Hooten, W. Michael

ABSTRACT Purpose To explore the opioid decision‐making process of prescribers in primary care, surgery, and subspecialty pain management. Methods This was a multistage qualitative‐qualitative study with clinicians involved in opioid prescribing and management from a single healthcare organization with locations in Minnesota, Florida, Arizona, and Wisconsin. Clinicians in this study included physicians, nurse practitioners (NPs), and physician assistants (PAs) practicing in primary care, surgery, or pain medicine. The interview guide was organized in three domains of a conceptual model for opioid use: (1) prescriber characteristics, (2) patient characteristics, and (3) practice environment characteristics. Individual interviews ( N = 20) were performed first, and data were summarized using a rapid template‐based approach. Subsequently, focus groups (FGs) ( N = 4) were conducted with an additional 21 clinicians to confirm and explore interview results. Data from interviews and FGs were analyzed using a common codebook. Results Findings were organized as decision factors into the three domains. Factors in the prescriber domain included characteristics such as formal pain management training, as well as factors that influenced knowledge and beliefs (e.g., advice from or observation of supervising clinicians and expert colleagues). Decision factors in the patient domain included patient pain etiology, comorbid medical or mental health conditions, and demographic characteristics. Clinicians' perceptions of these factors, such as viewing older age as having lesser risk for opioid misuse, influenced prescribing decisions. Clinicians also described challenges associated with “legacy patients” whose therapy was previously managed by a different clinician. Primary care clinicians, in particular, expressed difficulties managing post‐surgical or trauma‐related pain after care transition. Relevant decision factors reported by prescribers in the practice environment domain included guidelines and practice oversight. Most participants reported practicing in an environment that promoted conservative opioid use and having access to standardized institutional guidelines that reduced perceived decision‐making burden. Clinicians described how they used prescribing guidelines to help them communicate with patients about opioid use and prescribing decisions. Conclusions Intersecting prescriber, patient, and practice environment factors shape opioid analgesic prescribing decisions. Available resources in the practice environment, including peer input and institutional guidelines, may support clinician decision‐making and conversations with patients at the point of care, including in cases where patients have complex histories or personal characteristics that influence decision making.

Abstract Appropriate short-term use of opioids in opioid-naive adults can result in unintended prolonged opioid use (UPOU) which is associated with significant morbidity and mortality. The objective of this prospective case–control study was to identify incident cases of UPOU and to compare their characteristics with patients who did not progress to UPOU. Opioid-naive adults receiving an initial opioid prescription for surgical or nonsurgical indications were recruited at 3 clinical sites. Patients progressing to UPOU (cases) were identified 90 days after the initial prescription and compared with patients who did not progress to UPOU (controls). The status of opioid use was verified using urine drug tests. The cohort included 513 cases and 517 controls. The mean (SD) patient age was 49.6 (15.3) years and 694 (67.4%) were female. In an adjusted logistic regression analysis, several patient characteristics significantly associated with UPOU included ≥2 emergency department evaluations in the past year; prior spine, joint replacement, or cataract surgery; status as a current or former smoker; daily use of over-the-counter pain medications; opioid craving; and greater pain interference. Conversely, characteristics negatively associated with UPOU included postsurgical pain as the indication for the initial opioid prescription, prior pregnancy, greater widespread body pain, and lower levels of general activity. The findings of this study offer novel insights into the behavioral pain responses and patient characteristics associated with UPOU. These results will be used to promote strategies to identify at-risk patients and to deploy interventions targeting the modifiable risk factors for UPOU.

Abstract Objective To evaluate available evidence for the efficacy and safety of topical analgesics for neuropathic pain and to offer treatment guidance. Methods An expert panel searched PubMed (Medline) and reference lists of published articles for available literature assessing 8 categories of topical analgesics used to treat various neuropathic pain conditions. The panel rated the level of analgesic efficacy evidence for each treatment and considered safety, ease of use, and cost. The degree of consensus on the recommendations among the panelists was measured. Results There was strong evidence and high consensus that capsaicin 8% is effective for diabetic peripheral neuropathy and postherpetic neuralgia and that lidocaine is effective for postherpetic neuralgia. There was strong evidence and moderate consensus that capsaicin 8% could be effective for HIV-induced neuropathy. There was moderate evidence and high consensus that lidocaine is likely effective for diabetic peripheral neuropathy, idiopathic neuropathy, and postsurgical neuropathy and that capsaicin 8% might be effective for chemotherapy-induced peripheral neuropathy and complex regional pain syndrome. Evidence was weak for other topical medications, though the panel strongly agreed that antidepressants might help with postherpetic neuralgia, complex regional pain syndrome, postsurgical neuropathy, and post-traumatic neuropathy; that nonsteroidal anti-inflammatory drugs could help with postsurgical neuropathy; and that gabapentin might benefit vulvodynia. There was less agreement about whether antidepressants might benefit diabetic peripheral neuropathy, chemotherapy-induced peripheral neuropathy, and vulvodynia and whether capsaicin 8% could be effective for postsurgical neuropathy. Conclusions Recommendations were based on a survey and grading of existing literature and, when strong evidence was lacking, the collective clinical expertise of panelists.

Abstract Chronic overlapping pain conditions (COPCs) affect a wide population and incur a substantial disease burden including comorbid mental disorders. Although these comorbidities have been extensively documented, the longitudinal trajectories of their onset, particularly for those with three or more conditions, have been rarely studied. We conducted retrospective cohort studies to identify statistically significant COPCs and mental health trajectories in the All of Us Research Program (AoU v8, 338,170 persons) and the Mayo Data Warehouse (3,957,444 individuals). For each trajectory, cases were matched with controls by demographic factors. Logistic regression was then applied to assess the increased likelihood of the final condition given the prior conditions in that sequence. The significant trajectories were visualized as a “pain forest.” More than 88% of trajectories identified from AoU (Male: 78, Female: 361) were reproducible in the Mayo Data Warehouse data (Male: 361, Female: 1286), with female trajectories encompassing more than 96% of the male trajectories. The findings indicate that chronic low back pain generally occurs earlier than other conditions, while fibromyalgia tends to follow other COPCs. Endometriosis seems to be associated with an increased prevalence of COPCs in women. In addition, longer trajectories are associated with a greater risk of developing additional COPC or mental condition. The results offer new insights into the progression of COPCs and associated mental conditions, which may inform healthcare providers and patients in managing and preventing exacerbation of these conditions.

Abstract The availability of knowledge about the effects of buprenorphine on pain perception in healthy adults could help investigators select experimental tests with evidence of responsiveness to buprenorphine in nondiseased states. The purpose of this meta-narrative systematic review is to summarize the effects of buprenorphine on pain perception in healthy adults. Comprehensive database searches were conducted from inception dates through July 16, 2024. Inclusion criteria included all study designs involving healthy adults receiving buprenorphine and tests of pain perception. Risk of bias was assessed using a tool developed for randomized controlled trials (RCTs). A meta-narrative approach was used due to high levels of clinical heterogeneity. A total of 10 RCTs were included, and healthy adults comprised the comparator groups in all trials. Three RCTs had a low risk of bias, 6 had some concerns, and 1 had a high risk of bias. Six RCTs used intravenous buprenorphine, 3 used transdermal, and 1 study used intravenous and sublingual buprenorphine. The effects of buprenorphine on pain perception are influenced by the route of administration, dose, and pain stimulus modality. Considerable differences exist in the effects of intravenous and transdermal buprenorphine, but only 1 study used sublingual buprenorphine, which limited comparison with the other drug formulations. Based on these findings, recommendations for clinical trials are proposed. These recommendations should be cautiously interpreted due to the clinical heterogeneity, but they provide a framework for advancing the use of experimental pain tests in trials of buprenorphine involving comparator groups of healthy adults.

Background The past two decades have seen an increase in cannabis use due to both regulatory changes and an interest in potential therapeutic effects of the substance, yet many aspects of the substance and their health implications remain controversial or unclear. Methods In November 2020, the American Society of Regional Anesthesia and Pain Medicine charged the Cannabis Working Group to develop guidelines for the perioperative use of cannabis. The Perioperative Use of Cannabis and Cannabinoids Guidelines Committee was charged with drafting responses to the nine key questions using a modified Delphi method with the overall goal of producing a document focused on the safe management of surgical patients using cannabinoids. A consensus recommendation required ≥75% agreement. Results Nine questions were selected, with 100% consensus achieved on third-round voting. Topics addressed included perioperative screening, postponement of elective surgery, concomitant use of opioid and cannabis perioperatively, implications for parturients, adjustment in anesthetic and analgesics intraoperatively, postoperative monitoring, cannabis use disorder, and postoperative concerns. Surgical patients using cannabinoids are at potential increased risk for negative perioperative outcomes. Conclusions Specific clinical recommendations for perioperative management of cannabis and cannabinoids were successfully created.

Extracorporeal membrane oxygenation (ECMO) poses unique thrombotic and hemorrhagic risks, and the optimal anticoagulant choice is unknown. We systematically searched Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science Core Collection for randomized-, crossover-, retrospective cohort-, or parallel-designed clinical studies of adult patients receiving ECMO that compared heparin recipients with bivalirudin recipients. Meta-analysis was performed with random-effects models. The ROBINS-I tool was used to assess the risk of bias. Six retrospective observational studies met the inclusion criteria for the qualitative summary. Five studies were suitable for meta-analysis. Those who received heparin were more likely to experience circuit-related thrombosis (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.25–3.37, p = 0.005, I 2 = 0%) and die (OR 1.62, 95% CI 1.19–2.21, p = 0.002, I 2 = 0%) compared with those who received bivalirudin. There were no differences in major bleeding events between heparin and bivalirudin recipients (OR 1.83, 95% CI 0.55–6.09, p = 0.33, I 2 = 82.7%). In retrospective settings compared with heparin anticoagulation, bivalirudin was associated with less circuit-related thrombotic events and greater survival in adults supported on ECMO, without contributing to more bleeding complications. Prospective controlled studies comparing heparin and bivalirudin in adult ECMO patients are warranted to corroborate these findings.

Abstract Background Patients taking chronic opioids are at high risk of opioid induced adrenal insufficiency (OIAI). Previously, we showed that the prevalence of OIAI was 9% based on low morning cortisol, corticotropin (ACTH), and dehydroepiandrosterone sulfate (DHEAS). Data on the overnight metyrapone test to diagnose OIAI are sparse. We aimed to determine the prevalence of OIAI using overnight metyrapone test and identify changes in the steroid metabolome of patients treated with opioids. Methods Cross-sectional study of adult patients treated with opioid therapy of at least 20 morphine milligram equivalents (MME)/day for at least 3 months. Measurements included ACTH, cortisol, and DHEAS. Overnight metyrapone test was administered in all patients, and 24h urine steroid profiling was optional (25 steroids measured by liquid chromatography mass spectrometry1). All patients completed the quality-of-life survey (AddiQoL). Prevalence of OIAI was defined as sum of post-metyrapone 11-deoxycortisol and cortisol of <15 mcg/dL. Result: In 22 patients (median age 59 years [range, 38-74], 9, 41% women), median MME was 33 (20-161) mg, and median cumulative opioid exposure was 245 (10-2550) mg*years. Following the overnight metyrapone test, 7 (32%) patients were diagnosed with OIAI. Patients with OIAI had lower DHEAS concentrations (median of 21 mcg/dL[ 5-113] vs 54 [22-173], p =0. 03), but not cortisol (median 10[5.3-16] mcg/dL vs 13[5.3-22], p=0. 06) or ACTH (median 27[8.1-51] pg/mL vs 26[5.9-55], p=0.8). Patients with OIAI were treated with higher daily MME (100 mg[30-150] vs 30[20-161], p=0. 03) and had a higher cumulative exposure to opioids (median, 660 mg*years [250-2250] vs 150 [10-1288], p =0. 01). AddiQol scores were similar between groups (median of 68[56-84] vs 73[48-83], p= 0.97). Urine steroid profiling was performed in 18 patients. Patients with OIAI demonstrated 4 times lower total urine glucocorticoids (16334 mcg/24h vs 4377 mcg/24h, p=0. 003), all <10% of the reference range, and 3 times lower total urinary androgens (median of 805 mcg/24h vs 2320 mcg/24h, p=0.14). Conclusion Prevalence of OIAI using overnight metyrapone test is high at 32%. Patients diagnosed with OIAI were treated with higher doses of MME/day and had a higher cumulative exposure to opioids when compared to those without OIAI. Applying 24h urine steroid profiling we showed that total glucocorticoids are 4 times lower in those with OIAI (and all <10% of reference ranges) as opposed to those without OIAI. We showed that baseline measurements of ACTH, DHEAS, and cortisol may incorrectly exclude OIAI, and a dynamic test, such as overnight metyrapone test is needed when suspicion for OIAI is high. | 1. Hines JM, Bancos I, Bancos C, et al. High-Resolution, Accurate-Mass (HRAM) Mass Spectrometry Urine Steroid Profiling in the Diagnosis of Adrenal Disorders. Clin Chem. 2017;63(12): 1824-1835. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.