Perioperative pain optimization in the age of the opioid epidemic.

PURPOSE OF REVIEW: The opioid epidemic remains a constant and increasing threat to our society with overdoses and overdose deaths rising significantly during the COVID-19 pandemic. Growing evidence suggests a link between perioperative opioid use, postoperative opioid prescribing, and the development of opioid use disorder (OUD). As a result, strategies to better optimize pain management during the perioperative period are urgently needed. The purpose of this review is to summarize the most recent multimodal analgesia (MMA) recommendations, summarize evidence for efficacy surrounding the increased utilization of Enhanced Recovery After Surgery (ERAS) protocols, and discuss the implications for rising use of buprenorphine for OUD patients who present for surgery. In addition, this review will explore opportunities to expand our treatment of complex patients via transitional pain services. RECENT FINDINGS: There is ample evidence to support the benefits of MMA. However, optimal drug combinations remain understudied, presenting a target area for future research. ERAS protocols provide a more systematic and targeted approach for implementing MMA. ERAS protocols also allow for a more comprehensive approach to perioperative pain management by necessitating the involvement of surgical specialists. Increasingly, OUD patients taking buprenorphine are presenting for surgery. Recent guidance from a multisociety OUD working group recommends that buprenorphine not be routinely discontinued or tapered perioperatively. Lastly, there is emerging evidence to justify the use of transitional pain services for more comprehensive treatment of complex patients, like those with chronic pain, preoperative opioid tolerance, or substance use disorder. SUMMARY: Perioperative physicians must be aware of the impact of the opioid epidemic and explore methods like MMA techniques, ERAS protocols, and transitional pain services to improve the perioperative pain experience and decrease the risks of opioid-related harm.

Concomitant use of pre-emptive analgesia with local and general anesthesia in rat uterine pain surgical model.

Preemptive analgesia is used for postoperative pain management, providing pain relief with few adverse effects. In this study, the effect of a preemptive regime on rat behavior and c-fos expression in the spinal cord of the uterine surgical pain model was evaluated. It was a lab-based experimental study in which 60 female Sprague-Dawley rats; eight to 10 weeks old, weighing 150-300 gm were used. The rats were divided into two main groups: (i) superficial pain group (SG) (with skin incision only), (ii) deep pain group (with skin and uterine incisions). Each group was further divided into three subgroups based on the type of preemptive analgesia administered i.e., "tramadol, buprenorphine, and saline subgroups." Pain behavior was evaluated using the "Rat Grimace Scale" (RGS) at 2, 4, 6, 9 and 24 h post-surgery. Additionally, c-fos immunohistochemistry was performed on sections from spinal dorsal horn (T12-L2), and its expression was evaluated using optical density and mean cell count 2 hours postoperatively. Significant reduction in the RGS was noted in both the superficial and deep pain groups within the tramadol and buprenorphine subgroups when compared to the saline subgroup (p ≤ .05). There was a significant decrease in c-fos expression both in terms of number of c-fos positive cells and the optical density across the superficial laminae and lamina X of the spinal dorsal horn in both SD and DG (p ≤ .05). In contrast, the saline group exhibited c-fos expression primarily in laminae I-II and III-IV for both superficial and deep pain groups and lamina X in the deep pain group only (p ≤ .05). Hence, a preemptive regimen results in significant suppression of both superficial and deep components of pain transmission. These findings provide compelling evidence of the analgesic efficacy of preemptive treatment in alleviating pain response associated with uterine surgery.

Medical and genetic correlates of long-term buprenorphine treatment in the electronic health records.

Despite the benefits associated with longer buprenorphine treatment duration (i.e., >180 days) (BTD) for opioid use disorder (OUD), retention remains poor. Research on the impact of co-occurring psychiatric issues on BTD has yielded mixed results. It is also unknown whether the genetic risk in the form of polygenic scores (PGS) for OUD and other comorbid conditions, including problematic alcohol use (PAU) are associated with BTD. We tested the association between somatic and psychiatric comorbidities and long BTD and determined whether PGS for OUD-related conditions was associated with BTD. The study included 6686 individuals with a buprenorphine prescription that lasted for less than 6 months (short-BTD) and 1282 individuals with a buprenorphine prescription that lasted for at least 6 months (long-BTD). Recorded diagnosis of substance addiction and disorders (Odds Ratio (95% CI) = 22.14 (21.88-22.41), P = 2.8 × 10-116), tobacco use disorder (OR (95% CI) = 23.4 (23.13-23.68), P = 4.5 × 10-111), and bipolar disorder (OR(95% CI) = 9.70 (9.48-9.92), P = 1.3 × 10-91), among others, were associated with longer BTD. The PGS of OUD and several OUD co-morbid conditions were associated with any buprenorphine prescription. A higher PGS for OUD (OR per SD increase in PGS (95%CI) = 1.43(1.16-1.77), P = 0.0009), loneliness (OR(95% CI) = 1.39(1.13-1.72), P = 0.002), problematic alcohol use (OR(95%CI) = 1.47(1.19-1.83), P = 0.0004), and externalizing disorders (OR(95%CI) = 1.52(1.23 to 1.89), P = 0.0001) was significantly associated with long-BTD. Associations between BTD and the PGS of depression, chronic pain, nicotine dependence, cannabis use disorder, and bipolar disorder did not survive correction for multiple testing. Longer BTD is associated with diagnoses of psychiatric and somatic conditions in the EHR, as is the genetic score for OUD, loneliness, problematic alcohol use, and externalizing disorders.

Negative Urgency Linked to Craving and Substance Use Among Adults on Buprenorphine or Methadone.

Despite the effectiveness of medication-assisted treatment (MAT), adults receiving MAT experience opioid cravings and engage in non-opioid illicit substance use that increases the risk of relapse and overdose. The current study examines whether negative urgency, defined as the tendency to act impulsively in response to intense negative emotion, is a risk factor for opioid cravings and non-opioid illicit substance use. Fifty-eight adults (predominately White cis-gender females) receiving MAT (with buprenorphine or methadone) were recruited from online substance use forums and asked to complete self-report questionnaires on negative urgency (UPPS-P Impulsive Behavior Scale), past 3-month opioid cravings (ASSIST-Alcohol, Smoking, and Substance Involvement Screening Test), and non-opioid illicit substance use (e.g., amphetamines, cocaine, benzodiazepines). Results revealed that negative urgency was associated with past 3-month opioid cravings, as well as past month illicit stimulant use (not benzodiazepine use). These results may indicate that individuals high in negative urgency would benefit from receiving extra intervention during MAT.

Pain Management in Patients With Opioid Use Disorder on Extended-release Buprenorphine: A Case Report.

ABSTRACT: Persons with opioid use disorder (OUD) are receiving extended-release buprenorphine (ER-buprenorphine) for treatment of OUD. There are no clinical guidelines for management of patients with OUD on ER-buprenorphine experiencing acute or chronic pain. This case report describes 3 patient-involved, multidisciplinary approaches for pain management in various clinical scenarios, including a scheduled knee replacement, emergent surgery for an ischemic limb, and management of chronic pain from metastatic malignancy. These cases illustrate that adequate analgesia for patients who have received ER-buprenorphine is possible, and approaches can be individualized, with shared decision making between providers and patients addressing all barriers to optimize treatment outcomes. Options for acute pain management that can be considered include supplemental sublingual buprenorphine, nonopioid adjuncts, and short courses of full opioid agonists. Potential barriers that impact OUD and acute/chronic pain are provider bias, limited access to palliative care clinicians with addiction medicine training, and payor restrictions to adding sublingual buprenorphine for patients that are on ER-buprenorphine. Additional training for clinicians and other members of the health care team is recommended to improve patient-involved care of persons with OUD experiencing pain.

Effects of live-online, group mindfulness training on opioid use and anxiety during buprenorphine treatment: A comparative effectiveness RCT.

BACKGROUND: Office-based opioid treatment with buprenorphine has emerged as a popular evidence-based treatment for opioid use disorder. Unfortunately, psychosocial stress, anxiety, pain, and co-morbid substance use increase patients' risk for relapse. We designed this study to compare the effects of complementing buprenorphine treatment with 24 weeks of a live-online Mindful Recovery Opioid Care Continuum (M-ROCC) group to a time and attention-matched, live-online Recovery Support Group (RSG) active control condition. METHODS: We plan to enroll a maximum of N = 280 and randomize at least N = 192 patients prescribed buprenorphine through referrals from office-based and telemedicine buprenorphine treatment providers and social media advertisements. Participants will be randomly assigned to M-ROCC or RSG and will be blinded to their treatment condition. The primary outcome for this study will be biochemically confirmed periods of abstinence from illicit opioids, as measured by self-reported use and randomly collected, video-observed oral fluid toxicology testing during the final 12 weeks of study participation. Secondary outcomes include changes in Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety and pain interference scores between baseline and week 24. RESULTS: The trial was funded by the National Institutes of Health, HEAL Initiative through NCCIH (R33AT010125). Data collection is projected to end by September 2023, and we expect publication of results in 2024. CONCLUSION: If the M-ROCC intervention is found to be effective in this format, it will demonstrate that live-online mindfulness groups can improve outcomes and address common co-morbidities like anxiety and pain during buprenorphine treatment.

Quality of life and associated factors of heroin-dependent patients receiving methadone and buprenorphine maintenance treatment.

AIM: Although studies in Western countries have investigated the quality of life (QoL) of heroin users, limited research on this topic has been conducted in Asia. The present study assessed QoL in patients with heroin dependence receiving medications to treat opioid use disorder. METHODS: We performed a cross-sectional study of patients with heroin dependence receiving methadone and buprenorphine treatment. The demographic and substance use variables of patients receiving methadone and buprenorphine were compared. The Chinese Health Questionnaire (CHQ-12), Obsessive Compulsive Drug Use Scale (OCDUS), and World Health Organization Quality of Life Short Form Taiwan version (WHOQOL-BREF-T) were administered to measure patient mental health problems, addiction severity, and QoL, respectively. Multivariate regression was used to identify the factors associated with QoL. RESULTS: A total of 149 patients receiving methadone and 31 receiving buprenorphine completed the questionnaires. Individuals in the buprenorphine group were more likely to be married (p = 0.024) or employed (p = 0.024), have a higher educational level (p = 0.013), have lower drug craving (OCDUS: p = 0.035), or have higher QoL (WHOQOL-BREF-T: p = 0.004) than those in the methadone group. After adjustment for other variables, employment was positively associated with the physical, psychological, and environmental domains of QoL. Receiving buprenorphine treatment (p = 0.032) and longer treatment duration (p = 0.016) were associated with higher psychological QoL. CONCLUSION: Several factors were associated with QoL in patients with heroin dependence. Some measures may improve their QoL, such as reducing employment barriers, improving treatment adherence, or increasing accessibility to buprenorphine treatment.

Effect of transversus abdominis plane block with or without buprenorphine after inguinal hernia surgery on postoperative pain.

INTRODUCTION: Transversus abdominis plane (TAP) has been mentioned as having bene-ficial effects on chronic pain after hernioplasty. This study assessed the effects of TAP block on acute and persistent postoperative pain after inguinal hernia surgery, with or without buprenorphine. MATERIAL AND METHODS: 64 patients were allocated to group R ( n = 32) and received 20 mL of 0.25% ropivacaine for TAP block; group RB ( n = 32) received 20 mL of 0.25% ropivacaine containing 300 µg of buprenorphine for TAP block. The primary outcome was the analgesic and antihyperalgesic effect of buprenorphine. The duration of analgesia, analgesic consumption, postoperative pain scores at rest and sitting up to 48 hours, and the effect on wound hyperalgesia were evaluated. Secondary outcomes included the incidence of side effects and complications. RESULTS: The median (IQR) duration of analgesia in group R was 386.5 (37.25) minutes vs. 868 (41.3) minutes in the RB group. Median pain scores on sitting were found to be significantly better in group RB than in group R at 6, 12, and 24 hours ( P < 0.001). The wound hyperalgesia index showed a significant difference between groups ( P < 0.001). The incidence of persistent postoperative pain was 6.25% in the R group, as compared to 0% in the RB group. Otherwise, the patients did not have any further complications associated with the block. CONCLUSIONS: The results demonstrated that TAP block with buprenorphine reduced acute postoperative pain severity, but we did not find a difference between groups in persistent pain.

Comparing Three Formulations of Buprenorphine in an Incisional Pain Model in Mice.

This study compared the therapeutic effects in mice of 3 different formulations of buprenorphine. These formulations were standard buprenorphine hydrochloride (Bup-HCL) and 2 different extended-release buprenorphine formulations (Bup-ER and Ethiqa-XR [Bup-XR]). Drugs were evaluated based on their ability to attenuate thermal hypersensitivity in a mouse plantar incisional pain model. We hypothesized that Bup-HCL would attenuate postoperative thermal hypersensitivity at 20 min after administration, and that Bup-ER and Bup-XR would attenuate thermal hypersensitivity at 40 min after administration. Male C57BL6/J mice were randomly assigned to 1 of 4 treatment groups: 1) saline, 5 mL/kg SC, once; 2) Bup-HCL, 0.1 mg/kg SC, once; 3) Bup-ER, 1 mg/kg, SC, once; and 4) Bup-XR, 3.25 mg/kg, SC, once. Thermal hypersensitivity was assessed on the day before surgery and again on the day of surgery at 20, 40, 60, 90, and 120 min after drug administration. Thermal hypersensitivity after surgery was not different among the Bup-HCL, Bup-ER and Bup-XR groups at any timepoint. In addition, all buprenorphine treatment groups showed significantly less thermal hypersensitivity after surgery than did the saline group. Subjective observations suggested that mice that received Bup-ER or Bup-XR became hyperactive after drug administration (83 and 75% of mice tested, respectively). Our results indicate that Bup-HCL, Bup-ER, or Bup-XR attenuate thermal hyper- sensitivity related to foot incision by 20 min after administration.

Postpartum Extended-Release Buprenorphine Tissue Necrosis.

BACKGROUND: Extended-release buprenorphine (XRB) may improve medication for opioid use disorder continuation among postpartum individuals. However, obstetric clinicians have relatively little experience with XRB. We describe two cases of XRB-related tissue necrosis in postpartum individuals to highlight recommended injection technique and management strategies for this rare complication. CASES: One patient developed tissue necrosis after her initial injection. Her wound was expectantly managed. Another patient on long-term XRB developed tissue necrosis within 1 day of injection. General surgery excised the depot. Both instances were attributed to injection of XRB intradermally rather than subcutaneously. Both patients continued monthly XRB without recurrence, suggesting that this complication is not an allergy. CONCLUSION: Clinicians should be able to prevent, recognize, and manage tissue necrosis, a rare complication of XRB injection.

A Case of Acute Opioid Withdrawal after Liposuction Surgery in a Patient on Extended-release Buprenorphine.

BACKGROUND: The US Food and Drug Administration approved the once-monthly injectable extended-release buprenorphine product to treat moderate-to-severe opioid use disorders. The patient in our case report had a liposuction procedure and immediately started having opioid withdrawal symptoms after the procedure. CASE DESCRIPTION: The patient is a 27-year-old African-American woman who injects drugs and has morbid obesity. She enrolled in a medications for addiction treatment program and opted to get treated with extended-release buprenorphine monthly injections. She tolerated them well for a span of 6 months. In one clinic visit, she reported opioid withdrawal symptoms and started purchasing and using sublingual buprenorphine from her acquaintances. On review of history, she underwent liposuction surgery and this triggered the opioid withdrawal symptoms. Examining her abdomen revealed surgical scars at the site of the buprenorphine injection and the residual buprenorphine depot was not palpable.A subcutaneous injection of 300-mg extended release buprenorphine was administered in the right periumbilical area in this clinic visit. The following week, she was doing well and denied any withdrawal symptoms. DISCUSSION: This is a unique case of "iatrogenic opioid withdrawal" after a fairly common surgical procedure. The extended-release buprenorphine formulation solidifies when it comes into contact with bodily fluids forming a depot. The depot and surrounding adipose tissue may have been removed during the patient's liposuction procedure, causing an immediate drop in buprenorphine levels leading to acute opioid withdrawal.This case report highlights the precautions that need to be taken before patients go for a surgical procedure like liposuction.

Expert consensus-based guidance on approaches to opioid management in individuals with advanced cancer-related pain and nonmedical stimulant use.

BACKGROUND: Clinicians treating cancer-related pain with opioids regularly encounter nonmedical stimulant use (i.e., methamphetamine, cocaine), yet there is little evidence-based management guidance. The aim of the study is to identify expert consensus on opioid management strategies for an individual with advanced cancer and cancer-related pain with nonmedical stimulant use according to prognosis. METHODS: The authors conducted two modified Delphi panels with palliative care and addiction experts. In Panel A, the patient's prognosis was weeks to months and in Panel B the prognosis was months to years. Experts reviewed, rated, and commented on the case using a 9-point Likert scale from 1 (very inappropriate) to 9 (very appropriate) and explained their responses. The authors applied the three-step analytical approach outlined in the RAND/UCLA to determine consensus and level of clinical appropriateness of management strategies. To better conceptualize the quantitative results, they thematically analyzed and coded participant comments. RESULTS: Consensus was achieved for all management strategies. The 120 Experts were mostly women (47 [62%]), White (94 [78%]), and physicians (115 [96%]). For a patient with cancer-related and nonmedical stimulant use, regardless of prognosis, it was deemed appropriate to continue opioids, increase monitoring, and avoid opioid tapering. Buprenorphine/naloxone transition was inappropriate for a patient with a short prognosis and of uncertain appropriateness for a patient with a longer prognosis. CONCLUSION: Study findings provide urgently needed consensus-based guidance for clinicians managing cancer-related pain in the context of stimulant use and highlight a critical need to develop management strategies to address stimulant use disorder in people with cancer. PLAIN LANGUAGE SUMMARY: Among palliative care and addiction experts, regardless of prognosis, it was deemed appropriate to continue opioids, increase monitoring, and avoid opioid tapering in the context of cancer-related pain and nonmedical stimulant use. Buprenorphine/naloxone transition as a harm reduction measure was inappropriate for a patient with a short prognosis and of uncertain appropriateness for a patient with a longer prognosis.

Inpatient Low-dose Transitions From Full Agonist Opioids Including Methadone Onto Long-acting Depot Buprenorphine: Case Series From a Multicenter Clinical Trial.

OBJECTIVES: Persons with opioid use disorder (OUD) suffer disproportionately from morbidity and mortality related to serious addiction-related infections requiring hospitalization. Long-acting buprenorphine (LAB) is an underused medication for OUD that may facilitate linkage to care and treatment retention when administered before hospital discharge. Transition onto buprenorphine in the inpatient setting is often complicated by pain, active infection management, potential surgical interventions, and risk of opioid withdrawal in transition from full agonists to a partial agonist. METHODS: The COMMIT Trial is a randomized controlled trial evaluating LAB administered by infectious disease physicians and hospitalists compared with treatment as usual for persons with OUD hospitalized with infections. We report a case series of participants on full agonist opioids including methadone who were transitioned to sublingual buprenorphine using low-dose ( microdosing ) strategies followed by LAB injection. RESULTS: Seven participants with current opioid use disorder and life-threatening infections, all with significant concurrent pain and many requiring surgical intervention, underwent low-dose transitions starting at buccal buprenorphine doses ranging from 225 µg to 300 µg 3 times a day on the first day. All were well tolerated with average time to LAB injection of 7.5 days (range, 5-10 days). CONCLUSIONS: Inpatient low-dose buprenorphine transition from full agonist opioids including methadone onto LAB is feasible even in those with complex hospitalizations for concurrent infections and/or surgery. This strategy facilitates dosing of LAB before hospital discharge when risk of opioid relapse and overdose are significant.

Postoperative buprenorphine continuation in stabilized buprenorphine patients: A population cohort study.

BACKGROUND AND AIMS: Sudden discontinuation of buprenorphine in the treatment of opioid use disorder can increase the risk of subsequent relapse and overdose. Little is known about buprenorphine use in the perioperative period. The aim of this study was to determine the rate of buprenorphine continuation after hospital discharge following surgery and factors associated with continuation. DESIGN: A population-based retrospective cohort study was conducted using administrative data from Ontario, Canada, between 2012 and 2018. The cohort included individuals on continuous buprenorphine prior to surgery. Logistic regression modeling was used to estimate the association of buprenorphine continuation with demographic, opioid agonist treatment, surgical and health service use factors. SETTING: Administrative databases from Institute for Clinical Evaluative Sciences (ICES) were used, which capture the Ontario, Canada, population. The data sets describe physician billing, monitoring of controlled substances and hospital discharges. PARTICIPANTS: Adults (≥ 18 years, n = 2176) had received a buprenorphine/naloxone product continuously for at least 60 days for the treatment of opioid use disorder and subsequently underwent a surgical procedure. MEASUREMENTS: Continuation (versus discontinuation) of buprenorphine prescriptions in the 14 days after surgical discharge was recommended. Exposures included demographic, comorbidity, opioid agonist treatment, surgical and health service use characteristics. FINDINGS: About 176 (8.1%) of the 2176 patients discontinued buprenorphine after surgery. Inpatient surgery (versus ambulatory) was associated with reduced odds of continuation, with an unadjusted odds ratio (OR) of 0.17 [95% confidence interval (CI) = 0.12-0.25] and an adjusted OR of 0.16 (95% CI = 0.11-0.23) after accounting for age, sex, rural residence, neighborhood income quintile, Charlson comorbidity index, psychiatric hospitalizations in the past 5 years and recent dispensed supply of buprenorphine (number needed to harm of 6.6). CONCLUSIONS: In Ontario, Canada, from 2012 to 2018, most patients receiving continuous preoperative buprenorphine therapy continued buprenorphine use after surgery. Inpatient surgery was a strong predictor of discontinuation compared with ambulatory procedures.

Trends in smoking during pregnancy stratified by the use of opioid agonist therapy and the contribution of smoking to poor outcome in neonates prenatally exposed to opioid agonist treatment.

High rates of cigarette smoking have been observed in pregnant women on opioid agonist therapy (OAT). However, it is unclear if these rates have changed overtime in line with the general population and the degree to which smoking contributes to poor outcomes in neonates born to women on OAT. Women who gave birth in Western Australia (WA) between 2003 and 2018 were identified from whole-population midwives records. Linked records were used to identify women who had been dispensed OAT during pregnancy and those who had smoking during pregnancy. Temporal changes in smoking during pregnancy were examined for women on OAT (n = 1059) and women not on OAT (n = 397,175) using Joinpoint regression. In women treated with OAT during pregnancy, neonatal outcomes were compared between smoking and non-smoking women using generalised linear models. During the study period, 76.3% of women on OAT smoked during pregnancy compared with 12.0% of the general population. There was a decrease in the prevalence of smoking during pregnancy among women not on OAT (APC: - 5.7, 95%CI: - 6.3, - 5.2), but not in women on OAT (APC: 0.8, 95%CI: - 0.4, 2.1). For women receiving OAT, smoking was associated with an increased odds of low birth weight (OR: 1.57, 95%CI: 1.06, 2.32) and neonatal abstinence syndrome (OR: 1.34, 95%CI: 1.01, 1.78) compared with non-smoking. Despite reductions in the prevalence of smoking during pregnancy in the general population, similar reductions have not occurred in pregnant women on OAT. The high prevalence of smoking in pregnant women on OAT is contributing to poor neonatal outcomes.

Effects of Opioids on Immune and Endocrine Function in Patients with Cancer Pain.

OPINION STATEMENT: Opioids are an important treatment in managing cancer pain. Uncontrolled pain can be detrimental to function and quality of life. Common adverse effects of opioids such as sedation, constipation and nausea are well recognised, but opioid effects on the endocrine and immune systems are less apparent. The evidence for the immunomodulatory effects of opioids suggest that some opioids might be immunosuppressive and that their use might be associated with reduced survival and increased rates of infection in patients with cancer. However, the quality of this evidence is limited. Opioid-induced endocrinopathies, in particular opioid-induced hypogonadism, may also impact cancer survival and impair quality of life. But again, evidence in patients with cancer is limited, especially with regard to their management. There are some data that different opioids influence immune and endocrine function with varying outcomes. For example, some opioids, such as tramadol and buprenorphine, demonstrate immune-sparing qualities when compared to others. However, most of this data is preclinical and without adequate clinical correlation; thus, no opioid can currently be recommended over another in this context. Higher opioid doses might have more effect on immune and endocrine function. Ultimately, it is prudent to use the lowest effective dose to control the cancer pain. Clinical presentations of opioid-induced endocrinopathies should be considered in patients with cancer and assessed for, particularly in long-term opioid users. Hormone replacement therapies may be considered where appropriate with support from endocrinology specialists.

Perioperative Management of Extended-Release Buprenorphine: A Narrative Review and Case Series.

BACKGROUND: Perioperative management of formulations of buprenorphine used for the treatment of opioid use disorder and/or pain are common clinical challenges. Care strategies are increasingly recommending continuation of buprenorphine while administering multimodal analgesia including full agonist opioids. While this "simultaneous strategy" is relatively simple for the shorter-acting sublingual buprenorphine formulation, best practices are needed for the increasingly prescribed extended-release buprenorphine (ER-buprenorphine). To our knowledge there are no prospective data to guide perioperative management of patients on ER-buprenorphine. Herein we provide a narrative review, report on the perioperative experiences of a series of patients maintained on ER-buprenorphine, and propose recommendations for perioperative ER-buprenorphine management based on best evidence, clinical experience, and our judgments. CASES: Here we present clinical data describing the perioperative experiences of patients maintained on extended-release buprenorphine who recently underwent a variety of surgeries ranging from outpatient inguinal hernia repair to multiple inpatient surgeries for source control in sepsis, at different medical centers throughout the United States. These patients were identified via an email solicitation to substance use disorder treatment providers throughout a nationwide healthcare system, requesting cases of patients maintained on extended-release buprenorphine who had recently undergone surgery. We report here on all of the cases received. DISCUSSION: Extrapolating from these and recently published case reports, we describe an approach to perioperative management of extended-release buprenorphine.

"I'm Clean and Sober, But Not Necessarily Free": Perceptions of Buprenorphine Among Patients in Long-Term Treatment.

BACKGROUND: Patients receiving buprenorphine for the treatment of opioid use disorder (OUD) experience a roughly 50% reduction in mortality risk relative to those not receiving medication. Longer periods of treatment are also associated with improved clinical outcomes. Despite this, patients often express desires to discontinue treatment and some view taper as treatment success. Little is known about the beliefs and medication perspectives of patients engaged in long-term buprenorphine treatment that may underlie motivations to discontinue. METHODS: This study was conducted at the VA Portland Health Care System (2019-2020). Qualitative interviews were conducted with participants prescribed buprenorphine for ≥2 years. Coding and analysis were guided by directed qualitative content analysis. RESULTS: Fourteen patients engaged in office-based buprenorphine treatment completed interviews. While patients expressed strong enthusiasm for buprenorphine as a medication, the majority expressed the desire to discontinue, including patients actively tapering. Motivations to discontinue fell into 4 categories. First, patients were troubled by perceived side effects of the medication, including effects on sleep, emotion, and memory. Second, patients expressed unhappiness with being "dependent" on buprenorphine, framed in opposition to personal strength/independence. Third, patients expressed stigmatized beliefs about buprenorphine, describing it as "illicit," and associated with past drug use. Finally, patients expressed fears about buprenorphine unknowns, including potential long-term health effects and interactions with medications required for surgery. CONCLUSIONS: Despite recognizing benefits, many patients engaged in long-term buprenorphine treatment express a desire to discontinue. Findings from this study may help clinicians anticipate patient concerns and can be used to inform shared decision-making conversations regarding buprenorphine treatment duration.

Treatment of Acute Pain in Patients on Naltrexone: A Narrative Review.

PURPOSE OF REVIEW: The tissue damage and trauma associated with surgery almost always result in acute postoperative pain. The intensity of postoperative pain can range from mild to severe. Naltrexone is suitable for patients who do not wish to be on an agonist treatment such as methadone or buprenorphine. However, naltrexone has been shown to complicate postoperative pain management. RECENT FINDINGS: Multiple studies have found that the use of naltrexone can increase the opioid requirement for postoperative pain control. Other modalities exist that can help outside of opioids such as ketamine, lidocaine/bupivacaine, duloxetine, and non-pharmacological management can help manage pain. Multimodal pain regiments should also be employed in patients. In addition to traditional methods for postoperative pain management, other methods of acute pain control exist that can help mitigate opioid dependence and help control pain in patients who use naltrexone for their substance use disorders.

Efficacy and Safety of Buprenorphine in a Single-Shot Peripheral Nerve Block: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The purpose of this study was to evaluate the safety and efficacy of buprenorphine compared with placebo in prolonging the duration of analgesia in single-injection peripheral nerve block. The systematic review and meta-analysis were conducted following the PRISMA statement and Review Manager was used for meta-analysis. Outcomes were calculated using the mean difference (MD) with 95% confidence interval (CI) for continuous data. For dichotomous outcomes, effect sizes were estimated by calculating pooled risk ratio (RR) with 95% CI. Statistical heterogeneity was estimated by the I2 statistic. Compared with placebo, buprenorphine prolonged the duration of analgesia by an average of 8 hours (MD, 8.01; 95% CI, 6.79 to 9.24; P < .00001). The cumulative pain scores within 24 hours (MD, -0.8; 95% CI, -1.21 to -0.40; P < .0001) and the 24-hour opioid consumption (MD, -5.56; 95% CI, -10.60 to -0.52; P = .03) after surgery was lower with buprenorphine group. Conversely, buprenorphine increased the incidence of postoperative nausea and vomiting (PONV) (RR, 1.67; 95% CI, 1.16 to 2.39; P = .006). Buprenorphine is effective in prolonging analgesia, decreasing pain scores and opioid consumption, however, it increases the risk of PONV.