Withdrawal during outpatient low dose buprenorphine initiation in people who use fentanyl: a retrospective cohort study

Kilaru A., Perrone J., Lowenstein M., Nelson L., Spadaro A., Faude S., Siaw-Asamoah A., Snider C., Thakrar A.

Bird H.E., Huhn A.S., Dunn K.E.

Pilarinos A., Bingham B., Kwa Y., Joe R., Grant C., Fast D., Buxton J.A., DeBeck K.

Limited research examines buprenorphine-naloxone interest among adolescents and young adults (AYA). This longitudinal study examined factors associated with initial buprenorphine-naloxone interest and the time to a positive change in buprenorphine-naloxone interest or enrollment, in addition to identifying reasons for buprenorphine-naloxone disinterest. The study derived data from a cohort of street-involved AYA in Vancouver, Canada between December 2014 and June 2018. The analysis was restricted to AYA who reported weekly or daily illicit opioid use in the last six months but had not initiated buprenorphine-naloxone. The study examined factors associated with initial buprenorphine-naloxone interest using multivariable logistic regression, while multivariable Cox regression identified factors associated with the time to a positive change in buprenorphine-naloxone interest or actual enrollment over follow-up among AYA initially disinterested in buprenorphine-naloxone. Of 281 participants who reported weekly illicit opioid use but were not on buprenorphine-naloxone, 52 (18.5 %) AYA reported initial buprenorphine-naloxone interest, while 68 (24.2 %) AYA who were initially disinterested in buprenorphine-naloxone reported interest or enrollment over follow-up. In multivariable logistic regression, initial interest was positively associated with older age (Adjusted Odds Ratio [AOR] = 1.09, 95 % Confidence Interval [CI]: 1.03–1.15), but negatively associated with self-reported Indigenous identity (AOR = 0.22, 95 % CI: 0.07–0.68). In multivariable Cox regression, recent detoxification program access (Adjusted Hazard Ratio [AHR] = 0.85, 95 % CI: 0.73–0.98) was positively associated with the time to a positive change in buprenorphine-naloxone interest or enrollment. Common reasons for buprenorphine-naloxone disinterest included not wanting opioid agonist treatments (OAT) (initial n = 67, follow-up n = 105); not wanting to experience precipitated withdrawal (initial n = 42, follow-up n = 54), being satisfied with or preferring other OAT (initial n = 33, follow-up n = 52), not knowing what buprenorphine-naloxone is (initial n = 27, follow-up n = 9), previous negative treatment experiences (initial n = 19, follow-up n = 20), and wanting to continue opioid use (initial n = 13, follow-up n = 9), among others. We documented persistent disinterest in buprenorphine-naloxone among AYA, though participants' reasons for disinterest provide insight into the potential benefits of expanding micro-dosing induction; ensuring treatment is culturally safe; and communicating changes in buprenorphine-naloxone programming to AYA. Nevertheless, a need remains to improve the continuum of harm reduction and treatment supports for AYA.

Dunn K.E., Bird H.E., Bergeria C.L., Ware O.D., Strain E.C., Huhn A.S.

BackgroundOpioid withdrawal can be expressed as both a spontaneous and precipitated syndrome. Although spontaneous withdrawal is well-characterized, there is no operational definition of precipitated opioid withdrawal.MethodsPeople (N = 106) with opioid use disorder maintained on morphine received 0.4 mg intramuscular naloxone and completed self-report (Subjective Opiate Withdrawal Scale, SOWS), visual analog scale (VAS), Bad Effects and Sick, and observer ratings (Clinical Opiate Withdrawal Scale, COWS). Time to peak severity and minimal clinically important difference (MCID) in withdrawal severity were calculated. Principal component analysis (PCA) during peak severity were conducted and analyzed with repeated measures analyses of variance (ANOVA).ResultsWithin 60 min, 89% of people reported peak SOWS ratings and 90% of people had peak COWS scores as made by raters. Self-reported signs of eyes tearing, yawning, nose running, perspiring, hot flashes, and observed changes in pupil diameter and rhinorrhea/lacrimation were uniquely associated with precipitated withdrawal. VAS ratings of Bad Effect and Sick served as statistically significant severity categories (0, 1–40, 41–80, and 81–100) for MCID evaluations and revealed participants' identification with an increase of 10 [SOWS; 15% maximum percent effect (MPE)] and 6 (COWS; 12% MPE) points as meaningful shifts in withdrawal severity indicative of precipitated withdrawal.ConclusionData suggested that a change of 10 (15% MPE) and 6 (12% MPE) points on the SOWS and COWS, respectively, that occurred within 60 min of antagonist administration was identified by participants as a clinically meaningful increase in symptom severity. These data provide a method to begin examining precipitated opioid withdrawal.

D’Onofrio G., Hawk K.F., Perrone J., Walsh S.L., Lofwall M.R., Fiellin D.A., Herring A.

This cohort study examines the incidence of precipitated withdrawal comparing traditional sublingual buprenorphine with a 7-day extended-release injectable initiated in the emergency department (ED).

Noel M., Abbs E., Suen L., Samuel L., Dobbins S., Geier M., Soran C.S.

Buprenorphine treatment significantly reduces morbidity and mortality for people with opioid use disorder. Fear of precipitated withdrawal remains a barrier to starting buprenorphine for patients who use synthetic opioids, particularly fentanyl. We aim to evaluate the development and implementation of a buprenorphine low dose overlap initiation (LDOI) protocol in an urban public health community pharmacy.We performed a retrospective chart review of patients with nonprescribed fentanyl use (N = 27) to examine clinical outcomes of a buprenorphine LDOI schedule, named the Howard Street Method, dispensed from a community pharmacy in San Francisco from January to December 2020.Twenty-seven patients were prescribed the Howard Street Method. Twenty-six patients picked up the prescription and 14 completed the protocol. Of those who completed the protocol, 11 (79%) reported no symptoms of withdrawal and 3 (21%) reported mild symptoms. Four patients (29%) reported cessation of full opioid agonist use and 10 (71%) reported reduction in their use by the end of the protocol. At 30 days, 12 patients (86%) were retained in care and 10 (71%) continued buprenorphine. At 180 days, 6 patients (43%) were retained in care and 2 (14%) were still receiving buprenorphine treatment.We found that a LDOI blister-pack protocol based at a community pharmacy was a viable intervention for starting buprenorphine treatment and a promising alternative method for buprenorphine initiation in an underresourced, safety-net population of people using fentanyl.

Spadaro A., Faude S., Perrone J., Thakrar A.P., Lowenstein M., Delgado M.K., Kilaru A.S.

Robert M., Jouanjus E., Khouri C., Fouilhé Sam‐Laï N., Revol B.

The current opioid epidemic in the United States began 20 years ago and has become the leading cause of accidental deaths in the country. This crisis prompted us to explore trends in opioid abuse and dependence worldwide. We sought to identify other countries at high-risk of opioid use disorders, using the World Health Organization's (WHO) pharmacovigilance database.We performed a disproportionality analysis using VigiBase, the WHO Global Individual Case Safety Report (ICSR) database. Five opioids used worldwide were included: oxycodone, fentanyl, morphine, tramadol, and codeine. We extracted all ICSRs associated with the drugs of interest, considered as suspect medication and recorded up until 5 June 2021, using the narrow Standardised MedDRA Query (SMQ) for drug abuse and dependence. Countries with at least one ICSR for each of the five opioids were retained. The relationship between the use of a drug (i.e. an opioid) and the occurrence of an adverse drug reaction (i.e. drug abuse and dependence) for each country was assessed by calculating the information component (IC) and its 99.9% CI [IC0005 ; IC9995 ], using a quasi-Bayesian confidence propagation neural network (BCPNN). A hierarchical cluster analysis (Ward's method) of the IC0005 value for each of the five opioids was performed to identify subgroups of countries with similar reported risks of opioid abuse and dependence.Among 21 countries, the optimal number of clusters was calculated to be four, each with a Jaccard index >0.5 (0.95, 0.78, 0.65 and 0.75, respectively). Six countries with the highest signals of drug abuse and dependence were identified in cluster 1, with significant CIs for the five opioids of interest (IC0005 > 0), ranging from 0.9 to 5.8 for the lower endpoint.There appear to be four distinct clusters of countries with similar opioid abuse and dependence profiles. The group with the highest reported risk for the opioids oxycodone, fentanyl, morphine, tramadol and codeine includes Australia, Canada, France, Germans, the United Kingdom and the United States.

Gondré-Lewis M.C., Abijo T., Gondré-Lewis T.A.

The heroin epidemic has existed for decades, but a sharp rise in opioid overdose deaths (OODs) jolted the nation in the mid-twenty-teens and continues as a major health crisis to this day. Although the new wave of OODs was initially approached as a rural problem impacting a White/Caucasian demographic, surveillance records suggest severe impacts on African Americans and urban-dwelling individuals, which have been largely underreported. The focus of this report is on specific trends in OOD rates in Black and White residents in states with a significant Black urban population and declared as hotspots for OOD: (Maryland (MD), Illinois (IL), Michigan (MI), and Pennsylvania (PA)), and Washington District of Columbia (DC). We compare OODs by type of opioid, across ethnicities, across city/rural demographics, and to homicide rates using 2013–2020 data acquired from official Chief Medical Examiners’ or Departments of Health (DOH) reports. With 2013 or 2014 as baseline, the OOD rate in major cities (Baltimore, Chicago, Detroit, Philadelphia) were elevated two-fold over all other regions of their respective state. In DC, Wards 7 and 8 OODs were consistently greater than other jurisdictions, until 2020 when the rate of change of OODs increased for the entire city. Ethnicity-wise, Black OOD rates exceeded White rates by four- to six-fold, with fentanyl and heroin having a disproportionate impact on Black opioid deaths. This disparity was aggravated by its intersection with the COVID-19 pandemic in 2020. African Americans and America’s urban dwellers are vulnerable populations in need of social and political resources to address the ongoing opioid epidemic in under-resourced communities.

Coish R., Hardial J.

Medication for opioid use disorder (OUD) with methadone or buprenorphine/naloxone is recommended for pregnant women with OUD. Traditional buprenorphine/naloxone induction requires patients to be in moderate withdrawal before the first dose of medication to minimize the chances of precipitated withdrawal. The low-dose buprenorphine "microinduction" (Bernese) method was described in 2016 and involves giving small doses of buprenorphine to patients for whom opioid withdrawal was not desirable. This method is being used widely in Vancouver in the context of high rates of overdose due to fentanyl poisoning.A 24-year-old woman, in her first pregnancy, with severe opioid and stimulant use disorder successfully started on buprenorphine/naloxone through a low-dose-induction protocol. The dose was started at 0.5 mg sublingual daily and slowly increased to 18 mg over 17 days. She continued to use fentanyl/heroin during the induction. She did not experience precipitated withdrawal and was able to stop using nonprescribed opioids once at a therapeutic dose of buprenorphine/naloxone.This represents the first documented case of successful buprenorphine/naloxone low-dose induction in pregnancy. First-line recommendations still remain to use traditional buprenorphine/naloxone induction when patients present in withdrawal. Obtaining informed consent regarding the lack of research on low-dose induction in pregnancy as well as discussion of risks and benefits is essential.Low-dose induction with buprenorphine/naloxone was successfully done in an outpatient setting. This represents a novel way of initiation of medication for OUD, which may enhance choice and collaboration between health care providers and women impacted by substance use in pregnancy.

Jablonski L.A., Bodnar A.R., Stewart R.W.

Buprenorphine is a life-saving treatment for opioid use disorder (OUD). Low-dose initiation (LDI) is an emerging buprenorphine initiation strategy that circumvents barriers associated with standard initiation. This study aims to describe tolerability and completion of LDI using intravenous (IV) buprenorphine and to define dosing protocols in a cohort of patients hospitalized in an urban academic hospital. Data was collected via retrospective chart review for IV buprenorphine LDI cases initiated between September 1, 2020 and February 28, 2021. Cases were excluded if diagnostic criteria for OUD was not met, Clinical Opiate Withdrawal Scale (COWS) scores were not recorded, or sublingual (SL) buprenorphine was given within 24 h before IV buprenorphine. Completion of LDI and COWS data were assessed for all cases. Cases were categorized based on adherence to a dosing strategy and LDI indication, including OUD and acute pain, non-prescribed fentanyl exposure, and transition from methadone. Seventy-two cases were identified, and thirteen cases were excluded, leaving 59 cases in the population. Of these cases, 72.9% (43/59) tolerated LDI, and 91.5% (54/59) completed buprenorphine initiation. Forty-four (44/59, 75%) cases were adherent. Median duration of LDI within the adherent group was 23.7 h (IQR 22.8–27.0), 37.1 h (IQR 36.2–40.9), and 48.8 h (IQR 47.0–52.4) for the “rapid,” “moderate,” and “slow” dosing strategies, respectively. IV buprenorphine LDI was tolerated and completed in a majority of patients. Dosing protocols allowed for rapid transition to sublingual buprenorphine. Acute pain or recent methadone or fentanyl exposure may inform IV LDI dosing strategy selection.

Varshneya N.B., Thakrar A.P., Lambert E., Huhn A.S.

Kaliamurthy S., Jegede O., Hermes G.

The micro-induction method of initiating buprenorphine is becoming a popular method for initiating buprenorphine in patients with Opioid Use Disorder, who are on full opioid agonists, either prescribed or non-prescribed, in order to avoid precipitated withdrawal. Given the rising concerns around illicit fentanyl use, this method of initiating buprenorphine has become another tool for clinicians to help patients with Opioid Use Disorder, even when multiple full opioid agonists are involved. While the process for initiating buprenorphine through this process is well studied, the characteristics of patients who are able to tolerate this initiation method in an outpatient setting is not.We present the cases of two patients with Opioid Use Disorder in a community-based methadone maintenance program in whom micro-induction methods were used to initiate buprenorphine without lowering the methadone dose. Both patients successfully transitioned to buprenorphine without precipitated withdrawal. One of the patients was also using fentanyl at the time of induction and was able to abstain from fentanyl use following the induction process.Initiating Buprenorphine using micro-induction strategies in a community based outpatient clinic in patients who are already on full opioid agonists is feasible, in these particular cases, the methadone dose or concurrent fentanyl use did not affect the outcome. We present the characteristics of the patient and the community clinic hoping that this helps more clinicians in replicating this induction strategy.

Suen L.W., Lee T.G., Silva M., Walton P., Coffin P.O., Geier M., Soran C.S.

Fear and risk of precipitated withdrawal are barriers for initiating buprenorphine in individuals with opioid use disorder, particularly among those using fentanyl. A buprenorphine rapid overlap initiation (ROI) protocol (also knownas "rapidmicro-dosing") utilizing small, escalating doses of buprenorphine can overcome this barrier, reaching therapeutic doses in 3 to 4 days. We sought to demonstrate the feasibility of implementing a buprenorphine ROI protocol for buprenorphine initiation in the outpatient setting.We conducted a retrospective chart review of patients prescribed an outpatient ROI protocol at the Office-based Buprenorphine Induction Clinic from October to December 2020. The ROI protocol utilizes divided doses of sublingual buprenorphine tablets and blister packaging for easier dosing. Patients were not required to stop other opioid use and were advised to follow up on day 4 of initiation.Twelve patients were included, of whom eleven (92%) were using fentanyl at intake. Eleven patients picked up their prescription. Seven patients returned for follow-up (58%), and all 7 completed the ROI protocol. One patient reported any withdrawal symptoms, which were mild. At 30 days, 7 patients (58%) were retained in care, and 5 (42%) were still receiving buprenorphine treatment, 4 (33%) of whom had been abstinent from nonprescribed opioid use for ≥2 weeks.The ROI protocol was successful in initiating buprenorphine treatment for patients in our outpatient clinic, many of whom were using fentanyl. The ROI protocol may offer a safe alternative to traditional buprenorphine initiation and warrants further study.

Spadaro A., Sarker A., Hogg-Bremer W., Love J.S., O’Donnell N., Nelson L.S., Perrone J.

Casey S., Mcgovern S., Regan S., Wakeman S.E.

Background: Illicitly manufactured fentanyl (IMF) presence has increased reports of buprenorphine precipitated withdrawal and may impact medication for opioid use disorder (MOUD) experiences and preferences. Methods: Cross-sectional survey administered by a clinical research coordinator of adults treated by an addiction consult team or bridge clinic who had prior experience with MOUD. Results: Among 100 respondents surveyed, 36% identified as female, 11% black, 9% Hispanic, 79% white, 29% had stable housing, 93% used fentanyl, and 65% injected commonly. 51% were currently treated with methadone, 41% were currently treated with sublingual buprenorphine, 12% were currently treated with extended-release buprenorphine, and 1% were currently treated with extended-release naltrexone. Most reported their current MOUD managed withdrawal and cravings well; 83.7% for methadone, 70.4% for sublingual buprenorphine, and 91.7% for extended-release buprenorphine. 75.8% of participants who tried buprenorphine reported ever experiencing precipitated withdrawal. Even so, 43.1% of those not being treated with buprenorphine were willing to start. Two-thirds reported cravings or withdrawal had worsened since IMF and 55% said IMF impacted MOUD decision making; however, 59% did not feel more worried about taking MOUD since IMF. Most (86%) had heard about low-dose buprenorphine initiation, 52.3% of those who had heard of it had tried it, and 57.8% reported positive experiences. 40% had heard of high-dose buprenorphine, 60% of those tried it, and 54.2% had positive experiences. The factors most likely to increase participants’ willingness to start MOUD were immediate access (85%), rapid titration (87%), hearing positive things from friends (82%), and getting MOUD from their doctor (63%). Conclusions: Despite IMF impacting withdrawal, cravings, and MOUD decision making, most patients felt MOUD managed symptoms well. Experiences with alternative buprenorphine initiations were positive. Access to low-barrier treatment with immediate medication initiation, aggressive dose escalation, office-based treatment, and peer-based messaging around MOUD may increase treatment uptake.

Laxton S.J.

Williams B.E., Martin S.A., Hoffman K.A., Andrus M.D., Dellabough-Gormley E., Buchheit B.M.

Abstract Introduction Buprenorphine is an effective first-line treatment for opioid use disorder (OUD) that substantially reduces morbidity and mortality. For patients using illicitly-manufactured fentanyl (IMF), however, transitioning to buprenorphine can be challenging. Evidence is lacking for how best to make this transition in the outpatient setting. A shared decision-making (SDM) approach has been found to benefit patients with OUD but has not been studied for buprenorphine initiation. We sought to explore participants’ experiences with a SDM approach to buprenorphine initiation. Methods Participants were seeking care at a low barrier, telehealth buprenorphine clinic. Clinicians implemented a standardized SDM approach whereby they offered patients using IMF three options for buprenorphine initiation (traditional, low-dose, and QuickStart). They elicited patient goals and preferences and discussed the pros and cons of each method to come to a shared decision. Patients meeting study criteria were invited to participate in semi-structured qualitative interviews 1–2 weeks after the initial visit. Interviews focused on experiences with the clinical visit, suggestions for enhancing the treatment experience, and patient factors affecting the method they chose. Interviews were coded and analyzed using reflexive thematic analysis. Results Twenty participants completed interviews. Participants’ mean age was 33, they were 50% female, predominantly white (16 [80%]), and most had Medicaid insurance (19 [95%]). We identified three important themes. First, participants found SDM acceptable and a positive addition to their OUD treatment. They felt their opinion mattered and reported that SDM gave them important control over their care plan. Second, patient goals, preferences, and past experiences with buprenorphine-associated withdrawal impacted what type of buprenorphine initiation method they chose. Finally, participants had advice for clinicians to improve SDM counseling. Participant recommendations included ensuring patients are informed that withdrawal (or “feeling sick”) can occur with any initiation method, that buprenorphine will eventually “block” fentanyl effects once at a high enough dose, and that clinicians provide specific advice for tapering off fentanyl during a low dose initiation. Conclusions For patients with OUD using IMF, shared decision-making is an acceptable approach to buprenorphine initiation in the outpatient setting. It can enhance patient autonomy and lead to an individualized approach to OUD care.

Biggerstaff M.E., Miker K.

Suen L.W., Chiang A.Y., Jones B.L., Soran C.S., Geier M., Snyder H.R., Neuhaus J., Myers J.J., Knight K.R., Bazazi A.R., Coffin P.O.

ImportanceThe rise of high-potency opioids such as fentanyl makes buprenorphine initiation challenging due to the risks of precipitated withdrawal, prompting the exploration of strategies, such as low-dose initiation (LDI) of buprenorphine. However, no comparative studies on LDI outcomes exist.ObjectiveTo evaluate outpatient outcomes associated with 2 LDI protocols of buprenorphine among individuals with opioid use disorder (OUD) using fentanyl.Design, Setting, and ParticipantsThis cohort study analyzed data on adults with OUD who self-reported daily fentanyl use and underwent buprenorphine initiation using LDI. Data were extracted from the electronic health records of 2 substance use disorder treatment clinics using a specialty behavioral health pharmacy in San Francisco, California, from May 2021 to November 2022.ExposuresType of LDI protocol selected by individuals: 4-day or 7-day protocol.Main Outcomes and MeasuresThe primary outcome was successful buprenorphine initiation, defined as self-reported LDI completion and pickup of a refill maintenance prescription, and buprenorphine retention. Logistic regression with generalized estimating equations assessed associations between LDI protocol (4-day vs 7-day) and successful initiation, adjusting for multiple attempts, age, gender identity, race and ethnicity, and housing status. Kaplan-Meier survival curves were used to estimate buprenorphine retention, and survival curves were adjusted using a fitted Cox proportional hazards regression model.ResultsA total of 126 individuals (median [IQR] age, 35 [29-44] years; 90 identified as men [71%]; 26 [21%] identified as Black or African American, 20 [16%] as Latine, and 66 [52%] as White individuals) with 175 initiation attempts were included. Across attempts, 72 (41%) had a 4-day LDI protocol and 103 (59%) had a 7-day protocol. Initiation was successful in 60 attempts (34%), including 27 (38%) among 4-day protocol and 29 (28%) among 7-day protocol attempts. Buprenorphine retention rate at 28 days was 21% for a 4-day protocol and 18% for a 7-day protocol. Logistic regression found no significant differences between LDI protocols and successful initiation, while repeated LDI attempts had lower odds of success (second attempt: adjusted odds ratio [AOR], 0.30 [95% CI, 0.14-0.66]; third or more attempt: AOR, 0.22 [95% CI, 0.09-0.53]). Unadjusted and adjusted survival models did not detect a significant difference in retention between LDI protocol types.Conclusions and RelevanceThis cohort study found that among people with OUD using fentanyl and attempting outpatient LDI of buprenorphine, successful buprenorphine initiation and retention rates were low. Future studies should examine interventions to improve LDI success and increase buprenorphine uptake and retention.

Thakrar A.P., Christine P.J., Siaw-Asamoah A., Spadaro A., Faude S., Snider C.K., Delgado M.K., Lowenstein M., Kampman K., Perrone J., Nelson L.S., Kilaru A.S.

ImportanceBuprenorphine treatment of opioid use disorder (OUD) is safe and effective, but opioid withdrawal during treatment initiation is associated with poor retention in care. As fentanyl has replaced heroin in the drug supply, case reports and surveys have indicated increased concern for buprenorphine-precipitated withdrawal (PW); however, some observational studies have found a low incidence of PW.ObjectiveTo estimate buprenorphine PW incidence and assess factors associated with PW among emergency department (ED) or hospitalized patients.Design, Setting, and ParticipantsThis retrospective cohort study at 3 academic hospitals in Philadelphia, Pennsylvania, included adults with OUD who underwent traditional or high-dose buprenorphine initiation between January 1, 2020, and December 31, 2021. Exclusion criteria included low-dose buprenorphine initiation and missing documentation of opioid withdrawal severity within 4 hours of receiving buprenorphine.ExposureBuprenorphine initiation with an initial dose of at least 2 mg of sublingual buprenorphine after a Clinical Opiate Withdrawal Scale (COWS) score of 8 or higher. Additional exposures included 4 predefined factors potentially associated with PW: severity of opioid withdrawal before buprenorphine (COWS score of 8-12 vs ≥13), initial buprenorphine dose (2 vs 4 or ≥8 mg), body mass index (BMI) (<25 vs 25 to <30 or ≥30; calculated as weight in kilograms divided by height in meters squared), and urine fentanyl concentration (0 to <20 vs 20 to <200 or ≥200 ng/mL).Main Outcome and MeasuresThe main outcome was PW incidence, defined as a 5-point or greater increase in COWS score from immediately before to within 4 hours after buprenorphine initiation. Logistic regression was used to estimate the odds of PW associated with the 4 aforementioned predefined factors.ResultsThe cohort included 226 patients (150 [66.4%] male; mean [SD] age, 38.6 [10.8] years). Overall, 26 patients (11.5%) met criteria for PW. Among patients with PW, median change in COWS score was 9 points (IQR, 6-13 points). Of 123 patients with confirmed fentanyl use, 20 (16.3%) had PW. In unadjusted and adjusted models, BMI of 30 or greater compared with less than 25 (adjusted odds ratio [AOR], 5.12; 95% CI, 1.31-19.92) and urine fentanyl concentration of 200 ng/mL or greater compared with less than 20 ng/mL (AOR, 8.37; 95% CI, 1.60-43.89) were associated with PW.Conclusions and RelevanceIn this retrospective cohort study, 11.5% of patients developed PW after buprenorphine initiation in ED or hospital settings. Future studies should confirm the rate of PW and assess whether bioaccumulated fentanyl is a risk factor for PW.