Caring for Hospitalized Adults With Opioid Use Disorder in the Era of Fentanyl: A Review.

Importance: The rise of fentanyl and other high-potency synthetic opioids across US and Canada has been associated with increasing hospitalizations and unprecedented overdose deaths. Hospitalization is a critical touchpoint to engage patients and offer life-saving opioid use disorder (OUD) care when admitted for OUD or other medical conditions. Observations: Clinical best practices include managing acute withdrawal and pain, initiating medication for OUD, integrating harm reduction principles and practices, addressing in-hospital substance use, and supporting hospital-to-community care transitions. Fentanyl complicates hospital OUD care. Fentanyl's high potency intensifies pain, withdrawal, and cravings and increases the risk for overdose and other harms. Fentanyl's unique pharmacology has rendered traditional techniques for managing opioid withdrawal and initiating buprenorphine and methadone inadequate for some patients, necessitating novel strategies. Further, co-use of opioids with stimulants drugs is common, and the opioid supply is unpredictable and can be contaminated with benzodiazepines, xylazine, and other substances. To address these challenges, clinicians are increasingly relying on emerging practices, such as low-dose buprenorphine initiation with opioid continuation, rapid methadone titration, and the use of alternative opioid agonists. Hospitals must also reconsider conventional approaches to in-hospital substance use and expand clinicians' understanding and embrace of harm reduction, which is a philosophy and set of practical strategies that supports people who use drugs to be safer and healthier without judgment, coercion, or discrimination. Hospital-to-community care transitions should ensure uninterrupted access to OUD care after discharge, which requires special consideration and coordination. Finally, improving hospital-based addiction care requires dedicated infrastructure and expertise. Preparing hospitals across the US and Canada to deliver OUD best practices requires investments in clinical champions, staff education, leadership commitment, community partnerships, quality metrics, and financing. Conclusions and Relevance: The findings of this review indicate that fentanyl creates increased urgency and new challenges for hospital OUD care. Hospital clinicians and systems have a central role in addressing the current drug crisis.

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-associated Wounds: Clinical Experience From a Low-barrier Wound Care Clinic in Philadelphia.

ABSTRACT: The veterinary sedative xylazine is spreading in unregulated opioid supplies across North America. Among people who use drugs with repeated exposure to xylazine, a distinct wound type has emerged. Here, we describe these wounds and share our experience treating them in a nurse-led, low-barrier wound care clinic in Philadelphia, PA. We propose a reimagining of wound treatment across settings to better serve people who use drugs, and we advocate for stronger protections against the harms of an increasingly adulterated drug supply. Our perspective from the epicenter of the xylazine crisis can inform the response of communities across the country who are starting to face harms associated with xylazine.

Trends in Before Medically Advised Discharges for Patients With Opioid Use Disorder, 2016-2020.

This study examines discharge trends for opioid-related admissions from 2016-2020 with a focus on admissions with opioid use disorder and an injection-related infection.

A conceptual framework for how structural changes in emerging acute substance use service models can reduce stigma of medications for opioid use disorder.

Stigma toward people taking medication for opioid use disorder (MOUD) is prevalent, harmful to the health and well-being of this population, and impedes MOUD treatment resource provision, help-seeking, and engagement in care. In recent years, clinicians have implemented new models of MOUD-based treatment in parts of the United States that integrate buprenorphine initiation into emergency departments and other acute general medical settings, with post-discharge linkage to office-based treatment. These service models increase access to MOUD and they have potential to mitigate stigma toward opioid use and MOUD. However, the empirical literature connecting these emerging service delivery models to stigma outcomes remains underdeveloped. This paper aims to bridge the stigma and health service literatures via a conceptual model delineating how elements of emerging MOUD service models can reduce stigma and increase behavior in pursuit of life goals. Specifically, we outline how new approaches to three key processes can counter structural, public, and self-stigma for this population: (1) community outreach with peer-to-peer influence, (2) clinical evaluation and induction of MOUD in acute care settings, and (3) transition to outpatient maintenance care and early recovery. Emerging service models that target these three processes can, in turn, foster patient empowerment and pursuit of life goals. There is great potential to increase the well-being of people who use opioids by reducing stigma against MOUD via these structural changes.

Association of Urine Fentanyl Concentration With Severity of Opioid Withdrawal Among Patients Presenting to the Emergency Department.

BACKGROUND AND AIMS: Fentanyl is involved in most US drug overdose deaths and its use can complicate opioid withdrawal management. Clinical applications of quantitative urine fentanyl testing have not been demonstrated previously. The aim of this study was to determine whether urine fentanyl concentration is associated with severity of opioid withdrawal. DESIGN: This is a retrospective cross-sectional study. SETTING: This study was conducted in 3 emergency departments in an urban, academic health system from January 1, 2020, to December 31, 2021. PARTICIPANTS: This study included patients with opioid use disorder, detectable urine fentanyl or norfentanyl, and Clinical Opiate Withdrawal Scale (COWS) recorded within 6 hours of urine drug testing. MEASUREMENTS: The primary exposure was urine fentanyl concentration stratified as high (>400 ng/mL), medium (40-399 ng/mL), or low (<40 ng/mL). The primary outcome was opioid withdrawal severity measured with COWS within 6 hours before or after urine specimen collection. We used a generalized linear model with γ distribution and log-link function to estimate the adjusted association between COWS and the exposures. FINDINGS: For the 1127 patients in our sample, the mean age (SD) was 40.0 (10.7), 384 (34.1%) identified as female, 332 (29.5%) reported their race/ethnicity as non-Hispanic Black, and 658 (58.4%) reported their race/ethnicity as non-Hispanic White. For patients with high urine fentanyl concentrations, the adjusted mean COWS (95% confidence interval) was 4.4 (3.9-4.8) compared with 5.5 (5.1-6.0) among those with medium and 7.7 (6.8-8.7) among those with low fentanyl concentrations. CONCLUSIONS: Lower urine fentanyl concentration was associated with more severe opioid withdrawal, suggesting potential clinical applications for quantitative urine measurements in evolving approaches to fentanyl withdrawal management.

Transitioning off methadone: A qualitative study exploring why patients discontinue methadone treatment for opioid use disorder.

INTRODUCTION: Patients who discontinue methadone for opioid use disorder are at increased risk of overdose and death. We know little about how patients make the decision to stop treatment. This study explored reasons why patients discontinue methadone treatment. METHODS: We conducted 20 individual semi-structured patient interviews and two staff focus groups, each with five participants, at two opioid treatment programs in Baltimore, MD, in the United States from June 2021 to May 2022. Patient interviews and staff focus groups covered three domains: 1) reasons why patients may want to discontinue methadone; 2) perspectives about the ideal length of methadone treatment; and 3) changes that could improve retention. We used a modified grounded theory approach to code interviews, identify emergent themes, and develop a conceptual model. RESULTS: We identified three themes related to patients' internal relationships to methadone: patients (1) viewed methadone as a bridge to opioid-free recovery, (2) believed that long-term methadone damages the body, and (3) felt that methadone increases craving for cocaine; and three themes related to their external relationships with opioid treatment programs and society at large: patients (4) viewed daily dosing as burdensome, (5) feared methadone inaccessibility could trigger relapse, and (6) experienced stigma from friends, family, and peers. Patients with internal reasons planned to stop as soon as possible and asked for education about perceived side effects and treatment for cocaine craving to promote retention. Patients with external reasons were willing to continue for longer and asked for adaptive take-home policies and reduced societal stigma around methadone. CONCLUSIONS: Patients want to discontinue methadone either because of their internal relationship to methadone and its real or perceived side effects, or because of their external experiences with opioid treatment programs and societal stigma of methadone. To improve retention, clinical and policy changes should consider responses to both of these categories of reasons.

Safety and preliminary outcomes of short-acting opioid agonist treatment (sOAT) for hospitalized patients with opioid use disorder.

BACKGROUND: Patients with opioid use disorder (OUD) frequently leave the hospital as patient directed discharges (PDDs) because of untreated withdrawal and pain. Short-acting opioids can complement methadone, buprenorphine, and non-opioid adjuvants for withdrawal and pain, however little evidence exists for this approach. We described the safety and preliminary outcomes of short-acting opioid agonist treatment (sOAT) for hospitalized patients with OUD at an academic hospital in Philadelphia, PA. METHODS: From August 2021 to March 2022, a pharmacist guided implementation of a pilot sOAT protocol consisting of escalating doses of oxycodone or oral hydromorphone scheduled every four hours, intravenous hydromorphone as needed, and non-opioid adjuvants for withdrawal and pain. All patients were encouraged to start methadone or buprenorphine treatment for OUD. We abstracted data from the electronic health record into a secure platform. The primary outcome was safety: administration of naloxone, over-sedation, or a fall. Secondary outcomes were PDDs and respective length of stay (LOS), discharges on methadone or buprenorphine, and discharges with naloxone. We compared secondary outcomes to hospitalizations in the 12 months prior to the index hospitalization among the same cohort. RESULTS: Of the 23 cases, 13 (56.5%) were female, 19 (82.6%) were 40 years or younger, and 22 (95.7%) identified as White. Twenty-one (91.3%) regularly injected opioids and four (17.3%) were enrolled in methadone or buprenorphine prior to hospitalization. sOAT was administered at median doses of 200-320 morphine milligram equivalents per 24-h period. Naloxone administration was documented once in the operating room, over-sedation was documented once after unsanctioned opioid use, and there were no falls. The PDD rate was 44% with median LOS 5 days (compared to PDD rate 69% with median LOS 3 days for prior admissions), 65% of sOAT cases were discharged on buprenorphine or methadone (compared to 33% for prior admissions), and 65% of sOAT cases were discharged with naloxone (compared to 19% for prior admissions). CONCLUSIONS: Pilot implementation of sOAT was safe. Compared to prior admissions in the same cohort, the PDD rate was lower, LOS for PDDs was longer, and more patients were discharged on buprenorphine or methadone and with naloxone, however efficacy for these secondary outcomes remains to be established.

Precipitated opioid withdrawal after buprenorphine administration in patients presenting to the emergency department: A case series.

Objectives: Buprenorphine is a highly effective medication for the treatment of opioid use disorder, but it can cause precipitated withdrawal (PW) from opioids. Incidence, risk factors, and best approaches to management of PW are not well understood. Our objective was to describe adverse outcomes after buprenorphine administration among emergency department (ED) patients and assess whether they met the criteria for PW. Methods: This study is a case series using retrospective chart review in a convenience sample of patients from 3 hospitals in an urban academic health system. This study included patients who were reported by clinicians as potential cases of PW. Relevant clinical data were abstracted from the electronic health record using a structured retrospective chart review instrument. Results: A total of 13 cases were included and classified into the following 3 categories: (1) PW after buprenorphine administration consistent with guidelines (n = 5), (2) PW after deviating from guidelines (n = 4), and (3) protracted opioid withdrawal with no increase in Clinical Opiate Withdrawal Scale score (n = 4). A total of 11 patients had urine drug testing positive for fentanyl, and 11 patients received additional doses of buprenorphine for symptom management. Of the patients, 5 had self-directed hospital discharges, and 6 were ultimately discharged with prescriptions for buprenorphine. Conclusions: Cases of adverse outcomes after buprenorphine administration in the ED and hospital meet criteria for PW, although some cases may have represented protracted opioid withdrawal. Further investigation into the incidence, risk factors, management of PW as well as patient perspectives is needed to expand and sustain the use of buprenorphine in EDs and hospitals.

Does a Survivorship Model of Opioid Use Disorder Improve Public Stigma or Policy Support? A General Population Randomized Experiment.

BACKGROUND: The chronic disease model of opioid use disorder (OUD) is promoted by many public health authorities, yet high levels of stigma persist along with low support for policies that would benefit people with OUD. OBJECTIVE: Determine if a survivorship model of OUD, which does not imply a chronic, relapsing disease state, compared to a chronic disease model improves public stigma and support for opioid-related policies. Explore if race or gender moderates any effect. DESIGN: Online, vignette-based randomized study. PARTICIPANTS: US adults recruited through a market research firm. INTERVENTION: Participants viewed one of 8 vignettes depicting a person with OUD in sustained remission. Vignettes varied in terms of the OUD model (survivorship, chronic disease) and vignette individual's race (Black, White) and gender (man, woman). MAIN MEASURES: (1) Public stigma measured by desire for social distance, perceptions of dangerousness, and overall feelings toward the vignette individual. (2) Support for 7 opioid-related policies. Overall feelings were measured on a feelings thermometer (0/cold-100/warm). Stigma and policy support responses were measured on Likert scales dichotomized to indicate a positive (4, 5) or negative/indifferent (1-3) response. KEY RESULTS: Of 1440 potential participants, 1172 (81%) were included in the analysis. Exposure to the survivorship model resulted in warmer feelings (mean 72, SD 23) compared to the chronic disease (mean 67, SD 23; difference 4, 95%CI 1-6). There was no effect modification from the vignette individual's race or gender. There was no significant difference between OUD models on other measures of public stigma or support for policies. CONCLUSIONS: The survivorship model of OUD improved overall feelings compared to the chronic disease model, but we did not detect an effect of this model on other domains of public stigma or support for policies. Further refinement and testing of this novel, survivorship model of OUD could improve public opinions.

Changes in Alcohol Consumption by Beverage Type Attributable to the COVID-19 Pandemic for 10 States, March 2020 to November 2020: An Ecological Simulation-based Analysis.

OBJECTIVES: Consumption of high potency alcohol is associated with greater healthcare burden, yet little attention has been placed on the change in types of alcohol consumed during the COVID-19 pandemic. We estimate the change in alcohol consumption by beverage type attributable to the COVID-19 pandemic. METHODS: The National Institute on Alcohol Abuse and Alcoholism provided apparent alcohol consumption ("consumption") by beverage type for 10 states for January 2017 through November 2020 based on sales and tax data. The 38-month period to February 2020 was used to train quasi-Poisson regression models. The models then predicted the monthly consumption based on the historical trends in the absence of the COVID-19 pandemic from March through November 2020. The difference between the observed and predicted is the change in consumption attributable to the COVID-19 pandemic. RESULTS: Beyond what was expected based on historical trends, spirits consumption increased significantly for 6 states (Colorado, Massachusetts, Missouri, North Dakota, Minnesota, and Tennessee) ranging from 4% (95% confidence interval [CI] 1%-6%) to 17% (95% CI 6%-28%) which is equivalent to 7 (95% CI 2-18) to 32 95% CI 12-48) excess standard spirits drinks per-capita; Alaska, Florida, Illinois, and Kentucky had no significant change. Wine consumption increased 10% (95% CI 3%-18%) in Colorado and 8% (95% CI 3%-12%) in Tennessee. Wine consumption in Alaska decreased 6% (95% CI, 3%-10%) and beer consumption decreased 8% (95% CI 4%-11%). CONCLUSIONS: During the COVID-19 pandemic, spirits consumption increased relative to wine and beer. Increased consumption of higher potency alcohol beverages could lead to higher alcohol-related healthcare and societal burden.

Micro-dosing Intravenous Buprenorphine to Rapidly Transition From Full Opioid Agonists.

For patients with opioid use disorder transitioning from methadone or requiring opioid analgesia, initiating buprenorphine for opioid use disorder can be difficult because of the risk of precipitated withdrawal. Low-dose initiation, also known as micro-dosing, is an alternative to standard initiation. Prior studies relied on nonstandard dosing of tablets or films, patches, or buccal formulations, all of which are unavailable in many hospitals. We report a novel approach to micro-dosing using intravenous buprenorphine. Two patients, one on methadone maintenance and another requiring postoperative opioid analgesia, were transitioned to buprenorphine with concurrent full-agonist opioids and without precipitated withdrawal.

Evidence of Buprenorphine-precipitated Withdrawal in Persons Who Use Fentanyl.

OBJECTIVES: Buprenorphine can precipitate withdrawal in opioid-dependent persons with recent fentanyl use. However, the prevalence of this phenomenon is not clinically established. We sought to evaluate the incidence of buprenorphine-precipitated withdrawal in persons who use fentanyl. METHODS: We collected self-report data on opioid withdrawal symptoms after buprenorphine use, and, as a comparator, after methadone use, in 1679 individuals seeking treatment for opioid use disorder across 49 addiction treatment centers in the United States. RESULTS: The odds of developing severe withdrawal symptoms significantly increased when taking buprenorphine within 24 hours after fentanyl use (OR = 5.202, 95% CI = 1.979-13.675, P = 0.001), and within 24 to 48hours after fentanyl use (OR = 3.352, 95% CI =1.237-9.089, P = 0.017). As expected, patients did not report significantly higher rates of withdrawal when taking methadone after fentanyl use. Of those who waited less than 24hours after fentanyl before using buprenorphine or methadone, 22.19% (n = 152 of 685) and 11.56% (n = 23 of 199), respectively, reported severe opioid withdrawal. CONCLUSIONS: This study supports previous anecdotal reports of buprenorphine-precipitated withdrawal from fentanyl. The odds of withdrawal symptoms significantly increased when taking buprenorphine after recent (within 48 hours) fentanyl use, however, this relationship was not observed in persons taking methadone, suggesting that this effect is specific to buprenorphine. Further research is urgently needed to describe the pharmacokinetics of non-medical fentanyl use to improve buprenorphine inductions strategies.