Median Morphine Equivalent Dose Research Articles

QOL-05. OPIATE UTILIZATION AND PREDICTIVE FACTORS IN PATIENTS UNDERGOING SURGERY FOR GLIOMAS

Abstract INTRODUCTION Opiate dependence is a national crisis. The use of opiate in patients diagnosed with gliomas undergoing surgery is not well understood. OBJECTIVE The objective of this study was to evaluate opiate use in patients undergoing surgery for gliomas and risk factors for prolonged opiate use. METHODS A retrospective chart review was conducted on patients ≥ 18 years who underwent surgery for glioma from 1/2016 to 1/2020. Clinical data was collected and opiate dose was calculated as morphine equivalent dose (MED). Clinical data prior to surgery, during surgery, and post-operative setting were collected. Descriptive statistics (means, frequencies, and percentages) were used to characterize the study population. Chi-square, with Fisher’s exact test, was used to determine associations for categorical variables. Linear and negative binomial regression models were used to predict MED doses with patient characteristics. RESULTS 180 patients were included in the analysis. The median MED at the time of surgery was 23.5 (IQR: 1.6, 72.5). 57 patients (46.04%) continued to take opiates after surgery. During adjuvant treatment the median MED was 45 (IQR: 45- 45) and the median length patients remaining on opiates was 59 days (IQR: 33- 168.5), with the longest usage being 1459 days. History of substance use, chronic headaches and other pain syndromes were not associated with increased use of opiates at the time of surgery. However, these factors were associated with higher morphine use after surgery. Male had a slightly higher dose (< 0.001) at the time of surgery compared to women. Peri-operative use at the time of surgery did not predict the MED and length of opiate use as outpatient. CONCLUSION Nearly half of the patients continued to use opiate beyond the peri-operative setting as outpatient at a higher median MED on median period of 59 days suggesting opportunities for improvement in opiate management post operatively.

Variation by default: cesarean section discharge opioid prescription patterns and outcomes in Military Health System hospitals: a retrospective longitudinal cohort study

BackgroundTo examine factors associated with post-Cesarean section analgesic prescription variation at hospital discharge in patients who are opioid naïve; and examine relationships between pre-Cesarean section patient and care-level factors and discharge morphine equivalent dose (MED) on outcomes (e.g., probability of opioid refill within 30 days) across a large healthcare system.MethodsThe Walter Reed Institutional Review Board provided an exempt determination, waiver of consent, and waiver of HIPAA authorization for research use in the present retrospective longitudinal cohort study. Patient records were included in analyses if: sex assigned in the medical record was “female,” age was 18 years of age or older, the Cesarean section occurred between January 2016 to December 2019 in the Military Health System, the listed TRICARE sponsor was an active duty service member, hospitalization began no more than three days prior to the Cesarean section, and the patient was discharged to home < 4 days after the Cesarean section.ResultsAcross 57 facilities, 32,757 adult patients had a single documented Cesarean section procedure in the study period; 24,538 met inclusion criteria and were used in analyses. Post-Cesarean section discharge MED varied by facility, with a median MED of 225 mg and median 5-day supply. Age, active duty status, hospitalization duration, mental health diagnosis, pain diagnosis, substance use disorder, alcohol use disorder, gestational diabetes, discharge opioid type (combined vs. opioid-only medication), concurrent tubal ligation procedure, single (vs. multiple) births, and discharge morphine equivalent dose were associated with the probability of an opioid prescription refill in bivariate analyses, and therefore were included as covariates in a generalized additive mixed model (GAMM). Generalized additive mixed model results indicated that non-active duty beneficiaries, those with mental health and pain conditions, those who received an opioid/non-opioid combination medication, those with multiple births, and older patients were more likely to obtain an opioid refill, relative to their counterparts.ConclusionSignificant variation in discharge pain medication prescriptions, as well as the lack of association between discharge opioid MED and probability of refill, indicates that efforts are needed to optimize opioid prescribing and reduce unnecessary healthcare variation.

Impact of a tiered discharge opioid algorithm on prescriptions and patient-reported outcomes after open gynecologic surgery

ObjectiveTo compare discharge opioid refills, prescribed morphine equivalent dose and quantity, and longitudinal patient-reported outcomes before and after implementation of a tiered opioid prescribing algorithm among women undergoing open gynecologic...

Enhanced recovery after cystectomy in patients with preoperative narcotic use.

The aim of this study was to evaluate the outcomes of radical cystectomy with an enhanced recovery after surgery (ERAS) protocol in patients with a history of chronic preoperative narcotic use compared to narcotic-naive patients. We identified 553 patients who underwent open radical cystectomy with ERAS. Preoperative narcotic use was identified in 34 patients who were then matched to 68 narcotic-naive patients. Postoperative outcomes, opioid use, and visual analog scale (VAS) pain scores were analyzed and compared. All routes of opioid use were recorded and converted to a morphine equivalent dose (MED). Patients with preoperative narcotic use reported higher median VAS pain scores per day (postoperative day [POD1]: 5.2 vs. 3.9, p=0.003; POD2: 5.1 vs. 3.6, p<0.001; POD3: 4.6 vs. 3.8, p=0.004) and used significantly more opioids (median MED) per day (POD1: 13.2 vs. 10.0, p=0.02; POD2: 11.3 vs. 6.4, p=0.003; POD3: 10.2 vs. 5.0, p=0.005) following surgery. Preoperative narcotic users were noted to have a significantly higher incidence of 90-day re-admissions (41.2% vs. 20.6%, p=0.03). There was no difference in median hospital stay (4 vs. 4 days, p=0.6), 30-or 90-day complications (64.7% vs. 60.3%, p=0.8 and 82.4% vs. 75.0%, p=0.4, respectively) or gastrointestinal complications (29.4% vs. 26.5%, p=0.8), including postoperative ileus (11.8% vs. 20.6%, p=0.2). Patients with preoperative narcotic exposure report higher pain scores and require more opioid use following radical cystectomy with ERAS and are more likely to be re-admitted within 90 days. However, there was no observed difference in hospital stay or complications.

Dynamic changes in the pancreatitis activity scoring system during hospital course in a multicenter, prospective cohort.

The primary aim was to validate the Pancreatitis Activity Scoring System (PASS) in a multicenter prospectively ascertained acute pancreatitis (AP) cohort. Second, we investigated the association of early PASS trajectories with disease severity and length of hospital stay (LOS). Data were prospectively collected through the APPRENTICE consortium (2015-2018). AP severity was categorized based on revised Atlanta classification. Delta PASS (ΔPASS) was calculated by subtracting activity score from baseline value. PASS trajectories were compared between severity subsets. Subsequently, the cohort was subdivided into three LOS subgroups as short (S-LOS): 2-3days; intermediate (I-LOS): 3-7days; and long (L-LOS): ≥7days. The generalized estimating equations model was implemented to compare PASS trajectories. There were 434 subjects analyzed including 322 (74%) mild, 86 (20%) moderately severe, and 26 (6%) severe AP. Severe AP subjects had the highest activity levels and the slowest rate of decline in activity (P=0.039). Focusing on mild AP, L-LOS subjects (34%) had 28 points per day slower decline; whereas, S-LOS group (13%) showed 34 points per day sharper decrease compared with I-LOS (53%; P<0.001). We noticed an outlier subset with a median admission-PASS of 466 compared with 140 in the rest. Morphine equivalent dose constituted 80% of the total PASS in the outliers (median morphine equivalent dose score=392), compared with only 25% in normal-range subjects (score=33, P value<0.001). This study highlighted that PASS can quantify AP activity. Significant differences in PASS trajectories were found both in revised Atlanta classification severity and LOS groups, which can be harnessed in AP monitoring/management (ClincialTrials.gov number, NCT03075618).

Intravenous Ketamine as an Adjunct to Procedural Sedation During Burn Wound Care and Dressing Changes.

Little has been published regarding intravenous (IV) ketamine for burn wound care in adult patients. Ketamine may serve as a safe alternative to provide conscious sedation and limit opioid administration to patients. The purpose of this study was to characterize IV ketamine use during burn wound care and establish its potential role as a safe adjunct to opioid and benzodiazepine medications. This is a retrospective review of adult patients admitted to a regional burn center who received IV ketamine for burn wound care. Patient demographics, medications, and ketamine-related adverse effects including hypertension and dysphoric reactions were recorded. Cardiopulmonary complications were also tracked. Thirty-six patients met inclusion criteria; fifty total cases were performed. The median patient age was 37 (interquartile range [IQR]: 28-55] years with a median burn size of 9.5 (IQR: 4.0-52) %TBSA. The median ketamine dose administered was 1.2 (IQR: 0.8-2.1) mg/kg. IV midazolam was administered in almost all cases (98%) at a median dose of 3.0 (IQR: 2.0-5.0) mg. Opioids were administered in 13 of 50 cases (26%) at a median morphine equivalent dose of 10 (IQR: 5.0-18) mg. In 46 cases (92%), patients denied unpleasant recall of medication. Dysphoric reactions were observed in three cases (6%). Ketamine-induced hypertension occurred in three cases (6%) and all immediately responded to IV labetalol. There were no cardiopulmonary complications. These findings suggest that IV ketamine provides a safe analgesia and sedative option for burn wound care. Given these findings, IV ketamine for burn wound care warrants further study.

Long-term use of opioids in 210 officially registered patients with chronic noncancer pain in Taiwan: A cross-sectional study.

Prescribing opioids for chronic noncancer pain has been strictly regulated for two decades in Taiwan. The aim of this study was to survey the patients' perspectives and potential drawbacks following long-term use of opioids. An observational cross-sectional survey using the Taiwanese version of Brief Pain Inventory was conducted among outpatients with chronic noncancer pain registered by the Taiwan Food and Drug Administration. Patients were also asked about their sexual behavior, depression, opioid misuse behaviors, and use of complementary and alternative medicine. For 210 of 328 outpatients (64.0%), the median pain duration was 96 months and opioid treatment duration was 57 months. The median morphine equivalent dose was 150 mg/d, with 30.5% of patients exceeding the daily watchful dose, defined as 200 mg of morphine equivalent dose. Pain reduction after taking opioids was ∼50% in the past week. The top three diagnoses were chronic pancreatitis, spinal cord injury, and neuralgia. The leading side effects were constipation (46.7%), and decreased sexual desire (69.5%) and satisfaction (57.9%). Depression was currently diagnosed in 55.2% of patients. Twenty patients (9.5%) displayed at least one aberrant behavior in the past month. Only 76 (36.2%) patients had ever received nerve block procedures, and 118 (56.2%) tried complementary and alternative medicine. This nationwide survey described the concurrent pain intensity, daily function, and various adverse effects by long-term opioids among 210 monitored outpatients with chronic noncancer pain in Taiwan. More efforts are suggested to reduce opioid prescriptions in the 30% of patients exceeding daily watchful dose.

Co-prescription of naloxone as a Universal Precautions model for patients on chronic opioid therapy—Observational study

ABSTRACTBackground: The epidemic of lethal prescription opioid overdose is one of the most pressing public health problems in the United States. In an ambulatory clinic setting, current practice guidelines suggest that health care providers should screen patient's aberrant drug-related behaviors. Given the difficulty of predicting which patients on chronic opioid therapy (COT) will experience opioid overdose, a new paradigm of harm reduction is called for. In previous studies, naloxone, an opioid antagonist, was given only to high-risk patients. However, if naloxone is co-prescribed in a Universal Precautions manner for all patients receiving COT, this may have a significant impact on intentional and unintentional opioid overdose deaths. Methods: Adult patients treated with COT for chronic noncancer pain are eligible study participants at the University of New Mexico Pain Center. The primary goal of this 1-year study was to develop an efficient Universal Precautions model for co-prescribing of naloxone with COT in the ambulatory clinic setting. Outcome measures included demographic data, detailed medical and substance use history, current morphine equivalent dose (MED), other “high-risk” medications used, and opioid misuse risk. Results: One hundred and sixty-four patients were enrolled in this study. All subjects were educated about the risks of opioid overdose and provided naloxone rescue kits. No overdoses occurred in the study population. Follow-up data illustrated that approximately 57% of the cohort had depressive disorder, the median MED was 90 mg/day, and the median Current Opioid Misuse Measure score (COMM) was 5.0. Conclusions: The ambulatory co-prescribing of naloxone in a Universal Precautions model for all patients prescribed COT can be adopted as a useful public health intervention. This study illustrates a model that can be used to educate patients, caregivers, and an interdisciplinary team of health care professionals in an academic medical center.

Analysis of opioid-mediated analgesia in Phase III studies of methylnaltrexone for opioid-induced constipation in patients with chronic noncancer pain.

BackgroundSubcutaneous methylnaltrexone is efficacious and well tolerated for opioid-induced constipation (OIC) but may theoretically disrupt opioid-mediated analgesia.MethodsOpioid use, pain intensity, and opioid withdrawal (Objective Opioid Withdrawal Scale [OOWS] and Subjective Opiate Withdrawal Scale [SOWS] scores) were reported in a randomized, double-blind trial with an open-label extension (RCT) and an open-label trial (OLT) evaluating safety in adults with chronic noncancer pain. In the RCT, patients taking ≥50 mg of oral morphine equivalents daily with <3 rescue-free bowel movements weekly received methyl naltrexone 12 mg once daily (n=150), every other day (n=148), or placebo (n=162) for 4 weeks, followed by open-label methylnaltrexone 12 mg (as needed [prn]; n=364) for 8 weeks. In the OLT, patients (n=1,034) on stable opioid doses with OIC received methylnaltrexone 12 mg prn for up to 48 weeks.ResultsMinimal fluctuations of median morphine equivalent dose from baseline (BL) were observed in the RCT double-blind period (BL, 154.8–161.0 mg/d; range, 137.1–168.0 mg/d), RCT open-label period (BL, 156.3–174.6; range, 144.0–180.0) and OLT (BL, 120 mg/d; range, 117.3–121.1 mg/d). No significant change from BL in pain intensity score occurred in any group at weeks 2 or 4 (both P≥0.1) of the RCT double-blind period, and scores remained stable during the open-label period and in the OLT (mean change, −0.2 to 0.1). Changes from BL in OOWS and SOWS scores during the double-blind period were not significantly impacted by methylnaltrexone exposure at weeks 2 or 4 (P>0.05 for all).ConclusionMethylnaltrexone did not affect opioid-mediated analgesia in patients with chronic noncancer pain and OIC.

Characteristics of patients receiving long-term opioid therapy for chronic noncancer pain: a cross-sectional survey of patients attending the Pain Management Centre at Hamilton General Hospital, Hamilton, Ontario

Characteristics of patients receiving long-term opioid therapy (≥6 months) for chronic noncancer pain are poorly understood. We conducted a cross-sectional survey of this patient population to explore demographic variables, pain relief, functional improvement, adverse effects and impressions of an educational pamphlet on long-term opioid therapy. We invited 260 adult patients presenting to the Pain Management Centre at the Hamilton General Hospital, Hamilton, Ontario, with chronic noncancer pain to complete a 20-item survey. Patients who presented for procedures were not eligible for our study. We used adjusted logistic regression models to explore the association between higher morphine equivalent dose and pain relief, functional improvement, adverse events and employment. The survey was completed by 170 patients (a response rate of 65.4%). Most respondents (87.6%; 149 out of 170) were receiving long-term opioid therapy, and the median morphine equivalent dose was 180 mg daily (interquartile range 60-501). Most respondents reported at least modest (>40%) opioid-specific pain relief (74.1%; 106 out of 143) and functional improvement (67.6%; 96 out of 142), and 46.5% (66 out of 142) reported troublesome adverse effects that they attributed to their opioid use. Most patients were receiving disability benefits (68.3%; 99 out of 145) and, among those respondents who were less than 65 years of age (90.3%; 131 out of 145), 10 (7.6%) were working full-time and 14 (10.7%) part-time. In our adjusted analyses, higher morphine equivalent dose was associated with greater self-reported functional improvement (odds ratio [OR] 1.45, 95% confidence interval [CI] 1.07-1.96) but not with pain relief (OR 1.38, 95% CI 1.00-1.89), troublesome adverse effects (OR 0.92, 95% CI 0.70-1.20) or employment (OR 0.80, 95% CI 0.56-1.15). Most outpatients receiving long-term opioid therapy for chronic noncancer pain at a tertiary care chronic pain clinic reported at least moderate pain relief and functional improvement; however, adverse effects were common and few patients were engaged in competitive employment.

(451) Efficacy and safety of methylnaltrexone for opioid-induced constipation in patients with chronic noncancer pain: a placebo crossover analysis

In patients with chronic noncancer pain, efficacy of subcutaneous methylnaltrexone (MNTX) for treatment of opioid-induced constipation (OIC) was examined in a 4-week, randomized, controlled trial (RCT), followed by an 8-week open-label extension. To examine the reproducibility of findings from the RCT, data from placebo (PBO)-treated patients who crossed over to open-label MNTX were analyzed. Adults with <3 rescue-free bowel movements (RFBMs; bowel movement[s] occurring without any laxative in the prior 24 hours) per week, and taking ≥50 mg oral morphine equivalent/day, were randomized to receive MNTX 12 mg or PBO for 4 weeks followed by open-label MNTX (prn) for 8 weeks. Patients were evaluated during both phases according to: 1) RFBMs within 4 hours of the first dose, 2) percentage of injections resulting in any RFBM within 4 hours, and 3) percentage of patients experiencing ≥3 RFBMs/week and 1 RFBM increase over baseline. Patients (n=134, median morphine equivalent dose: 150 mg/day) experienced approximately 1 RFBM/week at baseline. Under PBO conditions, 10% of patients experienced a RFBM within 4 hours of first dose, and 9% of all PBO injections resulted in any RFBM within 4 hours. By contrast, during open-label MNTX, these percentages were 46% and 35%. When expressed according to percentage of patients experiencing ≥3 RFBMs/week and 1 RFBM increase over baseline, weekly values ranged from 35-41% during PBO treatment; at Week 5 during open-label MNTX, this percentage increased to >70% and remained relatively stable throughout the extension phase. Most common adverse events during MNTX treatment were abdominal pain (9.7% vs. 1.5% for PBO) and nausea (5.2% vs. 6.7%). Findings during PBO treatment further establish the nature of OIC and support that little or no gastrointestinal tolerance develops over time. Findings under open-label conditions establish the reproducibility and durability of MNTX for treatment of OIC. Supported by Salix Pharmaceuticals, Inc. In patients with chronic noncancer pain, efficacy of subcutaneous methylnaltrexone (MNTX) for treatment of opioid-induced constipation (OIC) was examined in a 4-week, randomized, controlled trial (RCT), followed by an 8-week open-label extension. To examine the reproducibility of findings from the RCT, data from placebo (PBO)-treated patients who crossed over to open-label MNTX were analyzed. Adults with <3 rescue-free bowel movements (RFBMs; bowel movement[s] occurring without any laxative in the prior 24 hours) per week, and taking ≥50 mg oral morphine equivalent/day, were randomized to receive MNTX 12 mg or PBO for 4 weeks followed by open-label MNTX (prn) for 8 weeks. Patients were evaluated during both phases according to: 1) RFBMs within 4 hours of the first dose, 2) percentage of injections resulting in any RFBM within 4 hours, and 3) percentage of patients experiencing ≥3 RFBMs/week and 1 RFBM increase over baseline. Patients (n=134, median morphine equivalent dose: 150 mg/day) experienced approximately 1 RFBM/week at baseline. Under PBO conditions, 10% of patients experienced a RFBM within 4 hours of first dose, and 9% of all PBO injections resulted in any RFBM within 4 hours. By contrast, during open-label MNTX, these percentages were 46% and 35%. When expressed according to percentage of patients experiencing ≥3 RFBMs/week and 1 RFBM increase over baseline, weekly values ranged from 35-41% during PBO treatment; at Week 5 during open-label MNTX, this percentage increased to >70% and remained relatively stable throughout the extension phase. Most common adverse events during MNTX treatment were abdominal pain (9.7% vs. 1.5% for PBO) and nausea (5.2% vs. 6.7%). Findings during PBO treatment further establish the nature of OIC and support that little or no gastrointestinal tolerance develops over time. Findings under open-label conditions establish the reproducibility and durability of MNTX for treatment of OIC. Supported by Salix Pharmaceuticals, Inc.

Lack of correlation between the dose of fentanyl sublingual spray for breakthrough cancer pain and the dose of around-the-clock opioid for persistent pain

Fentanyl sublingual spray is indicated for the treatment of breakthrough cancer pain (BTCP) in opioid-tolerant patients. This analysis evaluated the correlation between the dose of around-the-clock (ATC) opioid for persistent pain and effective dose of fentanyl sublingual spray for BTCP during the 26-day open-label portion of a phase 3, randomized, placebo-controlled trial. Adult opioid-tolerant patients with 1-4 episodes of BTCP were titrated to a dose of sublingual fentanyl spray (100, 200, 400, 600, 800, 1200, or 1600 mcg) that provided effective analgesia for 2 consecutive BTCP episodes. Of the 130 patients who received fentanyl sublingual spray, 98 (75.4%) completed the titration period. For those achieving successful titration , opioids used for ATC pain management at baseline included oxycodone/oxycodone hydrochloride (75.8%), morphine/morphine sulfate (41.1%), fentanyl/fentanyl citrate (40.0%), hydrocodone/hydrocodone acetaminophen (32.6%), hydromorphone/hydromorphone hydrochloride (31.6%), and methadone/methadone hydrochloride (13.7%). For BTCP, 93.5% (n=86) of patients reported using only oral opioids at baseline; commonly reported medications included hydromorphone hydrochloride (23%), oxycodone (22%), hydrocodone/acetaminophen (22%), and oxycodone/acetaminophen (16%). During the open-label phase, the median morphine equivalent dose of ATC opioid was 200.0 mg (range, 60.0-7545.0 mg). The median dose of fentanyl sublingual spray was 800 mcg and the most common doses were 800 mcg (24.5%) and 1200 mcg (20.4%). Based on the Spearman rank correlation, there was no clinical correlation observed between the successful dose of fentanyl sublingual spray for BTCP and ATC morphine equivalent dose (r=0.351, n=98). The lack of apparent correlation between ATC and BTCP dose underscores the importance of individual patient titration when determining an effective dose of fentanyl sublingual spray for BTCP. Technical editorial andmedical writing assistance provided by Synchrony Medical Communications, LLC, funded by INSYS Therapeutics.

Surgical management of prostate cancer metastatic to the spine

Significant improvements in neurological function and pain relief are the benefits of aggressive surgical management of spinal metastatic disease. However, there is limited literature regarding the management of tumors with specific histological features. In this study, a series of patients undergoing spinal surgery for metastatic prostate cancer were reviewed to identify predictors of survival and functional outcome. The authors retrospectively reviewed the records of all patients who were treated with surgery for prostate cancer metastases to the spine between 1993 and 2005 at a single institution. Particular attention was given to initial presentation, operative management, clinical and neurological outcomes, and factors associated with complications and overall survival. Forty-four patients underwent a total of 47 procedures. The median age at spinal metastasis was 66 years (range 50-84 years). Twenty-four patients had received previous external-beam radiation to the site of spinal involvement, with a median dose of 70 Gy (range 30-74 Gy). Frankel scores on discharge were significantly improved when compared with preoperative scores (p = 0.001). Preoperatively, 32 patients (73%) were walking and 33 (75%) were continent. On discharge, 36 (86%) of 42 patients were walking, and 37 (88%) of 42 were continent. Preoperatively, 40 patients (91%) were taking narcotics, with a median morphine equivalent dose of 21.5 mg/day, and 28 patients (64%) were taking steroids, with a median dose of 16 mg/day. At discharge, the median postoperative morphine equivalent dose was 12 mg/day, and the median steroid dose was 0 mg/day (p < 0.001). Complications occurred in 15 (32%) of 47 procedures, with 9 (19%) considered major, and there were 4 deaths within 30 days of surgery. The median overall survival was 5.4 months. Gleason score (p = 0.002), total number of metastases (p = 0.001), and the degree of spinal canal compression (p = 0.001) were independent predictors of survival. Age > or = 65 years at the time of surgery was an independent predictor of a postoperative complication (p = 0.005). In selected patients with prostate cancer metastases to the spine, aggressive surgical decompression and spinal reconstruction is a useful treatment option. The results show that on average, neurological outcome is improved and use of analgesics is reduced. Gleason score, metastatic burden, and degree of spinal canal compression may be associated with survival following surgery, and thus should be considered carefully prior to opting for surgical management.