Severe outcomes following pediatric cannabis intoxication: a prospective cohort study of an international toxicology surveillance registry.

INTRODUCTION: An increasing number of jurisdictions have legalized recreational cannabis for adult use. The subsequent availability and marketing of recreational cannabis has led to a parallel increase in rates and severity of pediatric cannabis intoxications. We explored predictors of severe outcomes in pediatric patients who presented to the emergency department with cannabis intoxication. METHODS: In this prospective cohort study, we collected data on all pediatric patients (<18 years) who presented with cannabis intoxication from August 2017 through June 2020 to participating sites in the Toxicology Investigators Consortium. In cases that involved polysubstance exposure, patients were included if cannabis was a significant contributing agent. The primary outcome was a composite severe outcome endpoint, defined as an intensive care unit admission or in-hospital death. Covariates included relevant sociodemographic and exposure characteristics. RESULTS: One hundred and thirty-eight pediatric patients (54% males, median age 14.0 years, interquartile range 3.7-16.0) presented to a participating emergency department with cannabis intoxication. Fifty-two patients (38%) were admitted to an intensive care unit, including one patient who died. In the multivariable logistic regression analysis, polysubstance ingestion (adjusted odds ratio = 16.3; 95% confidence interval: 4.6-58.3; P < 0.001)) and cannabis edibles ingestion (adjusted odds ratio = 5.5; 95% confidence interval: 1.9-15.9; P = 0.001) were strong independent predictors of severe outcome. In an age-stratified regression analysis, in children older than >10 years, only polysubstance abuse remained an independent predictor for the severe outcome (adjusted odds ratio 37.1; 95% confidence interval: 6.2-221.2; P < 0.001). As all children 10 years and younger ingested edibles, a dedicated multivariable analysis could not be performed (unadjusted odds ratio 3.3; 95% confidence interval: 1.6-6.7). CONCLUSIONS: Severe outcomes occurred for different reasons and were largely associated with the patient's age. Young children, all of whom were exposed to edibles, were at higher risk of severe outcomes. Teenagers with severe outcomes were frequently involved in polysubstance exposure, while psychosocial factors may have played a role.

Opioid overdoses involving xylazine in emergency department patients: a multicenter study.

INTRODUCTION: Illicit opioids, consisting largely of fentanyl, novel synthetic opioids, and adulterants, are the primary cause of drug overdose fatality in the United States. Xylazine, an alpha-2 adrenergic agonist and veterinary tranquilizer, is being increasingly detected among decedents following illicit opioid overdose. Clinical outcomes in non-fatal overdose involving xylazine are unexplored. Therefore, among emergency department patients with illicit opioid overdose, we evaluated clinical outcome differences for patients with and without xylazine exposures. METHODS: This multicenter, prospective cohort study enrolled adult patients with opioid overdose who presented to one of nine United States emergency departments between 21 September 2020, and 17 August 2021. Patients with opioid overdose were screened and included if they tested positive for an illicit opioid (heroin, fentanyl, fentanyl analog, or novel synthetic opioid) or xylazine. Patient serum was analyzed via liquid chromatography quadrupole time-of-flight mass spectroscopy to detect current illicit opioids, novel synthetic opioids, xylazine and adulterants. Overdose severity surrogate outcomes were: (a) cardiac arrest requiring cardiopulmonary resuscitation (primary); and (b) coma within 4 h of arrival (secondary). RESULTS: Three hundred and twenty-one patients met inclusion criteria: 90 tested positive for xylazine and 231 were negative. The primary outcome occurred in 37 patients, and the secondary outcome occurred in 111 patients. Using multivariable regression analysis, patients positive for xylazine had significantly lower adjusted odds of cardiac arrest (adjusted OR 0.30, 95% CI 0.10-0.92) and coma (adjusted OR 0.52, 95% CI 0.29-0.94). CONCLUSIONS: In this large multicenter cohort, cardiac arrest and coma in emergency department patients with illicit opioid overdose were significantly less severe in those testing positive for xylazine.

Metabolic Acidosis: Differentiating the Causes in the Poisoned Patient.

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.

Predictors of severe outcome following opioid intoxication in children.

INTRODUCTION: While the opioid crisis has claimed the lives of nearly 500,000 in the U.S. over the past two decades, and pediatric cases of opioid intoxications are increasing, only sparse data exist regarding risk factors for severe outcome in children following an opioid intoxication. We explore predictors of severe outcome (i.e., intensive care unit [ICU] admission or in-hospital death) in children who presented to the Emergency Department with an opioid intoxication. METHODS: In this prospective cohort study we collected data on all children (0-18 years) who presented with an opioid intoxication to the 50 medical centers in the US and two international centers affiliated with the Toxicology Investigators Consortium (ToxIC) of the American College of Medical Toxicology, from August 2017 through June 2020, and who received a bedside consultation by a medical toxicologist. We collected relevant demographic, clinical, management, disposition, and outcome data, and we conducted a multivariable logistic regression analysis to explore predictors of severe outcome. The primary outcome was a composite severe outcome endpoint, defined as ICU admission or in-hospital death. Covariates included sociodemographic, exposure and clinical characteristics. RESULTS: Of the 165 (87 females, 52.7%) children with an opioid intoxication, 89 (53.9%) were admitted to ICU or died during hospitalization, and 76 did not meet these criteria. Seventy-four (44.8%) children were exposed to opioids prescribed to family members. Fentanyl exposure (adjusted OR [aOR] = 3.6, 95% CI: 1.0-11.6; p = 0.03) and age ≥10 years (aOR = 2.5, 95% CI: 1.2-4.8; p = 0.01) were independent predictors of severe outcome. CONCLUSIONS: Children with an opioid toxicity that have been exposed to fentanyl and those aged ≥10 years had 3.6 and 2.5 higher odds of ICU admission or death, respectively, than those without these characteristics. Prevention efforts should target these risk factors to mitigate poor outcomes in children with an opioid intoxication.

Consensus Development of a Core Content for a Standardized Medical Toxicology Curriculum for Medical Students.

BACKGROUND: Currently, no standardized core content in medical toxicology exists for medical students. The goals of this study were to (1) assess the current state and needs of medical toxicology clerkships and (2) develop a consensus-derived list of core topics that should be covered during a medical toxicology clerkship. METHODS: We assembled a task force established by the American College of Medical Toxicology (ACMT) of nine experts in medical toxicology or emergency medicine. We developed a needs assessment survey that was sent to all medical student clerkship directors in medical toxicology. Based on their responses, we used a modified Delphi process to develop a consensus of core topics that should be covered during a medical student clerkship. RESULTS: Nineteen out of 42 (45%) clerkship directors completed the survey; 18 met inclusion criteria. The majority of clerkships were 4 weeks in duration with an average of 15 students/year. The three most common teaching methods used were bedside teaching (n = 17/18), classroom teaching (n = 17/18), and journal club (n = 14/18). All the clerkship directors (n = 18/18) reported they would use a standardized curriculum as well as educational content developed by ACMT. There was overwhelming consensus on the core topics which included, but were not limited to, pharmacology/toxicology; drugs; drugs of abuse; natural products; pharmacological basis of antidote use; toxicologic syndromes; vital sign abnormalities; initial management; supportive and other care; withdrawal syndrome management; industrial, household, and environmental toxins; differential diagnosis by clinical findings; and ABCs-resuscitation. CONCLUSION: The ACMT task force developed a medical toxicology clerkship core content. The task force also identified a need for shared resources among clerkships.

No laughing matter - Myeloneuropathy due to heavy chronic nitrous oxide abuse.

Chronic nitrous oxide abuse is a known cause of myeloneuropathy. Nitrous oxide irreversibly inactivates vitamin B12 causing demyelination of the dorsal spinal columns, clinically indistinguishable from that which is caused by vitamin B12 deficiency. We report a 37-year-old female who presented with ataxia, loss of lower extremity proprioception, demyelination of her cervical dorsal spinal columns, and other laboratory and physical exam findings consistent with nitrous oxide abuse. The patient reported daily use in excess of 500 nitrous oxide cartridges, also known as "whippits". Nitrous oxide myeloneuropathy should be included in the differential diagnoses for emergency medicine physicians when evaluating a patient with bilateral neurologic deficits and ataxia.

Accidental Chlorine Gas Exposure in a Pediatric Patient: A Case Report.

INTRODUCTION: Chlorine gas is a known irritant of the respiratory tract, which may cause damage to various systems depending on time of exposure and concentration of the gas. Current treatments are mainly supportive. While no definitive studies have been completed to date, it has been noted that treatment with a sodium bicarbonate solution via nebulizer may lead to improved outcomes for patients dealing with chlorine gas exposure. CASE REPORT: We present a case of a nine-year-old child arriving at the emergency department after exposure to chlorine gas. Complete recovery from his symptoms occurred rapidly with the administration of nebulized sodium bicarbonate. DISCUSSION: Inhaled chlorine gas acts as a mucous membrane irritant, with symptoms usually beginning within minutes of exposure. Inhaled nebulized sodium bicarbonate has been suggested as a therapy for chlorine exposure. Although its mechanism of action is not well understood, it is thought that inhaled sodium bicarbonate neutralizes the hydrochloric acid formed when the chlorine gas reacts with the water in the lungs. CONCLUSION: Nebulized sodium bicarbonate solution at a low concentration appeared to rapidly and effectively reverse the symptoms due to chlorine gas inhalation in a young child.

Bug off! Severe toxicity following inhalational exposure to N, N-diethyl-meta-toluamide (DEET).

N, N-diethyl-meta-toluamide (DEET) is an insect repellent currently used by millions of people since 1956. DEET has an excellent safety profile and has remarkable protection against mosquitoes, ticks and various other arthropods. Toxicity is unusual, and is generally associated with incorrect, or overuse of the product. We report a patient with severe toxicity following inhalational exposure to a "bug bomb". containing 98% DEET.

Correction to: The Toxicology Investigators Consortium Case Registry-The 2017 Annual Report.

Please note the Collaborators for this article listed in the Acknowledgements.

The Toxicology Investigators Consortium Case Registry-the 2017 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Case Registry was established by the American College of Medical Toxicology in 2010. The Registry collects data from participating sites with the agreement that all bedside medical toxicology consultations will be entered. The objective of this eighth annual report is to summarize the Registry's 2017 data and activity with its additional 7577 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from 1 January to 31 December 2017. Detailed data was collected from these cases and aggregated to provide information which includes demographics (e.g., age, gender, race, ethnicity), reason for medical toxicology evaluation (e.g., intentional pharmaceutical exposure, envenomation, withdrawal from a substance), agent and agent class, clinical signs and symptoms (e.g., vital sign abnormalities, organ system dysfunction), treatments and antidotes administered, fatality, and life support withdrawal data. Females were involved in 50.4% of cases. Transgender demographic information collection was initiated in 2017 to better represent the population and there were 36 cases involving transgender patients. Adults aged 19-65 were the most commonly reported age group. Non-opioid analgesics were the most commonly reported agent class, with acetaminophen again the most common agent reported. There were 93 fatalities reported in 2017. Treatment interventions were frequently reported with 30.6% receiving specific antidotal therapy. Major trends in demographics and exposure characteristics remained similar to past years' reports. While treatment interventions were commonly required, fatalities were rare.