High-dose Buprenorphine Research Articles

Average Daily Dose Trajectories for Episodes of Buprenorphine Treatment for Opioid Use Disorder.

High-dose (≥24 mg) buprenorphine daily doses (BDD) may be important in treating patients with opioid use disorder (OUD) to improve retention and prevent overdose, particularly in the context of increased illicit fentanyl use. This study sought to: (1) identify trajectories for average BDD among patients initiating buprenorphine treatment for OUD and (2) assess patient characteristics associated with these identified trajectories. Buprenorphine treatment episodes among patients in the US Veterans Healthcare Administration (VHA) from federal fiscal years 2006 to 2020 were identified. Group-based trajectory modeling (GBTM) was used to identify BDD trajectories based on weekly averages of BDD over the 180 days after buprenorphine episode initiation. A total of 79 303 buprenorphine treatment episodes among 44 583 patients were included in the analytic sample. GBTM identified 9 latent trajectories for BDD: (1) moderate dose, early discontinuation (10.1%), (2) moderate dose, delayed discontinuation (4.5%), (3) moderate dose, moderate-paced discontinuation (5.2%), (4) low-moderate dose, delayed discontinuation (7.0%), and (5) low-moderate dose, early discontinuation (21.1%), (6) low dose retention (9.6%), (7) low-moderate dose retention (16.7%), (8) moderate dose retention (18.6%), and (9) high dose retention (7.4%). Patient BDD can broadly be characterized as low [2-4 mg/day], low-moderate (6-8 mg/day), moderate (12-18 mg/day), and high dose (≥ 24 mg/day). Patients with episodes in the high BDD trajectory have the lowest social risk (eg, lowest rate of past-year history of homelessness) and the lowest diagnosed rate of physical and mental health-related comorbidities compared to those following other trajectories. BDD ranges widely and patient characteristics are significantly different between those episodes following differing BDD trajectories. Future research on the association between BDD and subsequent patient outcomes (eg, overdose) needs to carefully consider these differences in baseline characteristics.

89EMF The Utility of High Dose Buprenorphine in Producing Prolonged Suppression of Opioid Withdrawal

89EMF The Utility of High Dose Buprenorphine in Producing Prolonged Suppression of Opioid Withdrawal

Is buprenorphine maternal dose associated with neonatal opioid withdrawal syndrome severity?

Neonatal opioid withdrawal syndrome (NOWS) is a drug withdrawal syndrome occurring mainly after in utero opioid exposure. Buprenorphine is commonly used for opioid withdrawal. Studies are conflicted about a potential dose effect OBJECTIVE: The aim of our study was to investigate the impact of buprenorphine maternal maintenance therapy on the NOWS based on NOWS duration, birth weight and therapy. We conducted a retrospective study analysing data from infants admitted for NOWS in two Neonatal Intensive Care Unit between January 2010 and December 2020. Nonpreterm infants born to mothers who were treated with buprenorphine or therapy during pregnancy and who had a Lipsitz score of 4 or higher. A total of 75 term newborns were hospitalized for the treatment of NOWS from mother substituted with buprenorphine during the study inclusion period. The duration of NOWS differed significantly between all dose cohorts, with higher doses of maternal buprenorphine maintenance correlating with longer length of NOWS duration. Infants exposed to high doses required 17 days [10; 23], while infants exposed to intermediate doses required 7 days [2; 16] and infants exposed to low doses required 3 days [2; 5], with p-values < .003. Infants exposed to high doses required a longer time to regain their birth weight and higher morphine doses as therapy compared to others. Infants exposed to low doses, intermediate doses, and high doses of buprenorphine demonstrated dose-dependent increases in the durations of hospitalization, respectively. Increased doses of maternal buprenorphine during pregnancy are correlated with NOWS severity. Our study shows that increased doses of maternal buprenorphine during pregnancy are correlated with NOWS severity. Exploring low doses and having different ranges are a new argument to define the impact of maternal buprenorphine consumption.

Association of Daily Doses of Buprenorphine With Urgent Health Care Utilization

Higher buprenorphine doses may benefit the increasing number of individuals using fentanyl and other synthetic opioids, but there is little empirical evidence on the efficacy of such higher doses. To examine the association between higher buprenorphine doses (above 16 mg and 24 mg) and subsequent emergency department (ED) or inpatient service use among patients diagnosed with opioid use disorder. This cross-sectional study was a retrospective analysis of health data from Optum's deidentified Clinformatics Data Mart Database from 2016 to 2021 for commercially insured individuals aged 18 years or older diagnosed with opioid use disorder (OUD). Eligible participants initiated buprenorphine after at least 90 days of enrollment and were dispensed at least a 14-day supply of buprenorphine. Data were analyzed from September 2023 through February 2024. Maximum buprenorphine dose received by a patient for 14 or more days: more than 24 mg, more than 16 mg to 24 mg, more than 8 mg to 16 mg, or 1 mg to 8 mg. Days from initiation of the maximum buprenorphine dose to an ED or inpatient visit for a behavioral health diagnosis, controlling for patient demographics, comorbid conditions, time to reaching maximum dose, buprenorphine discontinuation, and pre-buprenorphine health care utilization. A total of 35 451 individuals with an OUD diagnosis who began buprenorphine treatment were identified (mean [SD] age, 46.2 [15.1] years; 20 983 male [59.2%]; 3326 Black [9.4%], 2411 Hispanic [6.8%], 26 712 White [75.3%]). The most common dose was more than 8 mg to 16 mg daily (14 802 patients [42.9%]), with 9669 patients (27.3%) in the 1 mg to 8 mg tier, 10 329 patients (29.1%) in the 8 mg to 16 mg tier, and 651 patients (1.8%) in the tier receiving more than 24 mg. Among all patients receiving buprenorphine, 12.5% experienced an ED or inpatient visit. Survival analysis shows patients receiving doses more than 24 mg and between 16 mg to 24 mg had longer times to ED or inpatient use than patients receiving from 8 mg to 16 mg (time ratio [TR], 1.11; 95% CI, 1.02 to 1.20) and more than 24 mg (TR, 1.37; 95% CI, 1.04 to 1.81). Findings for doses above 16 mg daily were consistent for observation windows as short as 365 days (more than 24 mg: TR, 1.48; 95% CI, 1.01-2.18; more than 16 mg to 24 mg: TR, 1.19; 95% CI, 1.06-1.32). These findings contribute to the sparse empirical research regarding potential benefits of higher-dose buprenorphine treatment of individuals with OUD. Clinicians should be aware of the potential effects of higher buprenorphine doses on health care utilization while policymakers work to ensure equitable access to individuals who could potentially benefit from higher doses.

Buprenorphine-Precipitated Withdrawal Among Hospitalized Patients Using Fentanyl

Buprenorphine 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. To estimate buprenorphine PW incidence and assess factors associated with PW among emergency department (ED) or hospitalized patients. This 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. Buprenorphine 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). The 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. The 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. In 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.

Reconsidering the usefulness of long-term high-dose buprenorphine.

Buprenorphine has been successfully used for decades in the treatment of opioid use disorder, yet there are complexities to its use that warrant attention to maximize its utility. While the package insert of the combination product buprenorphine\naloxone continues to recommend a maximum dose of 16 mg daily for maintenance, the emergence of fentanyl and synthetic analogs in the current drug supply may be limiting the effectiveness of this standard dose. Many practitioners have embraced and appropriately implemented novel practices to mitigate the sequelae of our current crisis. It has become common clinical practice to stabilize patients with 24 - 32 mg of buprenorphine daily at treatment initiation. Many of these patients, however, are maintained on these high doses (>16 mg/d) indefinitely, even after prolonged stability. Although this may be a necessary strategy in the short term, there is little evidence to support its safety and efficacy, and these high doses may be exposing patients to more complications and side effects than standard doses. Commonly known side effects of buprenorphine that are likely dose-related include hyperhidrosis, sedation, decreased libido, constipation, and hypogonadism. There are also complications related to the active metabolite of buprenorphine (norbuprenorphine) which is a full agonist at the mu opioid receptor and does not have a ceiling on respiratory suppression. Such side effects can lead to medical morbidity as well as decreased medication adherence, and we, therefore, recommend that after a period of stabilization, practitioners consider a trial of decreasing the dose of buprenorphine toward standard dose recommendations. Some patients' path of recovery may never reach this stabilization phase (i.e., several months of adherence to medications, opioid abstinence, and other clinical indicators of stability). Side effects of buprenorphine may not have much salience when patients are struggling for survival and safety, but for those who are fortunate enough to advance in their recovery, the side effects become more problematic and can limit quality of life and adherence.

Diagnosis and Treatment of Presumed Naltrexone-XR-precipitated Opioid Withdrawal in a Patient Chronically Treated With Buprenorphine-XR: A Case Report.

Naltrexone, buprenorphine, and methadone are Food and Drug Administration-approved medications for the treatment of opioid use disorder in the United States. Naltrexone, an opioid antagonist, can precipitate opioid withdrawal if administered too quickly after the use of full or partial opioid agonists for those with either dependence or use disorder. We describe a case of severe precipitated opioid withdrawal syndrome after reported buprenorphine extended-release (XR) administration, despite the patient having been stable on buprenorphine-XR for several years, with no missed doses or recent opioid use. Naltrexone levels were sent and helped to diagnose suspected inadvertent naltrexone-XR administration in this patient, which was likely the etiology of his precipitated opioid withdrawal syndrome. We suggest the use of high-dose buprenorphine, as well as adjunctive medications including benzodiazepines, as a treatment strategy for naltrexone-XR precipitated withdrawal in the setting of chronic buprenorphine-XR treatment.

High-Dose Buprenorphine Initiation: A Scoping Review.

The aim of the study is to review and synthesize the literature on high-dose buprenorphine initiation (>12-mg total dose on day of initiation). A scoping review of literature about high-dose buprenorphine initiation was conducted. MEDLINE, Embase, PsycINFO, and Cochrane Central were searched. Randomized controlled trials, prospective and retrospective cohort studies, and case studies/reports published in English before February 13, 2023, were included. Fifteen studies reporting outcomes from 580 high-dose buprenorphine initiations were included. Eight studies were in inpatient settings, 3 in emergency departments, 3 in outpatient settings, and 1 in a first-responder setting. Four studies reported high-dose initiations among individuals exposed to fentanyl. There were no reported events of fatal or nonfatal overdose or respiratory depression, although adverse event reporting was inconsistent in published reports. The most reported side effects with high-dose buprenorphine initiation were nausea or vomiting (n = 17) and precipitated withdrawal (n = 7). The most serious reported adverse event was hypotension requiring oral hydration (n = 2). Most studies reported improvements in subjective or objective withdrawal symptoms. The duration of follow-up ranged from none to 8 months. High-dose buprenorphine initiation has not been associated with reported cases of overdose or respiratory depression. However, the current literature about high-dose buprenorphine is limited by inconsistent side effect reporting, limited power to detect rare safety events such as respiratory depression, limited follow-up data, and few comparison studies between high-dose and regular initiation protocols. Further prospective data are needed to evaluate the safety and effectiveness of this initiation strategy.

Buprenorphine Decreases Fetal Breathing Movements in Fetal Biophysical Profile Assessment [ID 2683456

INTRODUCTION: Ten percent of pregnant patients in our community receive medication-assisted therapy with buprenorphine during their prenatal course. The American College of Obstetricians and Gynecologists (ACOG) recommends antenatal testing for conditions when risk of stillbirth is greater than 0.8/1,000. Opioid use in pregnancy is associated with modest increased odds of stillbirth (odds ratio 1.3). Our hypothesis was that biophysical profile (BPP) in buprenorphine patients might be different than a control group of high-risk patients due to the effects of buprenorphine. METHODS: This retrospective chart review analyzed the BPP assessments of patients receiving buprenorphine compared to patients followed for chronic hypertension. Patients seen between July 1, 2016, and June 30, 2020, were evaluated. 131 patients were in the buprenorphine group and 46 patients were in the chronic hypertension control group. RESULTS: Patients receiving buprenorphine were more likely to have a fetal breathing score of zero than patients undergoing BPP for hypertension. There is a significant relationship between buprenorphine dosage and breathing motion assessment. Chi-squared test yielded a value of P=.04269. Patients on high-dose buprenorphine are more likely to have values of 0 on fetal breathing motion assessment than low-dose patients. CONCLUSION: This is the first study to show a dose-related effect of buprenorphine on fetal breathing movements. Previous research has shown buprenorphine effects on fetal brain structure. Current guidelines minimize the effects of maternal buprenorphine administration on fetal development. This study adds to prior research; further study on the dose-related long-term and short-term effects of buprenorphine on fetal development is encouraged.

Managing Opioid Withdrawal Symptoms During the Fentanyl Crisis: A Review.

Illicitly manufactured fentanyl (IMF) is a significant contributor to the increasing rates of overdose-related deaths. Its high potency and lipophilicity can complicate opioid withdrawal syndromes (OWS) and the subsequent management of opioid use disorder (OUD). This scoping review aimed to collate the current OWS management of study populations seeking treatment for OWS and/or OUD directly from an unregulated opioid supply, such as IMF. Therefore, the focus was on therapeutic interventions published between January 2010 and November 2023, overlapping with the period of increasing IMF exposure. A health science librarian conducted a systematic search on November 13, 2023. A total of 426 studies were screened, and 173 studies were reviewed at the full-text level. Forty-nine studies met the inclusion criteria. Buprenorphine and naltrexone were included in most studies with the goal of transitioning to a long-acting injectable version. Various augmenting agents were tested (buspirone, memantine, suvorexant, gabapentin, and pregabalin); however, the liberal use of adjunctive medication and shortened timelines to initiation had the most consistently positive results. Outside of FDA-approved medications for OUD, lofexidine, gabapentin, and suvorexant have limited evidence for augmenting opioid agonist initiation. Trials often have low retention rates, particularly when opioid agonist washout is required. Neurostimulation strategies were promising; however, they were developed and studied early. Precipitated withdrawal is a concern; however, the rates were low and adequately mitigated or managed with low- or high-dose buprenorphine induction. Maintenance treatment continues to be superior to detoxification without continued management. Shorter induction protocols allow patients to initiate evidence-based treatment more quickly, reducing the use of illicit or non-prescribed substances.

Dysphagia as a Missing Link Between Post-surgical- and Opioid-Related Pneumonia.

Postoperative pneumonia remains a common complication of surgery, despite increased attention. The purpose of our study was to determine the effects of routine surgery and post-surgical opioid administration on airway protection risk. Eight healthy adult cats were evaluated to determine changes in airway protection status and for evidence of dysphagia in two experiments. (1) In four female cats, airway protection status was tracked following routine abdominal surgery (spay surgery) plus low-dose opioid administration (buprenorphine 0.015mg/kg, IM, q8-12h; n = 5). (2) Using a cross-over design, four naive cats (2 male, 2 female) were treated with moderate-dose (0.02mg/kg) or high-dose (0.04mg/kg) buprenorphine (IM, q8-12h; n = 5). Airway protection was significantly affected in both experiments, but the most severe deficits occurred post-surgically as 75% of the animals exhibited silent aspiration. Oropharyngeal swallow is impaired by the partial mu-opioid receptor agonist buprenorphine, most remarkably in the postoperative setting. These findings have implications for the prevention and management of aspiration pneumonia in vulnerable populations.

ASAM elaborates on its buprenorphine dosing paper

Last week, ADAW featured a published paper recommending that higher doses of buprenorphine be used in the era of fentanyl (see “ASAM recommends higher doses if needed for treatment with buprenorphine,” ADAW, Jan. 7, 2024, https://onlinelibrary.wiley.com/doi/full/10.1002/adaw.33984). The American Society of Addiction Medicine (ASAM) did not have time to get back to us by deadline but did respond to our questions for this week's issue. Below are our questions, in italics, followed by their responses.

Treatment characteristics of chronic low back pain patients treated with buprenorphine buccal film or transdermal patch.

Aims: Retrospective insurance claims analysis exploring treatment characteristics in chronic low back pain patients prescribed buprenorphine buccal film (Belbuca®) or transdermal patches. Patients and methods: The first buprenorphine prescription (buccal film or transdermal patch) was an index event. Patients were observed over 6month pre- and post-index periods. Propensity score matching minimized the selection bias. Results: Buccal film patients had a higher buprenorphine daily dose (501.7 vs 270.9 µg; p <0.001). The patch-to-film switching rate was higher than vice versa (11.5 vs 3.8%; p <0.001). The buccal film showed a greater reduction in opioid prescriptions (-1.1 vs -0.7; p =0.012), daily morphine milligram equivalents (-12.6 vs -7.3; p <0.001) and opioid treatment duration (-13.4 vs -7.6days; p =0.022). Conclusion: Buccal film was associated with higher buprenorphine doses and a greater reduction of opioid burden.

NIDA study: 24 mg of buprenorphine better than 16

A study published in JAMA Network Open last week that was funded by the National Institute on Drug Abuse (NIDA) found that higher doses of buprenorphine are better than lower doses to promote treatment retention.

Predictive factors for acceptance of a long-acting opiate substitution treatment studied through social representations and internalized stigma

Opioid use disorder is a public health problem worldwide with a treatment gap partially due to sociocultural representation and stigma. Taking the opportunity of an authorization to a subcutaneous (SC) injectable solution of buprenorphine, the first and only injectable treatment for opioid dependence available in France, we investigate potential obstacles to its implementation in France. This study aimed to define the factors predicting the acceptance of a new SC form of opiate substitution treatment (OST) by comparing the social representations using an adapted version of the Explanatory Model Interview Catalogue (EMIC) and the internalized stigma of intravenous drug injection using the Internalized Stigma of Mental Illness Inventory (ISMI) between participants receiving OST likely to accept the SC form or not. We also observed whether the fear of an opiate withdrawal syndrome could influence this choice. Fifty OST patients were included, 54% of them accepted a new SC form of OST. Perceived causes of drug injection measured with EMIC were significantly lower among participants who would not accept the new SC form. No significant difference was found regarding the total score of the adapted ISMI or its items. The fear of opiate withdrawal syndrome did not seem to be statistically related to acceptance of a long-acting SC OST in either group. The most discriminating combination of factors in predicting patient acceptance of such treatment was related to the perceived causes of drug injection associated with a severe Diagnostic and Statistical Manual of Mental Disorders 5th version (DSM-5) diagnosis, and a lower alcohol consumption. We observed significant differences in social representations but not in internalized stigma between the two groups. Moreover, the predictive factors linked to the acceptance of a new SC form of OST suggest a multifactorial combination of elements that will have to be tested in a larger and prospective study delivering long-acting high-dose buprenorphine.

Validation of a pharmacological imaging challenge using 11C-buprenorphine and 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography to study the effects of buprenorphine to the rat brain.

Buprenorphine mainly acts as an agonist of mu-opioid receptors (mu-OR). High dose buprenorphine does not cause respiratory depression and can be safely administered to elicit typical opioid effects and explore pharmacodynamics. Acute buprenorphine, associated with functional and quantitative neuroimaging, may therefore provide a fully translational pharmacological challenge to explore the variability of response to opioids in vivo. We hypothesized that the CNS effects of acute buprenorphine could be monitored through changes in regional brain glucose metabolism, assessed using 18F-FDG microPET in rats. First, level of receptor occupancy associated with a single dose of buprenorphine (0.1 mg/kg, s.c) was investigated through blocking experiments using 11C-buprenorphine PET imaging. Behavioral study using the elevated plus-maze test (EPM) was performed to assess the impact of the selected dose on anxiety and also locomotor activity. Then, brain PET imaging using 18F-FDG was performed 30 min after injection of unlabeled buprenorphine (0.1 mg/kg, s.c) vs. saline. Two different 18F-FDG PET acquisition paradigms were compared: (i) 18F-FDG injected i.v. under anesthesia and (ii) 18F-FDG injected i.p. in awake animals to limit the impact of anesthesia. The selected dose of buprenorphine fully blocked the binding of 11C-buprenorphine in brain regions, suggesting complete receptor occupancy. This dose had no significant impact on behavioral tests used, regardless of the anesthetized/awake handling paradigm. In anesthetized rats, injection of unlabeled buprenorphine decreased the brain uptake of 18F-FDG in most brain regions except in the cerebellum which could be used as a normalization region. Buprenorphine treatment significantly decreased the normalized brain uptake of 18F-FDG in the thalamus, striatum and midbrain (p < 0.05), where binding of 11C-buprenorphine was the highest. The awake paradigm did not improve sensitivity and impact of buprenorphine on brain glucose metabolism could not be reliably estimated. Buprenorphine (0.1 mg/kg, s.c) combined with 18F-FDG brain PET in isoflurane anesthetized rats provides a simple pharmacological imaging challenge to investigate the CNS effects of full receptor occupancy by this partial mu-OR agonist. Sensitivity of the method was not improved in awake animals. This strategy may be useful to investigate de desensitization of mu-OR associated with opioid tolerance in vivo.

High-Dose Buprenorphine Initiation in the Emergency Department Among Patients Using Fentanyl and Other Opioids

This cohort study examines buprenorphine treatment initiation, response, and follow-up among patients presenting to California emergency departments (EDs) who reported fentanyl or other opioid use.

Impact of Administering Buprenorphine to Overdose Survivors Using Emergency Medical Services.

To evaluate the efficacy and safety of utilizing emergency medical services units to administer high dose buprenorphine after an overdose to treat withdrawal symptoms, reduce repeat overdose, and provide a next-day substances use disorder clinic appointment to initiate long-term treatment. This was a retrospective matched cohort study of patients who experienced an overdose and either received emergency medical services care from a buprenorphine-equipped ambulance or a nonbuprenorphine-equipped ambulance in Camden, New Jersey, an urban community with high overdose rates. There were 117 cases and 123 control patients in the final sample. Compared with a nonbuprenorphine-equipped ambulance, exposure to a buprenorphine-equipped ambulance was associated with greater odds of engaging in opioid use disorder treatment within 30 days of an emergency medical services encounter (unadjusted odds ratio: 5.62, 95% confidence interval, 2.36 to 13.39). Buprenorphine-equipped ambulance engagement did not decrease repeat overdose compared to the comparison group. Patients who received buprenorphine experienced a decrease in withdrawal symptoms. Their clinical opiate withdrawal scale score decreased from an average of 9.27 to 3.16. buprenorphine-equipped ambulances increased on-scene time by 6.12 minutes. Patients who encountered paramedics trained to administer buprenorphine and able to arrange prompt substance use disorder treatment after an acute opioid overdose demonstrated a decrease in opioid withdrawal symptoms, an increase in outpatient addiction follow-up care, and showed no difference in repeat overdose. Patients receiving buprenorphine in the out-of-hospital setting did not experience precipitated withdrawal. Expanded out-of-hospital treatment of opiate use disorder is a promising model for rapid access to buprenorphine after an overdose in a patient population that often has limited contact with the health care system.

294 Rapid High-dose Buprenorphine Induction for Fentanyl-Using Patients by Paramedics

To describe the characteristics and clinical outcomes among patients who report a primary use of fentanyl participating in a pilot project of emergency medical services (EMS) high-dose buprenorphine field initiation.

High-dose buprenorphine results in a greater occurrence of postoperative hyperthermia than morphine in a randomized clinical trial in cats undergoing ovariohysterectomy.

To compare the thermoregulatory and analgesic effects of high-dose buprenorphine versus morphine in cats undergoing ovariohysterectomy. 94 client-owned cats. Cats were randomized to receive either buprenorphine 0.24 mg/kg or morphine 0.1 mg/kg subcutaneously (SC) during recovery from ovariohysterectomy. Body temperature measurements were obtained before anesthesia, during anesthesia (averaged), at extubation, and 2, 4, and 16 to 20 hours postoperatively. Signs of pain were assessed, and demographic characteristics were compared between groups. The effects of treatment and time on body temperature, point prevalence of hyperthermia (> 39.2 °C), and pain scores were compared with linear or generalized mixed-effect models. Cats receiving morphine (vs. buprenorphine) were older and heavier (both, P ≤ 0.005). Other group characteristics did not differ between treatments. Cats receiving buprenorphine (vs. morphine) had higher postoperative temperatures (P = 0.03). At 2, 4, and 16 to 20 hours after extubation, the point prevalence of hyperthermia was greater (P = 0.001) for cats receiving buprenorphine (55% [26/47], 44% [21/47], and 62% [27/43], respectively) versus morphine (28% [13/46], 13% [6/46], and 47% [21/44], respectively). There were no differences in pain scores between groups or over time. Five cats receiving buprenorphine and 6 receiving morphine required rescue analgesia within the 24-hour period. Administration of buprenorphine (0.24 mg/kg SC), compared with morphine (0.1 mg/kg SC), resulted in higher body temperatures without an apparent advantage with regard to analgesia during the first 20 postoperative hours than morphine. Opioid-induced postoperative hyperthermia could confound the diagnosis of fever from different sources.