Opioid-related Symptom Distress Scale Research Articles

High-dose dexamethasone in low pain responders undergoing total knee arthroplasty: a randomised double-blind trial

BackgroundPostoperative pain after total knee arthroplasty (TKA) is a continuing problem despite optimised multimodal analgesia. Previous studies have shown preoperative glucocorticoids to reduce postoperative pain, but knowledge about specific doses and effects in specific patient groups is lacking. MethodsA two-centre, double-blind, two-arm study comparing preoperative dexamethasone (1 mg kg−1vs 0.3 mg kg−1 i.v.) on postoperative pain in 160 planned TKA subjects with low preoperative pain catastrophising and no opioid use. Subjects received multimodal analgesia with paracetamol, cyclooxygenase-2 inhibitors, local anaesthetic infiltration analgesia, and rescue opioids. The primary outcome was percentage of subjects experiencing moderate to severe pain (visual analogue scale >30 mm) upon ambulation at 24 h. Secondary outcomes included pain scores, postoperative inflammation (C-reactive protein), opioid and antiemetics use, and ‘Quality of Recovery-15’ and ‘Opioid-Related Symptom Distress Scale’, length of stay, readmissions, and complications up to Day 90. ResultsA total of 157 subjects (80 vs 77) were included. No difference was found between groups in the incidence of subjects experiencing visual analogue scale >30 on ambulation 24 h after surgery (56% vs 53%, relative risk =1.07, confidence interval: 0.8–1.4, P=0.65). No differences in other pain outcomes or use of rescue opioids and antiemetics, in Quality of Recovery-15 and Opioid-Related Symptom Distress Scale, length of stay, readmissions, or complications. C-reactive protein values were comparable at 24 h (13 [6–25] mg L−1vs 16 [9–38] mg L−1, P = 0.07), but lower at 48 h (26 [9–52] mg L−1vs 50 [30–72] mg L−1, P<0.01) in the high-dose group. ConclusionUse of 1 mg kg−1vs 0.3 mg kg−1 i.v. dexamethasone in low pain responders after TKA did not improve early postoperative pain or other outcomes in contrast to benefits in a high pain responder population. Clinical trial registrationNCT03758170 (first registration 29-11-2018).

Naloxegol and Postoperative Urinary Retention: A Randomized Trial.

Background: Naloxegol antagonizes peripheral opioid-related side effects without preventing opioid-related analgesia. However, the effect of naloxegol on opioid-induced bladder dysfunction remains unknown. Hypothesis: patients given naloxegol have lower residual bladder urine volume than those given placebo. Methods: 136 patients scheduled for elective hip and knee surgery were randomized to oral naloxegol or placebo given the morning of surgery, and on the first two postoperative mornings. Residual urine volume was measured ultrasonographically within 30 min after voiding once in the morning and once in the afternoon for two postoperative days. Opioid-related Symptom Distress Scale (ORSDS), the need for indwelling urinary catheterization, and quality of recovery (QoR) score were secondary outcomes. Results: 67 were randomized to naloxegol and 64 to placebo. We did not identify a significant effect on urine residual volume, with an estimated ratio of geometric means of 0.9 (0.3, 2.6), p = 0.84. There were no significant differences in ORSDS or QoR. There were 19 (29%) patients assigned to naloxegol who needed indwelling urination catheterization versus 7 (11%) patients in the placebo group, p = 0.012. Conclusions: Our results do not support use of naloxegol for postoperative urinary retention after hip and knee surgery.

High-dose steroids in high pain responders undergoing total knee arthroplasty: a randomised double-blind trial

BackgroundTotal knee arthroplasty (TKA) is associated with moderate-to-severe postoperative pain despite multimodal opioid-sparing analgesia. Pain catastrophising or preoperative opioid therapy is associated with increased postoperative pain. Preoperative glucocorticoid improves pain after TKA, but dose-finding studies and benefit in high pain responders are lacking. MethodsA randomised double-blind controlled trial with preoperative high-dose intravenous dexamethasone 1 mg kg−1 or intermediate-dose dexamethasone 0.3 mg kg−1 in 88 patients undergoing TKA with preoperative pain catastrophising score >20 or regular opioid use was designed. The primary outcome was the proportion of patients experiencing moderate-to-severe pain (VAS >30) during a 5 m walk 24 h postoperatively. Secondary outcomes included pain at rest during nights and at passive leg raise, C-reactive protein, opioid use, quality of sleep, Quality of Recovery-15 and Opioid-Related Symptom Distress Scale, readmission, and complications. ResultsModerate-to-severe pain when walking 24 h postoperatively was reduced (high dose vs intermediate dose, 49% vs 79%; P<0.01), along with pain at leg raise at 24 and 48 h (14% vs 29%, P=0.02 and 12% vs 31%, P=0.03, respectively). C-reactive protein was reduced in the high-dose group at both 24 and 48 h (both P<0.01). Quality of Recovery-15 was also improved (P<0.01). ConclusionsWhen compared with preoperative dexamethasone 0.3 mg kg−1 i.v., dexamethasone 1 mg kg−1 reduced moderate-to-severe pain 24 h after TKA and improved recovery in high pain responders without apparent side-effects. Clinical trial registrationNCT03763734.

Supporting pharmacogenetic-guided opioid prescriptions for post-operative pain: The design, protocol and preliminary results of the OTP study

The interindividual variability in opioid response is an issue that contributes to the ongoing opioid crisis. Current evidence suggests this variability can be attributed to genetic factors. The pharmacogenetics of Opioid Treatment for acute post-operative Pain (OTP) project was a prospective study that aimed to identify genetic markers associated with opioid treatment outcomes. Healthy patients undergoing third-molar extractions were recruited from dental offices located within the Greater Toronto Area. Participants were evaluated using the Brief Pain Inventory Short Form, the Opioid Related Symptom Distress Scale, and the Leeds Dependence Questionnaire. Seventy-two participants had an active opioid prescription. Participants were prescribed one of the following opioids: codeine, morphine, hydromorphone, tramadol, or oxycodone. The majority of participants were female (57%), ranging from 16 to 44 years of age. Pain severity, pain interference, and side effects declined over the seven-day post-operative period. Additionally, 4% of participants displayed medium to high risk of dependence. It is anticipated that OTP will enable the development of a genetic test for opioid use and facilitate the introduction of this test into routine healthcare practice. The OTP study represents a novel approach to opioid treatment and has significant implications for future interventions targeting the ongoing opioid crisis. Employing a pharmacogenomic-guided strategy for prescribing opioids may improve patients’ response to this treatment and, in so doing, increase adherence to the target treatment plan. Optimized prescriptions may also provide public healthcare systems with beneficial savings and reduce the risks associated with opioid use.

What Pain Levels Do TSA Patients Experience When Given a Long-acting Nerve Block and Multimodal Analgesia?

The pain experience for total shoulder arthroplasty (TSA) patients in the first 2 weeks after surgery has not been well described. Many approaches to pain management have been used, with none emerging as clearly superior; it is important that any approach minimizes postoperative opioid use. (1) With a long-acting nerve block and comprehensive multimodal analgesia, what are the pain levels after TSA from day of surgery until postoperative day (POD) 14? (2) How many opioids do TSA patients take from the day of surgery until POD 14? (3) What are the PainOUT responses at POD 1 and POD 14, focusing on side effects from opioids usage? From January 27, 2017 to December 6, 2017, 154 TSA patients were identified as potentially eligible for this prospective, institutional review board-approved observational study. Of those, 46 patients (30%) were excluded (either because they were deemed not appropriate for the study, research staff were not available, patients were not eligible, or they declined to participate), and another six (4%) had incomplete followup data and could not be studied, leaving 102 patients (66%) for analysis here. Median preoperative pain with movement was 7 (interquartile range [IQR], 5-9) and 13 of 102 patients used preoperative opioids. All patients received a single-injection bupivacaine interscalene block with adjuvant clonidine, dexamethasone, and buprenorphine. Multimodal analgesia included acetaminophen, NSAIDs, and opioids. The primary outcome was the Numerical Rating Scale (NRS) pain score with movement on POD 14. The NRS pain score ranges from 0 (no pain) to 10 (worst pain possible). Secondary outcomes included NRS pain scores at rest and with movement (day of surgery, and PODs 1, 3, 7 and 14), daily analgesic use from day of surgery to POD 14 (both oral and intravenous), Opioid-Related Symptom Distress Scale (which assesses 12 symptoms ranging from 0 to 4, with 4 being the most distressing; the composite score is the mean of the 12 symptom-specific scores) on POD 1, and the PainOut questionnaire on POD 1 and POD 14. The PainOut questionnaire includes questions rating nausea, drowsiness, itching from 0 (none) to 10 (severe), as well as rating difficulty staying asleep from 0 (does not interfere) to 10 (completely interferes). The median NRS pain scores with movement were 2 (IQR, 0-5) on POD 1, 5 (IQR, 3-6) on POD 3, and the pain score was 3 (IQR, 1-5) on POD 14. Median total opioid use (converted to oral morphine equivalents) was 16 mg (4-50 mg) for the first 24 hours, 30 mg (8-63 mg) for the third, and 0 mg (0-20 mg) by the eighth 24-hour period, while the most frequent number of activations of the intravenous patient-controlled analgesia device was 0. Median PainOut scores on POD 1 and POD 14 for sleep interference, nausea, drowsiness and itching were 0, and the median composite Opioid-Related Symptom Distress Scale score on day 1 was 0.3 (IQR, 0.1-0.5). Clinicians using this protocol, which combines a long-acting, single-injection nerve block with multimodal analgesia, can inform TSA patients that their postoperative pain will likely be less than their preoperative pain, and that on average they will stop using opioids after 7 days. Future research could investigate what the individual components of this protocol contribute. Larger cohort studies or registries would document the incidence of rare complications. Randomized controlled trials could directly compare analgesic effectiveness and cost-benefits for this protocol versus alternative strategies, such as perineural catheters or liposomal bupivacaine. Perhaps most importantly, future studies could seek ways to further reduce peak pain and opioid usage on POD 2 and POD 3. Level IV, therapeutic study.

Effects of Korean hand acupressure on opioid-related nausea and vomiting, and pain after caesarean delivery using spinal anaesthesia

ObjectiveThis study examined the effects of Korean hand acupressure on opioid-related nausea and vomiting, and pain after caesarean delivery. MethodsFifty participants were randomly assigned to an acupressure group or a control group. Korean hand acupressure discs were applied for 24 h onto 12 acupressure points (K-9, F-4 for nausea and vomiting; M-3, M-4, L-4, H-2, H-3, H-7 for abdominal pain; and I-38, J-2 for back pain). Nausea and vomiting incidences, the opioid-related symptom distress scale scores, and pain scores were analysed using chi-square test, Fisher's exact test, Mann-Whitney U test, or the repeated-measures analysis of variance. ResultsThe acupressure group had lower incidences of nausea and vomiting, as well as significant improvements in the opioid-related symptom distress scores for nausea, vomiting, and pain. The acupressure group required fewer rescue antiemetics and analgesics. ConclusionKorean hand acupressure can relieve nausea and vomiting, as well as pain after caesarean delivery.

AnAnkle Trial study protocol: a randomised trial comparing pain profiles after peripheral nerve block or spinal anaesthesia for ankle fracture surgery

IntroductionAnkle fracture surgery is a common procedure, but the influence of anaesthesia choice on postoperative pain and quality of recovery is poorly understood. Some authors suggest a benefit of peripheral...

Patient-controlled epidural analgesia or multimodal pain regimen with periarticular injection after total hip arthroplasty: a randomized, double-blind, placebo-controlled study.

The optimal postoperative analgesia after primary total hip arthroplasty remains in question. This randomized, double-blind, placebo-controlled study compared the use of patient-controlled epidural analgesia (PCEA) with use of a multimodal pain regimen including periarticular injection (PAI). We hypothesized that PAI would lead to earlier readiness for discharge, decreased opioid consumption, and lower pain scores. Forty-one patients received PAI, and forty-three patients received PCEA. Preoperatively, both groups were administered dexamethasone (6 mg, orally). The PAI group received a clonidine patch and sustained-release oxycodone (10 mg), while the PCEA group had placebo. Both groups received combined spinal-epidural anesthesia and used an epidural pain pump postoperatively; the PAI group had normal saline solution, while the PCEA group had bupivacaine and hydromorphone. The primary outcome, readiness for discharge, required the discontinuation of the epidural, a pain score of <4 (numeric rating scale) without parenteral narcotics, normal eating, minimal nausea, urination without a catheter, a dry surgical wound, no acute medical problems, and the ability to independently transfer and walk 12.2 m (40 ft). The mean time to readiness for discharge (and standard deviation) was 2.4 ± 0.7 days (PAI) compared with 2.3 ± 0.8 days (PCEA) (p = 0.86). The mean length of stay was 3.0 ± 0.8 days (PAI) compared with 3.1 ± 0.7 days (PCEA) (p = 0.46). A significant mean difference in pain score of 0.74 with ambulation (p = 0.01; 95% confidence interval [CI], 0.18 to 1.31) and 0.80 during physical therapy (p = 0.03; 95% CI, 0.09 to 1.51) favored the PCEA group. The mean opioid consumption (oral morphine equivalents in milligrams) was significantly higher in the PAI group on postoperative day 0 (43 ± 21 compared with 28 ± 23; p = 0.002) and postoperative days 0 through 2 (136 ± 59 compared with 90 ± 79; p = 0.004). Opioid-Related Symptom Distress Scale (ORSDS) composite scores for severity and bothersomeness as well as scores for nausea, vomiting, and itchiness were significantly higher in the PCEA group (p < 0.05). Quality of Recovery-40 scores and patient satisfaction were similar. PAI did not decrease the time to discharge and was associated with higher pain scores and greater opioid consumption but lower ORSDS scores compared with PCEA. The choice for analgesic regimen may depend on a particular patient's threshold for pain and the potential side effects.

Effects of parecoxib on analgesia benefit and blood loss following open prostatectomy: a multicentre randomized trial.

BackgroundThis multi-centre, prospective, randomized, double-blind, placebo-controlled study was designed to test the hypotheses that parecoxib improves patients’ postoperative analgesia without increasing surgical blood loss following radical open prostatectomy.Methods105 patients (64 ± 7 years old) were randomized to receive either parecoxib or placebo with concurrent morphine patient controlled analgesia. Cumulative opioid consumption (primary objective) and the overall benefit of analgesia score (OBAS), the modified brief pain inventory short form (m-BPI-sf), the opioid-related symptom distress scale (OR-SDS), and perioperative blood loss (secondary objectives) were assessed.ResultsIn each group 48 patients received the study medication for 48 hours postoperatively. Parecoxib significantly reduced cumulative opioid consumption by 24% (43 ± 24.1 mg versus 57 ± 28 mg, mean ± SD, p=0.02), translating into improved benefit of analgesia (OBAS: 2(0/4) versus 3(1/5.25), p=0.01), pain severity (m-BPI-sf: 1(1/2) versus 2(2/3), p < 0.01) and pain interference (m-BPI-sf: 1(0/1) versus 1(1/3), p=0.001), as well as reduced opioid-related side effects (OR-SDS score: 0.3(0.075/0.51) versus 0.4(0.2/0.83), p=0.03). Blood loss was significantly higher at 24 hours following surgery in the parecoxib group (4.3 g⋅dL−1 (3.6/4.9) versus (3.2 g⋅dL−1 (2.4/4.95), p=0.02).ConclusionsFollowing major abdominal surgery, parecoxib significantly improves patients’ perceived analgesia. Parecoxib may however increase perioperative blood loss. Further trials are needed to evaluate the effects of selective cyclooxygenase-2 inhibitors on blood loss.Trial registrationClinicalTrials.gov Identifier: NCT00346268

Effect of a Preoperative Gabapentin on Postoperative Analgesia in Patients with Inflammatory Bowel Disease Following Major Bowel Surgery: A Randomized, Placebo‐Controlled Trial

Postoperative pain management for patients with inflammatory bowel disease (IBD) can be challenging. These patients have a high tolerance to pain medication, and relative contraindications to the use of epidural analgesia, limiting the pain management options. We evaluated the effect of a single preoperative gabapentin dose on opioid consumption for patients with IBD undergoing abdominal surgery. Secondary outcomes were postoperative pain scores, opioid-related side effects, and patient's length of hospital stay. Following Research Ethics Board approval and informed written consent, patients were randomly allocated into 2 groups receiving either 600 mg of oral gabapentin or placebo 1 hour before the surgery. A blinded anesthesiologist recorded pain scores at rest and movement twice daily for 2 postoperative days. Also recorded were opioid consumption, time of return of bowel function, time to discharge, and opioid-related side effects on the opioid-related symptom distress scale (ORSDS). Seventy-two patients completed the study. The difference in opioid consumption (P = 0.4169) and pain scores measured at rest and movement on all 4 postoperative visits was not statistically significant. There was no significant difference between gabapentin and placebo on all the 11 symptoms reported on the ORSDS. There was a slight increase in length of hospital stay in the placebo group, but the return of bowel function was similar between the groups. This study examined the effect of a single preoperative administration of gabapentin in patients with IBD undergoing major bowel surgery. Our results suggest a single preoperative oral dose of gabapentin 600 mg does not reduce postoperative pain scores, opioid consumption, or opioid-related side effects.

Performance Characteristics and Validation of the Opioid-Related Symptom Distress Scale for Evaluation of Analgesic Side Effects After Orthopedic Surgery

The Opioid-Related Symptom Distress Scale (ORSDS) is a 4-point scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness) for 12 symptoms. The symptom-specific ORSDS is the average of the 3 symptom distress dimensions. The composite ORSDS is the average of 12 symptom-specific scores. The ORSDS was validated for outpatient laparoscopic cholecystectomy (under general anesthesia) by assessment of internal consistency, content validity, construct validity, principal components analysis, known group validity, responsiveness, and opioid dose dependency. Additional validation studies were suggested. We investigated performance characteristics and validity of the ORSDS for postoperative analgesia after 4 types of anesthetic and analgesic regimens. The ORSDS and validation questions were administered to 4 groups of 50 orthopedic patients. Peripheral nerve blockade (Peripheral) was performed for distal upper extremity surgery; neuraxial anesthesia (Neuraxial) was performed for anterior cruciate ligament reconstruction; combined spinal-epidural anesthesia/femoral nerve block/epidural analgesia (Regional) was performed for total knee arthroplasty; and general anesthesia/IV opioids (GA) was performed for posterior lumbar spine fusion. All patients also received oral opioid analgesics. Median composite ORSDS scores on postoperative day 1 were 0.19 (Peripheral), 0.52 (Neuraxial), 0.51 (Regional), and 0.94 (GA). The following symptoms had median symptom-specific ORSDS scores >0: Neuraxial = drowsiness, dry mouth; Regional = dizziness, dry mouth; GA = nausea, fatigue, dizziness, drowsiness, dry mouth. Problematic symptoms (symptoms for which at least 25%of patients reported symptom-specific ORSDS scores >1) were: all groups = drowsiness, dry mouth, fatigue; Neuraxial = nausea, dizziness, itchiness; Regional = nausea, dizziness, itchiness; GA = difficulty concentrating, headache, nausea, dizziness, itchiness. High symptom-specific ORSDS scores were associated with clinically meaningful adverse events. In some cases, relevant ORSDS scores were related to activity level, patient satisfaction, and nausea and vomiting measures. Many components occurred in correlated clusters. Responsiveness statistics (the ability of an instrument to detect changes once they have occurred) were high for nausea and vomiting. Linear regression analysis indicated that opioid use was associated with composite ORSDS scores for Peripheral, Regional, and GA. Validity of the ORSDS was supported by predetermined validation criteria, including measures of internal consistency, content validity, construct validity, principal components analysis, known group validity, responsiveness, and correlation with opioid intake. The ORSDS is a valid tool for assessment of opioid side effects after orthopedic surgery, and can be used in clinical trials involving a wide variety of anesthetic and analgesic regimens.

Development and longitudinal validation of the overall benefit of analgesia score: a simple multi-dimensional quality assessment instrument

BackgroundThe goal of this study was to develop and validate the overall benefit of analgesic score (OBAS), which assesses pain intensity and the opioid-related adverse effects. MethodsThe score was developed and validated in four trials (n=1470 patients). Data from randomized trial I were used to develop the OBAS (factor analysis). Data from randomized trial II were used to compare the resolution of rofecoxib’s analgesic effects between OBAS and pain scores. Randomized trial III (spine surgery) was conducted to evaluate prospectively the reliability of the OBAS and to compare its resolution of analgesic treatment with the opioid-related symptom distress scale (OR-SDS) and the modified brief pain inventory short form (m-BPI-sf). Trial IV was conducted to evaluate in patients with a moderate-to-high level of postoperative pain (after major abdominal surgery) the relation of OBAS and pain scores for patients’ satisfaction with analgesic therapy. ResultsThe seven-item OBAS yielded a higher resolution of analgesic treatment effects than pain scores, the OR-SDS and m-BPI-sf. The OBAS has a fair inter-rater reliability (concordance correlation of 0.71 c) and is more sensitive (P=0.03) in indicating the delivery of opioid boluses than the dedicated OR-SDS. The OBAS, but not pain scores at rest or pain scores during movement, explained significant variance in patients’ satisfaction with postoperative pain therapy. ConclusionsThe OBAS is a simple, multi-dimensional quality assessment instrument to measure patients’ benefit from postoperative pain therapy. Opioid symptom distress, pain relief, and patients’ satisfaction are combined in a reliable and valid tool.

Use of low-dose pregabalin in patients undergoing laparoscopic cholecystectomy

BackgroundThe objective of this study was to examine the effects of low-dose pregabalin on the analgesic efficacy, side-effects, and recovery profile in patients undergoing laparoscopic cholecystectomy. MethodsOne hundred and sixty-two patients aged 18–65 yr, of ASA physical status I–III, undergoing elective outpatient laparoscopic cholecystectomy were recruited and randomized in this prospective, placebo-controlled, double-blind study to receive one of the following study medications orally: pregabalin 50 mg, pregabalin 75 mg, or placebo, 1 h before surgery and then every 12 h after operation for a total of three doses. Postoperative numeric pain scores, analgesic consumption, recovery score (QoR-40), and side-effects (opioid-related symptom distress scale) were assessed in the early postoperative period (every 15 min during the first hour, at 90, 120 min, 6, and 12 h) and at days 1, 2, and 7. Data were analysed using an intention-to-treat method. ResultsCompared with the placebo group, the pain scores were lower in the pregabalin 75 mg group in the first 90 min after surgery (P<0.05). Pregabalin 50 mg resulted in pain reduction at 30 and 45 min (P<0.05) relative to placebo. The analgesic consumption, side-effects, and recovery scores were similar among the three groups. ConclusionsPerioperative administration of pregabalin 75 mg provided limited analgesic benefit in the postoperative period. An updated meta-analysis confirms this finding (see Supplementary material).

Development and validation of a composite score based on clinically meaningful events for the opioid-related symptom distress scale

To develop and validate a composite score based on clinically meaningful events (CMEs) for the opioid-related symptom distress scale (OR-SDS) that would be appropriate for use in postoperative clinical trials. Secondary analysis of data from 2 multi-site Phase III randomized clinical safety trials: a general surgery trial (N = 1,050) and a coronary artery bypass graft surgery trial (N = 1,636). Validating measures include daily opioid consumption and physician and patient global evaluations of study medication. We empirically defined CMEs for each symptom, using factor analysis and an area under the receiver-operating characteristic analysis of the severity and frequency items of the OR-SDS. Construct validity was examined by testing hypotheses of relationships between composite CME scores and opioid consumption and physician and patient evaluations of study medication. Hypotheses supporting the construct validity of the CME-based composite score were confirmed. Significant associations were found between higher numbers of CMEs with greater opioid consumption and lower likelihood of a positive evaluation of the study medication. The OR-SDS CME-based composite score demonstrates evidence of construct validity and appears appropriate for use in evaluating patients' opioid-related side effect burden in future postoperative clinical trials.

Reduction in Opioid-Related Adverse Events and Improvement in Function with Parecoxib followed by Valdecoxib Treatment after Non-Cardiac Surgery

Multimodal pain therapy including cyclo-oxygenase-2 inhibitors can result in optimal pain management with decreased opioid use and fewer opioid-related adverse events. Patient reported outcomes (PROs) help identify benefits in reduced opioid use and increased pain control. In this randomized, double-blind trial, patients (n = 1062) undergoing major non-cardiac elective surgery received either parenteral parecoxib for 3 days or placebo then oral valdecoxib or placebo for a total of 10 days, with both arms being allowed additional opioid analgesia. Clinically meaningful opioid-related adverse events were assessed daily using the Opioid-Related Symptom Distress Scale (OR-SDS). Pain severity and interference with function were evaluated daily using the modified Brief Pain Inventory exploratory form (mBPI-e). Additional validation work was undertaken to understand the psychometric properties of the two PROs. Detailed clinical results were reported elsewhere. Patients receiving parecoxib/valdecoxib achieved significantly better pain control and consumed 37% and 28% less opioid medication than the placebo group on day 2 and day 3, respectively. Over the 10-day treatment period, patients receiving parecoxib/valdecoxib consumed 31% less opioid medication. This coincided with significantly fewer (p < 0.0001) OR-SDS clinically meaningful events (CMEs) and lower mBPI-e scores from days 2-10 in the parecoxib/valdecoxib group compared with the placebo group. On day 3, the percentage of patients reporting one, two or three CMEs in the parecoxib/valdecoxib versus placebo group was 11.6% versus 13.0%, 2.3% versus 5.1%, and 0.8% versus 2.3%, respectively. The mean (+/- standard error) mBPI-e pain severity scores over days 2-10 were 2.47 +/- 0.04 for the parecoxib/valdecoxib group and 3.01 +/- 0.04 for the placebo group, and the mean mBPI-e pain interference scores were 1.73 +/- 0.04 and 2.19 +/- 0.04, respectively. Patients receiving parecoxib/valdecoxib had less pain interference on physical functioning, required less opioid medication and experienced fewer clinically meaningful opioid-related adverse events than patients receiving placebo.

A Randomized Double‐Blind Comparison of a Morphine–Fentanyl Combination vs. Morphine Alone for Patient‐Controlled Analgesia Following Bowel Surgery

An ideal patient-controlled analgesia (PCA) opioid would have both a rapid onset and a long duration of action, attributes, which are not available in currently existing opioids including morphine, the most widely used agent. A mixture of rapid onset and long-acting opioids may potentially achieve both these qualities. In a randomized, double-blind study, we compared a fentanyl-morphine combination with morphine alone for PCA, in 54 patients undergoing bowel surgery. The combination solution was prepared according to a 1:75 fentanyl to morphine potency ratio. The mixture contained fentanyl 13.33 mug/mL and morphine 1 mg/mL. The morphine alone solution contained 2 mg/mL. Patients were randomly allocated to one of the regimens and were then evaluated 4 times during the first 48 hours following surgery. Time to effect, visual analog pain scores, opioid consumption, demands, deliveries, and side effects on an opioid-related symptom distress scale were recorded. Groups were well matched for age, weight, and sex. There were no significant differences between groups in time to effect, PCA usage, pain scores or side effects other than the occurrence of nausea, which was lower for the combination group in 1 visit. Further studies are needed to explore the potential of different potency ratios and opioid combinations to achieve rapid and long-lasting pain control.

(880): Development and validity of a composite Clinicially Meaningful Events (CMEs) score based on the Opioid-Related Symptom Distress Scale (OR-SDS)

(880): Development and validity of a composite Clinicially Meaningful Events (CMEs) score based on the Opioid-Related Symptom Distress Scale (OR-SDS)

Dose-response relationship between opioid use and adverse effects after ambulatory surgery

This health outcomes analysis based on data from a randomized, double-blind, placebo-controlled trial determined dose-response relationship between opioid use and related symptoms. All patients received intravenous fentanyl on demand for pain predischarge, and oral acetaminophen 500 mg/hydrocodone 5 mg every 4–6 hours as needed postdischarge for up to 7 days postsurgery. Patients completed an opioid-related Symptom Distress Scale (SDS) questionnaire every 24 hours postdischarge for 7 days, which assessed 12 opioid-related symptoms by 3 ordinal measures: frequency, severity, and bothersomeness. Clinically meaningful events (CMEs) were defined based on the responses to this questionnaire. Opioid use was converted to morphine equivalent dose (MED). The dose-response relationship between composite SDS scores and MED on Day 1, on Days 0 and 1, and on Days 1–4, was assessed. SDS scores for all 12 symptoms within the 3 dimensions were significantly associated with MED on Day 1 ( F-value = 1.56; P = 0.04), as well as cumulative MED used on Days 0 and 1 ( F-value = 1.85; P<0.01). Patients with a specific CME used a higher MED than those without a CME on Day 1 ( P<0.001). Between Days 1 and 4, patients with a higher number of patient-CME-days used a significantly higher MED. Regression analyses suggested that once the MED reached a threshold, approximately every 4 mg increase in MED was related to 1 additional patient-CME-day ( P<0.01). A dose-response relationship empirically exists between MED and directly assessed opioid-related CMEs after ambulatory laparoscopic cholecystectomy. Once daily MED reaches a threshold, every 3–4 mg increase will be associated with 1 additional clinically meaningful opioid-related symptom, or 1 additional patient-day with an opioid-related CME.