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Background: In 2020, there were 36.7 million reported falls among older adults (65+) in the United States. Ethanol and other sedating substances may increase fall risk among older adults due to their effect on cognitive and physical function. We estimate the prevalence of these substances in blood specimens of older adults presenting with a fall injury at selected trauma centers., Methods: The initial study collected blood specimens from May 2020 through July 2021 from adults undergoing a trauma team evaluation at selected United States Level 1 trauma centers. We limited our study to older adults evaluated after a fall ( n  = 1,365) and selected a random sample ( n  = 300) based on age, sex, and trauma-center quotas. Medical health records and blood specimens obtained at trauma center presentation were analyzed. We estimated the prevalence of ethanol, benzodiazepines, cannabinoids, and opioids in the blood specimens. Two-sample tests of binomial proportions and Chi-square two-tailed tests were used to compare prevalence estimates of substances by demographic characteristics., Results: At least one substance was detected among 31.3% of samples analyzed. Prevalences of specific substances detected were 9.3% (95% CI: 6.0-12.6%) for benzodiazepines, 4.3% (95% CI: 2.0-6.7%) for cannabinoids, 8.0% (95% CI: 5.2-11.7%) for ethanol, and 15.0% (95% CI: 10.9-19.1%) for opioids. There were 18 deaths (6%; 95% CI: 3.6-9.3%). One-third of decedents had at least one substance detected in their blood., Discussion: Opioids were the most frequently detected substance, followed by benzodiazepines, ethanol, and cannabinoids. Substance use prevalence was not uniform across demographics, with differences observed by sex and age., Conclusions: This study provides insight into the frequency of the presence of substances that may contribute to fall risk and serious injury among older adults. Screening older adults for substances that impair cognitive and physical function can enhance clinical fall prevention efforts.

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.

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.

Introduction: Non-pharmaceutical fentanyl and its analogs have driven striking increases in opioid-associated overdose deaths. These highly potent opioids can be found at low concentrations in biological specimens. Little is known regarding the concentrations of these substances among survivors of non-fatal overdoses. In a locale where fentanyl is responsible for the majority of non-fatal opioid overdoses, we compared the concentration of fentanyl in blood to naloxone dosing in the presence and absence of a concurrent sedative-hypnotic exposure., Methods: In this pilot study, we enrolled adult patients presenting to the emergency department (ED) who: (1) arrived after an overdose requiring naloxone for the reversal of respiratory depression; and (2) who required venipuncture or intravenous access as part of their clinical care. Blood specimens ( n  = 20) underwent comprehensive toxicology testing, including the quantitation of fentanyl, fentanyl analogs, and naloxone, as well as the detection of common sedative-hypnotics and a wide range of other illicit and pharmaceutical substances. We then compared fentanyl concentrations to naloxone dosing in participants with and without a concomitant sedative-hypnotic exposure., Results: Nineteen of twenty participants (95%) were exposed to fentanyl prior to their overdose; the remaining participant tested positive for heroin metabolites. No participants reported pharmaceutical fentanyl use. Fentanyl analogs - acetylfentanyl or carfentanil - were present in three specimens. In 11 cases, fentanyl and its metabolites were the only opioids identified. Among the fentanyl-exposed, blood concentrations ranged from <0.1-19 ng/mL with a mean of 6.2 ng/mL and a median of 3.6 ng/mL. There was no relationship between fentanyl concentration and naloxone dose administered for reversal. We detected sedative-hypnotics (including benzodiazepines, muscle relaxants, and antidepressants) in nine participants. Among the sedative-hypnotic exposed, fentanyl concentrations were lower, but naloxone dosing was similar to those without a concomitant exposure., Conclusions: In this study, we found that: 1) fentanyl was present in the blood of nearly all participants; 2) fentanyl concentrations were lower among study participants with concomitant sedative-hypnotic exposure; and 3) the dose of naloxone administered for overdose reversal was not associated with the measured fentanyl concentration in blood specimens. Our results underscore the role that tolerance and concomitant drug exposure play in the precipitation and resuscitation of management of opioid overdose.

Objective: To compare user self-identification of nonpharmaceutical fentanyl exposure with confirmatory urine drug testing in emergency department (ED) patients presenting after heroin overdose., Methods: This was a cross-sectional study of adult ED patients who presented after a heroin overdose requiring naloxone administration. Participants provided verbal consent after which they were asked a series of questions regarding their knowledge, attitudes and beliefs toward heroin and nonpharmaceutical fentanyl. Participants also provided urine samples, which were analyzed using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry to identify the presence of fentanyl, heroin metabolites, other clandestine opioids, common pharmaceuticals and drugs of abuse., Results: Thirty participants were enrolled in the study period. Ten participants (33%) had never required naloxone for an overdose in the past, 20 participants (67%) reported recent abstinence, and 12 participants (40%) reported concomitant cocaine use. Naloxone was detected in all urine drug screens. Heroin or its metabolites were detected in almost all samples (93.3%), as were fentanyl (96.7%) and its metabolite, norfentanyl (93.3%). Acetylfentanyl was identified in nine samples (30%) while U-47700 was present in two samples (6.7%). Sixteen participants self-identified fentanyl in their heroin (sensitivity 55%); participants were inconsistent in their qualitative ability to identify fentanyl in heroin., Conclusions: Heroin users presenting to the ED after heroin overdose requiring naloxone are unable to accurately identify the presence of nonpharmaceutical fentanyl in heroin. Additionally, cutting edge drug testing methodologies identified fentanyl exposures in 96.7% of our patients, as well as unexpected clandestine opioids (like acetylfentanyl and U-47700).

Context: Synthetic cannabinoid use has increased in many states, and medicinal and/or recreational marijuana use has been legalized in some states. These changes present challenges to law enforcement drug recognition experts (DREs) who determine whether drivers are impaired by synthetic cannabinoids or marijuana, as well as to clinical toxicologists who care for patients with complications from synthetic cannabinoids and marijuana. Our goal was to compare what effects synthetic cannabinoids and marijuana had on performance and behavior, including driving impairment, by reviewing records generated by law enforcement DREs who evaluated motorists arrested for impaired driving., Methods: Data were from a retrospective, convenience sample of de-identified arrest reports from impaired drivers suspected of using synthetic cannabinoids (n = 100) or marijuana (n = 33). Inclusion criteria were arrested drivers who admitted to using either synthetic cannabinoids or marijuana, or who possessed either synthetic cannabinoids or marijuana; who also had a DRE evaluation at the scene; and whose blood screens were negative for alcohol and other drugs. Exclusion criteria were impaired drivers arrested with other intoxicants found in their drug or alcohol blood screens. Blood samples were analyzed for 20 popular synthetic cannabinoids by using liquid chromatography-tandem mass spectrometry. Delta-9-tetrahydrocannabinol (THC) and THC-COOH were quantified by gas chromatography-mass spectrometry. Statistical significance was determined by using Fisher's exact test or Student's t-test, where appropriate, to compare the frequency of characteristics of those in the synthetic cannabinoid group versus those in the marijuana group., Results: 16 synthetic cannabinoid and 25 marijuana records met selection criteria; the drivers of these records were arrested for moving violations. Median age for the synthetic cannabinoid group (n = 16, 15 males) was 20 years (IQR 19-23 years). Median age for the marijuana group (n = 25, 21 males) was 20 years (IQR 19-24 years) (p = 0.46). In the synthetic cannabinoid group, 94% (15/16) admitted to using synthetic cannabinoids. In the marijuana group, 96% (24/25) admitted to using marijuana. Blood was available for testing in 96% (24/25) of the marijuana group; 21 of these 24 had quantitative levels of THC (mean + SD = 10.7 + 5 ng/mL) and THC-COOH (mean + SD = 57.8 + 3 ng/mL). Blood was available for testing in 63% (10/16) of the synthetic cannabinoid group, with 80% (8/10) of these positive for synthetic cannabinoids. Those in the synthetic cannabinoid group were more frequently confused (7/16 [44%] vs. 0/25 [0%], p ≤ 0.003) and disoriented (5/16 [31%] vs. 0/25 [0%], p ≤ 0.003), and more frequently had incoherent, slurred speech (10/16 [63%] vs. 3/25 [12%], p = 0.0014) and horizontal gaze nystagmus (8/16 [50%] vs. 3/25 [12%], p = 0.01) than those in the marijuana group., Conclusion: Drivers under the influence of synthetic cannabinoids were more frequently impaired with confusion, disorientation, and incoherent, slurred speech than drivers under the influence of marijuana in this population evaluated by DREs.