mg/L which are among the highest reported in the literature. Common clinical features were hallucinations, agitation, vomiting, sedation, hypertension, and mydriasis. One subject required intubation and admission to the intensive care unit, two required overnight admission, and the fourth was discharged following oral diazepam after observation. No subject suffered persistent injury., Conclusions: A close working relationship between pre-hospital emergency services, hospital-based clinical services, public health authorities, and analytical laboratories appears to be advantageous. Favourable clinical outcomes are observed from LSD poisoning despite high exposures with good supportive care.

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.)