Daily Opioid Dose Research Articles

The effects of opioid tapering on select endocrine measures in men and women with head and neck cancer-a longitudinal 12-month study.

Opioid treatment may affect endocrine measures in humans either through centrally or peripherally mediated mechanisms. There is a general lack of longitudinal studies examining endocrine measures in opioid-treated patients. To longitudinally follow the levels of select endocrine measures in men and women with head and neck cancer for 1 year, who after having completed radiotherapy began tapering opioids. This was a prospective, longitudinal, observational study. Testosterone and estradiol were measured in men and women, respectively. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS), and prolactin were measured in both sexes. Women were grouped based on if premenopausal or postmenopausal. Samples were collected when opioid tapering started and at 1, 3, 6, and 12 months after tapering start. Daily opioid doses at the same time points were registered. Twenty-five men and 12 women were followed for 12 months. In men, testosterone levels increased significantly during the first month after opioid tapering started (P < 0.001). Levels of testosterone, FSH, DHEAS, and prolactin changed significantly in men during the study period. A moderate correlation between opioid dose reduction and testosterone level increase in men aged ≤60 years was found (r s = -0.577, 95% CI -0.854 to -0.044, P = 0.039). In postmenopausal women (n = 10), levels of FSH and LH changed significantly during the study period. Previously known effects of opioids on endocrine measures in humans seem to be reversible as select endocrine measures changed significantly in men and postmenopausal women after opioid tapering was initiated.

Exceeding the guideline-recommended maximum daily dose of opioids for long-term treatment of non-cancer pain in Germany – a large retrospective observational study

BackgroundHigh-dose long-term opioid therapy (LTOT) has been associated with increased mortality and hospitalizations. Therefore, the evidence-based German guideline on LTOT for chronic non-cancer pain (CNCP) recommends to only exceed the maximum daily dose (MDD) of opioids in exceptional cases. This study aimed to determine the portion of LTOT patients who exceeded the guideline-recommended MDD and identify predictors of exceeding in administrative claims data.MethodsThe retrospective observational analysis of opioid prescriptions in patients receiving LTOT for CNCP was based on administrative claims by a large German statutory health insurance company. Patients with at least two quarters of opioid prescriptions between January 2018 and June 2019 were included and followed up for two years. Predictors were identified by logistic regression. In addition, the number of patients still in opioid therapy and the extent of exceeded MDDs were analyzed over time.ResultsThe sample consisted of 113,475 patients. Overall, 10.5% of the patients exceeded the guideline-recommended MDD averaged over the observation period. Strong predictors for exceeding the MDD were receiving opioid prescriptions from > 7 physicians (OR = 7.66, p < .001), receiving predominantly strong opioids (OR = 6.79, p < .001) and receiving opioids for at least one year prior to inclusion (OR = 5.35, p < .001). Within the non-exceeding group, 28.1% discontinued opioid therapy. In contrast, 9.9% of patients in the exceeding group discontinued opioid therapy, whereas the vast majority remained on treatment until the end of the observation period. Furthermore, a slight increase in prescribed doses was observed over time.ConclusionsThe results indicate that a moderate proportion of patients exceeded the guideline-recommended MDD. However, certain patient groups were more likely to receive high doses. This applied in particular to those who were already on treatment at the time of inclusion and continued to receive opioids until the end of the observation period. Further research should examine whether the continuous opioid therapy among the patients with exceeding the guideline-recommended MDD might be related to specific indications, a lack of therapeutic options or avoidance of withdrawal.Trial registrationGerman Clinical Trials Register (drks.de/search/en). Identifier: DRKS00024854. Registered 28 April 2021.

Is general practitioner involvement in the initiation of opioids for chronic non-cancer pain associated with opioid dose and concurrent drug use?

Objective Is the involvement of the regular general practitioner (GP) in the decision to initiate opioid treatment for chronic non-cancer pain (CNCP) associated with two main risk factors for serious adverse events: increased opioid dose and the concomitant use of prescribed benzodiazepines or benzodiazepine-related medications? Design and setting An anonymous web-based survey was conducted in the county of Rogaland, Norway, during the spring of 2021. Subjects GPs who self-reported applying at least once for reimbursement of opioids prescribed to treat CNCP. They were asked to answer the survey based on the last patient for whom they recalled submitting a reimbursement application. Main outcome measures 1) Total opioid dose in daily oral morphine equivalents (OMEQ). 2) Concurrent use of benzodiazepines and/or benzodiazepine-related drugs. Results The daily opioid dose was lower when the surveyed GPs initiated the opioid treatment (36 OMEQ, n = 25), than when others had initiated the treatment (108 OMEQ, n = 31, p = 0.001). For concurrent use of benzodiazepine or benzodiazepine-related drugs, no significant difference was found (33%, n = 9 with GP involvement vs. 47%, n = 16, p = 0.279 with no GP involvement). Conclusions GP involvement in the initiation of opioid medication for CNCP was associated with a lower opioid dose being prescribed. Implications GP involvement in the initiation of opioid prescriptions may facilitate safer prescribing.

Predictive Model for Opioid Use Disorder in Chronic Pain: A Development and Validation Study.

There are several questionnaires for the challenge of anticipating opioid use disorder (OUD). However, many are not specific for chronic non-cancer pain (CNCP) or have been developed in the American population, whose sociodemographic factors are very different from the Spanish population, leading to scarce translation into clinical practice. Thus, the aim of this study is to prospectively validate a predictive model for OUD in Spanish patients under long-term opioids. An innovative two-stage predictive model was developed from retrospective (n = 129) and non-overlapping prospective (n = 100) cohorts of real-world CNCP outpatients. All subjects used prescribed opioids for 6 or more months. Sociodemographic, clinical and pharmacological covariates were registered. Mu-opioid receptor 1 (OPRM1, A118G, rs1799971) and catechol-O-methyltransferase (COMT, G472A, rs4680) genetic variants plus cytochrome P450 2D6 (CYP2D6) liver enzyme phenotypes were also analyzed. The model performance and diagnostic accuracy were calculated. The two-stage model comprised risk factors related to OUD (younger age, work disability and high daily opioid dose) and provided new useful information about other risk factors (low quality of life, OPRM-G allele and CYP2D6 extreme phenotypes). The validation showed a satisfactory accuracy (70% specificity and 75% sensitivity) for our predictive model with acceptable discrimination and goodness of fit. Our study presents the results of an innovative model for predicting OUD in our setting. After external validation, it could represent a change in the paradigm of opioid treatment, helping clinicians to better identify and manage the risks and reduce the side effects and complications.

Efficacy and feasibility of enhanced recovery after open renal surgery in Cairo University Hospital: a cohort study

Aim This study aimed to assess the efficacy of enhanced recovery after surgery (ERAS) regarding the reduction of length of hospital stay, incidence of complications, and readmission rate in patients undergoing open renal surgery. Settings and design This cohort study was conducted at the theater for urological surgeries at the Cairo University Teaching Hospital. Patients and methods The patients received general anesthesia using the standard center preferences. General anesthesia was supplemented by regional anesthesia in the form of erector spinae plane block (ESPB). Then patients were awakened using the ERAS protocol. Sixty-five adult patients (aged 18–60 years) of both sexes who were scheduled for open renal surgery under general anesthesia were included in the study. Patients with an American Association of Anesthesiologists physical status I or II were eligible. The visual analog scale (VAS) was used to assess the level of pain helping rapid recovery of all patients. Patients received ESPB after general anesthesia. Proper analgesia was assessed and evaluated to help patients with rapid ambulation and recovery. Days of hospital stay and postoperative pain were measured using the VAS score at specific intervals. In addition, the number of daily opioid doses administered, time to ambulation, time of indwelling nephrostomy tube and urethral catheter, and incidence of complications (secondary hemorrhage) were recorded. Results During our ERAS plan supplementing general anesthesia with ESPB in patients scheduled for open renal surgeries, VAS scores were significantly low which did not need extra analgesics in most cases, and the daily doses of nalbuphine required were significantly decreased. Early ambulation has shown a great improvement with a shorter hospital stay and early removal of drains and catheters with a lower incidence of complications. Conclusions ERAS is a multimodal approach to perioperative care that can be applied to any type of surgery, and it has been shown to improve patient recovery, reduce complications, enhance patient satisfaction, and lower hospitalization costs following open renal surgeries.

Intravenous Opioid Administration During Mechanical Ventilation and Use After Hospital Discharge

Guidelines recommend an analgesia-first strategy for sedation during mechanical ventilation, but associations between opioids provided during mechanical ventilation and posthospitalization opioid-related outcomes are unclear. To evaluate associations between an intravenous opioid dose received during mechanical ventilation and postdischarge opioid-related outcomes in medical (nonsurgical) patients. This retrospective cohort study evaluated adults receiving mechanical ventilation lasting 24 hours or more for acute respiratory failure and surviving hospitalization. Participants from 21 Kaiser Permanente Northern California hospitals from January 1, 2012, to December 31, 2019, were included. Data were analyzed from October 1, 2020, to October 31, 2023. Terciles of median daily intravenous fentanyl equivalents during mechanical ventilation. The primary outcome was the first filled opioid prescription in 1 year after discharge. Secondary outcomes included persistent opioid use and opioid-associated complications. Secondary analyses tested for interaction between opioid doses during mechanical ventilation, prior opioid use, and posthospitalization opioid use. Estimates were based on multivariable-adjusted time-to-event analyses, with death as a competing risk, and censored for hospice or palliative care referral, rehospitalization with receipt of opioid, or loss of Kaiser Permanente plan membership. The study included 6746 patients across 21 hospitals (median age, 67 years [IQR, 57-76 years]; 53.0% male). Of the participants, 3114 (46.2%) filled an opioid prescription in the year prior to admission. The median daily fentanyl equivalent during mechanical ventilation was 200 μg (IQR, 40-1000 μg), with terciles of 0 to 67 μg, more than 67 to 700 μg, and more than 700 μg. Compared with patients who did not receive opioids during mechanical ventilation (n = 1013), a higher daily opioid dose was associated with opioid prescriptions in the year after discharge (n = 2942 outcomes; tercile 1: adjusted hazard ratio [AHR], 1.00 [95% CI, 0.85-1.17], tercile 2: AHR, 1.20 [95% CI, 1.03-1.40], and tercile 3: AHR, 1.25 [95% CI, 1.07-1.47]). Higher doses of opioids during mechanical ventilation were also associated with persistent opioid use after hospitalization (n = 1410 outcomes; tercile 3 vs no opioids: odds ratio, 1.44 [95% CI, 1.14-1.83]). No interaction was observed between opioid dose during mechanical ventilation, prior opioid use, and posthospitalization opioid use. In this retrospective cohort study of patients receiving mechanical ventilation, opioids administered during mechanical ventilation were associated with opioid prescriptions following hospital discharge. Additional studies to evaluate risks and benefits of strategies using lower opioid doses are warranted.

Low-dose ketamine infusion to facilitate opioid tapering in chronic non-cancer pain with opioid-use disorder: a historical cohort study

BackgroundLong-term opioid use is associated with pharmacological tolerance, a risk of misuse and hyperalgesia in patients with chronic pain (CP). Tapering is challenging in this context, particularly with comorbid opioid-use...

Age-Related Risk of Serious Fall Events and Opioid Analgesic Use

Opioid analgesics may be associated with increased risk of falls, particularly among older adults. To quantify the age-related risk of serious fall events among adults prescribed opioids by opioid exposure, time from initiation, and daily dose. This population-based cohort study conducted in New South Wales, Australia, used data linking national pharmaceutical claims to national and state datasets, including information on sociodemographic characteristics, clinical characteristics, medicines use, health services utilization, and mortality (POPPY II study). It included adults (18 years or older) who initiated prescription opioid treatment, which was defined as no prior dispensing during the preceding 365 days, between January 1, 2005, and December 31, 2018. Data were analyzed from February to June 2023. Time-dependent periods of opioid exposure were evaluated from dispensing records. Serious fall events identified from emergency department, hospitalization, and mortality records. Negative binomial models were used to assess associations between time-dependent opioid exposure (overall, by time from initiation, and by dose), age, and risk of fall events. Models were adjusted for known fall risk factors, including other fall risk-increasing drugs, frailty risk, and prior serious fall events. The cohort comprised 3 212 369 individuals who initiated prescription opioid treatment (1 702 332 women [53%]; median [IQR] age at initiation, 49 [32-65] years). Overall, 506 573 serious fall events were identified, including 5210 fatal falls. During exposure to opioids, the risk of serious fall events was elevated among all age groups; compared with the group aged 18 to 44 years, this risk was highest among those 85 years or older (adjusted incident rate ratio, 6.35; 95% CI, 6.20-6.51). Across all age groups, the first 28 days following opioid initiation was a time of increased serious fall risk; this risk increased with age. Among individuals aged 18 to 84 years, associations were identified between higher daily opioid doses and serious fall events. The results of this cohort study suggest that prescription opioids were associated with increased risk of serious fall events among adults of all ages, with individuals 85 years or older at greatest risk. These risks should be considered when prescribing opioids, particularly for individuals with preexisting risk factors or when opioids are prescribed at higher doses. Targeted falls prevention efforts may be most effective within the first month following opioid initiation.

Mismatched Postsurgical Opioid Prescription to Liver Transplant Patients: A Retrospective Cohort Study From a Single High-volume Transplant Center.

Improper opioid prescription after surgery is a well-documented iatrogenic contributor to the current opioid epidemic in North America. In fact, opioids are known to be overprescribed to liver transplant patients, and liver transplant patients with high doses or prolonged postsurgical opioid use have higher risks of graft failure and death. This is a retrospective cohort study of 552 opioid-naive patients undergoing liver transplant at an academic center between 2012 and 2019. The primary outcome was the discrepancy between the prescribed discharge opioid daily dose and each patient's own inpatient opioid consumption 24 h before discharge. Variables were analyzed with Wilcoxon and chi-square tests and logistic regression. Opioids were overprescribed in 65.9% of patients, and 54.3% of patients who required no opioids the day before discharge were discharged with opioid prescriptions. In contrast, opioids were underprescribed in 13.4% of patients, among whom 27.0% consumed inpatient opioids but received no discharge opioid prescription. The median prescribed opioid daily dose was 333.3% and 56.3% of the median inpatient opioid daily dose in opioid overprescribed and underprescribed patients, respectively. Importantly, opioid underprescribed patients had higher rates of opioid refill 1 to 30 and 31 to 90 d after discharge, and the rate of opioid underprescription more than doubled from 2016 to 2019. Opioids are both over- and underprescribed to liver transplant patients, and opioid underprescribed patients had higher rates of opioid refill. Therefore, we proposed to prescribe discharge opioid prescriptions based on liver transplant patients' inpatient opioid consumption to provide patient-centered opioid prescriptions.

Effect of a Multidisciplinary Review Panel on Daily Morphine Milligram Equivalents for Patients With Chronic Pain.

Physicians and other health care professionals are challenged regularly to balance managing pain for patients with chronic pain receiving chronic opioid therapy (COT) with following the national guidelines and standards regarding daily morphine milligram equivalents (MME). This quality improvement project aimed to determine the effect of referral to a multidisciplinary review panel on daily MME for patients receiving COT for chronic pain. This quality improvement project included patients who had an established relationship with a primary care or community internal medicine clinician at a large health care organization and were referred to a newly created multidisciplinary review panel for their recommendations regarding treatment of pain. Criteria for patient referral were diagnosis of a chronic, painful condition, and use of chronic opioid medications. These patients were selected and referred at the discretion of their primary care clinician from January 2, 2019, through December 31, 2020. Data for this project were collected at the time of initial referral to the panel and 6 months after recommendations. The daily MME were assessed at the 2 time points. Thirteen patients were referred to the review panel during the project period. The median daily MME at the time of referral was 180. Daily MME decreased by a median of 14 MME after 6 months. The MME did not increase during the project period for any participants. Referral of patients receiving COT to a multidisciplinary review panel may reduce their daily opioid dose.

Evaluation of Patient's Quality of Life before and after Implantation of Abbott's Proclaim™ XR Spinal Cord Stimulator with BurstDR™ Stimulation in Chronic Pain Syndrome.

Background and Objectives: In case of the ineffectiveness of pharmacological and non-pharmacological treatments in managing chronic neuropathic pain, spinal cord stimulation (SCS) with BurstDR™ stimulation may reduce pain and increase the quality of life. The term "burst" refers to a series of stimulation impulses that are compressed into small packets and separated by intervals of latency. Materials and Methods: A group of 30 consecutive patients who received the BurstDR™ stimulator using the minimally invasive percutaneous method was selected. Patients selected for our study underwent numerous spinal surgeries before SCS implantation. In the study, analgesics and co-analgesics and their doses used by patients before and 6 months after SCS implantation were examined and compared. Using the visual analogue scale (VAS), pain was compared before and after the procedure. Patients` quality of life was assessed using the Oswestry Disability Index (ODI). Results: We observed a significant reduction in opioid daily doses by an average of 32.4% (±36.1%) and a reduction in paracetamol daily doses by an average of 40% (±33.4%). There was a reduction in pregabalin doses as well. Ketoprofen daily dose reduction was 85.4 mg. The mean VAS difference before and after procedure was 3.9 (±2.3), and the mean difference in ODI was 12.9 (±9), which benefits operative treatment. The VAS and ODI results were statistically significant as well. Conclusions: According to our research, BurstDR™ stimulation improves the quality of life by reducing doses of analgesics and the level of pain.

Relationship Between Pain and Delirium in Critically Ill Adults.

Although opioids are frequently used to treat pain, and are an important risk for ICU delirium, the association between ICU pain itself and delirium remains unclear. We sought to evaluate the relationship between ICU pain and delirium. Prospective cohort study. A 32-bed academic medical-surgical ICU. Critically ill adults (n = 4,064) admitted greater than or equal to 24 hours without a condition hampering delirium assessment. None. Daily mental status was classified as arousable without delirium, delirium, or unarousable. Pain was assessed six times daily in arousable patients using a 0-10 Numeric Rating Scale (NRS) or the Critical Care Pain Observation Tool (CPOT); daily peak pain score was categorized as no (NRS = 0/CPOT = 0), mild (NRS = 1-3/CPOT = 1-2), moderate (NRS = 4-6/CPOT = 3-4), or severe (NRS = 7-10/CPOT = 5-8) pain. To address missingness, a Multiple Imputation by Chained Equations approach that used available daily pain severity and 19 pain predictors was used to generate 25 complete datasets. Using a first-order Markov model with a multinomial logistic regression analysis, that controlled for 11 baseline/daily delirium risk factors and considered the competing risks of unarousability and ICU discharge/death, the association between peak daily pain and next-day delirium in each complete dataset was evaluated. Among 14,013 ICU days (contributed by 4,064 adults), delirium occurred on 2,749 (19.6%). After pain severity imputation on 1,818 ICU days, mild, moderate, and severe pain were detected on 2,712 (34.1%), 1,682 (21.1%), and 894 (11.2%) of the no-delirium days, respectively, and 992 (36.1%), 513 (18.6%), and 27 (10.1%) of delirium days (p = 0.01). The presence of any pain (mild, moderate, or severe) was not associated with a transition from awake without delirium to delirium (aOR 0.96; 95% CI, 0.76-1.21). This association was similar when days with only mild, moderate, or severe pain were considered. All results were stable after controlling for daily opioid dose. After controlling for multiple delirium risk factors, including daily opioid use, pain may not be a risk factor for delirium in the ICU. Future prospective research is required.

Opioid dose risk, clinician and patient characteristics, and adherence to opioid prescribing recommendations in chronic non-cancer pain.

This study aims to assess associations between morphine-equivalent daily dose (MEDD) of opioids, clinician and patient characteristics, and prescriber adherence to guidelines for long-term opioid therapy (LTOT) in chronic noncancer pain (CNCP) and to elucidate potential relationships associated with increased-risk opioid prescribing. Retrospective cross-sectional study. Academic health system's 33 primary care clinics. Adults (≥18 years old) prescribed LTOT (10 + outpatient prescriptions in the past year) for CNCP. Electronic health record data on prescribed opioids (for MEDD), clinician/patient characteristics, and adherence rates to LTOT guideline-concordant recommendations. A total of 2,738 patients were eligible, 61.6 percent Lower, 15.7 percent Moderate, and 22.7 percent Higher Risk MEDD (<50, 50-89, and ≥90 mg/day, respectively). Higher MEDD correlated (p < 0.001) with Medicare insurance, current cigarette smoking, higher pain intensity and interference scores, and the presence of opioid use disorder diagnoses. Male clinicians more frequently prescribed (p < 0.001) and male patients were more likely to be prescribed (p < 0.001) higher MEDD compared to their female counterparts. Higher Risk MEDD was associated with higher coprescribed benzodiazepines (p = 0.015), lower depression screening (p = 0.048), urine drug testing (p = 0.003), comparable active treatment agreement (p = 0.189), opioid misuse risk screening (p = 0.619), and prescription drug monitoring checks (p = 0.203). This study documented that higher MEDD was associated with risks of worse health outcomes without improved adherence to opioid prescribing guideline recommendations. Enhanced clinician awareness of factors associated with MEDD has the potential to mitigate LTOT risks and improve overall patient care.

As-needed opioid dosing for emergency patients with a daily use of opioids.

Patients with a daily use of opioids have a higher risk of insufficient pain treatment during hospitalization than other patients. This study aimed to examine whether as-needed opioid doses (PRN) were adequately adjusted when patients were admitted to the emergency department (ED) with pain. Patients, with a daily use of opioids, who received PRN opioid within the first 3 h after admission at the ED at Aarhus University Hospital, Denmark, were prospectively included from February 2021 to June 2021. The primary outcome was the proportion of patients receiving an inadequate initial dose of PRN opioid, here defined as <15% of daily dose of opioids (DDO) based on sparse evidence, but aligning with the prevailing clinical practice. Secondary outcomes included risk of an inadequate PRN dose in relation to DDO (patients were dichotomized into two groups (DDO <60 or ≥60 mg/day). Among 252 patients admitted to the ED with a daily use of opioids, 149 were admitted with pain and 82 received a PRN opioid dose within 3 h. Twenty-seven out of 82 (33%) patients received a PRN dose of <15% of DDO (95% CI: 23.7-43). When dichotomised; 10 out of 50 (20%) patients with a DDO <60 mg/day (95% CI: 10.0-33.7) versus 17 out of 32 (53.1%) patients with a DDO ≥60 mg/day (95% CI: 34.7-70.9) received an inadequate PRN dose (relative risk, RR: 2.65 [95% CI: 1.4-5.1]). Patients with daily use of opioids presenting in the ED with acute pain had a high risk of inadequate PRN opioid dose, especially if the DDO was high. Awareness about and education focusing on sufficient PRN doses for patients with a daily use of opioids is (still) called for.

Trajectories of opioid consumption as predictors of patient-reported outcomes among individuals attending multidisciplinary pain treatment clinics.

This study aimed to identify opioid consumption trajectories among persons living with chronic pain (CP) and put them in relation to patient-reported outcomes 6 months after initiating multidisciplinary pain treatment. This study used data from the Quebec Pain Registry (2008-2014) linked to longitudinal Quebec health insurance databases. We included adults diagnosed with CP and covered by the Quebec public prescription drug insurance plan. The daily cumulative opioid doses in the first 6 months after initiating multidisciplinary pain treatment were transformed into morphine milligram equivalents. An individual-centered approach involving principal factor and cluster analyses applied to longitudinal statistical indicators of opioid use was conducted to classify trajectories. Multivariate regression models were applied to evaluate the associations between trajectory group membership and outcomes at 6-month follow-up (pain intensity, pain interference, depression, and physical and mental health-related quality of life). We identified three trajectories of opioid consumption: "no or very low and stable" opioid consumption (n = 2067, 96.3%), "increasing" opioid consumption (n = 40, 1.9%), and "decreasing" opioid consumption (n = 39, 1.8%). Patients in the "no or very low and stable" trajectory were less likely to be current smokers, experience polypharmacy, use opioids or benzodiazepine preceding their first visit, or experience pain interference at treatment initiation. Patients in the "increasing" opioid consumption group had significantly greater depression scores at 6-month compared to patients in the "no or very low and stable" trajectory group. Opioid consumption trajectories do not seem to be important determinants of most PROs 6 months after initiating multidisciplinary pain treatment.

Risk Factors for Self-Harm Ideation Among Persons Treated With Opioids for Chronic Low Back Pain.

Chronic pain is a significant health concern that adversely affects all aspects of life, including emotional well-being. Opioids are prescribed for the management of refractory, severe chronic pain, although they have been associated with adverse effects, including addiction and overdose. The aim of this study was to examine factors that predict thoughts of self-harm among adults with chronic pain who are prescribed opioids. Seven hundred sixty-five (N=765) persons with opioid-treated chronic lower back pain completed the Current Opioid Misuse Measure (COMM) and other validated questionnaires as part of a larger study. Response to 1 question from the COMM ("How often have you seriously thought about hurting yourself?") was used to assess suicide risk on a 5-point scale (0=never; 4=very often). Participants were categorized into 3 groups according to their responses to the self-harm question: never (N=628; 82.1%), seldom or sometimes (N=74; 9.7%), and often or very often (N=63; 8.2%). Multivariate adjusted odds ratio (aOR) analyses indicated that reports of alcohol or drug overuse within the past month (aOR=1.41,[95% CI 1.11-1.78]), posttraumatic stress (PTSD; aOR=1.24,[1.07 to 1.44]), pain catastrophizing (aOR=1.03,[1.01 to 1.05]), not loving oneself (aOR=0.99,[.98-1.00]) and poor perceived mental health (aOR=0.94,[.92 to 97]) were most associated with thoughts of self-harm. Importantly, the ideation frequency of self-harm was highest among individuals treated with higher daily doses of opioids. These results support the need for continued monitoring of adults treated with opioids for chronic pain, particularly among those on high-dose opioids who present with increased negative affect and concerns of substance misuse.

Concurrent Gabapentin and Opioid Use and Risk of Mortality in Medicare Recipients with Non-Cancer Pain.

Gabapentin is prescribed for pain and is perceived as safe generally. However, gabapentin can cause respiratory depression, exacerbated by concomitant central nervous system depressants (e.g., opioids), a concern for vulnerable populations. We compared mortality rates among new users of either gabapentin or duloxetine with or without concurrent opioids in the 20% Medicare sample. We conducted a new-user design retrospective cohort study, in Medicare enrollees ages 65-89 years with noncancer chronic pain and no severe illness who filled prescriptions between 2015 and 2018 for gabapentin (n = 233,060) or duloxetine (n = 34,009). Daily opioid doses, estimated in morphine milligram equivalents (MMEs), were classified into none, low (0 < MME < 50), and high (≥ 50 MME), based on Centers for Disease Control and Prevention (CDC) recommendations. The outcomes were all-cause mortality (primary) and out-of-hospital mortality (secondary). We used inverse probability of treatment weighting to adjust for differences between gabapentin and duloxetine users. During 116,707 person-years of follow-up, 1,379 patients died. All-cause mortality rate in gabapentin users was 12.16 per 1,000 person-years vs. 9.94 per 1,000 in duloxetine users. Risks were similar for users with no concurrent opioids (adjusted hazard ratio (aHR) = 1.03, 95% confidence interval (CI): 0.80-1.31) or low-dose daily opioids (aHR = 1.06, 95% CI: 0.63-1.76). However, gabapentin users receiving concurrent high-dose daily opioids had an increased rate of all-cause mortality compared with duloxetine users on high-dose opioids (aHR = 2.03, 95% CI: 1.19-3.46). Out-of-hospital mortality yielded similar results. In this retrospective cohort study of Medicare beneficiaries, concurrent use of high-dose opioids and gabapentin was associated with a higher all-cause mortality risk than that for concurrent use of high-dose opioids and duloxetine.

Impact of Dexmedetomidine Infusion on Opioid and Benzodiazepine Doses in Ventilated Pediatric Patients in the Cardiac Intensive Care Unit.

Dexmedetomidine (DEX) is frequently used as an adjunct agent for prolonged sedation in the intensive care unit (ICU), though its effect on concomitant opioids or benzodiazepines infusions is unclear. We explored the impact of DEX on concomitant analgosedation in a cohort of ventilated pediatric patients in a cardiac ICU, with stratification of patients according to duration of ventilation (< 5 versus ≥ 5 days) following DEX initiation. We conducted a retrospective analysis on ventilated patients receiving a DEX infusion ≥ 24 h and at least one other sedative/analgesic infusion (January 2011-June 2021). We evaluated trends of daily doses of opioids and benzodiazepines from 24 h before to 72 h following DEX initiation, stratifying patients based on ventilation duration after DEX initiation (< 5 versus ≥ 5 days). After excluding 1146 patients receiving DEX only, 1073 patients were included [median age 234 days (interquartile range 90, 879)]. DEX was associated with an opioid infusion in 99% of patients and a benzodiazepine infusion in 62%. Among patients ventilated for < 5 days (N = 761), opioids increased in the first 24 h following DEX initiation [+ 1.12 mg/kg/day (95% CI 0.96, 1.23), P < 0.001], then decreased [- 0.90 mg/kg/day (95% CI - 0.89, - 0.71), P < 0.001]; benzodiazepines slowly decreased [- 0.20 mg/kg/day (95% CI - 0.21, - 0.19), P < 0.001]. Among patients ventilated for ≥ 5 days (N = 312), opioid administration doubled [+ 2.09 mg/kg/day (95% CI 1.82, 2.36), P < 0.001] in the first 24 h, then diminished minimally [- 0.18 mg/kg/day (95% CI - 0.32, - 0.04), P = 0.015] without returning to baseline; benzodiazepine administration decreased minimally [- 0.03 mg/kg/day (95% CI - 0.05, - 0.01), P = 0.010]. Similar trends were confirmed when adjusting for age, gender, surgical complexity, recent major invasive procedures, duration of mechanical ventilation before DEX initiation, extubation within 72 h following DEX initiation, mean hourly DEX dose, and use of neuromuscular blocking infusion. While in patients ventilated < 5 days opioids initially increased and then quickly decreased in the 72 h following DEX initiation, among patients ventilated ≥ 5 days opioids doubled, then decreased only minimally; benzodiazepines decreased minimally in both groups, although more slowly in the long-ventilation cohort. These findings may inform decision-making on timing of DEX initiation in ventilated patients already being treated with opioid or benzodiazepine infusions.

Fracture risk and opioid use in patients aged 17-64 years: An analysis of administrative claims data.

The objective of this work is to describe the risk of fracture in adults aged 17 to 64 years across categories of daily opioid dose. A retrospective analysis of insurance claims data. Information from a private health insurance provider for the years 2003-2014 for enrolled individuals living in Iowa. Patients who were aged 17 to 64 years and prescribed an opioid were followed for the length of opioid treatment plus 30 days to determine whether a fracture occurred. Average daily morphine milligram equivalent (MME) was determined for patients who received a prescription for opioids. The outcome of interest was incident fracture following opioid treatment initiation. Cox proportional hazard models were used to compare the risk of fracture across categorical groups of average daily MME. Inverse probability weighting was used to control for patient-level variables. In total, 316,024 individual patients were identified in the administrative claims data as having an opioid prescription from 2003 to 2014, and 3038 fractures occurred during follow-up (9.6 fractures per 1000 opioid-prescribed patients). Relative to the lowest quartile of prescribed opioid (⟨22 MME), patients in each higher prescribed level were more likely to experience a fracture (22-36 MME Hazard Ratio (HR) = 1.35, 95% Confidence Interval (CI): 1.21-1.51; 37-50 MME HR = 1.38, 95% CI: 1.24-1.54; ⟩50 MME HR = 1.35, 95% CI: 1.20-1.52). We observed an increased fracture risk in all three higher categories of opioid exposure relative to the lowest category (⟨22 MME). The risk of a fracture should be considered in opioid treatment decisions.

Identification of Factors Contributing to Methadone-Induced Daytime Sleepiness in Cancer Patients and Proposal of the Conversion Ratio from Other Opioids to Oral Methadone: A Retrospective Cohort Study.

When methadone is used to treat cancer pain, the Japanese health insurance system recommends to determine the starting dose according to the equivalency conversion table based on the morphine-equivalent daily dose (MEDD) of prior opioids proposed by the National Comprehensive Cancer Network. Owing to the wide range in variability of the conversion table, methadone increases the incidence of daytime sleepiness. To identify the factors associated with daytime sleepiness and propose a conversion ratio from pretreatment MEDD to oral methadone that decreases the risk of daytime sleepiness. Retrospective cohort study. One hundred patients who started oral methadone to relieve cancer pain at Ashiya Municipal Hospital (Hyogo, Japan) from January 1, 2013, to August 31, 2022, were enrolled. The primary endpoint, the conversion ratio from pretreatment MEDD to oral methadone without daytime sleepiness, was determined using receiver operator characteristic (ROC) curve analysis. The incidence of daytime sleepiness within seven days of methadone initiation was 40.0%. The factors identified as contributing to daytime sleepiness were pretreatment MEDD (odds ratio [OR]: 0.941, 95% confidence interval [CI]: 0.916-0.966, p <0.001) and methadone dose (OR: 1.395, 95% CI: 1.178-1.652, p <0.001). The conversion ratio from pretreatment MEDD to oral methadone was 0.24, with an area under the ROC curve of 0.909 (p <0.001). Daytime sleepiness developed when methadone dose is high relative to pretreatment MEDD. To the best of our knowledge, this is the first study to suggest the conversion ratio from pretreatment MEDD to oral methadone without causing daytime sleepiness.