Opioid-related Adverse Events Research Articles

Patient-controlled subcutaneous analgesia with hydromorphone versus oral oxycodone for opioid titration of cancer pain: A prospective multicenter randomized trial.

12124 Background: Studies have shown that oral oxycodone sustained-release (SR) tablets can be used for opioid titration. The European Society for Medical Oncology (ESMO) guidelines for adult cancer pain recommend opioid titration through the parenteral route, usually the intravenous or subcutaneous route. Patient-controlled subcutaneous analgesia (PCSA) with hydromorphone needs further evaluation for opioid titration. This prospective multicenter study was designed to compare the efficacy and safety of hydromorphone PCSA with oral oxycodone SR tablets for opioid titration of cancer pain. Methods: Eligible patients with cancer pain were randomly assigned in a 1:1 ratio to the PCSA group or the oxycontin group for dose titration. Different titration methods were given in both groups depending on whether the patient had an opioid tolerance. The primary endpoint of this study was time to successful titration (TST). Results: A total of 256 patients completed this study. The PCSA group had a significantly lower TST compared with the oxycontin group (median [95% confidence interval (CI)], 5.5 [95%CI: 2.5-11.5] hours vs. 16.0 [95%CI: 11.5-22.5] hours; p< 0.001). PCSA reduced the frequency of breakthrough pain (Btp), especially in patients with opioid tolerance. The number of Btp was 121±28 times and 186±31 times in the PCSA and oxycontin groups, respectively ( p< 0.001). The 12-hour numeric rating scale (NRS) score was significantly lower in the PCSA group than that in the oxycontin group (median [95%CI], 2.5 [95%CI: 1.4-2.9] vs. 4.4[95%CI: 3.2-5.8]) ( p< 0.001). Similar equivalent morphine consumption and significantly improved quality of life were observed in the two groups. No between-group difference in the incidence of opioid-related adverse effects was observed. Conclusions: Compared with oral oxycodone SR tablet, the use of PCSA with hydromorphone achieved faster pain relief and a shorter titration duration for patients with cancer pain without increasing adverse events. Clinical trial information: ChiCTR2000037845 .

Exploratory study investigating the efficacy and safety of olanzapine prophylaxis for opioid-induced nausea and vomiting (JORTC-PAL20).

TPS12151 Background: In opioid therapy for cancer pain, it is essential to manage opioid-related adverse effects. Opioid-induced nausea and vomiting (OINV) is common, occurring in 20–40% of patients during initial opioid treatment or after opioid doses are increased. Tolerance to OINV develops within a few days to a week. In patients with cancer, OINV results in decreased quality of life as well as failure to relieve pain due to poor opioid adherence, thus increasing the psychological barriers to opioid use. Therefore, antiemetics are used for OINV prophylaxis, but their efficacy and safety in this context have not yet been fully elucidated. Olanzapine is a promising antiemetic for prophylaxis against nausea and vomiting induced by highly emetogenic chemotherapy, and it is less likely to cause extrapyramidal symptoms than haloperidol and prochlorperazine. We are conducting this exploratory study to evaluate the efficacy and safety of olanzapine prophylaxis against OINV. Methods: This single-arm, single-center exploratory study will evaluate the prophylactic antiemetic efficacy and safety of olanzapine (5 mg PO once a day for 5 days) in patients with cancer pain reserving initial regular opioid therapy. Thirty-five patients will be enrolled. This study was designed to provide preliminary efficacy data, with a primary objective of assessing the proportion of patients who achieved complete control (CC) of OINV during 120 hours of opioid treatment. CC was defined as the absence of emetic episodes, the lack of a need for rescue medication to treat nausea, and minimal or no nausea (3 or less on an 11-point categorical scale). Secondary endpoints include the following: the complete response (CR) rate, defined as the percentage of patients with no emetic episodes and no rescue medication use; the total control (TC) rate, defined as the percentage of patients with no emetic episodes, no rescue medication use, and no nausea during the 120 hours of opioid treatment; the time from opioid initiation to the first emetic episode; the time from opioid initiation to the first administration of a rescue antiemetic; the time to treatment failure, defined as the time from opioid initiation to the first emetic episode or to the administration of a rescue antiemetic; the number of emetic episodes; the levels of nausea, anorexia, sleepiness, pain, and fatigue, all determined using a numerical rating scale (0–10); the impact of antiemetic therapy on daily life severity and patient satisfaction, determined using a 7-grade categorical scale; and adverse events graded by PRO-CTCAE ver.1.0 and CTCAE ver. 5.0. The study is currently open, and 25 patients have been enrolled at time of abstract submission. Clinical trial information: jRCTs031220008 .

Ultrasound-Guided Techniques for Postoperative Analgesia in Patients Undergoing Laparoscopic Sleeve Gastrectomy: Erector Spinae Plane Block vs. Quadratus Lumborum Block

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a common bariatric surgery. Regional anesthetic techniques decrease postoperative pain, narcotic analgesic requirements, and opioid-related adverse effects in patients scheduled for bariatric surgery. OBJECTIVES: The research team conducted this clinical trial to assess the effects of bilateral ultrasound (US)-guided erector spinae plane block (ESPB) on postoperative pain scores and postoperative analgesics consumption compared with bilateral US-guided quadratus lumborum block (QLB) in the first 24 hours following LSG. STUDY DESIGN: A randomized, double-blind, prospective, single-center study. SETTING: Ain-Shams University Hospitals. METHODS: Patients: One hundred twenty morbidly obese patients were scheduled for LSG. Intervention: Were randomly assigned to 3 groups (40 each): bilateral US-guided ESPB, bilateral US-guided QLB, or control (C) group. Measurements: The time to first rescue analgesia (ketorolac) was considered as a primary outcome. The time to perform the block, the duration of anesthesia, the time to first ambulation, the visual analog scale (VAS) at rest, VAS at movement, the total nalbuphine consumption (mg), the total requirements of rescue analgesia (ketorolac) over the first 24 hours after surgery and the study safety profile were considered as secondary outcomes. RESULTS: The time to perform the block and the duration of anesthesia were higher in the QLB group compared to other groups, with significant differences between ESPB and C groups (P < 0.001, P < 0.001, respectively). The ESPB and QLB groups were superior to the C group as regards the time to first rescue analgesia, the total dose of rescue analgesia, and the total nalbuphine consumption (P < 0.001, P < 0.001, P < 0.001, respectively). In the C group, VAS-R and VAS-M readings were higher in the first 18 hours after surgery (P < 0.001, P < 0.001, respectively). In the rest 6 hours of 24 hours after surgery, the QLB group had lower VAS-R and VAS-M readings than the C group (P < 0.001, P < 0.001, respectively). More patients in the C group had higher incidences of nausea and vomiting (P = 0.011, P = 0.002, respectively). In the C group, the time to first ambulation, the length of PACU stay, and the hospital stay were higher in comparison to the ESPB and QLB groups (P < 0.001, P < 0.001, P < 0.001, respectively). More patients in the ESPB and QLB groups were satisfied with postoperative pain management protocol (P < 0.001). LIMITATIONS: The lack of postoperative respiratory assessment (e.g., spirometry) precluded the identification of either ESPB or QLB effects on pulmonary functions in such patients. CONCLUSION: Bilateral ultrasound-guided erector spinae plane block and bilateral ultrasound-guided quadratus lumborum block provided adequate postoperative pain control and reduced postoperative analgesic requirements for morbidly obese patients scheduled for laparoscopic sleeve gastrectomy with priority to bilateral erector spinae plane block. KEY WORDS: Obesity, bariatric surgery, ultrasound, erector spinae plane block, quadratus lumborum block, postoperative, pain, analgesia

Comparison of postoperative analgesic effects of erector spinae plane block and quadratus lumborum block in laparoscopic liver resection: study protocol for a randomized controlled trial

BackgroundCompared with open surgery, laparoscopic liver resection is a minimally invasive surgical technique. However, a number of patients experience moderate-to-severe postoperative pain after laparoscopic liver resection. This study aims to compare the postoperative analgesic effects of erector spinae plane block (ESPB) and quadratus lumborum block (QLB) in patients undergoing laparoscopic liver resection.MethodsOne hundred and fourteen patients undergoing laparoscopic liver resection will be randomly allocated to three groups (control, ESPB, or QLB) in a 1:1:1 ratio. In the control group, participants will receive systemic analgesia consisting of regular NSAIDs and fentanyl-based patient-controlled analgesia (PCA) according to the institutional postoperative analgesia protocol. In the two experimental groups (ESPB or QLB group), the participants will receive preoperative bilateral ESPB or bilateral QLB in addition to systemic analgesia according to the institutional protocol. ESPB will be performed at the 8th thoracic vertebra level with ultrasound guidance before surgery. QLB will be performed in the supine position on the posterior plane of the quadratus lumborum with ultrasound guidance before surgery. The primary outcome is cumulative opioid consumption 24 h after surgery. Secondary outcomes are cumulative opioid consumption, pain severity, opioid-related adverse events, and block-related adverse events at predetermined time points (24, 48, and 72 h after surgery). Differences in plasma ropivacaine concentrations in the ESPB and QLB groups would be investigated, and the quality of postoperative recovery among the groups will be compared.DiscussionThis study will reveal the usefulness of ESPB and QLB in terms of postoperative analgesic efficacy and safety in patients undergoing laparoscopic liver resection. Additionally, the study results will provide information on the analgesic superiority of ESPB versus QLB in the same population.Trial registrationProspectively registered with the Clinical Research Information Service on August 3, 2022; KCT0007599.

Comparison of Different Modeling Approaches for Prescription Opioid Use and Its Association With Adverse Events.

Previous research linking opioid prescribing to adverse drug events has failed to properly account for the time-varying nature of opioid exposure. This study aimed to explore how the risk of opioid-related emergency department visits, readmissions, or deaths (composite outcome) varies with opioid dose and duration, comparing different novel modeling techniques. A prospective cohort of 1,511 hospitalized patients discharged from 2 McGill-affiliated hospitals in Montreal, 2014-2016, was followed from the first postdischarge opioid dispensation until 1 year after discharge. Marginal structural Cox proportional hazards models and their flexible extensions were used to explore the association between time-varying opioid use and the composite outcome. Weighted cumulative exposure models assessed cumulative effects of past use and explored how its impact depends on the recency of exposure. The patient mean age was 69.6 (standard deviation= 14.9) years; 57.7% were male. In marginal structural model analyses, current opioid use was associated with a 71% increase in the hazard of opioid-related adverse events (adjusted hazard ratio = 1.71, 95% confidence interval: 1.21, 2.43). The weighted cumulative exposure results suggested that the risk cumulates over the previous 50 days of opioid consumption. Flexible modeling techniques helped assess how the risk of opioid-related adverse events may be associated with time-varying opioid exposures while accounting for nonlinear relationships and the recency of past use.

A Comprehensive Review on the Efficacy of Nerve Blocks in Reducing Postoperative Anesthetic and Analgesic Requirements.

The purpose of this article review is to investigate whether or not nerve blocks are beneficial in minimizing the amount of postoperative anesthetic and analgesic medication required, hence improving patient outcomes and reducing healthcare costs. This review investigates several different kinds of nerve blocks, their administration techniques, and the anatomical and physiological aspects that influence nerve block effectiveness. It analyzes the impact of nerve blocks on opioid use, postoperative pain scores, and the incidence of opioid-related adverse effects by compiling the findings of numerous large-scale, randomized, controlled trials. Infection, hematoma, nerve injury, and systemic toxicity are some potential complications of nerve blocks discussed in the article. It concludes with recommendations for optimizing nerve block techniques in clinical practice and identifies areas that require further research, such as the development of new anesthetics and the identification of patient subgroups that would benefit the most from nerve blocks. In addition, it provides recommendations for optimizing nerve block techniques in clinical practice.

Sleep behavior traits and associations with opioid-related adverse events: a cohort study.

Opioid-related adverse events (OAEs), including opioid use disorders, overdose, and death, are serious public health concerns. OAEs are often associated with disrupted sleep, but the long-term relationship between poor sleep and subsequent OAE risk remains unknown. This study investigates whether sleep behavior traits are associated with incident OAEs in a large population cohort. 444 039 participants (mean age ± SD 57 ± 8 years) from the UK Biobank reported their sleep behavior traits (sleep duration, daytime sleepiness, insomnia-like complaints, napping, and chronotype) between 2006 and 2010. The frequency/severity of these traits determined a poor sleep behavior impacts score (0-9). Incident OAEs were obtained from hospitalization records during 12-year median follow-up. Cox proportional hazards models examined the association between sleep and OAEs. Short and long sleep duration, frequent daytime sleepiness, insomnia symptoms, and napping, but not chronotype, were associated with increased OAE risk in fully adjusted models. Compared to the minimal poor sleep behavior impacts group (scores of 0-1), the moderate (4-5) and significant (6-9) groups had hazard ratios of 1.47 (95% confidence interval [1.27, 1.71]), p < 0.001, and 2.19 ([1.82, 2.64], p < 0.001), respectively. The latter risk magnitude is greater than the risk associated with preexisting psychiatric illness or sedative-hypnotic medication use. In participants with moderate/significant poor sleep impacts (vs. minimal), subgroup analysis revealed that age <65 years was associated with a higher OAE risk than in those ≥65 years. Certain sleep behavior traits and overall poor sleep impacts are associated with an increased risk for opioid-related adverse events.

Implementation of required sedation assessment in nursing workflow to address naloxone utilization.

Opioid-related adverse drug events continue to occur. This study aimed to characterize the patient population receiving naloxone to inform future intervention efforts. We describe a case series of patients who received naloxone in the hospital during a 16-week time frame in 2016. Data were collected on other administered medications, reason for admission to the hospital, pre-existing diagnoses, comorbidities, and demographics. Twelve hospitals within a large healthcare system. 46,952 patients were admitted during the study period. 31.01 percent (n = 14,558) of patients received opioids, of which 158 received naloxone. Administration of naloxone. Main outcome of interest: Sedation assessment via Pasero Opioid-Induced Sedation Scale (POSS), administration of sedating medications. POSS score was documented prior to opioid administration in 93 (58.9 percent) patients. Less than half of patients had a POSS documented prior to naloxone administration with 36.8 percent documented 4 hours prior. 58.2 percent of patients received multimodal pain therapy with other nonopioid medications. Most patients received more than one sedating medication concurrently (n = 142, 89.9 percent). Our findings highlight areas for intervention to prevent opioid oversedation. Investing in electronic clinical decision support mechanisms, such as sedation assessment, could detect patients at risk for oversedation and ultimately prevent the need for naloxone. Coordinated order sets for pain management can reduce the percentage of patients receiving multiple sedating medications and promote the use of multimodal pain management in efforts to reduce opioid reliance while optimizing pain control.

Nurse Practitioner Perspectives of Setting-Specific Opioid Prescribing Guidelines in Ontario: A Qualitative Study

Aim: To investigate the views of Nurse Practitioners (NPs) regarding the development of setting-specific opioid prescribing guidelines. Background: There has been a rise in opioid-related deaths and adverse events in Canada in recent years. Although NPs make up a significant opioid prescriber group, no Canadian setting-specific guidelines exist to help guide their opioid prescribing. Methods: Purposive sampling was used to select NPs practicing in inpatient settings. One-on-one semi-structured interviews were conducted virtually with 14 NPs (n=14) from Ontario. Directed qualitative content analysis was used to interpret interview data. Findings: The majority of NPs interviewed (n=13, 92.8%) believe that setting-specific opioid prescribing guidelines would benefit their practice. Interview responses illustrated that NPs face several challenges associated with inpatient opioid prescribing. To help mitigate these challenges, they often consult a pharmacist and reference prescribing resources such as Lexicomp and UpToDate. Additionally, several NPs in our study formulated their own setting-specific opioid prescribing resources to help guide their prescribing. Furthermore, NPs who had transitioned to acute care from a primary health care setting experienced a lack of confidence with opioid prescribing in a specialty setting. Conclusion: The development of setting-specific NP opioid prescribing guidelines in Canada can improve the prescribing process for NPs by providing them with clear, evidence-based recommendations, thus reducing ambiguity and promoting positive patient outcomes. Future research should explore the possibility of adapting internationally published setting-specific opioid prescribing guidelines for Canadian practice and the unique opioid prescribing challenges NPs experience when transitioning from primary care to acute care settings.

Exploring incidence and risk factors for persistent postoperative opioid use in adult surgical patients: a systematic review protocol.

The objective of this review is to determine the incidence of persistent postsurgical use of opioids in adult patients and the associated risk factors. Surgery has been identified as an independent risk factor for unwarranted chronic opioid use, contributing to opioid-related harm in the community. Persistent opioid use after surgery is associated with morbidity and mortality from opioid-related adverse events, indicating a significant yet mitigable public health concern. There is substantial variation in the reported incidence and risk factors for postoperative opioid use, which require evaluation for future evidence-based risk-reduction strategies. This review will include studies investigating the persistent use of opioids after 90 postoperative days in adult (≥18y) patients undergoing surgery of any type, including cancer pain patients. Selected evidence must report on opioid use prior to surgery. Analytical and descriptive observational studies, and experimental and quasi-experimental studies, published in the last decade will be eligible for inclusion. The proposed study methods follow the JBI methodology for systematic reviews of prevalence and incidence. A systematic search will be conducted in PubMed, Embase, CINAHL, Cochrane Central, Web of Science, and a search of gray literature will include Google Scholar and ClinicalTrials.gov. Study selection, critical appraisal, and data extraction will be performed by 2 independent reviewers aided by the relevant JBI systematic review tools. We aim to produce a narrative synthesis of results and conduct a meta-analysis where feasible, in addition to subgroup analyses of suitable populations. The results are intended to promote safe, evidence-based postoperative opioid prescribing when considering risk factors for persistent postoperative opioid use.

447 Modulation of Patient Reported Outcomes and Opioid Consumption Following Open Craniotomy: The Efficacy and Safety of Subcutaneous Sumatriptan

INTRODUCTION: Traditional pain management regimens following open craniotomy commonly employ opioid medications. As a medication class, opioids present a considerable adverse effect profile and the potential for medication abuse. Alternative medication regimens to better address post-craniotomy pain while mitigating opioid-related adverse effects are insufficiently studied. However, as a dural-based 5-HT1D receptor agonist that regulates vasoconstriction and inflammatory peptide signaling, sumatriptan shows promise to improve pain scores and reduce opioid requirements. METHODS: This is a single academic center, retrospective cohort study of 130 consecutive adult patients undergoing open craniotomy between 7/2015 and 8/2021. Patients were divided between a Control and Sumatriptan cohort contingent upon administration of a single 6mg subcutaneous injection of sumatriptan within 1-hour of surgery completion and prior to opioid administration. Opioid consumption at 6, 12 and 24-hours postoperative and admission total, inpatient length of stay (LOS) and 30-day global representation/readmission were evaluated. RESULTS: 130 patients were equally divided between the Sumatriptan and Control cohorts for analysis. No difference in baseline demographics was noted. A significant reduction of mean pain score at 6, 12 and 24-hours following surgery substantially favored the Sumatriptan cohort (p &lt; 0.05). Further, a nonsignificant reduction in opioid requirements was observed at all timepoints favoring the sumatriptan cohort (p &gt; 0.05). 30-day global ED evaluation and readmission rates between cohorts were similar (p &gt; 0.05). Overall LOS in the Sumatriptan and Control cohorts were 5.3 ± 3.6 vs 6.5 ± 5.6 days (p &gt; 0.05). No difference in the rate of incisional or intracerebral hemorrhage was noted between cohorts (p &gt; 0.05). CONCLUSIONS: In the present study, patients in the Sumatriptan cohort demonstrated enhanced pain control and reduced opioid requirements suggesting sumatriptan represents a safe and efficacious agent for the modulation of pain following open craniotomy.

Efficacy of Intravenous Ibuprofen and Acetaminophen on Postoperative Pain and Tramadol Consumption in Laparoscopic Cholecystectomy: Prospective, Randomized, Double-blinded Clinical Trial

Background: Many techniques, including multimodal analgesia, have been used to manage postoperative pain after laparoscopic cholecystectomy (LC). Although the number of studies using intravenous ibuprofen (IV) is still limited, ibuprofen has been shown to have a potential role in managing postoperative pain. The primary outcome of this study is to evaluate and compare the impact of IV forms of ibuprofen and acetaminophen on 24-hour postoperative opioid consumption and pain management in patients undergoing LC. The second outcome of the study is to evaluate the impact of ibuprofen and acetaminophen on opioid-related adverse events (ORAE).&#x0D; Materials and Methods: This study was a prospective, randomized, double-blind clinical trial. Following ethical committee approval, 70 patients aged 18 to 65, American Society of Anesthesiology (ASA) score I- II, and those scheduled for LC were enrolled in the study. Patients were randomly divided into two groups. The control group (n=35) received 800 mg IV ibuprofen (group I) in 100 mL saline during surgery, while the acetaminophen group (n=35) received 1000 mg (group A). In the postoperative period, all patients received a patient-controlled analgesia (PCA) device with tramadol. The PCA device was set to a bolus dose of 10 mg and had a lockout time of 15 minutes. A blinded pain nurse assessed postoperative analgesia at 1, 2, 4, 6, 12, and 24 hours using a numerical rating scale (NRS). The incidence of postoperative nausea and vomiting (PONV), total tramadol consumption, and the need for additional analgesics during the 24-hour postoperative period were recorded.&#x0D; Results: Seventy patients who underwent LC participated in this study. The use of analgesic medications was statistically lower in group I than in the other group A. NRS scores between the IV ibuprofen and acetaminophen groups were statistically similar at 1, 2, 4, 6, 12, and 24 hours postoperatively (P&gt;0.05). 24-hour opioid consumption was statistically significantly higher in group A than in group I (P0.05). PONV rates were similar in the ibuprofen and acetaminophen groups (P&gt;0.05). ORAEs were similar between groups.&#x0D; Conclusion: Ibuprofen as part of tramadol-based multimodal analgesia reduced tramadol consumption compared to acetaminophen during the first 24 hours postoperatively following elective LC surgery. The IV ibuprofen-tramadol combination appeared superior to an acetaminophen-tramadol combination. ORAEs were similar in both groups.

Quantifying the impact of reduced opioid use in patients after emergency laparotomy

BackgroundEmergency laparotomies have high rates of morbidity and mortality. The evaluation and management of pain are crucial, as poorly managed pain may contribute to postoperative complications and increase the risk of mortality. This study aims to describe the relationship between opioid use and opioid-related adverse effects and identify what constitutes appropriate dose reductions to elicit clinically relevant benefits. MethodsThis was a retrospective, observational study of patients presenting for emergency laparotomy due to trauma from 2014 to 2018. The primary objective was to define clinical outcomes that may be significantly affected by changes in milligrams of morphine equivalent during the first 72 hours postoperatively; additionally, we sought to quantify the approximate differences in morphine equivalent that correlate with clinically meaningful outcomes such as hospital length of stay, pain scores, and time to first bowel movement. For descriptive summaries, patients were categorized into low, moderate, and high groups based on morphine equivalent requirements of 0 to 25, 25 to 50, and >50, respectively. ResultsA total of 102 (35%), 84 (29%), and 105 (36%) patients were stratified into the low, moderate, and high groups, respectively. Mean pain scores for postoperative days 0 to 3 (P = .034), time to first bowel movement (P = .002), and nasogastric tube duration (P = .003) were the clinical outcomes found to be significantly associated with morphine equivalent. Estimated clinically significant reductions in morphine equivalent for these outcomes ranged from 194 to 464. ConclusionClinical outcomes, such as pain scores, and opioid-related adverse effects, such as time to first bowel movement and nasogastric tube duration, may be linked with the amount of opioids used.

Barriers and facilitators to implementing medications for opioid use disorder and naloxone distribution in Veterans Affairs emergency departments.

Safer opioid prescribing patterns, naloxone distribution, and medications for opioid use disorder (M-OUD) are an important part of decreasing opioid-related adverse events. Veterans are more likely to experience these adverse events compared to the general population. Despite treatment guidelines and ED-based opioid safety programs implemented throughout Veterans Affairs (VA) Medical Centers, many Veterans with OUD do not receive these harm reduction interventions. Prior research in other health care settings has identified barriers to M-OUD initiation and naloxone distribution; however, little is known about how this may be similar or different for health care professionals in VA ED and urgent care centers. We conducted qualitative interviews with VA health care professionals and staff using a semistructured interview guide. We analyzed the data addressing barriers and facilitators to M-OUD treatment in the ED and naloxone distribution using descriptive matrix analysis, followed by team consensus. We interviewed 19 VA staff in various roles. Respondent concerns and considerations regarding the initiation of M-OUD in the ED included M-OUD initiation falling outside of ED's scope of providing acute treatment, lack of VA-approved M-OUD protocols and follow-up procedures, staffing concerns, and educational gaps. Respondents reported that naloxone was important but lacked clarity on who should prescribe it. Some respondents stated that an automated system to prescribe naloxone would be helpful, and others felt that it would not offer needed support and education to patients. Some respondents reported that naloxone would not address opioid misuse, which other respondents felt was a belief due to stigma around substance use and lack of education about treatment options. Our VA-based research highlights similarities of barriers and facilitators, seen in other health care settings, when implementing opioid safety initiatives. Education and training, destigmatizing substance use disorder care, and leveraging technology are important facilitators to increasing access to lifesaving therapies for OUD treatment and harm reduction.

Comparative Study of Opioid Initiation With Tramadol, Short-acting Hydrocodone, or Short-acting Oxycodone on Opioid-related Adverse Outcomes Among Chronic Noncancer Pain Patients.

To compare the safety profiles of low and high-dose tramadol, short-acting hydrocodone, and short-acting oxycodone therapies among chronic noncancer pain individuals. A retrospective cohort study of individuals with back/neck pain/osteoarthritis with an initial opioid prescription for tramadol, hydrocodone, or oxycodone was conducted using IQVIA PharMetrics Plus claims for Academics database (2006 to 2020). Two cohorts were created for separately studying opioid-related adverse events (overdoses, accidents, self-inflicted injuries, and violence-related injuries) and substance use disorders (opioid and nonopioid). Patients were followed from the index date until an outcome event, end of enrollment, or data end. Time-varying exposure groups were constructed and Cox regression models were estimated. A total of 1,062,167 (tramadol [16.5%], hydrocodone [61.1%], and oxycodone [22.4%]) and 986,809 (tramadol [16.5%], hydrocodone [61.3%], and oxycodone [22.2%]) individuals were in the adverse event and substance use disorder cohorts. All high-dose groups had elevated risk of nearly all outcomes, compared with low-dose hydrocodone. Compared with low-dose hydrocodone, low-dose oxycodone was associated with a higher risk of opioid overdose (hazard ratio: 1.79 [1.37 to 2.33]). No difference in risk was observed between low-dose tramadol and low-dose hydrocodone (hazard ratio: 0.85 [0.64 to 1.13]). Low-dose oxycodone had higher risks of an opioid use disorder, and low-dose tramadol had a lower risk of accidents, self-inflicted injuries, and opioid use disorder compared with low-dose hydrocodone. Low-dose oxycodone had a higher risk of opioid-related adverse outcomes compared with low-dose tramadol and hydrocodone. This should be interpreted in conjunction with the benefits of pain control and functioning associated with oxycodone use in future research.

Multitargeted Opioid Ligand Discovery as a Strategy to Retain Analgesia and Reduce Opioid-Related Adverse Effects.

The global "opioid crisis" has placed enormous pressure on the opioid ligand discovery community to produce novel opioid analgesics with superior opioid-related adverse-effect profiles compared with morphine. In this Perspective, the multitargeted opioid ligand strategy for the discovery of opioid analgesics with superior preclinical therapeutic indices relative to morphine is reviewed and discussed. Dual-targeted μ-opioid (MOP)/δ-opioid (DOP) ligands in which the in vitro DOP antagonist potency at least equals that of the MOP agonist activity, and are devoid of DOP or κ-opioid (KOP) agonist activity, are sufficiently promising candidates to warrant further investigation. Dual-targeted MOP/NOP partial agonists have superior preclinical therapeutic indices to morphine and/or fentanyl in nonhuman primates and are also considered promising. Based on the poor preclinical and clinical therapeutic indices of cebranopadol, which is a full agonist at MOP, DOP, and NOP receptors and a partial agonist at the KOP receptor, this pharmacologic template should be avoided.

Adverse outcomes associated with opioid prescription by dentists in the Veterans Health Administration: A national cross-sectional study from 2015 to 2018.

Opioids prescribed by dentists have been associated with serious adverse events, including opioid-related overdose and mortality. However, the downstream outcomes of opioids prescribed by dentists to Veterans who are at high risk for opioid misuse and overdose have yet to be determined. This was a national cross-sectional analysis of opioids associated with dental visits within the Veterans Health Administration from 2015 to 2018. Overprescribing was defined per guidelines as >120 morphine milligram equivalents (MME) or >3 days supply. The association of dental visit and patient characteristics was modeled separately for opioid-related poisoning and all-cause mortality using logistic regression. Of 137,273 Veterans prescribed an opioid by a dentist, 0.1% and 1.1% were associated with opioid-related poisoning and mortality, respectively. There was no difference in opioid poisoning within 6months for Veterans with opioid prescriptions >120 MME (aOR=1.25 [CI: 0.89-1.78]), but poisoning decreased in Veterans prescribed opioids >3-days supply (aOR=0.68 [CI: 0.49-0.96]). However, Veterans with opioids >120 MME were associated with higher odds of mortality within 6months (aOR=1.17 [95% CI: 1.05-1.32]) while there was no difference in prescriptions >3-days supply (aOR=1.12 [CI: 0.99-1.25]). Serious opioid-related adverse events were rare in Veterans and lower than other reports in the literature. Since nonopioid analgesics have superior efficacy for the treatment of acute dental pain, prescribing opioid alternatives may decrease opioid-related poisoning. Strategies for dentists to identify patients at high risk should be incorporated into the dental record.

Strategies to build and maintain competence in pain management: Insights from a SIAARTI survey on educational needs among Italian anesthesiologists.

Fulfilling educational needs in pain management should be a lifelong process, even involving physicians board certified in pain medicine such as the anesthesiologists/pain therapists. The aim of the study was to investigate Italian anesthesiologists' self-perceived competency, confidence, and interest to attend educational programs in relation to their seniority in pain management. SIAARTI members were sent an online questionnaire addressing the following items: education, skills (both soft and hard skills), technical expertise and engaged to participate between December 2020 and January 2021. Participants rated their competence based on the following range (no knowledge, knowledge, competence) while their agreement to attend educational courses was assessed using a 5-point Likert-type scale. Less than one in four participants declare to be dedicated to pain medicine activity with greater proportion among older (over 61 years) compared to younger ones (31-40 years). Regarding cancer and chronic noncancer pain a positive gradient of self-perceived competence has been observed in relation to seniority. In contrast, no gradient of self-perceived competence was reported about musculoskeletal and low back pain. Participants self-perceived competent in both opioid use and prevention of opioid-related adverse event while feeling less competent when managing drugs with abuse potential. The lowest competence has been observed in pediatric pain along with the lowest interest to attend educational courses. Participants were much and very much interested to education regarding cancer, noncancer, musculoskeletal, and low back pain, invasive analgesic procedures but less regarding items for which they declared less competence, such as use of pain scales, pain management in children, and use of drugs with abuse potential. This work provides first evidence of a summative assessment of competency and related educational needs' profile of anesthesiologists/pain therapists thus paving the way for developing a nationwide educational program to improve chronic pain care in Italy.

Opioid sparing effects of intravenous and oral acetaminophen in hip fracture patients: A population-based study

Study objectiveAcetaminophen (APAP) and intravenous acetaminophen (IVAPAP) has been proposed as a part of many opioid-sparing multimodal analgesic pathways. The aim of this analysis was to compare the effectiveness of IVAPAP with oral APAP on opioid utilization and opioid-related adverse effects. DesignRetrospective study of population-based database. PatientsThe Premier Healthcare database was queried patients undergoing surgery for a primary diagnosis of hip fracture from 2011 to 2019 yielding 245,976 patients. Primary exposure was use of IVAPAP or oral APAP on the day of surgery. InterventionsNone. MeasurementsThe primary outcome of interest was opioid utilization over the hospital stay, secondary outcomes included opioid-related adverse effects, length, and costs of hospital stay. Mixed effect models measured the association of IVPAP and APAP and outcomes. Main resultsIn the study population 30.67% (75,445) received at least 1 dose of IVAPAP on the day of surgery. Upon adjusting for relevant covariates, patients who received IVPAP on the day of surgery had slightly higher opioid use standardized by length of hospital stay (2.8% CI: 2%, 3.6%; p < .001), higher hospital cost (2.7% CI: 2.1%, 3.4%), and higher odds of naloxone use (1.18, CI: 1.1, 1.27; p < .001) when compared with patients who received oral APAP. ConclusionsIn this population, IVAPAP use on the day of surgery failed to reduce opioid use or associated opioid related adverse effects when compared with oral APAP. IVAPAP was associated with increased overall costs, opioid requirements, and naloxone use. These results do not support the use of IV over oral APAP routinely for hip fracture surgery patients.

Study protocol for a multisite randomized controlled trial of a peer navigator intervention for emergency department patients with nonfatal opioid overdose

BackgroundPatients presenting to emergency departments (EDs) after a nonfatal opioid-involved overdose are at high risk for future overdose and death. Responding to this risk, the New York City (NYC) Department of Health and Mental Hygiene operates the Relay initiative, which dispatches trained peer “Wellness Advocates” to meet patients in the ED after a suspected opioid-involved overdose and follow them for up to 90 days to provide support, education, referrals to treatment, and other resources using a harm reduction framework. MethodsIn this article, we describe the protocol for a multisite randomized controlled trial of Relay. Study participants are recruited from four NYC EDs and are randomized to receive the Relay intervention or site-directed care (the control arm). Outcomes are assessed through survey questionnaires conducted at 1-, 3-, and 6-months after the baseline visit, as well as through administrative health data. The primary outcome is the number of opioid-related adverse events, including any opioid-involved overdose or any other substance use-related ED visit, in the 12 months post-baseline. Secondary and exploratory outcomes will also be analyzed, as well as hypothesized mediators and moderators of Relay program effectiveness. ConclusionWe present the protocol for a multisite randomized controlled trial of a peer-delivered OD prevention intervention in EDs. We describe how the study was designed to minimize disruption to routine ED operations, and how the study was implemented and adapted during the COVID-19 pandemic. This trial is registered with ClinicalTrials.gov [NCT04317053].