National Institute on Drug Abuse Clinical Trials Network Meeting Report: Managing Patients Exposed to Xylazine-Adulterated Opioids in Emergency, Hospital and Addiction Care Settings.

Used as a veterinary sedative and not approved for human use, xylazine has been increasingly linked with opioid overdose deaths in the United States. A growing number of people have been exposed to xylazine in the illicit opioid supply (especially fentanyl) or in other drugs, particularly in some areas of the Northeast. Xylazine is an α-2 adrenergic agonist that decreases sympathetic nervous system activity. When combined with fentanyl or heroin, it is purported to extend the duration of the opioid's sedative effect and to cause dependence and an associated withdrawal syndrome; however, data to support these concerns are limited. Despite the escalating frequency of detection of xylazine in people with nonfatal and fatal opioid overdose, direct links to these outcomes have not been identified. Because the strongest causal link is to fentanyl coexposure, ventilatory support and naloxone remain the cornerstones of overdose management. Xylazine is also associated with severe tissue injury, including skin ulcers and tissue loss, but little is known about the underlying mechanisms. Nonetheless, strategies for prevention and treatment are emerging. The significance and clinical effects of xylazine as an adulterant is focused on 4 domains that merit further evaluation: fentanyl-xylazine overdose, xylazine dependence and withdrawal, xylazine-associated dermal manifestations, and xylazine surveillance and detection in clinical and nonclinical settings. This report reflects the Proceedings of the National Institute on Drug Abuse Center for the Clinical Trials Network convening of clinical and scientific experts, federal staff, and other stakeholders to describe emerging best practices for treating people exposed to xylazine-adulterated opioids. Participants identified scientific gaps and opportunities for research to inform clinical practice in emergency departments, hospitals, and addiction medicine settings.

Xylazine Adulteration of the Heroin-Fentanyl Drug Supply : A Narrative Review.

Xylazine is an animal sedative, approved by the U.S. Food and Drug Administration, that is commonly used in veterinary medicine and is not approved for human use. Since 2016, xylazine has consistently appeared in the illicitly manufactured fentanyl supply and has significantly increased in prevalence, likely due to its low cost, easy availability, and presumed synergistic psychoactive effect. Clinical experience along with the available pertinent research were used to review xylazine adulteration of the drug supply and provide guidance on the care of patients exposed to xylazine. This review discusses xylazine pharmacology, animal and human clinical effects, and what is known to date about care of patients experiencing acute overdose, xylazine-fentanyl withdrawal, and xylazine-associated wounds.

A Brief Educational Intervention to Increase ED Initiation of Buprenorphine for Opioid Use Disorder (OUD).

BACKGROUND: Despite the evidence in support of the use of buprenorphine in the treatment of OUD and increasing ability of emergency medicine (EM) clinicians to prescribe it, emergency department (ED)-initiated buprenorphine is uncommon. Many EM clinicians lack training on how to manage acute opioid withdrawal or initiate treatment with buprenorphine. We developed a brief buprenorphine training program and assessed the impact of the training on subsequent buprenorphine initiation and knowledge retention. METHODS: We conducted a pilot randomized control trial enrolling EM clinicians to receive either a 30-min didactic intervention about buprenorphine (standard arm) or the didactic plus weekly messaging and a monetary inducement to administer and report buprenorphine use (enhanced arm). All participants were incentivized to complete baseline, immediate post-didactic, and 90-day knowledge and attitude assessment surveys. Our objective was to achieve first time ED buprenorphine prescribing events in clinicians who had not previously prescribed buprenorphine in the ED and to improve EM-clinician knowledge and perceptions about ED-initiated buprenorphine. We also assessed whether the incentives and reminder messaging in the enhanced arm led to more clinicians administering buprenorphine than those in the standard arm following the training; we measured changes in knowledge of and attitudes toward ED-initiated buprenorphine. RESULTS: Of 104 EM clinicians enrolled, 51 were randomized to the standard arm and 53 to the enhanced arm. Clinical knowledge about buprenorphine improved for all clinicians immediately after the didactic intervention (difference 19.4%, 95% CI 14.4% to 24.5%). In the 90 days following the intervention, one-third (33%) of all participants reported administering buprenorphine for the first time. Clinicians administered buprenorphine more frequently in the enhanced arm compared to the standard arm (40% vs. 26.3%, p = 0.319), but the difference was not statistically significant. The post-session knowledge improvement was not sustained at 90 days in the enhanced (difference 9.6%, 95% CI - 0.37% to 19.5%) or in the standard arm (difference 3.7%, 95% CI - 5.8% to 13.2%). All the participants reported an increased ability to recognize patients with opioid withdrawal at 90 days (enhanced arm difference .55, 95% CI .01-1.09, standard arm difference .85 95% CI .34-1.37). CONCLUSIONS: A brief educational intervention targeting EM clinicians can be utilized to achieve first-time prescribing and improve knowledge around buprenorphine and opioid withdrawal. The use of weekly messaging and gain-framed incentivization conferred no additional benefit to the educational intervention alone. In order to further expand evidence-based ED treatment of OUD, focused initiatives that improve clinician competence with buprenorphine should be explored. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03821103.

Impact of a shelter-in-place order during the COVID-19 pandemic on the incidence of opioid overdoses.

INTRODUCTION: Since the beginning of the novel coronavirus (COVID-19) pandemic in the United States, there have been concerns about the potential impact of the pandemic on persons with opioid use disorder. Shelter-in-place (SIP) orders, which aimed to reduce the spread and scope of the virus, likely also impacted this patient population. This study aims to assess the role of the COVID-19 pandemic on the incidence of opioid overdose before and after a SIP order. METHODS: A retrospective review of the incidence of opioid overdoses in an urban three-hospital system was conducted. Comparisons were made between the first 100 days of a city-wide SIP order during the COVID-19 pandemic and the 100 days during the COVID-19 pandemic preceding the SIP order (Pre-SIP). Differences in observed incidence and expected incidence during the SIP period were evaluated using a Fisher's Exact test. RESULTS: Total patient visits decreased 22% from 46,078 during the Pre-SIP period to 35,971 during the SIP period. A total of 1551 opioid overdoses were evaluated during the SIP period, compared to 1665 opioid overdoses during the Pre-SIP period, consistent with a 6.8% decline. A Fisher's Exact Test demonstrated a p < 0.0001, with a corresponding Odds Ratio of 1.20 with a 95% confidence interval (1.12;1.29). CONCLUSION: The COVID-19 pandemic and the associated SIP order were associated with a statistically and clinically significant increase in the proportion of opioid overdoses in relation to the overall change in total ED visits.

A Case Report of a Novel Harm Reduction Intervention Used to Detect Opioid Overdose in the Emergency Department.

INTRODUCTION: As over 130 people die daily from opioid overdose in the United States, harm reduction strategies have become increasingly important. Because public restrooms are a common site for opioid overdose, emergency department waiting room restrooms (EDWRR) should be considered especially high-risk areas. CASE REPORT: We present the case of a patient found after a presumed opioid overdose in our EDWRR. Staff were alerted to his condition by a reverse motion detector (RMD), and rapidly treated him with naloxone. CONCLUSION: The RMD is a novel intervention that can save lives and should be considered in EDs with a high incidence of opioid overdose.

Sulfur Mustard Exposure from Dredged Artillery Shell in a Commercial Clammer.

A 40-year-old commercial fisherman presented with a blistering second degree burn to the right arm after handling a dredged and undetonated World War I-era sulfur mustard artillery shell. He sustained isolated second degree cutaneous injury requiring wound care and skin grafting. Sulfur mustard, or dichlorethylsulphide, is a vesicant chemical warfare agent that causes significant cutaneous chemical burn and is managed with burn wound care. Long-term effects include cosmetic disfigurement and increased risk of developing cancer. Sulfur mustard exposure is a rare but devastating injury when discarded artillery shells are encountered in coastal waters.

Double-blind, Randomized, Placebo-controlled Study Evaluating the Use of Platelet-rich Plasma Therapy (PRP) for Acute Ankle Sprains in the Emergency Department.

BACKGROUND: Over 23,000 people per day require treatment for ankle sprains. Platelet-rich plasma (PRP) is an autologous concentration of platelets that is thought to improve healing by promoting inflammation through growth factor and cytokine release. Studies to date have shown mixed results, with few randomized trials. OBJECTIVES: To determine patient function among patients randomized to receive standard therapy plus PRP, compared to patients who receive standard therapy plus sham injection (placebo). METHODS: Prospective, randomized, double-blinded, placebo-controlled trial. Patients with severe ankle sprains were randomized. Severity was graded on degree of swelling, ecchymosis, and ability to bear weight. PRP with lidocaine and bupivacaine was injected at the point of maximum tenderness by a blinded physician under ultrasound guidance. The control group was injected in a similar fashion with sterile 0.9% saline. Both groups had visual analog scale (VAS) pain scores and Lower Extremity Functional Scale (LEFS) on days 0, 3, and 8. LEFS and a numeric pain score were obtained via phone call on day 30. All participants were splinted, given crutches, and instructed to not bear weight for 3 days; at this time patients were reevaluated. RESULTS: There were 1156 patients screened and 37 were enrolled. Four withdrew before PRP injection was complete; 18 were randomized to PRP and 15 to placebo. There was no statistically significant difference in VAS and LEFS scores between groups. CONCLUSION: In this small study, PRP did not provide benefit in either pain control or function over placebo.

Recurrent respiratory depression associated with fentanyl transdermal patch gel reservoir ingestion.

BACKGROUND: Opioid abuse is common in the United States and is currently on the rise. Fentanyl transdermal patches (FTPs) have been on the market since 1991, and have recently become a popular source of opioids for abusers. There are currently two distinct FTP designs available on the market today; a gel reservoir system and a matrix construct. The gel reservoirs of FTPs contain massive amounts of fentanyl and are easily extractable for abuse. Ingesting the gel reservoir of an FTP is potentially lethal. CASE SERIES: In this case series, 4 patients ingested the gel reservoir of an FTP and experienced severe and recurrent respiratory depression necessitating continuous naloxone infusions. All patients responded adequately to initial prehospital doses of naloxone (0.8-2 mg intravenous) but developed recurrent respiratory depression within 2 h of presentation to the hospital. CONCLUSION: The gel reservoir of an FTP contains massive amounts of fentanyl. Ingestion of the gel may cause severe and recurrent respiratory depression necessitating repeated naloxone boluses, continuous naloxone infusion, and a prolonged observation period.

Overdose of propafenone surreptitiously sold as "Percocet".

BACKGROUND: Drug abuse is a common problem in the United States. Drugs can be acquired in many ways, and can be knowingly or mistakenly misrepresented when sold. Propafenone is an uncommonly encountered class IC antidysrhythmic that is a look-alike for the opioid, oxycodone/acetaminophen 5/325. OBJECTIVE: We report a case of propafenone overdose presenting with generalized tonic-clonic seizure and a widened QRS complex, occurring after the patient had reported ingesting "Percocet®" (Endo Pharmaceuticals, Chadds Ford, PA). CASE REPORT: A 17-year-old boy presented to the emergency department (ED) after a witnessed seizure lasting 2 min. The patient reported having ingested 6 "Percocet®" tablets that he purchased from a classmate. He noted feeling weak and dizzy approximately 3 h after the ingestion, just before the seizure. On arrival in the ED, the patient was awake and alert with a QRS length of 168 ms. A sodium bicarbonate bolus and infusion shortened the QRS length to 90 ms. The patient was discharged the following day with no further complications. The pills were identified as propafenone hydrochloride (HCl) 225-mg tablets. The classmate surreptitiously sold the pills as "Percocet®" due to their similar "512" imprint. CONCLUSIONS: Pharmaceutical drugs are often sold on the street, and often misrepresented. Propafenone HCl 225-mg is an uncommonly encountered pharmaceutical, but is a look-alike for oxycodone/acetaminophen 5/325. An overdose due to propafenone ingestion may present with seizures and a widened QRS complex.

Oxcarbazepine-induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS).

This is an image and brief case report of a 13-year-old boy who presented with severe rash and systemic symptoms after starting oxcarbazepine. The patient was diagnosed and treated for Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), a syndrome of fever, rash, and internal organ involvement secondary to medication administration. The image illustrates the rash seen with this drug reaction. The report is followed by a brief review of anticonvulsant hypersensitivity syndrome and DRESS.