Safety and Efficacy of Perioperative Intravenous Meloxicam for Moderate-to-Severe Pain Management in Total Knee Arthroplasty: A Randomized Clinical Trial.
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ABSTRACT: Objective
To evaluate the effect of perioperative meloxicam IV 30 mg on opioid consumption in primary total knee arthroplasty (TKA).Design
Multicenter, randomized, double-blind, placebo-controlled trial.Subjects
In total, 181 adults undergoing elective primary TKA.Methods
Subjects received meloxicam 30 mg or placebo via an IV bolus every 24 hours, the first dose administered prior to surgery as part of a multimodal pain management protocol. The primary efficacy parameter was total opioid use from end of surgery through 24 hours.Results
Meloxicam IV was associated with less opioid use versus placebo during the 24 hours after surgery (18.9 ± 1.32 vs 27.7 ± 1.37 mg IV morphine equivalent dose; P < 0.001) and was superior to placebo on secondary endpoints, including summed pain intensity (first dose to 24 hours postdosing, first dose to first assisted ambulation, and first dose to discharge) and opioid use (48-72 hrs., 0-48 hrs., 0-72 hrs., hour 0 to end of treatment, and the first 24 hours after discharge). Adverse events (AEs) were reported for 69.9% and 92.0% of the meloxicam IV and placebo groups, respectively; the most common AEs were nausea (40% vs. 59%), vomiting (16% vs 22%), hypotension (14% vs 15%), pruritus (15% vs 11%), and constipation (11% vs 13%).Conclusions
Perioperative meloxicam IV 30 mg as part of a multimodal analgesic regimen for elective primary TKA reduced opioid consumption in the 24-hour period after surgery versus placebo and was associated with a lower incidence of AEs typically associated with opioid use.
SUBMITTER: Berkowitz RD
PROVIDER: S-EPMC8185557 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) are recommended for multimodal postoperative pain management. We evaluated opioid-sparing effects and rehabilitative results after perioperative celecoxib administration for total knee arthroplasty.MethodsThis was a prospective, randomized, observer-blind control study. Eighty patients that underwent total knee arthroplasty were randomized into two groups of 40 each. The study group received a single 400 mg dose of celecoxib, one hour before surgery, and 200 mg of celecoxib every 12 hours for five days, along with patient-controlled analgesic (PCA) morphine. The control group received only PCA morphine for postoperative pain management. Visual analog scale (VAS) pain scores, active range of motion (ROM), total opioid use and postoperative nausea/vomiting were analyzed.ResultsGroups were comparable for age, pre-operative ROM, operation duration and intraoperative blood loss. Resting VAS pain scores improved significantly in the celecoxib group, compared with controls, at 48 hrs (2.13 +/- 1.68 vs. 3.43 +/- 1.50, p = 0.03) and 72 hrs (1.78 +/- 1.66 vs. 3.17 +/- 2.01, p = 0.02) after surgery. Active ROM also increased significantly in the patients that received celecoxib, especially in the first 72 hrs [40.8 degrees +/- 17.3 degrees vs. 25.8 degrees +/- 11.5 degrees , p = 0.01 (day 1); 60.7 degrees +/- 18.1 degrees vs. 45.0 degrees +/- 17.3 degrees , p = 0.004 (day 2); 77.7 degrees +/- 15.1 degrees vs. 64.3 degrees +/- 16.9 degrees , p = 0.004 (day 3)]. Opioid requirements decreased about 40% (p = 0.03) in the celecoxib group. Although patients suffering from post-operative nausea/vomiting decreased from 43% in control group to 28% in celecoxib group, this was not significant (p = 0.57). There were no differences in blood loss (intra- and postoperative) between the groups. Celecoxib resulted in no significant increase in the need for blood transfusions.ConclusionPerioperative celecoxib significantly improved postoperative resting pain scores at 48 and 72 hrs, opioid consumption, and active ROM in the first three days after total knee arthroplasty, without increasing the risks of bleeding.Trial registrationClinicaltrials.gov NCT00598234.
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Project description:BackgroundAn intravenous (IV) formulation of meloxicam was developed for moderate-to-severe pain management. This study evaluated the safety and efficacy of meloxicam IV after open abdominal hysterectomy. Meloxicam IV is an investigational product not yet approved by the US Food and Drug Administration.MethodsWomen (N = 486) with moderate-to-severe pain after open abdominal hysterectomy were enrolled in this multicenter, randomized, double-blind, placebo- and active-controlled trial. Subjects were randomized to receive a single dose of meloxicam IV (5-60 mg), placebo, or morphine (0.15 mg/kg) in ≤6 hours after morphine dosing on postoperative day 1 and were evaluated for 24 hours. Rescue morphine (≈0.15 mg/kg IV) was available if needed for pain not relieved by the study medication. In an open-label extension (N = 295), meloxicam IV was administered once daily for the remaining hospital stay (or per the investigator's discretion). The coprimary efficacy end points were the summed pain intensity difference (SPID24) and total pain relief (TOTPAR24) from hour 0 to 24 hours after dosing. Effect size, the standardized difference between means reported in standard deviation (SD) units, was calculated to indicate the magnitude of the difference in the mean analgesic effect measured for different intervention groups.ResultsSubjects who received morphine or meloxicam IV had a median time to first perceptible pain relief within 6-8 minutes. Morphine and meloxicam IV 5-60 mg produced statistically significant differences than placebo in SPID24 and TOTPAR24. SPID24 (standard error [SE]) for meloxicam IV 5-60 mg ranged from -56276.8 (3926.46) to -33517.1 (3930.1; P < .001); SPID24 (SE) for morphine and placebo were -29615.8 (3869.2; P < .001) and 4555.9 (3807.1), respectively. SPID24 effect sizes (95% confidence intervals) for the 60, 30, 15, 7.5, and 5 mg meloxicam IV doses and morphine were 1.93 (1.61-2.25), 2.00 (1.65-2.35), 1.70 (1.35-2.05), 1.28 (0.95-1.60), 1.25 (0.90-1.61), and 1.12 (0.77-1.45) SDs, respectively. TOTPAR24 (SE) for meloxicam IV 5-60 mg ranged from 3104.5 (155.28) to 4130.4 (191.17; P < .001); TOTPAR24 (SE) for morphine and placebo were 2723.3 (188.4; P < .001) and 1100.6 (185.4), respectively. TOTPAR24 effect sizes (95% confidence interval) for the 60, 30, 15, 7.5, and 5 mg meloxicam IV doses and morphine were 2.03 (1.70-2.35), 2.05 (1.70-2.40), 1.78 (1.43-2.13), 1.35 (1.03-1.67), 1.37 (1.01-1.72), and 1.10 (0.75-1.45) SDs, respectively. The mean total opioid consumed (SD) during the double-blind phase was 4.6 (8.17), 5.3 (8.85), 5.9 (7.85), 8.5 (9.67), 9.3 (9.47), 9.6 (8.12), and 16.0 (10.15) mg for patients in the 60, 30, 15, 7.5, and 5 mg meloxicam IV, morphine, and placebo groups, respectively. Generally, meloxicam IV was well tolerated, evidenced by the incidence of adverse events compared to placebo and lack of deaths and treatment-related serious adverse events.ConclusionsA meloxicam IV dose of 5-60 mg was generally well tolerated and appeared to reduce opioid consumption in subjects with moderate-to-severe pain after open abdominal hysterectomy. Once-daily administration of meloxicam IV produced analgesic effect within 6-8 minutes postdose that was maintained over a 24-hour dosing interval.
| S-EPMC6530966 | biostudies-literature
Project description:Patients undergoing total knee arthroplasty (TKA) report low satisfaction with postoperative pain control. The purpose of this study is to examine if there is a difference in post-operative pain for TKA patients without femoral nerve block receiving an intra-operative pericapsular injection of bupivacaine liposome suspension (EXPAREL; Pacira Pharmaceuticals, Inc., San Diego, California) versus a concentrated multi drug cocktail. Seventy TKA patients were randomly assigned to either the bupivacaine liposome or the multi-drug cocktail. Post-operative pain scores, morphine sulfate equivalence consumption values, adverse events, and overall pain control satisfaction scores were collected. Patients reported significantly higher pain level for the cocktail group on post-op day 1 (p < .05) and post-op day 2 (p < .01) versus the bupivacaine liposome group. This same trend was found for morphine sulfate equivalence consumption in the PACU (p < .01) and post-op day 2 (p < .01). Higher satisfaction in pain control (p < .001) and overall experience (p < .01) was also found in the bupivacaine liposome group. Finally, significantly more adverse events were found in the multi-drug group versus the bupivacaine liposome group (p < .05). The study findings demonstrated a non-inferior difference, albeit not a clinically significant difference, in patient-perceived pain scores, morphine sulfate equivalence consumption, adverse events, and overall satisfaction.
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Project description:BackgroundThe ability of preoperative intravenous glucocorticoids to control pain after total knee arthroplasty (TKA) has been examined in many studies, but it remains controversial. Therefore, we undertook a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of preoperative intravenous glucocorticoids for postoperative pain management after TKA.MethodsWe systematically searched RCTs from electronic databases, including PubMed, Embase, Web of Science, the Cochrane Library, the Chinese Wanfang Database, and the China National Knowledge Infrastructure database. The outcomes included visual analogue scale (VAS) scores at 6, 12, 24, 48, and 72 hours after TKA; the occurrence of postoperative nausea and vomiting (PONV); blood glucose at 6 and 24 hours after TKA; and the occurrence of infection.ResultsOf the identified studies, a total of 11 RCTs involving 1000 patients (glucocorticoids = 501, control = 499) were included in this meta-analysis. Compared with a placebo, preoperative intravenous glucocorticoids significantly reduced VAS scores at 6, 12, 24, and 48 hours, with decreases of 3.63 points, 6.81 points, 10.40 points, and 3.15 points, respectively, on a 110-point VAS. Moreover, intravenous glucocorticoids were associated with significant decreases of 19.4% and 16.8% in the occurrence of nausea and vomiting, respectively. However, intravenous glucocorticoids were also associated with increased blood glucose with no clinical importance at 6 hours after TKA. No significant difference was found in the occurrence of infection or in blood glucose at 24 hours after TKA.ConclusionPreoperative intravenous glucocorticoids are an effective and safe method to reduce postoperative pain and PONV in patients following TKA. More studies are necessary to identify the optimal dose and type of glucocorticoids for maximal pain control.
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Project description:BackgroundBetween 9% and 20% of patients experience moderate to severe persistent postoperative pain after total hip or knee arthroplasty. Severe immediate postoperative pain limits rehabilitation and is associated with the development of persistent postoperative pain. Therefore, perioperative analgesic and physiotherapeutic interventions are of interest to reduce persistent pain. In two systematic reviews with identical methodology, we aim to investigate the effects of (a) perioperative analgesic interventions and (b) physiotherapeutic interventions in reducing persistent pain after total hip and knee arthroplasty.MethodsWe will include randomised and cluster-randomised controlled trials on perioperative analgesic and physiotherapeutic interventions for patients undergoing elective total hip or knee arthroplasty for osteoarthritis. After contact with the authors, trials without pain data 3-24 months postoperatively will be excluded. Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and reference lists will be searched for eligible trials. Two authors will independently screen, extract data and assess the risk of bias. The primary outcome is pain scores 3-24 months postoperatively. Meta-analyses will be performed for interventions with two or more trials. We will conduct trial sequential analyses and assign Grading of Recommendations, Assessment, Development and Evaluation (GRADE) ratings.ConclusionNo previous review on reduction of persistent postoperative pain has included non-pharmacological or invasive analgesic techniques. These two reviews with identical methodology will summarise the evidence of analgesic and physiotherapeutic perioperative interventions to prevent persistent pain.Prospero registrationCRD42021284175.
| S-EPMC9315006 | biostudies-literature
Project description:Ischaemic preconditioning is a method of protecting tissue against ischaemia-reperfusion injury. It is an innate protective mechanism that increases a tissue's tolerance to prolonged ischaemia when it is first subjected to short burst of ischaemia and reperfusion. It is thought to provide this protection by increasing the tissue's tolerance to ischaemia, therby reducing oxidative stress, inflammation and apoptosis in the preconditioned tissue. We used microarrays to investigate the genomic response induced by ischaemic preconditioning in muscle biopsies taken from the operative leg of total knee arthroplasty patients in order to gain insight into the ischaemic preconditioning mechanism. Patients undergoing primary knee arthroplasty were randomised to control and treatment (ischaemic preconditioning) groups. Patients in the treatment group received a preconditioning stimulus immediately prior to surgery. The ischaemic preconditioning stimulus consisted of three five-minute periods of tourniquet insufflation on the lower operative limb, interrupted by five minute periods of reperfusion. All patients had a tourniquet applied to the lower limb after the administration of spinal anaesthesia, as per normal protocol for knee arthroplasty surgery. Muscle biopsies were taken from the quadriceps muscle of the operative knee at the immediate onset of surgery (T0) and at 1 hour into surgery (T1). Total RNA was extracted from biospies of four control and four treatment patients and hybridised to the Affymetrix Human U133 2.0 chip.
2010-04-12 | E-GEOD-21164 | biostudies-arrayexpress
Project description:We aimed to investigate whether perioperative magnesium sulfate administration was associated with the incidence of chronic persistent postoperative pain (PPP) following total knee arthroplasty (TKA). This retrospective observational study was performed at a single tertiary academic hospital. We reviewed the medical records of adult patients who were admitted between August 2012 and July 2017. Patients who received magnesium sulfate during surgery were the magnesium group. The presence of PPP, one year after TKA, was evaluated using a binary logistic regression analysis. A total of 924 patients were included in the analysis, and 148 patients (16.0%) experienced PPP one year after TKA. In the multivariable model, the magnesium group had a 62% lower rate of PPP one year after TKA compared to the control group (odds ratio (OR): 0.38, 95% confidence interval (CI): 0.16 to 0.90; p = 0.027). This finding was similar in the sensitivity analysis using propensity score adjustment (OR: 0.38, 95% CI: 0.16 to 0.93; p = 0.036). We showed that perioperative magnesium sulfate administration was associated with a lower rate of PPP one year after TKA. Our results suggest that magnesium sulfate administered perioperatively is effective for the alleviation of acute and chronic pain after surgery.
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Project description:ObjectiveOur objective was to study the use of pain medications for persistent knee pain and their predictors after revision total knee arthroplasty (TKA).MethodsWe examined whether demographic (gender, age) and clinical characteristics [BMI, co-morbidity measured by the Deyo-Charlson index (a 5-point increase), anxiety and depression] predict the use of NSAIDs and narcotic pain medications 2 and 5 years after revision TKA. Multivariable logistic regression adjusted for these predictors as well as operative diagnosis, American Society of Anesthesiologists class and distance from the medical centre.ResultsA total of 1533 patients responded to the 2-year questionnaire and 881 responded to the 5-year questionnaire. NSAID use was reported by 13.4% (206/1533) of patients at 2 years and 16.7% (147/881) at 5 years. Narcotic medication use was reported by 5.4% (83/1533) of patients at 2 years and 5.9% (52/881) at 5 years. Significant predictors of the use of NSAIDs for index TKA pain at 2 and 5 years were age >60-70 years [odds ratio (OR) 0.62 (95% CI 0.39, 0.98) and 0.46 (0.25, 0.85)] compared with age ≤60 years and a higher Deyo-Charlson index [OR 0.51 (95% CI 0.28, 0.93)] per 5-point increase at 5-year after revision TKA. Significant predictors of narcotic pain medication use for index TKA pain were age >60-70 years [OR 0.41 (0.21, 0.78)] and >70-80 years [0.40 (95% CI 0.22, 0.73)] at 2 years and depression [OR 4.58 (95% CI 1.58, 13.18)] at 5 years.ConclusionYounger age and depression were risk factors for the use of NSAIDs and narcotic pain medications for index TKA pain at 2- and 5-years after revision TKA.
| S-EPMC4165843 | biostudies-literature
Project description:BackgroundThe efficacy of intravenous acetaminophen in multimodal pain management in patients undergoing total knee arthroplasty (TKA) is controversial. The purpose of this meta-analysis was to compare the efficacy of intravenous acetaminophen versus placebo in TKA.MethodsRandomized controlled trials (RCTs) or retrospective cohort studies (RCSs) concerning related topics were retrieved from PubMed (1996-June 2018), Embase (1980-June 2018), and the Cochrane Library (CENTRAL June 2018). Any studies comparing intravenous acetaminophen with a placebo were included in this meta-analysis. Meta-analysis results were collected and analyzed by Stata 12.0. Subgroup analysis was performed according to the general characteristics of the patients.ResultsIn total, the patients from six studies met the inclusion criteria. Our meta-analysis results indicated that compared with a control group, intravenous acetaminophen was associated with reductions in total morphine consumption and visual analogue scale (VAS) score at postoperative day (POD) 3. However, there was no significant difference in morphine consumption at POD 1 or in VAS at POD 1 or POD 2. Moreover, there was no significant difference in the length of hospital stay.ConclusionsBased on our results, intravenous acetaminophen in multimodal management has shown better efficacy in pain relief at POD 3 and has morphine-sparing effects. High-quality studies with more patients are needed in the future.
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