Oral Morphine Equivalent Dose Research Articles

3-Dimensional versus standard 2-D laparoscopy for benign hysterectomy: A randomized clinical trial

ObjectiveOur aim was to evaluate possible short and long-term benefits of 3-dimensional (3-D) compared to 2-dimensional (2-D) laparoscopy for benign hysterectomy.Primary outcomes were long-term quality of life and postoperative pain. Secondary outcomes were operative time, surgical complications, time to return to work and length of hospitalization. Study designA randomized controlled trial conducted at two Danish university hospitals. In each arm, 190 patients were needed for an alpha of 3.3 % and a power of 90 %. For various reasons, however, the study was prematurely terminated after including 97 patients. Patients were randomized to either 2-D (n = 48) or 3-D (n = 49) laparoscopy. A laparoscopic hysterectomy was performed. Quality of life was assessed by the Short Form Health Survey 36 (SF-36) questionnaire at the time of inclusion and 6 weeks postoperatively. Postoperative pain was assessed using a Numeric Rating Scale (NRS) and by monitoring the amount of analgesic consumption. ResultsOut of the 97 randomized patients, 77 patients completed both SF-36 questionnaires. No significant differences in mental (p = 0.5) and physical status (p = 0.9) were found. The 2-D group had significantly higher pain-score registered in the post anesthesia care unit (PACU) (p = 0.004) and higher consumption of oral morphine equivalent dose (MEqD) (p = 0.003) than the 3-D group. This regardless a higher rate of minilaparotomies in the 2D (n = 7) than in the 3D (n = 1) group (p < 0.03). The 2-D group had also higher rate of Clavien-Dindo 2 (CD2) (n = 2) and Clavien-Dindo 3 (CD3) complications (n = 3) (p = 0.03) than 3-D (n = 0). The other secondary outcome parameters did not vary between groups. ConclusionsThe results are severely hampered by the premature termination of the study, as less than 25 percent of the patients were recruited. Thus, no firm conclusions can be drawn regarding the quality of life and many of the secondary outcomes, as the lack of difference may be attributed to a type 2 error. However, the significant differences in postoperative pain and in complication rates suggest a greater advantage of 3-D laparoscopy than originally expected. Despite the methodological problems, the current data deserve attention in a sparsely investigated field, emphasizing the urgent need for further studies.

High prevalence of severe pain is associated with low opioid availability in patients with advanced cancer: Combined database study and nationwide questionnaire survey in Japan.

Opioid availability for the palliative care of patients with advanced cancer is increasing globally. However, opioid availability remains extremely low in Japan. We investigated whether pain is appropriately controlled by low-dose opioid prescriptions in patients with advanced cancer in Japan. A web-based nationwide survey for caregivers from 2000 community comprehensive support care centers was performed in Japan to assess details about pain in the 30 days before patients died of end-stage cancer. Separately, the data for opioid prescription doses and medical services in the 90 days before the death of patients with cancer were extracted from a health insurance claim database. Responses from 1034 responders were retrieved and 665 patients were included. In total, 254 patients (38.2%) complained of severe-to-intolerable cancer-related pain. The median cumulative prescription dose of opioids in the 90 days before patient death was 311.0 mg by oral morphine equivalent doses. Multiple regression analyses across prefectures revealed that the proportion of patients with severe-to-intolerable cancer-related pain was negatively associated with the cumulative opioid consumption expressed as morphine-equivalent doses within 90 days before death. The very low availability of opioids for patients with end-stage cancer could result in high rate of severe-to-intolerable cancer-related pain patients. There were several limitations in this study, and the interpretations of the findings should be carefully. However, the increase in the absolute dose of opioids could improve the palliative care framework to the pain control levels of the global standard.

Erector spinae plane block reduces opioid consumption and improves incentive spirometry volume after cardiac surgery: A retrospective cohort study.

Effective postoperative pain management is vital in cardiac surgery to prevent opioid dependency and respiratory complications. Previous studies on the erector spinae plane (ESP) block have focused on single-shot applications or immediate postoperative outcomes. This study evaluates the efficacy of continuous ESP block vs conventional care in reducing opioid consumption and enhancing respiratory function recovery postcardiac surgery over 72 hours. A retrospective study at a tertiary hospital (January 2021-July 2022) included 262 elective cardiac surgery patients. Fifty-three received a preoperative ESP block, matched 1:1 with a control group (n = 53). The ESP group received 0.5% ropivacaine intraoperatively and 0.16% ropivacaine every 4 hours postoperatively. Outcomes measured were cumulative oral morphine equivalent (OME) dose within 72 hours postextubation, daily maximum numerical rating scale (NRS) ≥3, incentive spirometry volume, and %baseline performance, stratified by surgery type (sternotomy or thoracotomy). Significant OME reduction was observed in the ESP group (sternotomy: median decrease of 113 mg, 95% CI: 60-157.5 mg, p < 0.001; thoracotomy: 172.5 mg, 95% CI: 45-285 mg, p = 0.010). The ESP group also had a lower risk of daily maximum NRS ≥3 (adjusted OR sternotomy: 0.22, p < 0.001; thoracotomy: 0.07, p < 0.001), a higher incentive spirometry volumes (sternotomy: mean increase of 149 mL, p = 0.019; thoracotomy: 521 mL, p = 0.017), and enhanced spirometry %baseline (sternotomy: mean increase of 11.5%, p = 0.014; thoracotomy: 26.5%, p < 0.001). Continuous ESP block was associated with a reduction of postoperative opioid requirements, lower instances of pain scores ≥3, and improve incentive spirometry performance following cardiac surgery. These benefits appear particularly prominent in thoracotomy patients. Further prospective studies with larger sample size are required to validate these findings.

A comparison of opioid dose between home palliative care and hospital palliative care

ObjectiveWhile opioids are a key part of palliative care, few studies have evaluated opioid demand in the home care context. This study aims to compare opioid usage in home care and hospital care settings.MethodsThis cross-sectional study retrospectively recruited patients receiving palliative care in home care and hospital settings, between November 2018 and October 2020. Opioid prescriptions were standardized to oral morphine equivalent (OME) doses at 7 and 14 days prior to death and analyzed. Additional analysis performed multivariable linear regression on the outcome of OME at 7 days, adjusting for medical setting and confounders in patients with opioid prescriptions.ResultsAfter 21 exclusions, 209 patients (48 home care and 161 hospital care) were eligible for analysis. The home care group had a higher mean age (74.8 years) and Palliative Prognosis Score (50), than the hospital group (70.1 and 40, respectively). Mean OME at 7 and 14 days before death was numerically higher in the home care group (72.8 mg/day and 53.0 mg/day, respectively) than the hospital care group (57.7 mg/day and 35.7 mg/day). Student’s t-test produced p-values of 0.49 and 0.32, and the Wilcoxon rank sum test found p-values of 0.24 and 0.11 at 7 and 14 days, respectively. Multivariable regression analysis of the home care group found mean OME of 40.7 mg/day; 95% confidence interval [-0.62, 82.0 (mg/day)], p = 0.06. Additional analysis found a p-value of 0.06 for medical setting.ConclusionsWe did not find a statistically significant difference in opioid use between home care and hospital care. However, the numerically higher rate of use in the home care group suggests that further research is warranted.

Opioid-Related Respiratory Depression in Non-Cancer Patients, as Reported in the Japanese Adverse Drug Event Report Database.

Opioid-induced respiratory depression (RD) is a potentially life-threatening adverse drug event. This study used the Japanese Adverse Drug Event Report (JADER) database to investigate the profile of opioid-related RD in non-cancer patients. We analyzed data recorded in the JADER database between April 2004 and February 2020, which were downloaded from the Pharmaceutical and Medical Devices Agency website. Reporting odds ratios for RD were calculated for the 20 opioids approved in Japan, and daily dose and onset time were further analyzed for opioids used in chronic non-cancer pain (CNCP). Among the opioids, RD adverse event signals were detected for 22 combinations of opioids and administration routes in non-cancer patients. Of these combinations, transdermal buprenorphine and oral tramadol/acetaminophen were approved for CNCP and tended to be reported more frequently in elderly patients. The median daily doses of transdermal buprenorphine and oral tramadol/acetaminophen were 10.0 and 22.5 mg of daily oral morphine equivalent doses, respectively, which are within the standard range for starting dosage. The median time-to-onset of transdermal buprenorphine and oral tramadol/acetaminophen was 6.5 and 4.0 days, respectively, and 75% of cases were reported within 20 to 40 days after the start of treatment. The hazard type for both opioids was classified as early failure. Our findings suggest that elderly CNCP patients should be closely monitored after the start of opioid treatment, especially during the first week and, if possible, for 1 month, even if starting doses are within ranges recommended by the manufacturer and guidelines.

Sex Differences in Opioid Administration After Cardiac Surgery

ObjectivesAre there sex-based differences in the administration of opioid analgesic drugs among inpatients after cardiac surgery? DesignThis is a retrospective cohort study. SettingA tertiary academic referral centre. ParticipantsAdult patients who underwent cardiac surgery from 2014 to 2019. InterventionsNone Measurements and Main ResultsThe primary outcome was the cumulative oral morphine equivalent dose (OMED) for the post-operative admission. Secondary outcomes were the daily difference in OMED and the administration of non-opioid analgesics. We developed multivariable regression models controlling for known confounders, including weight and length of stay.A total of 3,822 patients (1,032 women and 2,790 men) were included. The mean cumulative OMED was 139 mg for women and 180 mg for men, and this difference remained significant after adjustment for confounders (adjusted mean difference [aMD], -33.21 mg; 95% confidence interval [CI], -47.05 to -19.36 mg; p < 0.001). The cumulative OMED was significantly lower in female patients on postoperative days 1 to 5, with the greatest disparity observed on day 5 (aMD, -89.83 mg; 95% CI, -155.9 to -23.80 mg; p = 0.009). By contrast, women were more likely to receive a gabapentinoid (OR, 1.91; 95% CI, 1.42 to 2.58; p < 0.001). We found no association between patient sex and the administration of other non-opioid analgesics or specific types of opioid analgesics. We found no association between patient sex and pain scores recorded within the first 48 hours following extubation, or the amount of opioid administered in close proximity to pain assessments. ConclusionsFemale sex was associated with significantly lower amounts of opioid administered after cardiac surgery.

Transdermal Rotigotine at End-of-Life for Parkinson's Disease: Association With Measures of Distress

BackgroundEnd-of-life (EOL) care for Parkinson's disease (PD) can be challenging when oral medications are no longer tolerated. MeasuresTo assess EOL prescribing for people with PD (PWP), focusing on rotigotine dosing and proxy measures of distress: benzodiazepine and opioid use. InterventionA retrospective audit of patient records from PWP who died between January 2019 and May 2022 at the Royal Hobart Hospital (RHH), Australia, was conducted. Data was systematically collated on demographics, symptoms, levodopa equivalent daily dose (LEDD) and rotigotine, oral morphine equivalent (OME) and benzodiazepine doses in the last 72 hours of life . OutcomesPain (72%), respiratory secretions (66%) and agitation (66%) were the most documented EOL symptoms. 83% (n = 52) of PWP were eligible for rotigotine and, of those, 13% (n = 7) received the correct dose, 38% (n = 20) a lower dose, 12% (n = 6) a higher dose and 37% (n = 19) did not receive any. Rotigotine dose was positively associated with total (P = 0.016) and PRN (P = 0.037) benzodiazepine dose. LEDD was positively associated with total benzodiazepine (P = 0.018) and total OME dose (P = 0.046). Contraindicated dopamine antagonists were prescribed for 43% of PWP and administered in 31% of those cases. ConclusionsRotigotine dose and admission LEDD were both associated with proxy measures of distress in the last 72 hours of life. This suggests cautious use of rotigotine at EOL. LEDD may help identify patients at risk of distress. Rates of inappropriate prescribing and symptom prevalence were high, indicating a need for further staff education to optimize the care of PWP.

Phase II Multi-Institutional Study of a Low-Dose (4 Gy) Palliative Response-Adapted Radiotherapy Regimen for Symptomatic Bone Metastases from Multiple Myeloma: Planned Interim Analysis of First 40 Patients

Painful bone lesions are common in patients with multiple myeloma (MM). Radiotherapy (RT) is effective in providing pain relief from MM bone lesions in over 80% of patients. There is no consensus as to the most effective dose or fractionation for palliation. Shorter courses of therapy are not only more convenient for patients, but they also have less impact on timing of systemic therapies. There is precedent for using 4 Gy in the palliation of lymphomas, which have similar radiosensitivity to myeloma. The primary objective of this trial is to determine whether treatment with a total dose of 4 Gy to a painful myeloma bone lesion achieves patient-reported pain reduction comparable to historical controls at 4 weeks. Patients with a known diagnosis of MM and a painful bone lesion that was not at the base of skull, in need of stabilization, or causing cord compression were treated with 4 Gy (2 Gy x 2 or 4 Gy x 1). Patients' pain was measured using the brief pain index (BPI) prior to treatment and at 2, 4, 8 weeks and 6 months following treatment. Pain response was determined by the international consensus on palliative radiotherapy and considered change in BPI and oral morphine equivalent dose (OMED). A planned interim analysis for futility was completed after 40 patients. Reirradiation with clinician choice regimens could be considered at ≥4 weeks following initial treatment for indeterminate pain response or pain progression. Forty patients were treated at 6 institutions between 2019 and 2022. Median age was 65 years with 40% women and 88% with an ECOG of 0-1. A complete response (CR) was defined as a BPI score of 0 with no concomitant increase in OMED. A partial response (PR) was defined as BPI reduction in 2 or more without analgesic increase, or an OMED reduction of 25% or more without an increase in pain. An indeterminate response (IR) was any response that is not captured by a CR, PR or pain progression. A CR was achieved in 48%, a PR in 38% of patients, an IR in 13% with 1 patient who refused participation. Pain response was achieved in 86% of patients. Seven patients (18%) requested reirradiation at ≥4 weeks. Median BPI at baseline and 4 weeks after RT for patients with CR, PR, and IR were 3.75 and 0, 4.00 and 1, and 5.25 and 4.75, respectively. Median change of BPI between baseline and 4 weeks after RT for all responders (CR and PR) was -3.25. The median PTV volume (cc) for patients with CR, PR and IR were 81, 140 and 226, respectively. Based on these results, the futility threshold was not met, and the recommendation by the DSMC is to continue the trial. In the first 40 patients who received 4 Gy palliation for painful bone lesions from multiple myeloma, there were 86% that had a pain response (48% CR, 38% PR). This low dose, response-adapted treatment, led to reirradiation in less than 20% of patients.

Long Term Outcomes of Conventional Palliative Radiotherapy in Bone Metastases of Lung Cancer: A Prospective Study

Bone metastases (BM) are highly prevalent in metastatic lung cancer (LC) leading to consequential morbidity and a decline in quality of life. The identification of oncogenes mutation and introduction of targeted therapy has prolonged the survival and therefore evaluation of long-term pain response rates, durability and re-irradiation (Re-RT) with conventional radiotherapy (RT) is crucial, especially in LMIC where penetration of stereotactic body radiotherapy for BM is poor. This prospective observational study included consecutive patients with histologically proven LC with radiologically confirmed BM. The primary objective was to evaluate the pain response rates in lung cancer patients with bone metastases treated with palliative RT. Palliative RT to BM was delivered using a conventional/conformal technique. The International Bone Metastases Consensus response criteria using Numeric Pain Rating Scale (NPRS) and Oral Morphine Equivalent Dose (OMED) was used to evaluate the pain response at 12, 24, and 52 weeks. Assuming the worst-case scenario, pain progression-free survival (PPFS) was calculated from the date of baseline assessment to the date of pain progression (PP) or death using Kaplan-Meier survival analysis. Known prognostic factors were evaluated using Cox regression analysis. From June 2020 to August 2022, 250 patients of NSCLC (94%) were accrued. The majority were male (66%), smokers (35%), lytic lesions (75%) and in the axial skeleton (82%). The oncogenic mutation was seen in 123 (49%) patients. At baseline, the mean OMED was 20mg/day (SD-21), and the mean pain score was 6 (SD-2.3). The majority (66%) received an 8 Gy single fraction with only 3% treated with SBRT. In evaluable patients, the CR and PR rates at 12 (n-161) and 24 weeks (n-121) were 34%, 40%, and 44%, 35% respectively. The indeterminate response rate (IRR) at 3 and 6 months were 18% while the rate of PP was 6%. On multivariate analysis, negative oncogene mutation {HR-0.34 (CI 0.22- 0.50), p<0.0001} and soft tissue mass {HR-0.46 (CI 0.31- 0.68) p<0.0001} were significant prognostic factors for pain progression. Of 71 evaluable patients at 1 year, 56% had a complete response with an ORR of 87%. In patients with oncogene mutation, the CR rates at 12 (n-101), 24 (n-77), and 52 weeks were 40%, 47%, and 60% with an ORR of 86%. PP is observed in less than 4%. Pain response was significantly more durable than mutation negative (8 vs 3 months, p-0.003). Re-RT rate was overall 11% (n = 27) and 8.2% in oncogene mutation patients. Re-RT rate with single-fraction was 8% and 3% with fractionated RT. The median time to Re-RT was 9.7 weeks. The PPFS was 70% and 60% at 12 and 24 weeks, respectively. This prospective study in an LC-specific population demonstrated excellent CR and PR rates with conventional RT. Durable pain relief with modest Re-RT rates with single fraction, particularly in oncogene mutation compels us to evaluate the role of SBRT for BM, especially in LMIC in a randomized setting.

Comparison of three analgesic regimens in women undergoing cervical brachytherapy

PURPOSEEffective periprocedural analgesia is an important aspect of cervical brachytherapy delivery, with implications for patient comfort and attendance for subsequent fractions. We compared the efficacy and safety of three analgesic modalities: intravenous patient-controlled analgesia (IV-PCA), continuous epidural infusion (CEI) and programmed-intermittent epidural bolus with patient-controlled epidural analgesia (PIEB-PCEA). METHODS AND MATERIALSNinety-seven brachytherapy episodes involving 36 patients between July 2016 and June 2019 in a single tertiary center were retrospectively reviewed. Episodes were divided into two key phases: Phase 1 (while applicator remained in situ) and Phase 2 (following applicator removal until discharge or 4 h). For the primary endpoint, pain scores were retrieved and analyzed by analgesic modality with respect to median score and an internally defined “unacceptable” pain experience (>20% of scores being ≥4/10; i.e., moderate or greater). Total nonepidural oral morphine equivalent dose (OMED) and toxicity/complication events were reported as secondary endpoints. RESULTSIn Phase 1, there was a significantly higher median pain score (p < 0.001) and more episodes with unacceptable pain scores (46%) in the IV-PCA group compared with either epidural modality (6–14%; p < 0.001).In Phase 2, we observed a greater median pain score (p = 0.007) and higher proportion of patient episodes with unacceptable pain scores (38%) in the CEI group compared with both the IV-PCA (13%) and PIEB-PCEA (14%) groups (p = 0.001).There was a significant difference in median OMED used throughout all phases across the PIEB-PCEA (0 mg), IV-PCA (70 mg), and CEI (15 mg) groups (p < 0.001). CONCLUSIONSPIEB-PCEA is safe and offers superior analgesia compared to IV-PCA or CEI for pain control after applicator placement in cervical brachytherapy.

Phase III, international, multicentre, double-blind, dose increment, parallel-arm, randomised controlled trial of duloxetine versus pregabalin for opioid-unresponsive neuropathic cancer pain.

TPS12146 Background: Management of neuropathic cancer pain (NCP) refractory to regular opioids remains an important challenge. The efficacy of pregabalin for NCP except chemotherapy-induced peripheral neuropathy has already been confirmed in two randomised controlled trials (RCTs) compared with placebo. Duloxetine offers the potential of analgesia in opioid refractory NCP. However, there are no RCT of duloxetine for the management of opioid-refractory NCP as a first line treatment. Both classes of drugs have the potential to reduce NCP, but there has been no head-to-head comparison for the efficacy and safety, especially given differing side effect profiles. Methods: An international, multicentre, double-blind, dose increment, parallel-arm, RCT. Eligibility criteria include: adult cancer patients experiencing NCP refractory to opioids; Brief Pain Inventory (BPI)-item 3 (worst pain) ≥4; Neuropathic Pain on the Leeds Assessment of Neuropathic Symptoms and Signs Pain Scale ≥12 despite of an adequate trial of regular opioid medication (≥60mg/day oral morphine equivalent dose). The study will recruit inpatients and outpatients in Japan and Australia. Participants will be randomised (1:1 allocation ratio) to duloxetine or pregabalin. Dose escalation is to day 14 and from day 14 to 21 is a dose de-escalation period to avoid withdrawal effects. Dose escalation schedule in each-arm is shown in Table 1. The primary endpoint is the mean difference in BPI item 3 over the previous 24 hours on day 14 between groups. Null hypothesis is there is no difference in BPI item 3 in the previous 24 hours on day 14 between both groups for patients with opioid refractory NCP. Comparison of the BPI item 3 on day 14 between duloxetine groups and pregabalin groups will be conducted using a two-sided Student’s t-test at a significance level of 5% according to the intention-to-treat principle. Point estimates and 95% CIs for the difference between two groups will be calculated. A sample size of 160 participants is required with 67 subjects enrolled to date. The DSMC last reviewed the trial in December 2022 and case accumulation expected to be completed by the end of 2024. Table 1：Dose escalation schedule in each-arm. Duloxetine Arm Stage 1 (Day 1-3): Duloxetine (30 mg) 1 capsule (morning) and Placebo 1 capsule (bedtime) Stage 2 (Day 4-7): Same as Stage 1 Stage 3 (Day 8-14): Duloxetine (30 mg) 1 capsule twice a day (morning and bedtime). Pregabalin Arm Stage 1 (Day 1-3): Pregabalin (25 mg) 1 capsule twice a day (morning and bedtime). Stage 2 (Day 4-7): Pregabalin (75 mg) 1 capsule twice a day (morning and bedtime). Stage 3 (Day 8-14): Pregabalin (75 mg) 2 capsules (150 mg) twice a day (morning and bedtime). Clinical trial information: ACTRN12620000656932 , jRCTs051190087.

Pre-operative sciatic nerve block vs postoperative surgeon-placed perineural stump catheter for prevention of phantom limb pain after below-knee amputation.

Pre-operative sciatic nerve block vs postoperative surgeon-placed perineural stump catheter for prevention of phantom limb pain after below-knee amputation.

Pericapsular nerve group (PENG) block for early pain management of elderly patients with hip fracture: a single-center double-blind randomized controlled trial

BackgroundThe pericapsular nerve group block (PENG) is a novel technique that blocks the articular branches of the hip joint. This study aimed to compare its effectiveness to a sham block...

Analgesic utilization in people with knee osteoarthritis: A population-based study using primary care data.

Osteoarthritis (OA) is a chronic painful condition that often affects large joints such as the knee. Treatment guidelines recommend paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids. Antidepressants and anti-epileptic drugs (AEDs) are commonly prescribed for chronic noncancer pain conditions including OA, as an off-label use. This study describes analgesic utilization in patients with knee OA at population level using standard pharmaco-epidemiological methods. This was a cross-sectional study between 2000 and 2014 using data from the U.K. Clinical Practice Research Datalink (CPRD). The use of antidepressants, AEDs, opioids, NSAIDs, and paracetamol was studied in adults with knee OA using the following measures: annual number of prescriptions, defined daily doses (DDD), oral morphine equivalent dose (OMEQ), and days' supply. In total, there were 8,944,381 prescriptions prescribed for 117,637 patients with knee OA during the 15-year period. There was a steady increase in the prescribing of all drug classes, except for NSAIDs, over the study period. Opioids were the most prevalent class prescribed in every study year. Tramadol was the most commonly prescribed opioid, with the number of DDD increasing from 0.11 to 0.71 DDDs per 1000 registrants in 2000 and 2014, respectively. The largest increase in prescribing was for AEDs, where the number of prescriptions increased from 2 to 11 per 1000 CPRD registrants. There was an overall increase in the prescribing of analgesics apart from NSAIDs. Opioids were the most frequently prescribed class; however, the greatest increase in prescribing between 2000 and 2014 was observed in AEDs.

S165 Impact of Patient Subgroups on the Efficacy and Safety of Methylnaltrexone for Opioid-Induced Constipation in Patients With Advanced Illness

Introduction: Methylnaltrexone (MNTX) is a peripherally acting µ-opioid receptor antagonist indicated for opioid-induced constipation (OIC) in patients with advanced illness who are receiving palliative care and in patients with chronic noncancer pain. We investigated if baseline patient characteristics impact the safety and efficacy of MNTX in those with advanced illness and OIC. Methods: This analysis pooled data from 2 randomized, double-blind, placebo (PBO)-controlled studies (study 302–NCT00402038; study 4000‒NCT00672477) in patients with advanced illness, including cancer. Study 302: Patients were randomized to receive subcutaneous (SC) MNTX 0.15 mg/kg or PBO every other day (QOD) for 2 weeks, with possible dose escalation to 0.30 mg/kg at week 2. Study 4000: Patients received weight-based SC MNTX 8 mg or 12 mg QOD or PBO for 2 weeks. The proportion of patients achieving a rescue-free laxation within 4 or 24 hours after the first dose of study drug was assessed in patient subgroups stratified by baseline age (< 65 vs ≥ 65), Eastern Cooperative Oncology Group (ECOG) status (≤ 2 vs > 2), cancer status, laxative type (osmotic agents, stimulants, stool softeners), and opioid requirement (oral morphine equivalent dose < 80 mg/d, 80 ‒ < 150 mg/d, and ≥ 150 mg/d). Treatment-emergent AEs (TEAEs), gastrointestinal (GI) TEAEs, and abdominal pain were evaluated. Results: Overall, 363 patients were included in this analysis (MNTX = 178; PBO = 185). Mean age was 67.8 years in the MNTX group and 66.7 years in the PBO group; 46.8% were men across all groups. A significantly greater proportion of patients receiving MNTX achieved rescue-free laxation within 4 hours (n = 111/178, 62.4% vs n = 31/185, 16.8%, P < .0001) and 24 hours (n = 135/178, 75.8% vs n = 81/185, 43.8%, P < .0001) of the first dose vs PBO. These trends were consistent across all subgroups (Table). Most patients experienced ≥ 1 TEAE in the overall population (MNTX 82.1%; PBO 76.2%); results were similar when stratified by baseline cancer, ECOG, opioid, or laxative group (Table). More than half of TEAEs were GI in nature; abdominal pain was more common in patients receiving MNTX across subgroups. Conclusion: MNTX treatment was superior to PBO in achieving RFL within 4 and 24 hours after the first dose, irrespective of patients’ cancer status, baseline ECOG status, or baseline opioid or laxative use. MNTX remained consistently safe across different baseline clinical and demographic characteristics. Table 1. - Rescue-free laxation response and treatment-emergent events by demographic and clinical characteristics subgroup Rescue-free laxation TEAEs Within 4 hours of the first dose Within 24 hours of the first dose Patients with ≥ 1TEAE Patients with gastrointestinal TEAE Patients with abdominal pain MNTX PBO MNTX PBO MNTX PBO MNTX PBO MNTX PBO Age, n (%) < 65 years 53 (63.9) 13 (14.6) 66 (79.5) 36 (40.4) 70 (84.3) 65 (73.0) 48 (57.8) 37 (41.6) 21 (25.3) 8 (9.0) ≥ 65 years 58 (61.1) 18 (18.8) 69 (72.6) 45 (46.9) 77 (80.2) 76 (79.2) 43 (44.8) 47 (49.0) 18 (18.8) 11 (11.5) Cancer status, n (%) Cancer 74 (63.8) 17 (14.9) 88 (75.9) 53 (46.5) 102 (87.9) 91 (79.8) 67 (57.8) 57 (50.0) 28 (24.1) 11 (9.6) Noncancer 37 (59.7) 14 (19.7) 47 (75.8) 28 (39.4) 44 (69.8) 50 (70.4) 24 (38.1) 27 (38.0) 11 (17.5) 8 (11.3) Functional status, n (%) ECOG ≤ 2 52 (66.7) 18 (22.5) 60 (76.9) 42 (52.5) 67 (85.9) 58 (72.5) 43 (55.1) 37 (46.3) 23 (29.5) 8 (10.0) ECOG > 2 59 (59.0) 13 (12.4) 75 (75.0) 39 (37.1) 80 (79.2) 83 (79.0) 48 (47.5) 47 (44.8) 16 (15.8) 11 (10.5) Baseline opioid dose in OME, n (%) < 80 mg/d 24 (57.1) 7 (12.3) 29 (69.0) 24 (42.1) 30 (71.4) 42 (73.7) 16 (38.1) 26 (45.6) 7 (16.7) 5 (8.8) 80 to < 150 mg/d 24 (61.5) 8 (19.0) 29 (74.4) 22 (52.4) 37 (94.9) 31 (73.8) 22 (56.4) 17 (40.5) 8 (20.5) 6 (14.3) ≥ 150 mg/d 63 (64.9) 16 (18.6) 77 (79.4) 35 (40.7) 80 (81.6) 68 (79.1) 53 (54.1) 41 (47.7) 24 (24.5) 8 (9.3) Baseline laxative regimen, n (%) Stimulants 86 (63.2) 21 (14.1) 104 (76.5) 64 (43.0) 113 (82.5) 118 (79.2) 73 (53.3) 68 (45.6) 29 (21.2) 17 (11.4) Osmotic agents 56 (65.9) 17 (20.7) 64 (75.3) 38 (46.3) 75 (88.2) 63 (76.8) 53 (62.4) 38 (46.3) 25 (29.4) 12 (14.6) Stool softeners 58 (63.0) 15 (15.3) 69 (75.0) 46 (46.9) 72 (78.3) 78 (79.6) 42 (45.7) 46 (46.9) 18 (19.6) 12 (12.2) ECOG = Eastern Cooperative Oncology Group; OME = oral morphine equivalent dose; MNTX = methylnaltrexone; PBO = placebo; TEAE = treatment-emergent adverse event.

Factors associated with persistent opioid use 6–12 months after primary total knee arthroplasty

Persistent pain following knee arthroplasty occurs in up to 20% of patients and may require ongoing analgesia, including extended opioid administration. A comprehensive secondary analysis was performed from results of a study that considered persistent postoperative pain in 242 patients who underwent unilateral knee arthroplasty using a standardised enhanced recovery programme. Opioid prescribing for 12 months before and 12 months after surgery was evaluated and converted to oral morphine equivalents. Demographic, functional, psychological and pain questionnaires were completed along with quantitative sensory testing and genetic analysis. Forty-nine percent of patients had at least one opioid prescription in the 12 months before surgery. Opioid prescriptions were filled in 93% of patients from discharge to 3 months and in 27% of patients ≥6 months after surgery. Persistent opioid use ≥6 months after surgery was strongly associated with pre-operative opioid use (RR 3.2, p < 0.001 (95%CI 1.9-5.4)). The median (IQR [range]) oral morphine equivalent daily dose was 3.6 (0.9-10.5 [0-100.0]) mg pre-operatively, 35.0 (22.5-52.5 [4.6-180.0]) mg in hospital, 12.8 (5.1-24.8 [0-57.9]) mg from discharge to 3 months and 5.9 (4.5-12.0 [0-44.5]) mg at ≥6 months following surgery. Predictors of increased daily oral morphine equivalent ≥6 months after surgery included increased average daily oral morphine equivalent dose compared with previous values (lag), increased body mass index and three or more comorbid pain sites. Persistent opioid use was not associated with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (RR 1.003, p = 0.655, 95%CI 0.65-1.002) or WOMAC function (RR 1.001, p = 0.99, 95%CI 0.99-1.03) outcomes 6 months after surgery. There was no association between persistent opioid use and pre-operative quantitative sensory testing results or psychological distress. Pre-operatively, patients with a higher body mass index, more comorbid pain sites and those who had filled an opioid prescription in the last 12 months, were at increased risk of persistent opioid use and a higher oral morphine equivalent daily dose ≥ 6 months after surgery. Strategies need to be developed to limit dose and duration of persistent opioid use in patients following knee arthroplasty surgery.

Long-term, high-dose opioid prescription for chronic non-cancer pain in primary care: an observational study.

Opioid prescriptions for chronic pain have risen sharply over the last 25 years; harms associated with these drugs are related to dose and length of use. The main aim of this study was to identify patients prescribed long-term, high-dose (LTHD) opioids in the community and to assess the prevalence of such use. An observational study of opioid prescribing in two demographically dissimilar GP practices in North Wales, UK. Details of opioid prescriptions were collected for 22 841 patients, of whom 1488 (6.5%) were being prescribed opioids on the census date. Exhaustive examination of the data identified all patients who were prescribed oral morphine equivalent doses of ≥120 mg/day for ≥1 year. All these patients were being prescribed ≥120 mg/day, as a single drug, morphine, oxycodone, fentanyl, or buprenorphine, irrespective of opioid polypharmacy. Across both practices, 1.71/1000 patients were identified as LTHD users of opioid medication for chronic non-cancer pain (CNCP). Prevalence was similar in the two practices. Repetition of the process until January 2021 showed no change in the pattern. This study offers confirmation that a significant group of patients are prescribed long-term opioid medication for chronic pain at doses that are unlikely to be effective in reducing pain, but are likely to have harmful consequences. The findings offer a simple, reliable, and practical method of data extraction to identify these patients individually from routinely collected prescribing data, which will help in monitoring and treating individuals and establishing the problem prevalence.

Analysis of Opioid Use in Patients Undergoing Open Versus Robotic Gastrectomy.

Minimally invasive, robotic gastrectomy is associated with better short-term outcomes and quicker functional recovery. However, the degree to which the robotic approach influences postoperative pain and opioid use after gastrectomy is unknown. Our primary aim was to determine whether the robotic approach to gastrectomy reduces postoperative opioid use compared with the open approach. Patients who underwent gastrectomy (November 2018 to September 2021) were identified retrospectively. Clinical characteristics, short-term surgical outcomes, oral morphine equivalent (OME) use, and pain scores were collected. Both groups were managed through an enhanced recovery program in the perioperative period. Of 81 patients, 50 underwent open and 31 underwent robotic gastrectomy. Compared with open gastrectomy patients, robotic gastrectomy patients had longer surgery time (360 vs. 288min), less blood loss (50 vs. 138mL), and shorter hospital stay (4 vs. 6days) (all medians, P<0.001). Robotic gastrectomy patients used lower OMEs on postoperative days 0-4 (all P<0.05) and in total for days 0-4 (total mean dose 65.0 vs. 169.5mg; P<0.001) than did open gastrectomy patients. The robotic gastrectomy patients were prescribed a lower mean OME dose than the open gastrectomy patients (19.0 vs. 29.0mg, respectively; P=0.001). Multivariable analysis showed that robotic approach was associated with lower opioid use (odds ratio 3.70; 95% CI 1.01-14.3; P=0.049). Compared with open gastrectomy, robotic gastrectomy reduces opioid use in the early postoperative period and is associated with fewer OME discharge prescriptions and shorter hospital stay.

Phase III, international, multicentre, double-blind, dose increment, parallel-arm, randomised controlled trial of duloxetine versus pregabalin for opioid-unresponsive neuropathic cancer pain: a JORTC-PAL16 trial protocol

IntroductionManagement of neuropathic cancer pain (NCP) refractory to regular opioids remains an important challenge. The efficacy of pregabalin for NCP except chemotherapy-induced peripheral neuropathy (CIPN) has already been confirmed in...

Abstract TP111: Pterygopalatine Fossa Blockade As Novel, Narcotic-sparing Treatment For Headache In Patients With Spontaneous Subarachnoid Hemorrhage - A Case Series

Background &amp; Purpose: Severe headache is a hallmark of spontaneous subarachnoid hemorrhage (SAH), affecting nearly 90% of patients during index hospitalization. In addition, up to 25% of SAH-survivors experience chronic headaches. Despite its high prevalence, means of management of headaches are limited, largely reliant on opioids, and often ineffective. Urgent efforts to reduce opioid use require innovative treatment strategies for the management of post-SAH headaches. Methods: This is a retrospective cohort comprising 12 adults who received bilateral pterygopalatine fossa (PPF) blockade from 9/2018 to 3/2021 for refractory headaches after spontaneous SAH. We examined pain scores, analgesic requirements and transcranial doppler ultrasound (TCD) parameters before and after the block placement. Descriptive statistics were calculated for all variables. Results: Twelve patients (mean age 54 years, 66% females, nine aneurysmal and three non-aneurysmal SAH) received PPF-block on post-bleed day 2 to 11 (median 6.5) during hospitalization in the neurointensive care unit. Hunt and Hess scores ranged from 1-3. Pain scale scores from 24-hour period before the block (8.8 ±1.4; mean, SD) decreased significantly to a mean of 5.1 (SD ± 3.0) until 20 hours post-block (p = 0.0156). Opioid use also decreased significantly from median (range) oral morphine equivalent dose (mg) administered in the 24h before the block of 22.5 (0-75) vs. 7.5 (0-45) after PPF-block (p=0.0391). Five (41%) patients had radiographic (but not clinical) vasospasm by TCD criteria before PPF-block; in four of these patients, TCD velocities improved on the day after PPF-block, in one patient velocities were increased on the day after PPF-block. The block was well tolerated with no adverse events of bleeding, infection, pain, or numbness at the injection site. Conclusion: These results demonstrate that PPF-blockade might be a promising alternative for managing post-SAH headaches. Further prospective controlled randomized powered to address the safety and efficacy of the PPF-block are warranted.