Diagnostic utility of capnography in emergency department triage for screening acidemia: a pilot study.

BACKGROUND: Capnography is a quantitative and reliable method of determining the ventilatory status of patients. We describe the test characteristics of capnography obtained during Emergency Department triage for screening acidemia. RESULTS: We performed an observational, pilot study of adult patients presenting to Emergency Department (ED) triage. The primary outcome was acidemia, as determined by the basic metabolic panel and/or blood gas during the ED visit. Secondary outcomes include comparison of estimated and measured respiratory rates (RR), relationships between end-tidal CO2 (EtCO2) and venous partial pressure of CO2, admission disposition, in-hospital mortality during admission, and capnogram waveform analysis. A total of 100 adult ED encounters were included in the study and acidemia ([Formula: see text] or [Formula: see text]) was identified in 28 patients. The measured respiratory rate (20.3 ± 6.4 breaths/min) was significantly different from the estimated rate (18.4 ± 1.6 breaths/min), and its area under the receiver operating curve (c-statistic) to predict acidemia was only 0.60 (95% CI 0.51-0.75, p = 0.03). A low end-tidal CO2 (EtCO2 < 32 mmHg) had positive (LR+) and negative (LR-) likelihood ratios of 4.68 (95% CI 2.59-8.45) and 0.34 (95% CI 0.19-0.61) for acidemia, respectively-corresponding to sensitivity 71.4% (95% CI 51.3-86.8) and specificity 84.7% (95% CI 74.3-92.1). The c-statistic for EtCO2 was 0.849 (95% CI 0.76-0.94, p = 0.00). Waveform analysis further revealed characteristically abnormal capnograms that were associated with underlying pathophysiology. CONCLUSIONS: Capnography is a quantitative method of screening acidemia in patients and can be implemented feasibly in Emergency Department triage as an adjunct to vital signs. While it was shown to have only modest ability to predict acidemia, triage capnography has wide generalizability to screen other life-threatening disease processes such as sepsis or can serve as an early indicator of clinical deterioration.

Psychostimulant drug co-ingestion in non-fatal opioid overdose.

Introduction: In 2019, there were over 16,000 deaths from psychostimulant overdose with 53.5% also involving an opioid. Given the substantial mortality stemming from opioid and psychostimulant co-exposure, evaluation of clinical management in this population is critical but remains understudied. This study aims to characterize and compare clinical management and outcomes in emergency department (ED) overdose patients with analytically confirmed exposure to both opioids and psychostimulants with those exposed to opioids alone. Methods: This was a secondary analysis of a prospective consecutive cohort of ED patients age 18+ with opioid overdose at 9 hospital sites from September 21, 2020 to August 17, 2021. Toxicologic analysis was performed using liquid chromatography quadrupole time-of-flight mass spectrometry. Patients were divided into opioid-only (OO) and opioid plus psychostimulants (OS) groups. The primary outcome was total naloxone bolus dose administered. Secondary outcomes included endotracheal intubation, cardiac arrest, troponin elevation, and abnormal presenting vital signs. We employed t-tests, chi-squared analyses and multivariable regression models to compare outcomes between OO and OS groups. Results: Of 378 enrollees with confirmed opioid overdose, 207 (54.8%) had psychostimulants present. OO patients were significantly older (mean 45.2 versus 40.6 years, p < 0.01). OS patients had significantly higher total naloxone requirements (mean total dose 2.79 mg versus 2.12 mg, p = 0.009). There were no significant differences in secondary outcomes. Conclusion: Approximately half of ED patients with confirmed opioid exposures were also positive for psychostimulants. Patients in the OS group required significantly higher naloxone doses, suggesting potential greater overdose severity.

A Decade in Review: Trends in Female Authorship in Peer-Reviewed Toxicology Journals.

BACKGROUND: Gender diversity in both emergency medicine and medical toxicology has grown over the last decade. However, disparities in promotion, awards, and speakership still exist. No studies have examined gender disparities in authorship in medical toxicology journals. RESEARCH QUESTIONS: Does the proportion of female first authors and female senior authors in medical toxicology publications increase over time? What factors predict female authorship in the first author or last author positions in two major medical toxicology journals? METHODS: We performed a retrospective review of all non-abstract publications in two medical toxicology journals, Clinical Toxicology and Journal of Medical Toxicology, between 2011 and 2020. We collected author names, number of authors, publication type, and publication year. Author names were used to identify author gender using Gender-API integrative tool. Data on the percentages of female medical toxicology fellows and medical toxicologists was provided by the American Board of Emergency Medicine (ABEM). RESULTS: A total of 2212 publications were reviewed and 2171 (97.9%) were included in the dataset. Overall, 31.7% of first authors were identified as female and 67.0% were identified as male by the Gender-API tool. There were 46.8% male-male author dyads, 24.2% female-male author dyads, 12.1% male-female author dyads, and 5.7% female-female author dyads. Predictors of female first authorship included research and case report articles, and percentage of ABEM female toxicologists. Predictors of female senior authorship included number of authors and percentage of ABEM female toxicologists. The proportion of female authorship in both categories increased over the study period. CONCLUSIONS: The frequency of female authorship in the first author position has grown over the last decade and is associated with increasing female representation in medical toxicology and specific manuscript subtypes, specifically research manuscripts.

Naloxone Use in Novel Potent Opioid and Fentanyl Overdoses in Emergency Department Patients.

Importance: Synthetic opioids, such as the fentanyl analogue and nitazene drug class, are among the fastest growing types of opioids being detected in patients in the emergency department (ED) with illicit opioid overdose (OD). However, clinical outcomes from OD of novel potent opioids (NPOs), specifically nitazenes, are unknown aside from small case series. Objective: To determine naloxone administration and clinical sequelae of patients who were in the ED with NPO overdose compared with fentanyl OD. Design, Setting, and Participants: This is a cohort study subgroup analysis of adults admitted to the ED and tested positive for NPOs among in the ongoing nationwide ToxIC Fentalog cohort study from 2020 to 2022. Patients who were in the ED with a presumed acute opioid OD and residual blood samples were included, and those testing positive for NPOs were analyzed. Patients were included in this analysis if their confirmatory testing was positive for an NPO analyte, such as brorphine, isotonitazene, metonitazene, and/or N-piperidinyl etonitazene. A comparison group included patients that were positive for fentanyl and devoid of any other analytes on toxicologic analysis. Exposures: Patients were exposed to NPOs, including brorphine, isotonitazene, metonitazene and/or N-piperidinyl etonitazene. Main Outcomes and Measures: The primary outcome was the total number of naloxone doses and total cumulative naloxone dose administered as part of routine clinical care following the OD. Naloxone requirements and clinical sequelae of NPO-positive patients were compared with those testing positive for fentanyl only. Results: During the study period, 2298 patients were screened, of whom 717 met inclusion criteria, 537 had complete laboratory testing data, with 11 (2.0%) positive for only fentanyl and 9 (1.7%) positive for NPOs (brorphine, isotonitazene, metonitazene, or N-piperidinyl etonitazene). The age range of patients was aged 20 to 57 years (4 males [44.4%] and 5 females [55.6%]). The NPO group received a statistically significantly higher mean (SD) number of naloxone boluses in-hospital (1.33 [1.50]) compared with the fentanyl group (0.36 [0.92]) (P = .02), which corresponded to a moderately large effect size (Cohen d = 0.78). Metonitazene overdose was associated with cardiac arrest and more naloxone doses overall. Metonitazene cases had a mean (SD) number of 3.0 (0) naloxone doses, and 2 of 2 patients (100%) with metonitazene overdoses were administered cardiopulmonary resuscitation. Conclusions and Relevance: In this cohort study of patients admitted to the ED with confirmed opioid overdose testing positive for NPOs, in-hospital naloxone dosing was high compared with patients who tested positive for fentanyl alone. Further study is warranted to confirm these preliminary associations.

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.

Cocaethylene cardiotoxicity in emergency department patients with acute drug overdose.

OBJECTIVES: Cocaine use results in over 500,000 emergency department (ED) visits annually across the United States and ethanol co-ingestion is reported in 34% of these. Commingling cocaine with ethanol results in the metabolite cocaethylene (CE), which is metabolically active for longer than cocaine alone. Current literature on the cardiotoxicity of CE compared to cocaine alone is limited and lacks consensus. This study aims to fill this gap in the literature and examine cardiovascular events in cocaine use as confirmed by urine toxicology versus CE exposure. METHODS: This was a secondary data analysis of a prospective cohort study of adult patients with acute drug overdose at two urban tertiary care hospital EDs over 4 years. Patients with positive urinary cocaine metabolites were analyzed, and outcomes were compared between patients with overdose and confirmed presence of cocaine on urine toxicology (cocaine group) and patients with cocaine and ethanol use (CE group). The primary outcome was cardiac arrest. Secondary outcomes included myocardial injury and hyperlactatemia. Data were analyzed using multivariable regression models. RESULTS: We enrolled a total of 199 patients (150 cocaine, 49 CE). Rates of cardiac arrest were significantly higher in the CE group compared to cocaine (6.1% vs. 0.67%, p = 0.048). Cocaine was significantly associated with myocardial injury compared to CE exposure (mean initial troponin 0.01 ng/ml vs. 0.16 ng/ml, p = 0.021), while hyperlactatemia was associated with CE exposure (mean initial lactate 4.1 mmol/L vs. 2.9 mmol/L, p = 0.038). CONCLUSIONS: When compared to cocaine exposure alone, CE exposure in ED patients with acute drug overdose was significantly associated with higher occurrence of cardiac arrest, higher mean lactate concentrations, and lower occurrence of myocardial injury.

Identification of a novel opioid, N-piperidinyl etonitazene (etonitazepipne), in patients with suspected opioid overdose.

BACKGROUND: Novel opioids in the illicit drug supply, such as the "nitazene" group of synthetic opioids, present an ongoing public health problem due to high potency and respiratory depressant effects. We describe three patients in whom N-piperidinyl etonitazene, a compound not previously reported in human exposure, was detected after suspected opioid overdose. Other substances that these patients tested for included fentanyl, cocaine, levamisole, phenacetin, benzoylecgonine, para-fluorofentanyl, presumptive heroin (tested as 6-monoacetylmorphine (6-MAM), morphine, and codeine), and tramadol. METHODS: This is a case series of patients with acute opioid overdose enrolled in an ongoing multicenter prospective cohort study. Data collected included reported substance use, clinical course, naloxone dose and response, outcome, and analytes detected in biological samples. RESULTS: Between October 6, 2020 and October 31, 2021, 1006 patients were screened and 412 met inclusion criteria. Of these, three patients (age 33-55) tested positive for N-piperidinyl etonitazene at one site in New Jersey over a period of three days in July 2021. Two patients reported the use of cocaine; one reported the use of heroin and alprazolam. All three patients received naloxone with improvement in their mental status (2 milligrams (mg) intranasally (IN); 8 mg IN; 0.08 mg intravenous (IV)). Two of three received subsequent doses for recurrence of opioid toxicity (0.4-0.6 mg IV). One patient was diagnosed with pneumonia and admitted to the intensive care unit, one was discharged from the Emergency Department (ED), and one used additional drug while in the ED and required admission for a naloxone infusion. None developed organ damage or sequelae. CONCLUSION: These cases represent a local outbreak of a novel "nitazene" opioid. Public health toxicosurveillance should incorporate routine testing of this emerging class of synthetic compounds in the illicit drug supply.

Hospital-wide cardiac arrest in situ simulation to identify and mitigate latent safety threats.

BACKGROUND: Cardiac arrest resuscitation requires well-executed teamwork to produce optimal outcomes. Frequency of cardiac arrest events differs by hospital location, which presents unique challenges in care due to variations in responding team composition and comfort levels and familiarity with obtaining and utilizing arrest equipment. The objective of this initiative is to utilize unannounced, in situ, cardiac arrest simulations hospital wide to educate, evaluate, and maximize cardiac arrest teams outside the traditional simulation lab by systematically assessing and capturing areas of opportunity for improvement, latent safety threats (LSTs), and key challenges by hospital location. METHODS: Unannounced in situ simulations were performed at a city hospital with multidisciplinary cardiac arrest teams responding to a presumed real cardiac arrest. Participants and facilitators identified LSTs during standardized postsimulation debriefings that were classified into equipment, medication, resource/system, or technical skill categories. A hazard matrix was used by multiplying occurrence frequency of LST in simulation and real clinical events (based on expert opinion) and severity of the LST based on agreement between two evaluators. RESULTS: Seventy-four in situ cardiac arrest simulations were conducted hospital wide. Hundreds of safety threats were identified, analyzed, and categorized yielding 106 unique latent safety threats: 21 in the equipment category, 8 in the medication category, 41 in the resource/system category, and 36 in the technical skill category. The team worked to mitigate all LSTs with priority mitigation to imminent risk level threats, then high risk threats, followed by non-imminent risk LSTs. Four LSTs were deemed imminent, requiring immediate remediation post debriefing. Fifteen LSTs had a hazard ratio greater than 8 which were deemed high risk for remediation. Depending on the category of threat, a combination of mitigating steps including the immediate fixing of an identified problem, leadership escalation, and programmatic intervention recommendations occurred resulting in mitigation of all identified threats. CONCLUSIONS: Hospital-wide in situ cardiac arrest team simulation offers an effective way to both identify and mitigate LSTs. Safety during cardiac arrest care is improved through the use of a system in which LSTs are escalated urgently, mitigated, and conveyed back to participants to provide closed loop debriefing. Lastly, this hospital-wide, multidisciplinary initiative additionally served as an educational needs assessment allowing for informed, iterative education and systems improvement initiatives targeted to areas of LSTs and areas of opportunity.

Macrophage Migration Inhibitory Factor as a Potential Biomarker in Acetaminophen Overdose: A Pilot Study.

Introduction: Acetaminophen overdose is a leading cause of liver failure in the United States. Macrophage migration inhibitory factor (MIF) is a cytokine that is released early and promotes acetaminophen toxicity in preclinical models. This cytokine could prove a useful biomarker in emergency department (ED) patients immediately following an acute acetaminophen overdose. Methods: We selected a convenience sample of thirteen patients from a prospective consecutive cohort of ED patients with suspected acute overdose. Research associates collected waste specimens for MIF analysis that remained after use for clinical care. Our team compared patients with confirmed acetaminophen overdose (n=9) to patients without acetaminophen exposure or liver injury (n=3) and a patient with liver injury in the absence of detectable acetaminophen (n=1). Results: In our acetaminophen group, all nine patients had measurable acetaminophen concentrations. Median MIF serum concentrations were 16.08 ng/mL (IQR 2.06, 91.40) in the overdose group compared with the control group serum concentrations of 0.19 ng/mL (IQR 0.05, 0.32) (p = 0.0091). Conclusion: In this pilot study, MIF was feasible to measure in specimens from an ED drug overdose cohort, and was significantly elevated in the acetaminophen group compared to non-acetaminophen controls without liver injury.

Prior use of medications for opioid use disorder in ED patients with opioid overdose: prevalence, misuse and overdose severity.

OBJECTIVES: Medications for opioid use disorder (MOUD) reduce opioid overdose (OD) deaths; however, prevalence and misuse of MOUD in ED patients presenting with opioid overdose are unclear, as are any impacts of existing MOUD prescriptions on subsequent OD severity. METHODS: This was a prospective observational cohort of ED patients with opioid OD at two tertiary-care hospitals from 2015 to 19. Patients with confirmed opioid OD (via urine toxicology) were included, while patients with alternate diagnoses, insufficient data, age < 18, and prisoners were excluded. OD severity was defined using: (a) hospital LOS (days); and (b) in-hospital mortality. Time trends by calendar year and associations between MOUD and study outcomes were calculated. RESULTS: In 2829 ED patients with acute drug OD, 696 with confirmed opioid OD were included. Overall, 120 patients (17%) were previously prescribed any MOUD, and MOUD prevalence was significantly higher in 2018 and 2019 compared to 2016 (20.1% and 27.8% vs. 8.8%, p < 0.05). Odds of MOUD misuse were significantly higher for methadone (OR 3.96 95% CI 2.57-6.12) and lowest for buprenorphine (OR 1.16, p = NS). Mean LOS was over 50% longer for methadone (3.08 days) compared to buprenorphine and naltrexone (both 2.0 days, p = NS). Following adjustment for confounders, buprenorphine use was associated with significantly shorter LOS (IRR -0.44 (95%CI -0.85, -0.04)). Odds of death were 30% lower for patients on any MOUD (OR 0.70, 95%CI 0.09-5.72), but highest in the methadone group (OR 0.82, 95%CI 0.10-6.74). CONCLUSIONS: While MOUD prevalence significantly increased over the study period, MOUD misuse occurred for patients taking methadone, and OD LOS overall was lower in patients with any prior buprenorphine prescription.

Respiratory failure in confirmed synthetic cannabinoid overdose.

CONTEXT: Synthetic cannabinoids (SCs) are a structurally heterogenous synthetic class of drugs of abuse. The objective was to describe the incidence of acute respiratory failure in Emergency Department (ED) patients with confirmed SC exposure, and to investigate the association between SC overdose with respiratory failure compared to non-SC overdose. METHODS: This was an observational cohort of ED patients ≥18 years with suspected cannabinoid overdose between 2015 and 2020 at two tertiary-care hospitals. Patient serum was analyzed via liquid chromatography/quadrupole time-of-flight mass spectrometry using a library with >800 drugs including novel psychoactive substances. The primary outcome was acute respiratory failure. DISCUSSION: Of 83 patients with suspected cannabinoid overdose, there were 29 confirmed SC overdoses: 5 F-MDMB-PICA (n = 18) and its metabolite 5OH-MDMB-PICA (n = 16), ADB-FUBINACA (n = 4), AB-CHIMINACA (n = 4), AB-FUBINACA (n = 1), AB-PINACA (n = 1), MDMB-4en-PINACA (n = 1), and 4 F-MDMB-BINACA (n = 1). Overall, incidence of acute respiratory failure was 31.3% (95%CI 21.6-42.4). Compared to non-SC overdose, confirmed SC overdose was significantly associated with respiratory failure (25.0% SC vs. 4.2% non-SC, p = 0.05). CONCLUSION: This study demonstrates that SCs are associated with respiratory failure. Since respiratory depression is a potentially lethal adverse effect of SC overdose, future research is warranted.

Delayed QT Prolongation: Derivation of a Novel Risk Factor for Adverse Cardiovascular Events from Acute Drug Overdose.

INTRODUCTION: In ED patients with acute drug overdose involving prescription medication and/or substances of abuse, severe QTc prolongation (> 500 ms) is predictive of adverse cardiovascular events (ACVE), defined as myocardial injury, ventricular dysrhythmia, shock, or cardiac arrest. However, it is unclear whether delayed severe QTc prolongation (dsQTp) is a risk factor for ACVE and if specific clinical factors are associated with occurrence of dsQTp. METHODS: A secondary analysis of a prospective cohort of consecutive adult ED patients with acute drug overdose was performed on patients with initial QTc < 500 ms. The predictor variable, dsQTp, was defined as initial QTc < 500 ms followed by repeat QTc ≥ 500 ms. The primary outcome was occurrence of ACVE. Multivariable logistic regression was performed to test whether dsQTp was an independent predictor of ACVE and to derive clinical factors associated with dsQTp. RESULTS: Of 2311 patients screened, 1648 patients were included. The dsQTp group (N = 27) was older than the control group (N = 1621) (51.6 vs 40.2, p < 0.001) and had a higher number of drug exposures (2.92 vs 2.16, p = 0.003). Following adjustment for age, sex, race/ethnicity, number of exposures, serum potassium, and opioid exposure, dsQTp remained an independent predictor of ACVE (aOR: 12.44, p < 0.0001). Clinical factors associated with dsQTp were age > 45 years and polydrug (≥ 3) overdoses. CONCLUSION: In this large secondary analysis of ED patients with acute drug overdose, dsQTp was an independent risk factor for in-hospital occurrence of ACVE.

Changes in alcohol-related hospital visits during COVID-19 in New York City.

BACKGROUND AND AIMS: Increased alcohol consumption has been proposed as a potential consequence of the coronavirus disease 2019 (COVID-19) pandemic. There has been little scrutiny of alcohol use behaviors resulting in hospital visits, which is essential to guide pandemic public policy. We aimed to determine whether COVID-19 peak restrictions were associated with increased hospital visits for alcohol use or withdrawal. Secondary objectives were to describe differences based on age, sex and race, and to examine alcohol-related complication incidence. DESIGN: Multi-center, retrospective, pre-post study. SETTING: New York City health system with five participating hospitals. PARTICIPANTS: Adult emergency department encounters for alcohol use, alcoholic gastritis or pancreatitis or hepatitis, alcohol withdrawal syndrome, withdrawal seizure or delirium tremens. MEASUREMENTS: Age, sex, race, site and encounter diagnosis. Encounters were compared between 2019 and 2020 for 1 March to 31 May. FINDINGS: There were 2790 alcohol-related visits during the 2019 study period and 1793 in 2020, with a decrease in total hospital visits. Of 4583 alcohol-related visits, median age was 47 years, with 22.3% females. In 2020 there was an increase in percentage of visits for alcohol withdrawal [adjusted odds ratio (aOR) = 1.34, 95% confidence interval (CI) = 1.07-1.67] and withdrawal with complications (aOR = 1.40, 95% CI = 1.14-1.72), and a decline in percentage of hospital visits for alcohol use (aOR = 0.70, 95% CI = 0.59-0.85) and use with complications (aOR = 0.71, 95% CI = 0.58-0.88). It is unknown whether use visit changes mirror declines in other chief complaints. The age groups 18-29 and 60-69 years were associated with increased visits for use and decreased visits for withdrawal, as were non-white race groups. Sex was not associated with alcohol-related visit changes despite male predominance. CONCLUSIONS: In New York City during the initial COVID-19 peak (1 March to 31 May 2020), hospital visits for alcohol withdrawal increased while those for alcohol use decreased.

Pilot survey of prescription opioid use patterns and engagement with harm-reduction strategies in emergency department patients.

Background: The United States is experiencing an opioid epidemic. The aim of this pilot study was to describe patterns of prescription opioid medication (POM) use, examine factors associated with opioid misuse and overdose, and assess knowledge of take-home naloxone, and other harm-reduction strategies as well as participation in medications for opioid use disorder (MOUD) among emergency department (ED) patients that have been prescribed opioid medications. Methods: This was a pilot survey of a convenience sample of adult ED patients with a past opioid prescription at one urban tertiary care hospital. The survey asked participants about patterns of opioid consumption, risk factors associated with opioid misuse, and knowledge of harm-reduction strategies. The survey tool consisted of mixed open- and closed-ended questions. Reported daily POM consumption was converted to milligram morphine equivalents (MME). Responses to survey questions were compared with daily MME in order to generate hypotheses for future research. Results: 50 individuals completed a survey. Of these, 56% reported taking opioids daily, and 24% reported greater than 100 MME daily opioid consumption. Many subjects reported history of psychiatric illness (34%) and previous substance abuse treatment (24%). The majority of patients (66%) were not aware of take-home naloxone programs to treat opioid overdose. Conclusions: In this pilot survey of ED patients with a pain-related chief complaint, many respondents reported risk factors for opioid misuse, and the majority of participants were unaware of the existence of important harm-reduction strategies, such as take-home naloxone programs, even among those with the highest daily POM use.

Biomarkers of endothelial dysfunction in cocaine overdose and overdose-related cardiovascular events.

Overdose of stimulant drugs has been associated with increased risk of adverse cardiovascular events (ACVE), some of which may be ascribed to endothelial dysfunction. The aims of this study were to evaluate biomarkers of endothelial dysfunction in emergency department (ED) patients with acute cocaine overdose and to assess the association between in-hospital ACVE in ED patients with any acute drug overdose. This was a prospective consecutive cohort study over 9 months (2015-2016) at two urban, tertiary-care hospital EDs. Consecutive adults (≥18 years) presenting with suspected acute drug overdose were eligible and separated into three groups: cocaine (n = 47), other drugs (n = 128), and controls (n = 11). Data were obtained from medical records and linked to waste serum specimens, sent as part of routine clinical care, for biomarker analysis. Serum specimens were collected and analyzed using enzyme-linked immunosorbent assay kit for three biomarkers of endothelial dysfunction: (a) endothelin-1 (ET-1), (b) regulated upon activation normal T cell expressed and secreted (RANTES), and (c) soluble intercellular adhesion molecule-1 (siCAM-1). Mean siCAM was elevated for cocaine compared with controls and other drugs (p < .01); however, mean RANTES and ET-1 levels were not significantly different for any drug exposure groups. Receiver operating characteristics curve analysis for prediction of in-hospital ACVE revealed excellent performance of siCAM-1 (area under curve, 0.86; p < .001) but lack of predictive utility for either RANTES or ET-1. These results suggest that serum siCAM-1 is a viable biomarker for acute cocaine overdose and that endothelial dysfunction may be an important surrogate for adverse cardiovascular events following any drug overdose.

First-Line Vasopressor and Mortality Rates in ED Patients with Acute Drug Overdose.

INTRODUCTION: While emergency department (ED) visits for acute drug overdose are at an all-time high, the importance of vasopressors to treat circulatory shock in this patient population remains unclear. This study investigated the association between first-line vasopressor and mortality, for both push-dose and infusion, in this patient population. METHODS: From a prospective cohort of consecutive ED patients with drug overdose at two urban teaching centers over 5 years, we performed a secondary data analysis of patients with circulatory shock, defined as hypotension requiring either vasopressors, high-dose insulin euglycemia therapy, or both. The first-line vasopressor (push-dose and infusion) was analyzed for associations with the primary outcome (in-hospital mortality) and secondary outcomes (24-hour mortality, ICU LOS). Subgroup analysis of beta-/calcium-channel blocker overdose was performed to evaluate impact of antidotal therapies. Data analysis included multivariable regression. RESULTS: Fifty-five patients with circulatory shock were analyzed, in whom there was 20% 24-hour mortality, 42% in-hospital mortality, 730-minute mean vasopressor duration, and 53.4-hour median ICU LOS. On multivariable analysis, there was significantly decreased adjusted odds of in-hospital mortality with first-line push-dose phenylephrine (aOR 0.06, CI 0.01-0.55), and significantly increased adjusted odds of in-hospital mortality with first-line push-dose epinephrine (aOR 60.8, CI 6.1-608). Of the first-line infusions, norepinephrine had the lowest odds of in-hospital mortality (aOR 0.80, CI 0.2-3.1). CONCLUSIONS: In ED patients with undifferentiated drug overdose and circulatory shock, the first-line vasopressor is associated with in-hospital mortality. First-line push-dose phenylephrine was associated with the lowest odds of in-hospital mortality. Future randomized studies are warranted for validation.

Antidotal Sodium Bicarbonate Therapy: Delayed QTc Prolongation and Cardiovascular Events.

BACKGROUND: Sodium bicarbonate therapy (SBT) is currently indicated for the management of a variety of acute drug poisonings. However, SBT effects on serum potassium concentrations may lead to delayed QTc prolongation (DQTP), and subsequent risk of adverse cardiovascular events (ACVE), including death. Emergency department (ED)-based studies evaluating associations between SBT and ACVE are limited; thus, we aimed to investigate the association between antidotal SBT, ECG changes, and ACVE. METHODS: This was a secondary data analysis of a consecutive cohort of ED patients with acute drug overdose over 3 years. Demographic and clinical data as well as SBT bolus dosage and infusion duration were collected, and outcomes were compared with an unmatched consecutive cohort of patients with potential indications for SBT but who did not receive SBT. The primary outcome was the occurrence of ACVE, and secondary outcomes were delayed QTc (Bazett) prolongation (DQTP), and death. Propensity score and multivariable adjusted analyses were conducted to evaluate associations between adverse outcomes and SBT administration. Planned subgroup analysis was performed for salicylates, wide QRS (> 100 ms), and acidosis (pH < 7.2). RESULTS: Out of 2365 patients screened, 369 patients had potential indications for SBT, of whom 31 (8.4%) actually received SBT. In adjusted analyses, SBT was found to be a significant predictor of ACVE (aOR 9.35, CI 3.6-24.1), DQTP (aOR 126.7, CI 9.8-1646.2), and death (aOR 11.9, CI 2.4-58.9). Using a propensity score model, SBT administration was associated with ACVE (OR 5.07, CI 1.8-14.0). Associations between SBT and ACVE were maintained in subgroup analyses of specific indications for sodium channel blockade (OR 21.03, CI 7.16-61.77) and metabolic acidosis (OR: 6.42, 95% CI: 1.20, 34.19). CONCLUSION: In ED patients with acute drug overdose and potential indications for SBT, administration of SBT as part of routine clinical care was an independent, dose-dependent, predictor of ACVE, DQTP, and death. This study was not designed to determine whether the SBT or acute overdose itself was causative of ACVE; however, these data suggest that poisoned patients receiving antidotal SBT require close cardiovascular monitoring.

Opioid Use Disorder and COVID-19: Biological Plausibility for Worsened Outcomes.

BACKGROUND: Alarms have been raised that COVID-19 may disproportionately affect certain populations with substance use disorders, particularly Opioid Use Disorder (OUD), however warnings have largely focused on social risks such as reduced availability of services. Objectives: This commentary highlights three plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19. Results: Opioid-related respiratory depression may amplify risks of hypoxemia from COVID-19 viral pneumonia. Complex opioid immune modulation may impact host response to COVID-19, though the effect direction and clinical significance are unclear. Drug-drug interactions may affect individuals with OUD who are co-administered medications for OUD and medications for COVID-19, particularly due to cardiac adverse effects. Conclusions/Importance: There are plausible biological mechanisms for potentially worsened outcomes in patients with OUD who contract COVID-19; these mechanisms require further study, and should be considered in individuals with OUD.