Administration Of Buprenorphine Research Articles

Use of Buprenorphine in the Prehospital Setting

Purpose: Buprenorphine is a lifesaving medication in opioid use disorder (OUD). Emergency Medical Services (EMS) play a crucial role in responding to opioid overdoses. The pre-hospital use of buprenorphine by EMS can expand access to this important medication. This article aims to provide a narrative review of the use of buprenorphine in the pre-hospital setting. Methods: This is a narrative review of recent publications that describe the use of buprenorphine to treat opioid withdrawal in the pre-hospital setting. Results: There are a few well done studies that describe protocols, safety, and efficacy of the administration of buprenorphine in the pre-hospital setting by EMS providers. The pharmacology of buprenorphine makes it advantageous in treating opioid use disorder. Proper patient selection and protocols for the administration of buprenorphine are key to the success of implementing pre-hospital buprenorphine programs. Conclusions: The pre-hospital administration of buprenorphine for opioid use disorder should be considered by EMS agencies.

Buprenorphine in the Intensive Care Unit: Commentary on the Unanswered Questions.

The removal of the X-waiver in the Mainstreaming Addiction Treatment (MAT) Act of 2023 has substantial implications for buprenorphine prescribing as one of the options to treat opioid use disorder. The purpose of this commentary is to discuss the unanswered questions regarding buprenorphine in the intensive care unit (ICU) including how the passage of the MAT Act will affect ICU providers, which patients should receive buprenorphine, what is the most appropriate route of administration and dose of buprenorphine, what medications interact with buprenorphine, and how can transitions of care be optimized for these patients.

The Efficacy of Buprenorphine in Preoperative and Postoperative Patients: A Literature Review.

Although research suggests that less than half of individuals who have surgical procedures report effective postoperative pain alleviation, the majority of patients endure acute postoperative discomfort. To lessen and manage postoperative pain, a variety of preoperative, intraoperative, and postoperative treatments and management methods are available. For several years an opioid called buprenorphine has become an effective tool to treat opioid use disorder (OUD) in patients across many different demographics. It has however endured barriers to its usage which can be seen when treating patients with chronic pain or postoperative pain, who also have an OUD. While buprenorphine may be underutilized within the clinical setting, the significantly low rates of chronic abuse when using the drug allow it to be an attractive treatment option for patients. This paper aims to explore a wide range of studies that examine buprenorphine as an analgesic and how it can be used for preoperative pain and postoperative pain. This paper will give an in-depth analysis of buprenorphine and its use in patients with chronic pain as well as OUD. A systematic literature review was performed by identifying studies through the database PubMed. The data from various publications were gathered with preference being given to publications within the last three years. We reviewed studies that examined the pain level of the patients after having buprenorphine. Despite long-available pharmacologic evidence and clinical research, buprenorphine has maintained a mystique as an analgesic. Its usage in the treatment of OUD was further influenced by its well-known safety benefits and relative lack of psychomimetic side effects compared to other opioids. For patients accustomed to long-term, high-dose opioids who may be experiencing hyperalgesia but have not been informed about this phenomenon by their doctors or the potential for buprenorphine to resolve it, buprenorphine's pronounced antihyperalgesic effect is a compelling pharmacologic characteristic that makes it particularly attractive as an option. When used in pre-, peri-, and postoperative circumstances, buprenorphine provides various pain-management benefits and patients can still benefit from effective pain management from mu-opioid agonists while remaining on buprenorphine. Buprenorphine can be continued at a reduced dose as needed to avoid withdrawal symptoms and to improve the analgesic efficiency of mu-opioid agonists used in combination with acute postoperative pain in light of the evidence at hand. Buprenorphine administration needs a patient-centered, multidisciplinary strategy that considers the benefits and drawbacks of the many perioperative therapy options to have the best chance of success.

Post-Overdose Extended-Release Buprenorphine Initiation Facilitated by a Partnership Between Emergency Medical Services and an Outpatient Substance Use Disorder Observation Unit.

People who experience a nonfatal opioid overdose and receive naloxone are at high risk of subsequent overdose death but experience gaps in access to medications for opioid use disorder. The immediate post-naloxone period offers an opportunity for buprenorphine initiation. Limited data indicate that buprenorphine administration by emergency medical services (EMS) after naloxone overdose reversal is safe and feasible. We describe a case in which a partnership between a low-barrier substance use disorder (SUD) observation unit and EMS allowed for buprenorphine initiation with extended-release injectable buprenorphine after naloxone overdose reversal. A man in his 40's with severe opioid use disorder and numerous prior opioid overdoses experienced overdose in the community. EMS was activated and he was successfully resuscitated with intranasal naloxone, administered by bystanders and EMS. He declined emergency department (ED) transport and consented to transport to a 24/7 SUD observation unit. The patient elected to start buprenorphine due to barriers attending opioid treatment programs daily. His largest barrier was unsheltered homelessness. His severe opioid withdrawal symptoms were successfully treated with 16/4 mg sublingual buprenorphine/naloxone and 300 mg extended-release injectable buprenorphine (XR-buprenorphine), without precipitated withdrawal. Two weeks later, he reported no interval fentanyl use. We describe the case of a patient successfully initiated onto XR-buprenorphine in the immediate post-naloxone period via a partnership between an outpatient low-barrier addiction programs and EMS. Such partnerships offer promise in expanding buprenorphine access and medication choice, particularly for the high-risk population of patients who decline ED transport.

The opioid buprenorphine differentially affects laryngeal and tracheal sensory receptors

The current study aims to determine mechanisms of impaired airway protection following opioid administration. Experiments were performed on N=10 anesthetized male Sprague Dawley rats. Bipolar fine wire electromyogram (EMG) wires were implanted in various muscles to evaluate breathing and swallowing. Swallows were evoked by activation of laryngeal touch receptors, tracheal mechanoreceptors, and tracheobronchial c-fibers as follows: A) Light laryngeal touch with a Von Frey filament; B) Rapid inflation of a balloon in the proximal trachea; C) Stimulation of the carina with thin polyethylene tubing. Trials were performed before and after buprenorphine administration (0.01 mg/kg IV). 2-Way ANOVA detected an effect of drug [F(1,16)=40.6, p<0.0001] and stimulus [F(2,19)=4.2, p=0.03] on swallow frequency. Post hoc comparisons showed that after buprenorphine administration, laryngeal touch evoked significantly more swallows (10±4) than tracheal distension (1±1, p=0.03) or carina stimulation (1±3, p=0.04), suggesting that laryngeal sensation is critical for airway protection following opioid administration. This has implications for prevention of aspiration pneumonia in populations that have an increased risk of reduced laryngeal sensation and are commonly treated with opioids (e.g., post-surgical, critically ill, and/or head and neck cancer patients). Research reported in this abstract was supported by NIH grants NS110169, HL155721, HL163008, HD110951, NS097781, OT20D001983, the Craig H. Neilsen Foundation Pilot Research Grant 546714, Kentucky Spinal Cord and Head Injury Research Trust, and the Commonwealth of Kentucky Challenge for Excellence. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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.

Development of opioid analgesic tolerance in rat to extended-release buprenorphine formulated for laboratory subjects.

Buprenorphine in an extended-release formulation intended for use in laboratory subjects is frequently administered to rats to provide extended analgesia without repeated handling. While levels of buprenorphine may persist in serum once extended-release buprenorphine has been introduced, exposure to opioids can cause opioid tolerance or opioid-induced hypersensitivity. This work examined the analgesic duration and efficacy of a single administration of extended-release buprenorphine intended for use in laboratory subjects in models of inflammatory pain and post-operative pain and the development of opioid tolerance in rat. After subcutaneous administration of 1 mg/kg extended-release buprenorphine, analgesic efficacy did not persist for the expected 72 hours. No changes were observed in mechanical thresholds in the hindpaws that were contralateral to the injury, suggesting a lack of centrally mediated opioid-induced hypersensitivity. To determine whether opioid tolerance arose acutely after one exposure to extended-release buprenorphine, we conducted the warm water tail flick assay; on Day 1 we administered either saline or extended-release buprenorphine (1 mg/kg) and on Day 3 we quantified the standard buprenorphine dose-response curve (0.1-3 mg/kg). Rats previously given extended-release buprenorphine displayed decreased analgesic responses after administration of standard buprenorphine as compared to the robust efficacy of standard buprenorphine in control subjects. Males appeared to show evidence of acute opioid tolerance, while females previously exposed to opioid did not demonstrate a decreased response at the doses examined. Taken together, these results suggest that opioid tolerance arises quickly in male rats after exposure to the extended-release formulation of buprenorphine. This tolerance may account for the brief period of antinociception observed.

Serotonin therapies for opioid-induced disordered swallow and respiratory depression.

Opioids are well-known to cause respiratory depression, but despite clinical evidence of dysphagia, the effects of opioids on swallow excitability and motor pattern are unknown. We tested the effects of the clinically relevant opioid buprenorphine on pharyngeal swallow and respiratory drive in male and female rats. We also evaluated the utility of 5-HT1A agonists (8-OH-DPAT and buspirone) to improve swallowing and breathing following buprenorphine administration. Experiments were performed on 44 freely breathing Sprague-Dawley rats anesthetized with sodium pentobarbital. Bipolar fine wire electrodes were inserted into the mylohyoid, thyroarytenoid, posterior cricoarytenoid, thyropharyngeus, and diaphragm muscles to measure electromyographic (EMG) activity of swallowing and breathing. We evaluated the hypotheses that swallowing varies by stimulus, opioids depress swallowing and breathing, and that 5-HT1A agonists improve these depressions. Our results largely confirmed the following hypotheses: 1) swallow-related EMG activity was larger during swallows elicited by esophageal distension plus oral water infusion than by either stimulus alone. 2) Buprenorphine depressed swallow in both sexes, but females were more susceptible to total swallow suppression. 3) Female animals were also more vulnerable to opioid-induced respiratory depression. 4) 8-OH-DPAT rescued breathing following buprenorphine-induced respiratory arrest, and pretreatment with the partial 5-HT1A agonist buspirone prevented buprenorphine-induced respiratory arrest in female animals. 5) 8-OH-DPAT enhanced mylohyoid and thyropharyngeus EMG amplitude during swallow but did not restore excitability of the swallow pattern generator following total suppression by buprenorphine. Our results highlight sex-specific and behavior-specific effects of buprenorphine and provide preclinical evidence of a 5HT1A agonist for the treatment of respiratory depression and dysphagia.NEW & NOTEWORTHY This is the first study, to our knowledge, to evaluate sex-specific effects of opioid administration on pharyngeal swallow. We expand on a small but growing number of studies that report a lower threshold for opioid-induced respiratory depression in females compared with males, and we are the first to produce this effect with the partial μ-opioid-receptor agonist buprenorphine. This is the first demonstration, to our knowledge, that activation of 5-HT1A receptors can improve swallow and breathing outcomes following systemic buprenorphine administration.

Salivary Therapeutic Monitoring of Buprenorphine in Neonates After Maternal Sublingual Dosing Guided by Physiologically Based Pharmacokinetic Modeling.

Opioid use disorder (OUD) during pregnancy is associated with high mortality rates and neonatal opioid withdrawal syndrome (NOWS). Buprenorphine, an opioid, is used to treat OUD and NOWS. Buprenorphine active metabolite (norbuprenorphine) can cross the placenta and cause neonatal respiratory depression (EC50 = 35 ng/mL) at high brain extracellular fluid (bECF) levels. Neonatal therapeutic drug monitoring using saliva decreases the likelihood of distress and infections associated with frequent blood sampling. An adult physiologically based pharmacokinetic model for buprenorphine and norbuprenorphine after intravenous and sublingual administration was constructed, vetted, and scaled to newborn and pregnant populations. The pregnancy model predicted that buprenorphine and norbuprenorphine doses would be transplacentally transferred to the newborns. The newborn physiologically based pharmacokinetic model was used to estimate the buprenorphine and norbuprenorphine levels in newborn plasma, bECF, and saliva after these doses. After maternal sublingual administration of buprenorphine (4 mg/d), the estimated plasma concentrations of buprenorphine and norbuprenorphine in newborns exceeded the toxicity thresholds for 8 and 24 hours, respectively. However, the norbuprenorphine bECF levels were lower than the respiratory depression threshold. Furthermore, the salivary buprenorphine threshold levels in newborns for buprenorphine analgesia, norbuprenorphine analgesia, and norbuprenorphine hypoventilation were observed to be 22, 2, and 162 ng/mL. Using neonatal saliva for buprenorphine therapeutic drug monitoring can facilitate newborn safety during the maternal treatment of OUD using sublingual buprenorphine. Nevertheless, the suitability of using adult values of respiratory depression EC50 for newborns must be confirmed.

Brain PET imaging using 11C-flumazenil and 11C-buprenorphine does not support the hypothesis of a mutual interaction between buprenorphine and benzodiazepines at the neuroreceptor level

Among opioids, buprenorphine presents a favorable safety profile with a limited risk of respiratory depression. However, fatalities have been reported when buprenorphine is combined to a benzodiazepine. Potentiation of buprenorphine interaction with opioid receptors (ORs) with benzodiazepines, and/or vice versa, is hypothesized to explain this drug-drug interaction (DDI). The mutual DDI between buprenorphine and benzodiazepines was investigated at the neuroreceptor level in nonhuman primates (n = 4 individuals) using brain PET imaging and kinetic modelling. The binding potential (BPND) of benzodiazepine receptor (BzR) was assessed using 11C-flumazenil PET imaging before and after administration of buprenorphine (0.2 mg, i.v.). Moreover, the brain kinetics and receptor binding of buprenorphine were investigated in the same individuals using 11C-buprenorphine PET imaging before and after administration of diazepam (10 mg, i.v.). Outcome parameters were compared using a two-way ANOVA. Buprenorphine did not impact the plasma nor brain kinetics of 11C-flumazenil. 11C-flumazenil BPND was unchanged following buprenorphine exposure, in any brain region (p > 0.05). Similarly, diazepam did not impact the plasma or brain kinetics of 11C-buprenorphine. 11C-buprenorphine volume of distribution (VT) was unchanged following diazepam exposure, in any brain region (p > 0.05). To conclude, our PET imaging findings do not support a neuropharmacokinetic or neuroreceptor-related mechanism of the buprenorphine/benzodiazepine interaction.

190 Health Disparities in Emergency Department Administration of Buprenorphine for Treatment of Opioid Use Disorder

190 Health Disparities in Emergency Department Administration of Buprenorphine for Treatment of Opioid Use Disorder

Technology-Assisted Buprenorphine Treatment in Rural and Nonrural Settings

Expansion of opioid use disorder treatment is needed, particularly in rural communities. To evaluate technology-assisted buprenorphine (TAB) efficacy (1) over a longer period than previously examined, (2) with the addition of overdose education, and (3) among individuals residing in rural communities. Two parallel, 24-week randomized clinical trials were conducted at the University of Vermont between February 1, 2018, and June 30, 2022. Participants were adults with untreated opioid use disorder from nonrural (trial 1) or rural (trial 2) communities. These trials are part of a programmatic effort to develop TAB protocols to improve treatment availability in underserved areas. Within each trial, 50 participants were randomized to TAB or control conditions. Participants in the TAB group completed bimonthly visits to ingest medication and receive take-home doses via a computerized device. They received nightly calls via an interactive voice response (IVR) system, IVR-generated random call-backs, and iPad-delivered HIV, hepatitis C virus (HCV), and overdose education. Control participants received community resource guides and assistance with contacting resources. All participants received harm reduction supplies and completed monthly assessments. The primary outcome was biochemically verified illicit opioid abstinence across monthly assessments. Secondary outcomes included self-reported opioid use in both groups and abstinence at bimonthly and random call-back visits, treatment adherence, satisfaction, and changes in HIV, HCV, and overdose knowledge among TAB participants. Fifty individuals (mean [SD] age, 40.6 [13.1] years; 28 [56.0%] male) participated in trial 1, and 50 (mean [SD] age, 40.3 [10.8] years; 30 [60.0%] male) participated in trial 2. Participants in the TAB group achieved significantly greater illicit opioid abstinence vs controls at all time points in both trial 1 (85.3% [128 of 150]; 95% CI, 70.7%-93.3%; vs 24.0% [36 of 150]; 95% CI, 13.6%-38.8%) and trial 2 (88.0% [132 of 150]; 95% CI, 72.1%-95.4%; vs 21.3% [32 of 150]; 95% CI, 11.4%-36.5%). High abstinence rates were also observed at TAB participants' bimonthly dosing visits (83.0% [95% CI, 67.0%-92.0%] for trial 1 and 88.0% [95% CI, 71.0%-95.0%] for trial 2). Treatment adherence was favorable and similar between trials (with rates of approximately 99% for buprenorphine administration, 93% for daily IVR calls, and 92% for random call-backs), and 183 of 187 urine samples (97.9%) tested negative for illicit opioids at random call-backs. iPad-delivered education was associated with significant and sustained increases in HIV, HCV, and overdose knowledge. In these randomized clinical trials of TAB treatment, demonstration of efficacy was extended to a longer duration than previously examined and to patients residing in rural communities. ClinicalTrials.gov Identifier: NCT03420313.

A comparative study on the dependence potential of thienorphine and buprenorphine

Background: As part of research to discover partial opioid agonists for new treatments of opioid abuse and dependency, thienorphine, a buprenorphine analogue, was synthesised and reported to be a potent, long-acting oripavine in multiple mammalian models. Thienorphine binds non-selectively to μ-, δ-, and κ-opioid receptors, and partially stimulates μ- and/or κ-opioid receptors in vitro. Compared with buprenorphine, thienorphine exhibits better analgesic effects and has higher oral bioavailability. Poor oral absorption and dependence have hindered the use of buprenorphine for detoxification therapy and relapse prevention in the clinic. The addiction potential of thienorphine is unknown, and is worthy of in-depth investigation. Methods: In the present study, we conducted a comparison of thienorphine and buprenorphine with respect to their physical and psychological dependence liabilities, using a naloxone-induced withdrawal test, a conditioned place preference test, and a self-administration experiment in rats. Results: In contrast to chronic buprenorphine administration, we failed to observe any severe abstinence syndromes in mice or rats treated with thienorphine after naloxone challenge in a physical dependence model. Compared with the dependence potentials of buprenorphine, rats treated with chronic thienorphine did not show a place conditioning response, self-administration, or psychological dependence. Conclusions: We demonstrated that thienorphine has a lower potential than buprenorphine for physical and psychological dependence. Our results indicate that thienorphine might be a good candidate to treat opioid addiction.

Serum Concentrations of a Long-acting Cat Formulation of Transdermal Buprenorphine in C57BL/6 Mice.

Long-acting analgesics such as extended-release buprenorphine are desirable in rodent medicine because they reduce need for administration of additional medication and provide stable drug levels. We measured the serum concentrations of buprenorphine after topical administration of a long-acting transdermal buprenorphine (LAT-bup) solution to female C57BL/6 mice. We hypothesized that LAT-bup dosed topically at 40mg/kg would achieve serum drug concentrations of greater than 1ng/mL, which is considered the therapeutic level for adequate analgesia in rodents. LAT-bup administered at 40mg/kg resulted in serum drug concentrations above 1ng/mL for all mice at time points 2, 4, 24, 48, 72, and 96 h (n = 3/time point), as assessed by liquid chromatography-mass spectrometry. No adverse effects were noted when LAT-bup was dosed at either 30mg/kg or 40mg/kg. We conclude that LAT-bup is easily administered to mice and achieves adequate blood levels for 96 h. Further studies evaluating analgesic efficacy are indicated.

Buprenorphine Continuation During Critical Illness Associated With Decreased Inpatient Opioid Use in Individuals Maintained on Buprenorphine for Opioid Use Disorder in a Retrospective Study.

The number of patients maintained on buprenorphine is steadily increasing. To date, no study has reported buprenorphine management practices for these patients during critical illness, nor its relationship with supplemental full-agonist opioid administration during their hospital stay. In this single-center retrospective study, we have explored the incidence of buprenorphine continuation during critical illness among patients receiving buprenorphine for the treatment of opioid use disorder. Additionally, we investigated the relationship between nonbuprenorphine opioid exposure and buprenorphine administration during the intensive care unit (ICU) and post-ICU phases of care. Our study included adults maintained on buprenorphine for opioid use disorder admitted to the ICU between December 1, 2014, and May 31, 2019. Nonbuprenorphine, full agonist opioid doses were converted to fentanyl equivalents (FEs). Fifty-one (44%) patients received buprenorphine during the ICU phase of care, with an average dose of 8 (8-12) mg/day. During the post-ICU phase of care, 68 (62%) received buprenorphine, with an average dose of 10 (7-14) mg/day. Lack of mechanical ventilation and acetaminophen use were also associated with buprenorphine use. Full agonist opioid use was more frequent on days when buprenorphine was not given (odds ratio [OR], 6.2 [95% CI, 2.3-16.4]; P<.001). Additionally, the average cumulative dose of opioids given on nonbuprenorphine administration days was significantly higher both in the ICU (OR, 1803 [95% CI, 1271-2553] vs OR, 327 [95% CI, 152-708] FEs/day; P<0.001) and after ICU discharge (OR, 1476 [95% CI, 962-2265] vs OR, 238 [95% CI, 150-377] FEs/day; P<.001). Given these findings, buprenorphine continuation during critical illness should be considered, as it is associated with significantly decreased full agonist opioid use.

Pharmacokinetics of buprenorphine and its metabolite norbuprenorphine in neutered male cats anesthetized with isoflurane

ObjectiveTo characterize the pharmacokinetics of buprenorphine and norbuprenorphine in isoflurane-anesthetized cats. Study designProspective experimental study. AnimalsA group of six healthy adult male neutered cats. MethodsCats were anesthetized with isoflurane in oxygen. Catheters were placed in a jugular vein for blood sampling and in a medial saphenous vein for buprenorphine and lactated Ringer’s solution administration. Buprenorphine hydrochloride (40 μg kg–1 over 5 minutes) was administered intravenously. Blood samples were collected before buprenorphine administration and at various times up to 12 hours after administration. Plasma buprenorphine and norbuprenorphine concentrations were measured using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time-concentration data using nonlinear mixed effect (population) modeling. ResultsA five-compartment model (three compartments for buprenorphine and two compartments for norbuprenorphine) best fitted the data. Typical value (% interindividual variability) for the three buprenorphine volumes of distribution, and the metabolic clearance to norbuprenorphine, the remaining metabolic clearance and the two distribution clearances were 157 (33), 759 (34) and 1432 (43) mL kg–1, and 5.3 (33), 16.4 (11), 58.7 (27) and 6.0 (not estimated) mL minute–1 kg–1, respectively. Typical values (% interindividual variability) for the two norbuprenorphine volumes of distribution, and the norbuprenorphine metabolic and distribution clearances were 1437 (30) and 8428 (not estimated) mL kg–1 and 48.4 (68) and 235.9 (not estimated) mL minute–1 kg–1, respectively. Conclusions and clinical relevanceThe pharmacokinetics of buprenorphine in isoflurane-anesthetized cats were characterized by a medium clearance.

Association of Early Opioid Withdrawal Treatment Strategy and Patient-Directed Discharge Among Hospitalized Patients with Opioid Use Disorder.

Medical hospitalizations for people with opioid use disorder (OUD) frequently result in patient-directed discharges (PDD), often due to untreated pain and withdrawal. To investigate the association between early opioid withdrawal management strategies and PDD. Retrospective cohort study using three datasets representing 362 US hospitals. Adult patients hospitalized between 2009 and 2015 with OUD (as identified using ICD-9-CM codes or inpatient buprenorphine administration) and no PDD on the day of admission. Opioid withdrawal management strategies were classified based on day-of-admission receipt of any of the following treatments: (1) medications for OUD (MOUD) including methadone or buprenorphine, (2) other opioid analgesics, (3) adjunctive symptomatic medications without opioids (e.g., clonidine), and (4) no withdrawal treatment. PDD was assessed as the main outcome and hospital length of stay as a secondary outcome. Of 6,715,286 hospitalizations, 127,158 (1.9%) patients had OUD and no PDD on the day of admission, of whom 7166 (5.6%) had a later PDD and 91,051 (71.6%) patients received some early opioid withdrawal treatment (22.3% MOUD; 43.4% opioid analgesics; 5.9% adjunctive medications). Compared to no withdrawal treatment, MOUD was associated with a lower risk of PDD (adjusted odds ratio [aOR] = 0.73, 95%CI 0.68-0.8, p < .001), adjunctive treatment alone was associated with higher risk (aOR = 1.13, 95%CI: 1.01-1.26, p = .031), and treatment with opioid analgesics alone was associated with similar risk (aOR 0.95, 95%CI: 0.89-1.02, p = .148). Among those with PDD, both MOUD (adjusted incidence rate ratio [aIRR] = 1.24, 95%CI: 1.17-1.3, p < .001) and opioid analgesic treatments (aIRR = 1.39, 95%CI: 1.34-1.45, p < .001) were associated with longer hospital stays. MOUD was associated with decreased risk of PDD but was utilized in < 1 in 4 patients. Efforts are needed to ensure all patients with OUD have access to effective opioid withdrawal management to improve the likelihood they receive recommended hospital care.

"Macrodosing" Sublingual Buprenorphine and Extended-release Buprenorphine in a Hospital Setting: 2 Case Reports.

To describe 2 case reports in which high-dose administration of sublingual buprenorphine/naloxone quickly stabilized fentanyl users who presented to the hospital. To discuss how early administration of extended-release buprenorphine, before the patient is discharged, may improve retention rates for outpatient buprenorphine treatment. Two case reports of fentanyl users presented to the emergency department at the general hospital in Timmins, Canada are described. They were rapidly stabilized on high-dose sublingual buprenorphine/naloxone and then transitioned within 24 to 36 hours to buprenorphine extended-release subcutaneous injection. In both cases, their withdrawal symptoms quickly resolved, without sedation or precipitated withdrawal. Both patients followed up with the outpatient clinic for another injection of extended-release buprenorphine. High-dose sublingual buprenorphine/naloxone followed by early administration of extended-release buprenorphine quickly and safely relieved withdrawal symptoms in 2 fentanyl users who presented to the hospital emergency department. This novel approach shows promise in improving treatment retention rates for patients using fentanyl. Further research is required to evaluate the safety and effectiveness of this approach.

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

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. 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. 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. 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.

Buprenorphine administration during gestation induces hepatotoxicity in the rat fetus

This study investigated the effect of buprenorphine (BUP) on the livers of pups exposed to this drug during the fetal stage. BUP decreased the activities of serum liver enzymes in exposed animals versus the controls. BUP (0.5mg/kg) decreased malondialdehyde levels and increased the glutathione levels in the liver of animals versus other groups. The superoxide dismutase activity was elevated in the BUP 0.5mg/kg group versus the control group. BUP (1mg/kg) induced histopathological changes in the livers of pups. In conclusion, BUP may induce hepatotoxicity in pups exposed to this drug during the fetal stage.