Racial/ethnic trends in opioid and polysubstance opioid overdose mortality in adolescents and young adults, 1999-2020.

OBJECTIVES: Previous reports have described variations in opioid overdose mortalities among different race/ethnicity groups. We have analyzed racial/ethnicity trends in opioid and polysubstance opioid overdose mortalities in adolescents and young adults to further characterize differences and potential sub-epidemics within this specific population. METHODS: We used mortality data from the U.S. Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) Multiple Cause of Death file from 1999 to 2020. Drug overdose mortalities were identified using International Classification of Diseases, Tenth Revision (ICD-10) codes. Joinpoint regression was used to examine mortality rates for all opioids, opioids with a stimulant, opioids with benzodiazepines, and opioids with alcohol among racial/ethnic groups (non-Hispanic white, non-Hispanic Black, Hispanic, non-Hispanic other) in adolescents and young adults. RESULTS: The Average Annual Percent Change (AAPC) for mortality due to opioid and polysubstance opioid overdose increased for all racial/ethnic groups where data was available for analysis from 1999 to 2020. For mortality due to any opioid and any opioid with a stimulant, the greatest AAPC was seen among non-Hispanic Blacks. CONCLUSIONS: Unprecedented increases in mortality due to opioid overdose occurred in the last two decades among adolescents and young adults. Heterogenous trends support the notion that the previously defined opioid overdose epidemic "waves" may not accurately depict the effects of the crisis in all race/ethnicity groups. Additionally, alarming increases in opioid-stimulant overdose mortality starting in 2012 further characterize the interrelated effects of the third and fourth waves.

Methamphetamine Poisoning After "Plugging" Intentional Recreational Rectal Use.

BACKGROUND: Methamphetamine is a commonly used illicit substance. The route of administration is usually parenteral, oral ingestion, or snorting. A less common route of administration is placing in the rectum. CASE REPORT: A 28-year-old man presented to the emergency department with acute methamphetamine toxicity within 30 min after intentional rectal administration of methamphetamine for recreational purposes. The patient had hypertension, tachycardia, drug-induced psychosis, elevated creatine kinase, and required rapid sequence intubation and admission to the intensive care unit. Our patient had no clinical evidence of bowel ischemia or injury at the time of discharge. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Rectal administration of methamphetamine is known as "plugging," "booty bumping," "keestering," and "butt whacking." The rectal administration of methamphetamine has the increased risk of severe acute methamphetamine toxicity, as rectal administration bypasses first-pass metabolism, allowing for a more acute onset and higher bioavailability of methamphetamine compared with oral administration. There is the potential for mesenteric ischemia and bowel injury after rectal methamphetamine. Close clinical monitoring for bowel and rectal ischemia or injury are recommended, in addition to management of the sympathomimetic toxidrome.

[CAFFEINE POISONING AND FATAL ARRHYTHMIAS: A CASE REPORT].

INTRODUCTION: Study Summary: In today's world, caffeine is the most commonly consumed psychostimulant globally. While moderate caffeine intake is generally safe, there have been reported cases of significant toxicity and even fatal outcomes. Although rare, increased awareness and clinical suspicion are crucial in identifying such cases and providing timely life-saving interventions. In this report, we present a case of a 27-year-old female patient who was hospitalized due to severe systemic and cardiac effects resulting from the ingestion of a large quantity of caffeine capsules as a suicide attempt. We provide a detailed account of the clinical presentation and the management of the patient, including the emergency room's life-saving interventions and the complex care provided in the intensive care unit until the patient's complete recovery. Our aim with this case presentation is to raise awareness about the severe consequences of caffeine intoxication, particularly the cardiac injury, and to highlight the state-of-the-art treatment approaches in addressing this issue.

A Threat to Military Combat Power: Dietary Supplements.

BACKGROUND: The use of dietary supplements by young warfighters is pervasive and comes with a readiness cost, especially in the deployed setting. Predatory targeting and marketing by various unscrupulous companies put this population at risk for a higher than baseline risk for adverse events. METHODS: We report on 6 serious adverse events experienced by warfighters while deployed in Kuwait and Afghanistan. Presented is a discussion of current practice gaps and solutions, as well as details regarding how polypharmacy contributes to the seriousness of the threat posed by problematic supplements. RESULTS: The morbidity associated with the 6 cases of dietary supplement adverse events compromised mission readiness and was costly in terms of health and health care expenditures. CONCLUSION: The military dietary supplement issue needs exposure, review, and action at the highest levels of government.

The rise of illicit fentanyls, stimulants and the fourth wave of the opioid overdose crisis.

PURPOSE OF REVIEW: This review provides an update on recently published literature on the rise of illicit fentanyls, risks for overdose, combinations with other substances, e.g. stimulants, consequences, and treatment. RECENT FINDINGS: Overdose due to illicit synthetic opioids (e.g. fentanyl and fentanyl analogs) continues to rise in the US both preceding and during the COVID-19 pandemic. Fentanyl-related overdose is rising in new geographic areas e.g. the western USA. Stimulant-related overdose is also increasing nationwide driven by methamphetamine and cocaine. Polysubstance use, e.g. the use of a stimulant along with an opioid is driving stimulant-related overdose. Other medical consequences of injection drug use are rising including HIV and hepatitis C infections. Medication approaches to treating opioid use disorder remain the standard of care and there are new promising pharmacological approaches to treating methamphetamine use disorder. SUMMARY: A 'fourth wave' of high mortality involving methamphetamine and cocaine use has been gathering force in the USA. Availability and use of illicit fentanyls are still the major drivers of overdose deaths and the current rise in stimulant-related deaths appears entwined with the ongoing opioid epidemic.

Massive suicidal ingestion of caffeine: a case report with investigation of the cardiovascular effect/concentration relationships.

BACKGROUND: Caffeine poisoning may cause life-threatening arrhythmias and hemodynamic failure. We aimed to investigate the toxicokinetics (TK), toxicodynamics (TD) and TK/TD relationships of caffeine in a case of poisoning. CASE REPORT: A 47-year-old male ingested pure anhydrous caffeine powder (70 g) in a suicide attempt. He developed agitation, tachycardia, and two episodes of ventricular fibrillation treated with defibrillation and tracheal intubation. He was successfully managed using intravenous infusions of esmolol and norepinephrine. METHODS: We modelled the time-course of plasma caffeine concentration (TK study using online liquid chromatography-tandem mass spectrometry), the time-course of blood lactate concentration and infusion rates of esmolol and norepinephrine (TD studies) and the TK/TD relationships. RESULTS: Caffeine TK was of first-order peaking at 258 mg/L with an elimination half-life of 46.2 h and clearance of 2.2 L/h. Caffeine-related effects on blood lactate (peak, 10 mmol/L at 1.25 h postingestion) were described by a Bateman-type equation (formation rate, 0.05 mmol/mg.h; elimination rate, 0.9 mmol/mg.h). Esmolol and norepinephrine infusion rates to reverse caffeine-related cardiovascular effects (peaks at 51-h postingestion) fitted well with a sigmoidal Emax model (EC50, 180.0 and 225.9 mg/L, respectively; Hill coefficient, 10.0). CONCLUSION: Massive caffeine ingestion is characterized by prolonged caffeine elimination. TK/TD relationships are helpful to quantify caffeine-related catecholaminergic effects.

Methamphetamine-related postmortem cases in Jeddah, Saudi Arabia.

A more than 500% increase in the number of deaths involving methamphetamine occurred between 2016 and 2018 in Jeddah, Saudi Arabia. As such, this report employed a validated liquid chromatography tandem mass spectrometry method to quantify methamphetamine and its metabolites in bodily fluids from 47 postmortem cases in which methamphetamine was involved. The mean age of the deceased was 33 years old (median: 30, range: 16-63), and 94% were male. Methamphetamine was co-ingested with another drug in 32 of the cases (68%); however, the deaths were only due to the combined toxicity of methamphetamine and another drug in 15 of the cases (32%). Of note, 13 of these deaths (28% of all deaths) involved heroin. When methamphetamine was the sole cause of death (32% of the studied cases), the median concentrations of methamphetamine and amphetamine were 527 and 128 ng/mL. When methamphetamine was combined toxicity with another drug, the median concentrations of methamphetamine and amphetamine decreased to 161 and 53 ng/mL. When deaths were unrelated to methamphetamine, the median concentrations of methamphetamine and amphetamine were 130 and 44 ng/mL, respectively. The highest median methamphetamine concentration was found in urine (5281 ng/mL), followed by stomach contents (878 ng/mL), bile (762 ng/mL), vitreous humor (3 ng/mL), and blood (208 ng/mL). Almost 40% of the studied cases involved violence, 61% were accidental, 21% were suicides, 17% were homicides, and 2% were natural deaths. Methamphetamine is highly addictive. Increases in deaths have been seen in various countries. More awareness, education and treatment programs are required to reduce the likelihood of addiction, crimes, suicide, and other fatalities resulting from methamphetamine abuse.

Suicidal attempt with caffeine overdose treated with dexmedetomidine: a case report.

BACKGROUND: Caffeine is a widely used dietary stimulant, and cases of caffeine overdoses, sometimes leading to death, are increasing. We encountered a case of caffeine intoxication resolved with administration of the sedative agent dexmedetomidine. CASE PRESENTATION: We administered dexmedetomidine for sedation and to suppress sympathetic nerve stimulation in the case of an 18-year-old Japanese male who ingested a massive dose of caffeine with the intention of committing suicide. The patient was in an excited state and had hypertension, sinus tachycardia, and hypokalemia with prominent QT prolongation. After dexmedetomidine administration, the patient's mental state, hemodynamics, and electrolyte levels were improved immediately. He was discharged without any sequelae 3 days later. CONCLUSION: Cases of acute caffeine intoxication with agitation, sympathetic overactivity and adverse cardiac events would benefit with dexmedetomidine treatment.

Massive ß1-Adrenergic Receptor Reaction Explains Irreversible Acute Arrhythmia in a Fatal Case of Acute Pure Caffeine Intoxication.

Caffeine, a naturally occurring purine-based alkaloid, is the most consumed psychostimulant worldwide. Since caffeine pharmacokinetics shows extreme interindividual variability, it is not easy to establish its toxic dose. Only a few cases of death due to acute caffeine intoxication have been described so far, the majority of which attributable to massive assumption of caffeine-based medications. We present a case of acute caffeine overdose due to ingestion of pure caffeine. The extremely high blood concentration of caffeine determined a strong cardiovascular response, leading to fatal arrhythmia, as supported by histological evidence of myocardial injury. Quantitation of catecholamines and their metabolites in urine samples was performed and showed level near the highest limit of normal ranges for norepinephrine and high level of epinephrine. Contraction band is a pathological modification of the myocell caused by the catecholaminergic action and can occur in conditions of alteration due to the interaction between calcium and catecholamines. We demonstrated the ß1-adrenoceptor involvement in our fatal case by immunohistochemical analysis.

A Review of Synthetic Cathinone-Related Fatalities From 2017 to 2020.

BACKGROUND: Synthetic cathinones (SCs) are designer analogs of the natural active principle of khat. Since their appearance on the black market in 2003, their popularity has increased annually, and they have become the most seized class of new psychoactive substances reported to the UNODC Early Warning Advisory system. The constant introduction of newly synthesized molecules makes this issue difficult to monitor. The authors reviewed the most recent SC-related fatalities worldwide to highlight new trends of consumption, reporting acute pharmacological and toxicological symptoms, scene investigations, analytical methods, and reported SC concentrations in diverse biological matrices. METHODS: A literature search was performed using scientific databases such as PubMed, Scopus, Science Direct, Web of Science, and Research Gate to identify relevant scientific publications from 2017 to 2020. In addition, a search was conducted through the EU EWS. RESULTS: From 2017 to 2020, 31 different SCs were identified in 75 reported fatal intoxications in the literature, alone or in combination with other substances. The most abused SCs were N-ethylpentylone, N-ethylhexedrone, and 4-chloromethcathinone. The EU EWS included less detail on 72 additional SC-related fatalities from 2017 to 2020. CONCLUSIONS: New SCs continuously replace older natural and synthetic stimulant drugs, making determining the cause of death difficult. Analytical methods and high-performance mass spectrometry instruments are essential to detect the low concentrations of these potent new SCs. Little data are available on the pharmacology of these new drugs; the evaluation of toxicological antemortem and postmortem findings provides critical data on the drug's pharmacology and toxicology and for the interpretation of new SC cases.

Stimulant storm - state health department psychostimulant age-adjusted mortality rate correlates with psychostimulant-based Michigan Poison Center case exposures over time.

BACKGROUND: Deaths attributable to psychostimulants with abuse potential have increased in the United States (US) in recent years. Methamphetamine use, in particular, has risen sharply. We evaluated the correlation between amphetamine- and methamphetamine-related case exposures reported to the Michigan Poison Center (MiPC) coinciding with psychostimulant age-adjusted mortality rates from the Michigan Department of Health and Human Services (MDHHS). METHODS: We compared amphetamine and methamphetamine exposures reported to the MiPC from 2012 to 2018, queried from ToxSentry® database, to MDHHS reports on resident death certificates with attributed death due to "overdose, regardless of intent" and related cause of death attributed to psychostimulants with abuse potential. Linear regression assessed goodness-of-fit. Slope with standard error and adjusted R2 were reported. Psychostimulants included methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA), dextroamphetamine, levoamphetamine, and methylphenidate. RESULTS: Psychostimulant deaths reported by MDHHS increased from 17 to 165 between 2012 and 2018. The average age-adjusted rate of psychostimulant-involved overdose deaths per 100,000 state residents rose from 0.2 to 1.8. Linear regression of MiPC amphetamine exposure rates with state health department-reported age-adjusted psychostimulant mortality rates yielded a slope of 1.93, SE 0.5, p value 0.035, and adjusted R2 0.55. Linear regression of MiPC methamphetamine exposure rates with state health department-reported age-adjusted psychostimulant mortality rates yielded a slope of 0.78, SE 0.27, p value 0.012, and adjusted R2 0.70 suggesting a strong correlation. CONCLUSION: Psychostimulant use and associated deaths in the US are increasing, representing an evolving public health threat. Michigan demonstrates consistency with national trends and data from the MiPC correlates strongly with state-reported age-adjusted psychostimulant mortality rates. Strengthening collaboration between poison centers and state health departments is critical for detection and mitigation efforts and can thereby inform resource allocation.

Methamphetamine-associated pulseless electrical activity in a young child.

This is a case report of a 19-month-old female who presented to the emergency department in cardiac arrest after methamphetamine exposure. Prior to presentation, she had seizure-like activity and then became unresponsive. On arrival, she had dilated pupils, intermittent clonus, and pulseless electrical activity. She was found to have full thickness circumferential burns of her bilateral lower extremities. She received 12 doses of epinephrine, cardiopulmonary resuscitation, and volume resuscitation after which she had return of spontaneous circulation and was transferred to the intensive care unit on an epinephrine drip. Initial laboratory studies showed a mixed metabolic and respiratory acidosis and hyperglycemia. An initial urine immunoassay for drugs of abuse was negative, however, 5 h later, a second urine immunoassay was positive for amphetamine. The first specimen was also sent for liquid chromatography-mass spectrometry analysis that later returned positive for methamphetamine and amphetamine. In retrospect, the initial urine screen was found to have evidence of amphetamine below the threshold for positivity (500 ng/mL), and the second urine specimen was highly positive, with an amphetamine level of >1450 ng/mL. In this case, what turned out to be a sub-threshold rather than undetectable level was clinically significant, highlighting the challenges of urine screening in cases of suspected poisoning syndromes with atypical presentations. Our case also suggests the possibility of PEA as a presentation of methamphetamine toxicity in a child.

Fatal 4-MEC Intoxication: Case Report and Review of Literature.

ABSTRACT: Synthetic cathinones are one of the major pharmacological families of new psychoactive substances and 4-methylethcathinone (4-MEC) has emerged in recent years as a recreational psychostimulant. We report a case of a 35-year-old man found dead and naked at home by his friend. Although no anatomic cause of death was observed at autopsy, toxicological analysis identified 4-MEC and hydroxyzine at therapeutic level (160 ng/mL). 4-Methylethcathinone was quantified in autopsy samples by a validated method consisting in liquid-liquid extraction and gas chromatography coupled to tandem mass spectrometry: peripheral blood, 14.6 µg/mL; cardiac blood, 43.4 µg/mL; urine, 619 µg/mL; vitreous humor, right 2.9 µg/mL and left 4.4 µg/mL; bile, 43.5 µg/mL; and gastric content, 28.2 µg/mL. The cause of death was 4-MEC intoxication and the manner of death could be either accidental or suicidal. The literature concerning 4-MEC was reviewed, focusing on distribution in classical postmortem matrices and 4-MEC metabolism and postmortem redistribution and stability.

Flakka: New Dangerous Synthetic Cathinone on the Drug Scene.

New psychoactive substances are being used as drugs and appear to be quite popular nowadays. Thanks to their specific properties, these drugs create inimitable experiences for intoxicated people. Synthetic cathinones are the most common compounds in these new drugs. Among them, α-pyrrolidopentadione (α-PVP), or "Flakka" (street name), is one of the most famous cathinone-designed drugs. Similar to other synthetic cathinone drugs, α-PVP can effectively inhibit norepinephrine and dopamine transmitters. The adverse reactions of α-PVP mainly include mania, tachycardia, and hallucinations. An increasing number of people are being admitted to emergency wards due to the consequences of their use. This work mainly summarizes the history, synthesis, pharmacology, toxicology, structure-activity relationship, metabolism, clinical process and health risks, poisoning and death, forensic toxicology, and legal status of α-PVP. We hope this review will help bring more attention to the exploration of this substance in order to raise awareness of its negative impacts on humans.

Recent trends and associated factors of amphetamine-type stimulant overdoses in emergency departments.

BACKGROUND: Emerging data indicate a resurgence of availability and harms of amphetamine-type stimulant (ATS) use. This study examined ATS overdose-involved emergency department (ED) visit trends and visit characteristics associated with ATS overdose. METHODS: Data from the Healthcare Cost and Utilization Project's (HCUP) 2010-2017 Nationwide Emergency Department Sample identified ATS overdose-involved visits. Predicted trend lines from 2010 to 2015 were fit using weighted logistic regression forany or only ATS-involved overdose using ICD-9-CM discharge diagnosis codes; percentage change from 2016 to 2017 used ICD-10-CM. Multivariable logistic regression examined characteristics in 2017 associated with only ATS-involved overdoses compared to drug overdoses not involving ATS. RESULTS: Every year from 2010 to 2015 the odds of any ATS overdose-involved ED visits increased 11 % (odds ratio [OR]: 1.11, 95 % CI: 1.09, 1.14) and 7 % for only ATS overdose-involved visits (OR: 1.07, 95 % CI: 1.04, 1.10). From 2016 to 2017, any and only ATS overdose-involved visit rates increased 19.1 % and 20.5 %, respectively (P < .05). In 2017, ATS overdose-involved visits (N = 42,428) accounted for 4.4 % of all drug overdose visits (N = 956,266). In adjusted regression models, characteristics more prevalent among patients with only ATS overdose included Western region; micropolitan and noncore urbanization levels; unintentional, undetermined, and assault intents; and cardiovascular effects. CONCLUSIONS: Our findings, coupled with the rising availability of ATS and related harms, underscore the expansion of current substance use and overdose prevention and response efforts to address stimulant use, particularly among groups at risk. Research to identify additional individual and community-level risk factors for increasing ATS overdose is warranted.

Vital Signs: Characteristics of Drug Overdose Deaths Involving Opioids and Stimulants - 24 States and the District of Columbia, January-June 2019.

INTRODUCTION: Provisional estimates indicate that drug overdose deaths increased in 2019 after a slight decrease in 2018. In 2018, overdose deaths primarily involved opioids, with continued increases in deaths involving illicitly manufactured fentanyls (IMFs). Deaths involving stimulants such as cocaine and methamphetamine are also increasing, mainly in combination with opioids. METHODS: CDC analyzed data on drug overdose deaths during January-June 2019 from 24 states and the District of Columbia (DC) in the State Unintentional Drug Overdose Reporting System to describe characteristics and circumstances of opioid- and stimulant-involved overdose deaths. RESULTS: Among 16,236 drug overdose deaths in 24 states and DC, 7,936 (48.9%) involved opioids without stimulants, 5,301 (32.6%) involved opioids and stimulants, 2,056 (12.7%) involved stimulants without opioids, and 943 (5.8%) involved neither opioids nor stimulants. Approximately 80% of overdose deaths involved one or more opioid, and IMFs were involved in three of four opioid-involved overdose deaths. IMFs, heroin, cocaine, or methamphetamine (alone or in combination) were involved in 83.8% of overdose deaths. More than three in five (62.7%) overdose deaths had documentation of at least one potential opportunity for overdose prevention intervention. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Identifying opportunities to intervene before an overdose death and implementing evidence-based prevention policies, programs, and practices could save lives. Strategies should address characteristics of overdoses involving IMFs, such as rapid overdose progression, as well as opioid and stimulant co-involvement. These efforts should be complemented by efforts to prevent initiation of prescription opioid and stimulant misuse and illicit drug use.

Fatal hemorrhage complicated with methamphetamine poisoning and its post-mortem CT features.

The purpose of this study was to assess the incidence of fatal hemorrhage complicated with methamphetamine (MA) poisoning and to examine the postmortem computed tomography (PMCT) features of fatal intracerebral hemorrhage (ICH) with and without MA poisoning. The study also attempted to determine the differences in PMCT between those two groups. Consecutive medicolegal autopsy data from November 2011 to February 2018 were searched for 3044 cases. First, the incidence and distribution of all cases of nontraumatic fatal hemorrhage with various causes were examined. Second, cases of ICH on the basal ganglia and brain stem were extracted. The PMCT findings were compared with respect to nine parameters: volume of hematoma, ventricular perforation, midline shift distance, aortic calcification, calcification of aortic valve, calcification of coronary artery, cardiothoracic ratio, circumference of ascending aorta, and volume of bladder contents. Of the 3044 cases, 97 were nontraumatic fatal hemorrhage; of these 97 cases, 20 were classified as MA poisoning with 9 ICH cases, and 60 cases were classified as non-MA poisoning with 14 ICH cases. A statistically significant difference in ages was observed between the two groups. On PMCT comparison of ICH, statistically significant differences were evident in the midline shift distance and calcification of the aortic valve. Forensic radiologists should be aware of the possibility of ICH with MA poisoning if fatal hemorrhage is detected on PMCT. Younger age, less calcification of the aortic valve, and a remarkable midline shift may be the keys to recognition.

Hyponatraemia and cerebral oedema due to a modafinil overdose.

Modafinil is a non-amphetamine stimulant that is prescribed for narcolepsy-associated sleepiness as well as reported off-licence uses among university students looking to improve wakefulness and focus. There is limited information in the medical literature about supratherapeutic modafinil dosage, symptomatology and management of overdose. We report a case of a healthy 32-year-old man who was found unconscious, having vomited, with an empty modafinil blister strip. At the emergency department, he presented with reduced Glasgow Coma Scale and prolonged episodes of vomiting. This acute presentation was conservatively managed in the intensive care unit. Antibiotics were also given for a suspected aspiration pneumonia. CT of the head showed cerebral oedema and biochemistry investigations revealed hyponatraemia. Result aetiology was unclear, however, it has been theorised to be secondary to a sizeable modafinil overdose.