Short-acting opioid prescriptions and Workers' Compensation using the National Ambulatory Medical Care Survey.

BACKGROUND: Short-acting opioids have been utilized for pain management with little known about their use in patients on Workers' Compensation (WC) insurance. Our goal was to investigate this association in the ambulatory care setting. METHODS: Using the National Ambulatory Medical Care Survey, visits from patients aged 18-64 during the years 2010 until 2018 were evaluated (excluding 2017 due to data availability). Demographic and co-morbidity data from each visit was obtained along with the visit year. The first short-acting opioid medication prescribed in the database was considered. Survey-weighted frequencies were evaluated. Logistic regression estimated the crude and adjusted odds ratios (OR) with 95% confidence intervals for the use of short-acting opioid prescription. RESULTS: There were 155,947 included visits with 62.5% for female patients. Most patients were White with 11.7% identifying as Black, and 6% identifying as another race. Over 13% of the sample was of Hispanic descent. WC was the identified insurance type in 1.6% of the sample population. Of these patients, 25.6% were prescribed a short-acting opioid, compared with 10.1% of those with another identified insurance. On multivariable regression, Black patients had increased odds of being prescribed a short-acting opioid compared to white patients (OR: 1.22, 95% CI: 1.11-1.34). Those on WC had 1.7-fold higher odds of being prescribed short-acting opioids (95% CI: 1.46-2.06). CONCLUSION: Certain patient characteristics, including having WC insurance, increased the odds of a short-acting opioid prescription. Further work is needed to identify prescribing patterns in specific high-risk occupational groups, as well as to elicit potential associated health outcomes.

Overdose Risk Associated with Opioid Use upon Hospital Discharge in Veterans Health Administration Surgical Patients.

OBJECTIVE: To determine an association between opioid use upon hospital discharge (ongoing and newly started) in surgical patients and risks of opioid overdose and delirium for the first year. DESIGN: Retrospective, cohort study. SETTING: Population-level study of Veterans Health Administration patients. SUBJECTS: All Veterans Health Administration patients (N = 64,391) who underwent surgery in 2011, discharged after one or more days, and without a diagnosis of opioid overdose or delirium from 90 days before admission through 30 days postdischarge (to account for additional opioid dosing in the context of chronic use). METHODS: Patients' opioid use was categorized as 1) no opioids, 2) tramadol only, 3) short-acting only, 4) long-acting only, 5) short- and long-acting. We calculated unadjusted incidence rates and the incidence rate ratio (IRR) for opioid overdose and drug delirium for two time intervals: postdischarge days 0-30 and days 31-365. We then modeled outcomes of opioid overdose and delirium for postdischarge days 31-365 using a multivariable extended Cox regression model. Sensitivity analysis examined risk factors for overdose for postdischarge days 0-30. RESULTS: Incidence of overdose was 11-fold greater from postdischarge days 0-30 than days 31-365: 26.3 events/person-year (N = 68) vs 2.4 events/person-year (N = 476; IRR = 10.80, 95% confidence interval [CI] = 8.37-13.92). Higher-intensity opioid use was associated with increasing risk of overdose for the year after surgery, with the highest risk for the short- and long-acting group (hazard ratio = 4.84, 95% CI = 3.28-7.14). Delirium (IRR = 10.66, 95% CI = 7.96-14.29) was also associated with higher opioid intensity. CONCLUSIONS: Surgical patients should be treated with the lowest effective intensity of opioids and be monitored to prevent opioid-related adverse events.

Time-to-Cessation of Postoperative Opioids: A Population-Level Analysis of the Veterans Affairs Health Care System.

OBJECTIVE: This study aims to determine 1) the epidemiology of perioperative opioid use; and 2) the association between patterns of preoperative opioid use and time-to-cessation of postoperative opioids. DESIGN: Retrospective, cohort study. SETTING: National, population-level study of Veterans Healthcare Administration (VHA) electronic clinical data. SUBJECTS: All VHA patients (n = 64,391) who underwent surgery in 2011, discharged after stays of ≥1 day, and receiving ≥1 opioid prescription within 90 days of discharge. METHODS: Patients' preoperative opioid use were categorized as 1) no opioids, 2) tramadol only, 3) short-acting (SA) acute/intermittent (≤ 90 days fill), 4) SA chronic (> 90 days fill), or 5) any long-acting (LA). After defining cessation as 90 consecutive, opioid-free days, the authors calculated time-to-opioid-cessation (in days), from day 1 to day 365, after hospital discharge. The authors developed extended Cox regression models with a priori identified predictors. Sensitivity analyses used alternative cessation definitions (30 or 180 consecutive days). RESULTS: Almost 60% of the patients received preoperative opioids: tramadol (7.5%), SA acute/intermittent (24.1%), SA chronic (17.5%), and LA (5.2%). For patients opioid-free preoperatively, median time-to-cessation of opioids postoperatively was 15 days. The SA acute/intermittent cohort (HR =1.96; 95% CI =1.92-2.00) had greater risk for prolonged time-to-cessation than those opioid-free (reference), but lower risk than those taking tramadol only, SA chronic (HR = 9.09; 95% CI = 8.33-9.09), or LA opioids (HR = 9.09; 95% CI = 8.33-10.00). Diagnoses of chronic pain, substance-use, or affective disorders were weaker positive predictors. Sensitivity analyses maintained findings. CONCLUSION: Greater preoperative levels of opioid use were associated with progressively longer time-to-cessation postoperatively.

Effectiveness of Short-Acting Opioid Escalation vs Initiation of a Long-Acting Opioid in Nursing Home Residents.

OBJECTIVES: Modifications to opioid regimens for persistent pain are typically made after an initial period of short-acting opioid (SAO) use. Regimen changes may include an escalation of the SAO dosage or an initiation of a long-acting opioid (LAO) as a switch or add-on therapy. This study evaluates the comparative effectiveness between these alternative regimens in nursing home residents. DESIGN: A retrospective observational cohort analysis of US long-stay nursing home residents. SETTING AND PARTICIPANTS: Nursing home resident data were obtained from the national Minimum Dataset (MDS) version 3.0 and linked Medicare data, 2011-2016. METHODS: Opioid regimen changes were identified using Part D dispensing claims to identify dosage escalation of SAOs, initiation of an LAO, or a switch to an LAO. Outcomes included indices of pain occurrence, frequency, and severity reported on the earliest MDS assessment within 3 months following the opioid regimen change. Resident attributes were described by opioid regimen cohort. Prevalence ratios of pain and depression indices were quantified using doubly robust inverse probability of treatment (IPT)-weighted log-binomial regression. RESULTS: The study cohorts included 2072 SAO dose escalations, 575 LAO add-on initiations, and 247 LAO switch initiations. After IPT weighting, we observed comparable effects on pain and mood across the opioid regimen cohorts. A substantial number of residents continued to report frequent/constant pain (36% in SAO Escalation Cohort, 42% in LAO Add-on Cohort, 42% in the LAO Switch Cohort). The distribution of depressive symptoms was similar regardless of the opioid regimen change. CONCLUSIONS AND IMPLICATIONS: Initiation of an LAO as an add-on to SAO or a switch from SAO had comparable effects on pain and mood to SAO dose escalation without initiation of an LAO. Although fewer residents reported any pain after the regimen change, persistent pain was reported by most residents.

Serious treatment-emergent adverse events in chronic low back pain patients treated with buprenorphine or oral opioids: a retrospective commercial claims analysis.

Aim: Explore the safety of Belbuca® (buprenorphine buccal film), buprenorphine transdermal patches and oral opioids for chronic low back pain (cLBP) treatment. Methods: The retrospective analysis of the MarketScan Commercial database (2018-2021) included treatment-naive cLBP adults. The first date of buprenorphine (Belbuca and transdermal patch) or opioid prescription was index date. Cohorts were defined based on the index medication. Observation included a 6-month pre-index period, while post-index lasted until the end of continuous insurance coverage. There were 44 relevant treatment-emergent adverse events (TEAEs) identified in the literature. Incidence rate ratio (IRR) and incidence rate difference (IRD) were used to compare serious TEAE rates (in 1000 person-years) between cohorts. Propensity-score matching minimized the selection bias. Results: Buprenorphine had lower rates of 15 serious TEAEs than oral opioids (all p ≤ 0.037), while higher rates only for serious dizziness (IRR 2.44, p = 0.011; driven by Belbuca), opioid abuse/dependence (IRR 3.13, p = 0.004; driven by patches) and cholecystitis (IRD 20.25, p = 0.044; an outlier). Additionally, a comparison between Belbuca and oral opioids showed lower rates of 13 serious TEAEs (all p ≤ 0.024) and a higher serious dizziness rate (IRR 3.17, p = 0.024). Although the rates of serious opioid abuse/dependence were similar (24.60 vs 26.93, p = 0.921), all Belbuca patients and none of the opioid patients had a positive history of these events. Belbuca also had lower rates of five serious TEAEs than transdermal patches (all p ≤ 0.018), including a serious opioid abuse/dependence (IRR 0.04, p < 0.001), but higher rates of serious cholecystitis (IRD 52.17, p = 0.035; an outlier) and suicidal ideation (IRD 156.50, p < 0.001; an outlier). Conclusion: Buprenorphine had a better safety profile than oral opioids in cLBP treatment. Belbuca showed a more favorable TEAE profile than buprenorphine transdermal patches and oral opioids.

Short-acting versus long-acting opioids for pediatric postoperative pain management.

INTRODUCTION: Opioids are potent analgesics commonly used to manage children's moderate to severe perioperative pain in children. A wide range of short and long-acting opioids are used to treat surgical pain and will be reviewed in this article. AREAS COVERED: Both short- and long-acting opioids contain unique therapeutic benefits and adverse effects; however, due to the side effect profile and safety concerns, lack of familiarity, and evidence with long-acting opioids to treat surgical pain, shorter-acting opioids have traditionally been used in children. Almost all opioids work by binding to the mu receptor. Methadone, a long-acting opioid, is an exception because it also has beneficial N-methyl-D-aspartate antagonist properties. Clinically methadone's properties could translate to improved analgesic outcomes, reduced risk of adverse events, less risk for acute hyperalgesia, tolerance and abuse potential, faster recovery, and reduced risk for chronic persistent surgical pain. This review article summarizes and compares the evidence of commonly used short and long-acting opioids for perioperative pain control in the pediatric population. EXPERT OPINION: Individualized methadone therapy using pharmacogenomics has the potential to transform opioid use in pain management by improving patient safety and analgesic outcomes, thereby addressing the gaps in current standardized ERAS protocols.

Safety and preliminary outcomes of short-acting opioid agonist treatment (sOAT) for hospitalized patients with opioid use disorder.

BACKGROUND: Patients with opioid use disorder (OUD) frequently leave the hospital as patient directed discharges (PDDs) because of untreated withdrawal and pain. Short-acting opioids can complement methadone, buprenorphine, and non-opioid adjuvants for withdrawal and pain, however little evidence exists for this approach. We described the safety and preliminary outcomes of short-acting opioid agonist treatment (sOAT) for hospitalized patients with OUD at an academic hospital in Philadelphia, PA. METHODS: From August 2021 to March 2022, a pharmacist guided implementation of a pilot sOAT protocol consisting of escalating doses of oxycodone or oral hydromorphone scheduled every four hours, intravenous hydromorphone as needed, and non-opioid adjuvants for withdrawal and pain. All patients were encouraged to start methadone or buprenorphine treatment for OUD. We abstracted data from the electronic health record into a secure platform. The primary outcome was safety: administration of naloxone, over-sedation, or a fall. Secondary outcomes were PDDs and respective length of stay (LOS), discharges on methadone or buprenorphine, and discharges with naloxone. We compared secondary outcomes to hospitalizations in the 12 months prior to the index hospitalization among the same cohort. RESULTS: Of the 23 cases, 13 (56.5%) were female, 19 (82.6%) were 40 years or younger, and 22 (95.7%) identified as White. Twenty-one (91.3%) regularly injected opioids and four (17.3%) were enrolled in methadone or buprenorphine prior to hospitalization. sOAT was administered at median doses of 200-320 morphine milligram equivalents per 24-h period. Naloxone administration was documented once in the operating room, over-sedation was documented once after unsanctioned opioid use, and there were no falls. The PDD rate was 44% with median LOS 5 days (compared to PDD rate 69% with median LOS 3 days for prior admissions), 65% of sOAT cases were discharged on buprenorphine or methadone (compared to 33% for prior admissions), and 65% of sOAT cases were discharged with naloxone (compared to 19% for prior admissions). CONCLUSIONS: Pilot implementation of sOAT was safe. Compared to prior admissions in the same cohort, the PDD rate was lower, LOS for PDDs was longer, and more patients were discharged on buprenorphine or methadone and with naloxone, however efficacy for these secondary outcomes remains to be established.

Health care resource use and cost differences by opioid therapy type among chronic noncancer pain patients.

The study assessed 12-month chronic pain (CP)-related health care utilization and costs among chronic noncancer pain (CNCP) patients who initiated various long-term opioid treatments. Treatments included monotherapy with long-acting opioids (mono-LAOs), mono-therapy with short-acting opioids (mono-SAOs), both LAOs and SAOs (combination), and opioid therapy initiated with SAO or LAO and switched to the other class (switch). Using MarketScan® claims databases (2006-2012), we identified CNCP patients with ≥90 days opioid supply after pain diagnosis and continuous enrollment 12 months before pain diagnosis (baseline period) and 12 months after opioid start (post-index period). Outcomes included CP-related health care utilization and costs. Among CNCP patients (n=21,203), the cohort distribution was 74% mono-SAOs, 22% combination, 2% mono-LAOs, and 2% switch. During follow-up, the average daily morphine equivalent dose was highest in mono-LAO patients (96.4 mg) compared with combination patients (89.8 mg), switch patients (64.3 mg), and mono-SAO patients (36.2 mg). After adjusting for baseline differences, the mono-LAO cohort had lower total CP-related costs ($4,933) compared with the mono-SAO ($8,604), switch ($10,470), and combination ($15,190) cohorts (all: P<0.05). Mono-LAO patients had greater CP-related prescription costs but lower medical costs than the other cohorts during the follow-up period, including lower CP-related hospitalizations (1% vs 11%-20%), emergency department visits (4% vs 11%-18%), and diagnostic radiology use (21% vs 54%-61%) (all: P<0.001). Use of pain-related medications and other treatment modalities was also significantly lower in the mono-LAO cohort relative to the other cohorts. CNCP patients using long-term monotherapy with LAOs had the lowest CP-related total health care costs in the 12 months after opioid initiation compared with mono-SAO, switch, or combination patients despite higher opioid daily doses and higher prescription costs. Future research accounting for severity and duration of pain would aid in determining the optimal long-term opioid regimen for CNCP patients.

Considerations for the use of short-acting opioids in general anesthesia.

Anesthesiologists play a critical role in facilitating a positive perioperative experience and early recovery for patients. Depending on the kind of procedure or surgery, a wide variety of agents and techniques are currently available to anesthesiologists to administer safe and efficacious anesthesia. Notably, the fast-track or ambulatory surgery environment requires the use of agents that enable rapid induction, maintenance, and emergence combined with minimal adverse effects. Short-acting opioids demonstrate a safe and rapid onset/offset of effect; that short effect is both predictable and precise. It also ensures easier titration and reduced or rapidly reversed side effects. Due to their distinct pharmacokinetic and pharmacodynamic properties, and, in one case, rapid extra-hepatic clearance of remifentanil, these agents have several applications in general anesthesia.

A randomized, double-blind, double-dummy comparison of short- and long-acting dihydrocodeine in chronic non-malignant pain.

Guidelines for opioid treatment of chronic non-malignant pain recommend long-acting over short-acting opioid formulations. The evidence for this recommendation is weak. This study is a randomized, double-blind, double-dummy, 8-week comparison of long-acting dihydrocodeine tablets (DHC-Continus) with short-acting dihydrocodeine tablets in 60 patients with chronic non-malignant pain who were referred to a multidisciplinary pain clinic. All patients used codeine-paracetamol tablets before the trial, and paracetamol was added in both groups during the trial. The primary outcome was stability in pain intensity, measured as the difference between the highest and least pain intensity reported on an 11-point numerical rating scale in a 7-day diary. The secondary outcomes were differences in quality of life, quality of sleep, depression, and episodes of breakthrough pain between the 2 formulations. Spontaneously reported adverse events were recorded. In all, 38 patients completed the trial, and 22 withdrew before the end. The reasons for withdrawal were adverse events, lack of efficacy, or both, and were similar between the groups. There were no significant differences in stability of pain intensity between groups. There were no significant differences between groups in quality of sleep, depression, health-related quality of life, or adverse events. Breakthrough pain was experienced in both groups during the trial. Long-acting dihydrocodeine was not observed to be superior for any of the outcomes in this trial. The results of this study do not support current guidelines recommending long-acting opioids.