Risk Of Opioid-related Adverse Events Research Articles

Orlando Veterans Affairs stratification tool for opioid risk mitigation (STORM) very high risk interdisciplinary team review: A brief report

BackgroundCompared to the general population, Veterans Health Administration (VHA) patients have higher rates of mental illness, chronic pain, and substance use disorders (SUD), conditions that increase risk for opioid-related adverse events. VHA developed the Stratification Tool for Opioid Risk Mitigation (STORM) and mandated case reviews by an interdisciplinary team (IDT) for patients identified as very high risk, a process implemented and led by clinical pharmacist practitioners at the Orlando Veterans Affairs Healthcare System (OVAHCS) in 2018. ObjectiveTo evaluate and describe the implementation and process for IDT reviews of patients identified as very high risk by the STORM clinical decision support tool at OVAHCS. MethodsA single center, retrospective, observational chart review was conducted. Veterans reviewed by the STORM IDT between January and September 2018 were reviewed for change in Morphine Equivalent Daily Dose (MEDD), naloxone, nonopioid analgesics, medications for SUD, benzodiazepines, engagement with clinical services (e.g., mental health, SUD, and pain clinic), and overdose or suicide attempts in the year prior versus the year after IDT review. The frequency of follow-up IDT reviews was evaluated. ResultsSeventeen patients were identified. Four were excluded due to nonopioid related death within 12 months after review. The average baseline MEDD was 82.2 mg (range 10–496 mg) and average 12 months after review was 7.5 mg (range 0 – 67.5 mg), a decrease of 74.7 mg, or 90.9% reduction. An increase in medications for SUD (3 patients; 23%), SUD engagement (3 to 6 patients), and urine drug tests was observed (79% increase). Benzodiazepine use decreased by 50%. ConclusionThis report provides insight on the IDT case review process at OVAHCS, a process that may vary widely across facilities. A reduction in MEDD, increase in SUD treatment, and improved risk mitigation was observed. The central role of clinical pharmacy and expanded process for continued follow-up warrants further study.

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.

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.

Implementing an intravenous ketamine protocol for acute pain in the medical-surgical setting.

A subanesthetic intravenous ketamine infusion is a safe and effective acute pain management modality for moderate to severely painful surgical procedures and may be useful in patients who are at increased risk for opioid-related adverse events. Despite its safety profile, intravenous ketamine is often restricted to the intensive care unit, which results in decreased patient access to this effective therapy. For clinicians who wish to implement an intravenous ketamine protocol in the medical-surgical setting, there are few resources available. In this brief report, we present our ketamine infusion protocol for acute pain and the clinical and financial outcomes 1 year after implementation. In our experience, ketamine infusions on the medical-surgical ward are safe and cost-effective when an established acute pain service protocol is followed. Nurse practitioners play an essential role in increasing patient access to intravenous ketamine infusions and leading change by collaborating with stakeholders to develop a protocol, training nurses and interdisciplinary team members, and providing ongoing support to nursing staff.

New opioid use and risk of opioid-related adverse events among adults with intellectual and developmental disabilities in Ontario, Canada.

Individuals with intellectual and developmental disability (IDD) can have a high prevalence of pain, which can be managed with prescription opioids. However, the prevalence of substance use disorder is also high in this population, raising concern about opioid-related adverse events. To assess the risk of opioid-related adverse events following opioid initiation among adults with versus without IDD. We conducted a population-based, propensity score matched cohort study on all adults starting prescription opioid therapy in Ontario, Canada, between January 2013 and December 2018. The outcomes of interest were opioid toxicity, new opioid use disorder (OUD) diagnosis and dose escalation (≥90 mg morphine or equivalent) in the year after opioid initiation. We used Cox proportional hazards models to assess the association between IDD diagnosis and each outcome. The hazards of opioid toxicity and OUD were significantly higher in those with IDD compared with those without IDD in unmatched analyses (opioid toxicity hazard ratio 3.19, 95% CI 2.81-5.18; OUD hazard ratio 2.36, 95% CI 2.10-2.65), whereas the hazard of dose escalation was significantly lower (hazard ratio 0.76, 95% CI 0.66-0.88). Findings were no longer significant in propensity score matched models for opioid toxicity and dose escalation, whereas the hazard of OUD diagnosis was attenuated substantially in those with IDD (hazard ratio 0.79, 95% CI 0.68-0.91). IDD diagnosis is not a driver of opioid-related harm. The increased risk we observed is likely driven by various risk factors often present in this population.

Association of injury after prescription opioid initiation with risk for opioid-related adverse events among older Medicare beneficiaries in the United States: A nested case-control study.

BackgroundInjury, prevalent and potentially associated with prescription opioid use among older adults, has been implicated as a warning sign of serious opioid-related adverse events (ORAEs) including opioid misuse, dependence, and poisoning, but this association has not been empirically tested. The study aims to examine the association between incident injury after prescription opioid initiation and subsequent risk of ORAEs and to assess whether the association differs by recency of injury among older patients.Methods and findingsThis nested case-control study was conducted within a cohort of 126,752 individuals aged 65 years or older selected from a 5% sample of Medicare beneficiaries in the United States between 2011 and 2018. Cohort participants were newly prescribed opioid users with chronic noncancer pain who had no injury or ORAEs in the year before opioid initiation, had 30 days or more of observation, and had at least 1 additional opioid prescription dispensed during follow-up. We identified ORAE cases as patients who had an inpatient or outpatient encounter with diagnosis codes for opioid misuse, dependence, or poisoning. During a mean follow-up of 1.8 years, we identified 2,734 patients who were newly diagnosed with ORAEs and 10,936 controls matched on the year of cohort entry date and a disease risk score (DRS), a summary score derived from the probability of an ORAE outcome based on covariates measured prior to cohort entry and in the absence of injury. Multivariate conditional logistic regression was used to estimate ORAE risk associated with any and recency of injury, defined based on the primary diagnosis code of inpatient and outpatient encounters. Among the cases and controls, 68.0% (n = 1,859 for cases and n = 7,436 for controls) were women and the mean (SD) age was 74.5 (6.9) years. Overall, 54.0% (n = 1,475) of cases and 46.0% (n = 1,259) of controls experienced incident injury after opioid initiation. Patients with (versus without) injury after opioid therapy had higher risk of ORAEs after adjustment for time-varying confounders, including diagnosis of tobacco or alcohol use disorder, drug use disorder, chronic pain diagnosis, mental health disorder, pain-related comorbidities, frailty index, emergency department visit, skilled nursing facility stay, anticonvulsant use, and patterns of prescription opioid use (adjusted odds ratio [aOR] = 1.4; 95% confidence interval (CI) 1.2 to 1.5; P < 0.001). Increased risk of ORAEs was associated with current (≤30 days) injury (aOR = 2.8; 95% CI 2.3 to 3.4; P < 0.001), whereas risk of ORAEs was not significantly associated with recent (31 to 90 days; aOR = 0.93; 95% CI 0.73 to 1.17; P = 0.48), past (91 to 180 days; aOR = 1.08; 95% CI 0.88 to 1.33; P = 0.51), and remote (181 to 365 days; aOR = 0.88; 95% CI 0.73 to 1.1; P = 0.18) injury preceding the incident diagnosis of ORAE or matched date. Patients with injury and prescription opioid use versus those with neither in the month before the ORAE or matched date were at greater risk of ORAEs (aOR = 5.0; 95% CI 4.1 to 6.1; P < 0.001). Major limitations are that the study findings can only be generalized to older Medicare fee-for-service beneficiaries and that unknown or unmeasured confounders have the potential to bias the observed association toward or away from the null.ConclusionsIn this study, we observed that incident diagnosis of injury following opioid initiation was associated with subsequent increased risk of ORAEs, and the risk was only significant among patients with injury in the month before the index date. Regular monitoring for injury may help identify older opioid users at high risk for ORAEs.

SA32 Continuity of Opioid Prescribing Among Older Adults on Long-Term Opioids

Previous research shows fragmentation of care among older adults maybe associated with high-risk opioid prescriptions. This project aims to describe the continuity of opioid prescribing and prescriber characteristics among older adults with chronic non-cancer pain (CNCP) who are on long-term opioid therapy (LTOT) and to evaluate the association of continuity of opioid prescribing and prescriber characteristics with the risk of opioid-related adverse events (ORAEs).

Opioid-related overdose and chronic use following an initial prescription of hydrocodone versus oxycodone.

Hydrocodone and oxycodone are prescribed commonly to treat pain. However, differences in risk of opioid-related adverse outcomes after an initial prescription are unknown. This study aims to determine the risk of opioid-related adverse events, defined as either chronic use or opioid overdose, following a first prescription of hydrocodone or oxycodone to opioid naïve patients. A retrospective analysis of multiple linked public health datasets in the state of Oregon. Adult patients ages 18 and older who a) received an initial prescription for oxycodone or hydrocodone between 2015-2017 and b) had no opioid prescriptions or opioid-related hospitalizations or emergency department visits in the year preceding the prescription were followed through the end of 2018. First-year chronic opioid use was defined as ≥6 opioid prescriptions (including index) and average ≤30 days uncovered between prescriptions. Fatal or non-fatal opioid overdose was indicated from insurance claims, hospital discharge data or vital records. After index prescription, 2.8% (n = 14,458) of individuals developed chronic use and 0.3% (n = 1,480) experienced overdose. After adjustment for patient and index prescription characteristics, patients receiving oxycodone had lower odds of developing chronic use relative to patients receiving hydrocodone (adjusted odds ratio = 0.95, 95% confidence interval (CI) 0.91-1.00) but a higher risk of overdose (adjusted hazard ratio (aHR) = 1.65, 95% CI 1.45-1.87). Oxycodone monotherapy appears to greatly increase the hazard of opioid overdose (aHR 2.18, 95% CI 1.86-2.57) compared with hydrocodone with acetaminophen. Oxycodone combined with acetaminophen also shows a significant increase (aHR 1.26, 95% CI 1.06-1.50), but not to the same extent. Among previously opioid-naïve patients, the risk of developing chronic use was slightly higher with hydrocodone, whereas the risk of overdose was higher after oxycodone, in combination with acetaminophen or monotherapy. With a goal of reducing overdose-related deaths, hydrocodone may be the favorable agent.

Budget impact and pharmacy costs with targeted use of oliceridine for postsurgical pain in patients at high risk of opioid-related adverse events

Background Oliceridine, a new class of μ-opioid receptor agonist, may be associated with fewer opioid-related adverse events (ORAEs) due to its unique mechanism of action. Thus, it may provide a cost-effective alternative to conventional opioids such as morphine. Patients and Methods Using a decision tree with a 24-hour time horizon, we calculated costs for medication and management of the three most common AEs (oxygen saturation <90%, vomiting, somnolence) following postoperative oliceridine or morphine in high-risk patients. Costs were enumerated as differences in cost of analgesics and resource utilization in the first 24 hours post-surgery. An economic model compared expected AEs and costs in a blended cohort where elderly/obese patients at higher risk for ORAEs received oliceridine while those presumed to be at lower risk received morphine with a cohort that received morphine alone. Results In high-risk patients, use of oliceridine resulted in overall savings of $363,944 (in 1,000 patients). Implementing a targeted approach of oliceridine utilization in patients with high risk for ORAEs can save a typical hospital system $122,296 in total cost of care. Conclusion Use of oliceridine in postoperative care among patients at high risk provides a favorable health economic benefit compared to the use of morphine.

Opioid-Limiting Pain Control After Transurethral Resection of the Prostate: A Randomized Controlled Trial

ObjectiveTo assess whether a multimodal opioid-limiting protocol and patient education intervention can reduce postoperative opioid use following transurethral resection of the prostate. MethodsThis prospective, non-blinded, single-institution, randomized controlled trial (NCT04102566) assigned 50 patients undergoing a transurethral resection of the prostate to either a standard of care control (SOC) or multimodal experimental group (MMG). The intervention included adding ibuprofen to the postoperative pain regimen, promoting appropriate opioid use while hospitalized, an educational intervention, and discharging without opioid prescription. Data regarding demographics, operative data, opioid use, pain scores, and patient satisfaction were compared. ResultsA total of 47 patients were included, n = 23 (MMG) and n = 24 (SOC). Demographic and operative findings were similar. Statistical analysis for noninferiority demonstrated non-inferior inpatient pain control (mean pain score 2.5 MMG vs 2.4 SOC, P = 0.0003). The multimodal group used significantly fewer morphine milligram equivalents after discharge (0 vs 4.1, P = 0.04). Inpatient use was reduced but did not reach statistical significance (6.0 vs 9.8, P = 0.2). Mean satisfaction scores with pain control were similar (9.6 MMG vs 9.2 SOC, P = 0.32). No opioid prescriptions were requested after discharge. Adverse events and medication side effects were infrequent and largely similar between groups. ConclusionImplementation of an opioid-limiting postoperative pain protocol and patient education resulted in no outpatient opioid use while maintaining patient satisfaction with pain control. Eliminating opioids following a common urologic procedure will decrease risk of opioid-related adverse events and have a positive downstream impact.

Trajectories of prescription opioid dose and risk of opioid-related adverse events among older Medicare beneficiaries in the United States: A nested case-control study.

BackgroundDespite the rising number of older adults with medical encounters for opioid misuse, dependence, and poisoning, little is known about patterns of prescription opioid dose and their association with risk for opioid-related adverse events (ORAEs) in older patients. The study aims to compare trajectories of prescribed opioid doses in 6 months preceding an incident ORAE for cases and a matched control group of older patients with chronic noncancer pain (CNCP).Methods and findingsWe conducted a nested case–control study within a cohort of older (≥65 years) patients diagnosed with CNCP who were new users of prescription opioids, assembled using a 5% national random sample of Medicare beneficiaries from 2011 to 2018. From the cohort with a mean follow-up of 2.3 years, we identified 3,103 incident ORAE cases with ≥1 opioid prescription in 6 months preceding the event, and 3,103 controls matched on sex, age, and time since opioid initiation. Key exposure was trajectories of prescribed opioid morphine milligram equivalent (MME) daily dosage over 6 months before the incident ORAE or matched controls. Among the cases and controls, 2,192 (70.6%) were women, and the mean (SD) age was 77.1 (7.1) years. Four prescribed opioid trajectories before the incident ORAE diagnosis or matched date emerged: gradual dose discontinuation (from ≤3 to 0 daily MME, 1,456 [23.5%]), gradual dose increase (from 0 to >3 daily MME, 1,878 [30.3%]), consistent low dose (between 3 and 5 daily MME, 1,510 [24.3%]), and consistent moderate dose (>20 daily MME, 1,362 [22.0%]). Few older patients (<5%) were prescribed a mean daily dose of ≥90 daily MME during 6 months before diagnosis or matched date. Patients with gradual dose discontinuation versus those with a consistent low dose, moderate dose, and increase dose were more likely to be younger (65 to 74 years), Midwest US residents, and receiving no low-income subsidy. Compared to patients with gradual dose discontinuation, those with gradual dose increase (adjusted odds ratio [aOR] = 3.4; 95% confidence interval (CI) 2.8 to 4.0; P < 0.001), consistent low dose (aOR = 3.8; 95% CI 3.2 to 4.6; P < 0.001), and consistent moderate dose (aOR = 8.5; 95% CI 6.8 to 10.7; P < 0.001) had a higher risk of ORAE, after adjustment for covariates. Our main findings remained robust in the sensitivity analysis using a cohort study with inverse probability of treatment weighting analyses. Major limitations include the limited generalizability of the study findings and lack of information on illicit opioid use, which prevents understanding the clinical dose threshold level that increases the risk of ORAE in older adults.ConclusionsIn this sample of older patients who are Medicare beneficiaries, 4 prescription opioid dose trajectories were identified, with most prescribed doses below 90 daily MME within 6 months before ORAE or matched date. An increased risk for ORAE was observed among older patients with a gradual increase in dose or among those with a consistent low-to-moderate dose of prescribed opioids when compared to patients with opioid dose discontinuation. Whether older patients are susceptible to low opioid doses warrants further investigations.

Total Intravenous Anesthesia Versus Inhalation Anesthesia on Postoperative Analgesia and Nausea and Vomiting After Bariatric Surgery: A Systematic Review and Meta-Analysis.

Anesthesia for patients with morbid obesity can be challenging because of increased risk of opioid-related adverse events, postoperative nausea and vomiting (PONV), and poor pain control. We conducted a systematic review and meta-analysis to compare the safety and efficacy of total intravenous anesthesia (TIVA) with inhalation anesthesia in patients undergoing bariatric surgery. We searched MEDLINE, EMBASE, CENTRAL, and the Clinical Trials Registry database from inception to July 22, 2020. Primary outcomes were postoperative pain and PONV scores. Secondary outcomes included opioid requirements, intraoperative time, complications, and time to recovery. Grading of Recommendations Assessment, Development, and Evaluation framework was used to rate the certainty of evidence. Among 722 studies identified in our search, 7 randomized studies involving a total of 682 patients met the inclusion criteria. Bariatric surgery with TIVA resulted in a lower incidence of nausea (relative risk [RR], 0.54; 95% CI, 0.31-0.94; P = 0.03; moderate certainty) and vomiting (RR, 0.31; 95% CI, 0.13-0.74; P = 0.008; moderate certainty). There was no difference in postoperative pain at 30 minutes, 1 hour, or 24 hours, or in postoperative opioid requirements. Patients undergoing bariatric surgery with TIVA had significantly lower incidence of PONV but no difference in postoperative pain when TIVA was compared to inhalation anesthesia techniques. These benefits should be considered in order to improve the quality of care and enhance recovery for the bariatric population, who are at an increased baseline risk of perioperative complications. Future adequately powered randomized controlled trials are needed to compare the efficacy of the anesthesia regimens in patients undergoing bariatric surgery.

Total Intravenous Anesthesia Versus Inhalation Anesthesia on Postoperative Analgesia and Nausea and Vomiting After Bariatric Surgery: A Systematic Review and Meta-Analysis.

Anesthesia for patients with morbid obesity can be challenging because of increased risk of opioid-related adverse events, postoperative nausea and vomiting (PONV), and poor pain control. We conducted a systematic review and meta-analysis to compare the safety and efficacy of total intravenous anesthesia (TIVA) with inhalation anesthesia in patients undergoing bariatric surgery. We searched MEDLINE, EMBASE, CENTRAL, and the Clinical Trials Registry database from inception to July 22, 2020. Primary outcomes were postoperative pain and PONV scores. Secondary outcomes included opioid requirements, intraoperative time, complications, and time to recovery. Grading of Recommendations Assessment, Development, and Evaluation framework was used to rate the certainty of evidence. Among 722 studies identified in our search, 7 randomized studies involving a total of 682 patients met the inclusion criteria. Bariatric surgery with TIVA resulted in a lower incidence of nausea (relative risk [RR], 0.54; 95% CI, 0.31-0.94; P = 0.03; moderate certainty) and vomiting (RR, 0.31; 95% CI, 0.13-0.74; P = 0.008; moderate certainty). There was no difference in postoperative pain at 30 minutes, 1 hour, or 24 hours, or in postoperative opioid requirements. Patients undergoing bariatric surgery with TIVA had significantly lower incidence of PONV but no difference in postoperative pain when TIVA was compared to inhalation anesthesia techniques. These benefits should be considered in order to improve the quality of care and enhance recovery for the bariatric population, who are at an increased baseline risk of perioperative complications. Future adequately powered randomized controlled trials are needed to compare the efficacy of the anesthesia regimens in patients undergoing bariatric surgery.

Characteristics of Opioid Prescriptions to Veterans With Chronic Gastrointestinal Symptoms and Disorders Dually Enrolled in the Department of Veterans Affairs and Medicare Part D.

Gastrointestinal (GI) symptoms and disorders affect an increasingly large group of veterans. Opioid use may be rising in this population, but this is concerning from a patient safety perspective, given the risk of dependence and lack of evidence supporting opioid use to manage chronic pain. We examined the characteristics of opioid prescriptions and factors associated with chronic opioid use among chronic GI patients dually enrolled in the DVA and Medicare Part D. In this retrospective cohort study, we used linked, national patient-level data (from April 1, 2011, to December 31, 2014) from the VA and Centers for Medicare & Medicaid Services to identify chronic GI patients and observe opioid use. Veterans who had a chronic GI symptom or disorder were dually enrolled in VA and Part D and received ≥1 opioid prescription dispensed through the VA, Part D, or both. Chronic GI symptoms and disorders included chronic abdominal pain, chronic pancreatitis, inflammatory bowel diseases, and functional GI disorders. Key outcome measures were outpatient opioid prescription dispensing overall and chronic opioid use, defined as ≥90 consecutive days of opioid receipt over 12 months. We described patient characteristics and opioid use measures using descriptive statistics. Using multiple logistic regression modeling, we generated adjusted odds ratios and 95% CIs to determine variables independently associated with chronic opioid use. The final model included variables outlined in the literature and our conceptual framework. We identified 141,805 veterans who had a chronic GI symptom or disorder, were dually enrolled in VA and Part D, and received ≥1 opioid prescription dispensed from the VA, Part D, or both. Twenty-six percent received opioids from the VA only, 69% received opioids from Medicare Part D only, and 5% were "dual users," receiving opioids through both VA and Part D. Compared to veterans who received opioids from the VA or Part D only, dual users had a greater likelihood of potentially unsafe opioid use outcomes, including greater number of days on opioids, higher daily doses, and higher odds of chronic use. Chronic GI patients in the VA may be frequent users of opioids and may have a unique set of risk factors for unsafe opioid use. Careful monitoring of opioid use among chronic GI patients may help to begin risk stratifying this group. and develop tailored approaches to minimize chronic use. The findings underscore potential nuances within the opioid epidemic and suggest that components of the VA's Opioid Safety Initiative may need to be adapted around veterans at a higher risk of opioid-related adverse events.

Opioid-related risk perceptions in chronic pain: influence of patient gender and previous misuse behaviors.

Little is known about the factors that influence providers' perceptions of patient risk for aberrant opioid use. Patient gender may interact with previous opioid misuse to influence these perceptions. We asked 131 physicians to view videos and vignettes for 8 virtual patients with chronic pain. Gender (male/female) and previous prescription opioid misuse (present/absent) varied across patients; the vignettes were otherwise balanced on demographic and clinical characteristics. For each patient, providers assessed 4 risk domains: opioid-related adverse events, opioid misuse or abuse, opioid addiction, and opioid diversion. Results indicated a significant gender-by-misuse interaction for risk of opioid misuse orabuse. When previous misuse behaviors were absent, providers rated men at higher risk; there was no gender difference when previous misuse behaviors were present. A significant gender-by-misuse interaction was found for risk of opioid-related adverse events. Providers perceived men to be at higher risk when previous misuse behaviors were absent; there was no gender difference when previous misuse behaviors were present. A significant gender-by-misuse interaction was found for risk of opioid addiction. Providers rated women at higher risk when previous misuse behaviors were present and men at higher risk when previous misuse behaviors were absent. There were significant main effects of gender and misuse for risk of opioid diversion. Providers rated men and those with previous misuse behaviors at higher risk. These results demonstrate that patient gender and previous opioid misuse have unique and interactive effects on provider perceptions of prescription opioid-related risks. Studies are needed to identify the mechanisms underlying these effects, such as gender-based stereotypes about risk-taking and drug abuse.

Do Formulation and Dose of Long-Term Opioid Therapy Contribute to Risk of Adverse Events among Older Adults?

Chronic non-cancer pain (CNCP) is highly prevalent in older adults and long-term opioid therapy (LTOT) has been used to manage chronic pain. However, the safety of LTOT among older adults with CNCP is not well-established and there is a need to identify therapy-related risk factors of opioid-related adverse events among older adults. To evaluate the relationship between opioid dose and formulation and the risk of opioid-related adverse events among Medicare-eligible older adults on LTOT. Nested case-control study. Older Medicare beneficiaries (N=35,189) who received > 3 opioid prescriptions with a total days-supply of >45 days within a 90-day period for CNCP between 2012 and 2016. This study utilized Medicare 5% medical and prescription claims data. Outcome measures included opioid-induced respiratory depression (OIRD), opioid overdose, all-cause mortality, and a composite outcome, defined as the first occurrence of any of the previous three events. Key independent variables were opioid formulation and opioid dose (measured in morphine milligram equivalents (MME)) prescribed during LTOT. Seventy-four OIRD, 133 overdose, 982 all-cause mortality, and 1122 composite outcome events were observed during follow-up. In unadjusted analyses, the use of combination opioids (OR: 4.52 [95%CI: 1.51-13.47]) was significantly associated with OIRD compared to short-acting (SA) opioids. In adjusted analyses, opioid-related adverse events were significantly associated with the use of LA (overdose OR: 13.00 [95%CI: 1.30-130.16] and combination opioids (overdose OR: 6.27 [95%CI: 1.91-20.55]; mortality OR: 2.75 [95%CI: 1.87-4.04]; composite OR: 2.82 [95%CI: 2.01-3.96]) when compared to SA opioids. When compared to an average dose of less than 20 MME, outcomes were significantly associated with doses of 20-50 MME (mortality OR: 1.61 [95%CI: 1.24-2.10]; composite OR: 1.59 [95%CI: 1.26-2.01]) and >50 MME (mortality OR: 1.99 [95%CI: 1.28-3.10]; composite OR: 2.09 [95%CI: 1.43-3.04]). Older adults receiving medically prescribed opioids at higher doses and those using LA and combination of LA and SA opioids are at increased risks for opioid-related adverse events, highlighting the need for close patient supervision.

Gabapentin reduces postoperative pain and opioid consumption in patients who underwent lumbar laminectomy

BackgroundPostoperative pain management solely with opioids elevates the risk of opioid-related adverse events during hospitalization and after discharge from the hospital. Clinical trials have demonstrated gabapentinoids as viable adjunctive treatments for spinal surgeries. However, only a few practice-based studies have examined the efficacy of gabapentin as an opioid-sparing agent for patients undergoing lumbar laminectomy in rural hospital settings. ObjectiveTo determine the effects of gabapentin on opioid consumption and pain perception in patients who underwent lumbar laminectomy at a rural community hospital. MethodsData were collected by retrospective chart reviews of 99 patients who underwent lumbar laminectomy at Yavapai Regional Medical Center from January 1, 2017, to July 1, 2019. The patients were stratified into 2 groups: those who were taking gabapentin as outpatients before surgery and were continued on the same dose postoperatively (n = 50, gabapentin group) and those who were not taking gabapentin preoperatively or postoperatively (n = 49, usual-treatment group). The primary end points were opioid consumption in morphine milligram equivalents (MME) and pain for 24 hours postsurgery. ResultsOutcomes from the mixed-model analysis of variance showed significant main effects of group and time for opioid consumption in MME (F1,97 = 4.3, P < 0.05 and F3,291 = 133.9, P < 0.001, respectively) and numerical pain scale scores (F1,99 = 4.0, P < 0.05 and F3,241 = 21.4, P < 0.001, respectively) and group-time interaction for opioid consumption in MME (F3,291 = 2.6, P = 0.05). Post hoc analyses showed that opioid consumption in MME was significantly lower in the gabapentin group than in the usual-treatment group for the first 6 hours postoperatively. The pain scores were significantly lower in the gabapentin group than in the usual-treatment group across all time periods. ConclusionPatients on gabapentin showed reductions in pain perception and postoperative opioid consumption. The results extend the findings from randomized trials to a real-world clinical setting. These data support using gabapentin in conjunction with opioids for pain management of patients undergoing lumbar laminectomy.

Association of Opioid Consumption Profiles After Hospitalization With Risk of Adverse Health Care Events

Although better pain management has guided policies for opioid use over the past few decades, evidence is limited regarding how patterns of use are associated with the risk of potentially avoidable opioid-related adverse events. To estimate the risk of harms associated with opioid dose and duration of use, and to ascertain whether the risk is modified by treatment indication and age. This ad hoc cohort study followed up patients who were enrolled in a cluster randomized trial of medication reconciliation between October 1, 2014, and November 30, 2016, 12 months after they were discharged from the McGill University Health Centre in Montreal, Quebec, Canada. To be eligible for this study, patients needed to have filled at least 1 opioid prescription 3 months after discharge. Patients with a history of using methadone or buprenorphine were excluded. Data analyses were performed between February 1, 2019, and February 28, 2020. Time-varying measures of opioid use included current use, daily morphine milligram equivalent (MME) dose, cumulative and continuous use duration, and type of ingredients in prescription opioids used. Hospitalization records, dispensed prescriptions records, and postdischarge interviews were used to evaluate adherence to the opioid prescriptions after discharge. Opioid-related emergency department visits, hospital readmissions, or all-cause death. Outcomes were ascertained using provincial medical services claims and hospitalization databases. Of 3486 participants in the cluster randomized trial (mean [SD] age of 69.6 [14.9] years; 2010 men [57.7%]), 1511 patients were included in this ad hoc cohort study. Among those with at least 1 opioid dispensation, 241 patients (15.9%) experienced an opioid-related emergency department visit, hospital readmission, or death. Results from marginal structural Cox proportional hazards regression models showed more than a 2-fold increase in the risk of opioid-related adverse events associated with a cumulative use duration of more than 90 days (adjusted hazard ratio, 2.56; 95% CI, 1.25-5.27) compared with 1 to 30 days. A 3-fold risk increase was found with a mean daily dose higher than 90 MME (adjusted hazard ratio, 3.51; 95% CI, 1.58-7.82) compared with 90 MME or lower. This study found an association between risk of adverse health care events and higher opioid doses and longer treatment duration. This finding can inform policies for limiting opioid duration and dose to attenuate the risk of avoidable morbidity.

Association of Gabapentinoids With the Risk of Opioid-Related Adverse Events in Surgical Patients in the United States

The use of gabapentinoids in multimodal postoperative analgesia is increasing; however, when coadministered with opioids, these drugs may potentiate central nervous system and respiratory depression. To evaluate the association between perioperative coadministration of gabapentinoids and opioids with inpatient opioid-related adverse events in surgical patients. This cohort study used propensity score trimming, stratification, and weighting of adults admitted for a major surgery between October 2007 and December 2017 who were treated with opioids on the day of surgery and included in the Premier Research database. Data analysis was conducted from February to April 2020. Gabapentinoids (gabapentin or pregabalin) coadministered with opioids starting the day of surgery vs opioid therapy without gabapentinoids. Primary outcome was opioid overdose. Secondary outcomes included respiratory complications, unspecified adverse effects of opioid use, and a composite of these 3 outcomes. Patients were followed up for as long as 30 days from the day of surgery until deviation from the initial treatment regimen or discharge. Gabapentinoids with opioids were administered to 892 484 of 5 547 667 eligible admissions (16.1%; mean [SD] age, 63.5 [11.8] years; 353 315 [39.6%] men). Among the 4 655 183 patients who received opioids only, the mean (SD) age was 63.7 (14.7) years, and 1 913 284 (41.1%) were men. Overall, 441 overdose events were identified, with absolute risks of 1.4 per 10 000 patients with gabapentinoid exposure and 0.7 per 10 000 patients receiving opioids only. Following propensity score trimming, the cohort included 737 383 patients exposed to gabapentinoids and 3 002 480 patients receiving opioids only. The primary analysis yielded the adjusted hazard ratio of 1.95 (95% CI, 1.49-2.55), and the number needed to treat for an additional overdose to occur was 16 914 patients (95% CI, 11 556-31 537 patients). Adjusted hazard ratios for secondary outcomes were 1.68 (95% CI, 1.59-1.78) for respiratory complications, 1.77 (95% CI, 1.61-1.93) for unspecified adverse effects of opioids, and 1.70 (95% CI, 1.62-1.79) for the composite outcome. The results were consistent across sensitivity analyses and subgroups identified by key clinical factors. In this real-world cohort study of patients who underwent major surgery, concomitant use of gabapentinoids with opioids was associated with increased risk of opioid overdose and other opioid-related adverse events; however, the absolute risk of adverse events was low.

Online Opioid Stewardship Training for Long-Term Care Staff

Opioids are often the first-line chronic pain management strategy for long-term care (LTC) residents who are also at increased risk for opioid-related adverse events. Therefore, there is a need to train LTC providers and staff about appropriate opioid use and alternative treatment strategies. Our interdisciplinary team worked with LTC partners to identify staff educational needs around opioid stewardship. Based on this need’s assessment, we developed eight modules about opioid use and risks for older adults, including those with dementia, recommendations for de-prescribing including other pharmacological and non-pharmacological alternatives, SBIRT, and motivational interviewing to determine “what matters”. Each 20-minute module contains didactic and video content that is appropriate for group staff training or individuals and provides rural LTC facilities access to needed training in their home communities. Within the first month of launching online, the program received over 1100 hits and LTC partners are incorporating modules into clinical staff training schedules.