Parecoxib Enhances Resveratrol against Human Colorectal Cancer Cells through Akt and TXNDC5 Inhibition and MAPK Regulation.

In this study, we discovered the mechanisms underlying parecoxib and resveratrol combination's anti-cancer characteristics against human colorectal cancer DLD-1 cells. We studied its anti-proliferation and apoptosis-provoking effect by utilizing cell viability 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, fluorescence microscope, gene overexpression, Western blot, and flow cytometry analyses. Parecoxib enhanced the ability of resveratrol to inhibit cell viability and increase apoptosis. Parecoxib in combination with resveratrol strongly enhanced apoptosis by inhibiting the expression of thioredoxin domain containing 5 (TXNDC5) and Akt phosphorylation. Parecoxib enhanced resveratrol-provoked c-Jun N-terminal kinase (JNK) and p38 phosphorylation. Overexpression of TXNDC5 and repression of JNK and p38 pathways significantly reversed the inhibition of cell viability and stimulation of apoptosis by the parecoxib/resveratrol combination. This study presents evidence that parecoxib enhances the anti-cancer power of resveratrol in DLD-1 colorectal cancer cells via the inhibition of TXNDC5 and Akt signaling and enhancement of JNK/p38 MAPK pathways. Parecoxib may be provided as an efficient drug to sensitize colorectal cancer by resveratrol.

Haemodynamics, side effects and safety of the combination of continuous femoral nerve block and intravenous parecoxib for pain management after Total Knee Arthroplasty: A pilot study.

Background: Total Knee Arthroplasty (TKA) is a well-established surgical procedure for the treatment of knee joint diseases. This operation leads to severe acute and chronic pain, and intravenous administration of parecoxib could provide significant pain relief. Objective: The aim of the study was to compare the hemodynamic data and safety profile of patients who received parecoxib compared to placebo following TKA. Methods: Ninety patients were followed during this study and were randomly assigned into two equal groups. Group P received parecoxib and Group C received the placebo. Exclusion criteria included age < 40 or > 80 years, ASA III or higher, obesity (>140 kg), allergy to local anaesthetics, opioid dependence, contraindications for subarachnoid anaesthesia, femoral block or the administration of parecoxib.The haemodynamic data collected were Systolic Arterial Pressure (SAP), Diastolic Arterial Pressure (DAP), Heart Rate (HR), Oxygen Saturation (Ox-Sat), blood transfusion requirements and side effects. Recordings were performed every hour for up to 10 hours and at 15min, 4, 8, 12, 24, 36 hours postoperatively. Results: The postoperative SAP and DAP data presented similar findings among groups (p>0.05) within the aforementioned time intervals. The postoperative HR data for both groups displayed no statistically significant difference between the two cohorts (p>0.05). Regarding the occurrence of transfusion, there is no statistically significant difference between the parecoxib and placebo cohorts. The frequency of side effects was negligible and could not be correlated with either group. Conclusion: Therefore, parecoxib did not render any noticeable impact on the hemodynamic profile of the patients.

Effects of parecoxib sodium on early cognitive impairment and inflammation levels in burned rats.

To study the effect of parecoxib sodium in alleviating inflammation in burned rats and restoring cognitive function in burned rats. 30 SPF grade SD rats were randomly divided into 6 groups: (1) Blank control group (Group C). (2) Sham surgery group (Group Sham). (3) Second-degree burn model (Group B). (4) Low-dose (1 mg/kg/d) parecoxib sodium (Group L+B). (5) Medium-dose (10 mg/kg/d) parecoxib sodium (Group M+B). (6) High-dose (20 mg/kg/d) parecoxib sodium (Group H+B). ELISA measures inflammatory factor IL-2, IL-6, TNF-α and IFN-γ, cognitive function factor NSE, cortisol and S-100ß. Combined with water maze and dark avoidance experiments to further verify the recovery of cognitive function in rats. The contents of IL-2, TNF-α and IL-6 in Group M+B were significantly lower than those in Group Sham (P<0.05), and the content of IFN-γ was significantly lower than that in Group Sham (P<0.05). The cognitive markers NSE, S-100ß and cortisol levels in Group M+B were significantly higher than those in Group Sham at 2h, 1d, 5d and 10d after operation (P<0.05). In the Group M+B dark-avoidance experiment, the number of probes and errors were not significantly different than those in Group Sham and Group C (P>0.05), and the number of times Group M+B found a platform in the water maze experiment and crossed the platform was second only to Group B and Group C. Parecoxib sodium can effectively reduce inflammation in burn rats and promote cognitive recovery in burn rats, and the optimal dose of parecoxib sodium for burn rats is 10 mg/kg.

Comparative Analysis of Ketorolac and Parecoxib for Postoperative Pain Management in Uvulopalatopharyngoplasty.

Background/Objectives: Uvulopalatopharyngoplasty (UPPP) is a prevalent surgical procedure for treating obstructive sleep apnea. Effective postoperative pain management is crucial for patient comfort and recovery. This study aimed to compare the analgesic efficacies of parecoxib and ketorolac in patients undergoing UPPP. Methods: A prospective, randomized, double-blind study was conducted on 83 patients who received either parecoxib (40 mg intravenously every 12 h) or ketorolac (30 mg intravenously every 8 h) for 2 days following UPPP. Postoperative pain and swallowing discomfort were assessed using visual analog scales (VASs) at 4, 24, 48, and 72 h. The time to resume eating and adverse reactions were also recorded. Results: At 24 and 48 h postoperatively, the mean VAS score was significantly higher in the ketorolac group compared to the parecoxib group (5.0 ± 2.3 vs. 3.6 ± 2.2, p = 0.005 and 3.9 ± 2.2 vs. 2.5 ± 1.7, p < 0.001, respectively). However, no significant difference in the mean VAS scores was observed between the two groups at 72 h postoperatively. With regards to postoperative swallowing pain, the ketorolac group exhibited significantly higher mean VAS scores than the parecoxib group at 4, 24, 48, and 72 h postoperatively. Conclusions: Intravenous parecoxib may offer superior analgesic benefits in the early postoperative period, particularly in alleviating swallowing pain, compared to ketorolac in UPPP procedures.

Parecoxib and 5-Fluorouracil Synergistically Inhibit EMT and Subsequent Metastasis in Colorectal Cancer by Targeting PI3K/Akt/NF-κB Signaling.

Colorectal cancer is one of the most common causes of cancer mortality worldwide, and innovative drugs for the treatment of colorectal cancer are continually being developed. 5-Fluorouracil (5-FU) is a common clinical chemotherapeutic drug. Acquired resistance to 5-FU is a clinical challenge in colorectal cancer treatment. Parecoxib is a selective COX-2-specific inhibitor that was demonstrated to inhibit metastasis in colorectal cancers in our previous study. This study aimed to investigate the synergistic antimetastatic activities of parecoxib to 5-FU in human colorectal cancer cells and determine the underlying mechanisms. Parecoxib and 5-FU synergistically suppressed metastasis in colorectal cancer cells. Treatment with the parecoxib/5-FU combination induced an increase in E-cadherin and decrease in ß-catenin expression. The parecoxib/5-FU combination inhibited MMP-9 activity, and the NF-κB pathway was suppressed as well. Mechanistic analysis denoted that the parecoxib/5-FU combination hindered the essential molecules of the PI3K/Akt route to obstruct metastatic colorectal cancer. Furthermore, the parecoxib/5-FU combination could inhibit reactive oxygen species. Our work showed the antimetastatic capacity of the parecoxib/5-FU combination for treating colorectal cancers via the targeting of the PI3K/Akt/NF-κB pathway.

Application of multimodal standardized analgesia under the concept of enhanced recovery after surgery in laparoscopic radical colorectal cancer surgery.

Aims: To observe the efficacy and safety of multimodal standardized analgesia in patients undergoing laparoscopic radical colorectal cancer surgery. Methods: A prospective, double-blind, randomized study of patients who were admitted to our hospital between December 2020 and March 2022 with a diagnosis of colorectal cancer and who intended to undergo elective laparoscopic radical colorectal cancer surgery was conducted. The participants were randomly divided into two intervention groups, namely, a multimodal standardized analgesia group and a routine analgesia group. In both groups, the visual analogue scale (VAS) pain scores while resting at 6 h, 24 h, 48 h and 72 h and during movement at 24 h, 48 h and 72 h; the number of patient controlled intravenous analgesia (PCIA) pump button presses and postoperative recovery indicators within 3 days after surgery; the interleukin-6 (IL-6) and C-reactive protein (CRP) levels on the 1st and 4th days after surgery; and the incidence of postoperative adverse reactions and complications were recorded. Results: Compared with the control group, the multimodal standardized analgesia group had significantly lower VAS pain scores at different time points while resting and during movement (P<0.05), significantly fewer PCIA pump button presses during the first 3 postoperative days (P<0.05), and significantly lower IL-6 and CRP levels on the 1st postoperative day (P<0.05). There was no statistically significant difference in the time to out-of-bed activity, the time to first flatus, the IL-6 and CRP levels on the 4th postoperative day or the incidence of postoperative adverse reactions and complications between the two groups (P >0.05). Conclusion: For patients undergoing laparoscopic radical colorectal cancer surgery, multimodal standardized analgesia with ropivacaine combined with parecoxib sodium and a PCIA pump had a better analgesic effect, as it effectively inhibited early postoperative inflammatory reactions and promoted postoperative recovery and did not increase the incidence of adverse reactions and complications. Therefore, it is worthy of widespread clinical practice.

Parecoxib inhibits tumorigenesis and angiogenesis in hepatocellular carcinoma through ERK-VEGF/MMPs signaling pathway.

Parecoxib, a well-recognized nonsteroidal anti-inflammatory drug, has been reported to possess anticancer properties in various tumor types. In this work, we aimed to investigate the potential anticancer effects of parecoxib on hepatocellular carcinoma (HCC) cells. To assess the impact of parecoxib on HCC cell proliferation, we employed Cell Counting Kit-8, colony formation, and 5-ethynyl-2'-deoxyuridine assays. Hoechst/propidium iodide (PI) double staining and flow cytometry were performed to evaluate apoptosis and cell cycle analysis. Wound healing and transwell assays were utilized to assess cell migration and invasion. Tube formation assay was employed to analyze angiogenesis. Protein levels were determined using western blotting, and mRNA expression levels were assessed using quantitative real-time polymerase chain reaction (PCR). A xenograft mouse model was used to confirm the antitumor effects of parecoxib on HCC tumors in vivo. Our data demonstrated that parecoxib effectively inhibited the proliferation of HCC cells in a dose- and time-dependent manner. In addition, parecoxib induced cell cycle arrest in the G2 phase and promoted apoptosis. Moreover, parecoxib hindered tumor migration and invasion by impeding the epithelial-mesenchymal transition process. Further investigation showed that parecoxib could significantly suppress angiogenesis through the inhibition of extracellular signal-regulated kinase (ERK)-vascular endothelial growth factor (VEGF) axis. Notably, treatment with the ERK activator phorbol myristate acetate upregulated the expression of matrix metalloproteinase (MMP)-2, MMP-9, and VEGF and reversed the function of parecoxib in HCC cells. Besides, parecoxib displayed its antitumor efficacy in vivo. Collectively, our results suggest that parecoxib ameliorates HCC progression by regulating proliferation, cell cycle, apoptosis, migration, invasion, and angiogenesis through the ERK-VEGF/MMPs signaling pathway.

The Efficacy of the Combination of Continuous Femoral Nerve Block and Intravenous Parecoxib on Rehabilitation in Patients Undergoing Total Knee Arthroplasty: A Double-Blind, Randomized Clinical Trial.

BACKGROUND AND AIM: The optimal strategy for the management of postoperative pain after total knee arthroplasty (TKA) remains challenging, while its treatment is crucial to increase patients' outcomes. This study aimed to investigate the effects of parecoxib as add-on therapy, in a standard postoperative pain management protocol, represented by the continuous femoral nervous block. We studied its influence on rehabilitation indices and pain scores in patients undergoing TKA. MATERIAL AND METHODS: This is a single-center, prospective, double-blind, randomized, placebo-controlled trial. All patients were operated with the use of subarachnoid anesthesia, and divided into two groups for postoperative analgesia. Both groups received a continuous femoral nerve block. One of the groups received intravenous parecoxib, while the other received a placebo. The primary investigated outcome was the range of motion (ROM). Recordings were noted at different times postoperatively. Bromage score (BS), visual analog scale (VAS), and the State-Trait Anxiety Inventory (STAI) were also studied. RESULTS: A total of 90 patients were included and analyzed. ROM was significantly better (p<0.001) and pain scores were significantly lower (p=0.007) in the parecoxib group. No statistically significant difference was found with regard to BS between the two groups. A significant correlation was found between ROM and VAS pain scores at 12 hours (p=0.02), while ROM was inversely correlated with STAI postoperatively. CONCLUSIONS: The use of intravenous parecoxib is effective in improving rehabilitation indices and provides decreased postoperative pain scores after TKA.

Parecoxib decreases cellular growth and Bcl-2 protein levels in primary cultures of keloid fibroblasts.

Keloids seem to overexpress cyclo-oxygenase-2 (COX-2), suggesting a role in its deregulated pathway in inducing an altered epithelial-mesenchymal interaction, which may be responsible for the overgrowth of dermal components resulting in scars or keloid lesions. This study aimed to evaluate the effect of Parecoxib, a COX-2 inhibitor, on cell growth in fibroblast primary cultures obtained from human keloid tissues. Tissue explants were obtained from patients who underwent intralesional excision of untreated keloids; central fractions were isolated from keloid tissues and used for establishing distinct primary cultures. Appropriate aliquots of Parecoxib, a COX-2 inhibitor were diluted to obtain the concentration used in the experimental protocols in vitro (1, 10 or 100 µM). Treatment with Parecoxib (at all concentrations) caused a significant decrease in cellular growth from 24 hours onwards, and with a maximum at 72 hours (P < .02). Moreover, at 72 hours Parecoxib significantly reduced cellular vitality. Parecoxib treatment also induced an increase in fragmented nuclei with a maximum effect at 100 µM and a significant decrease in Bcl-2 and an increase in activated caspase-3 protein levels at 72 hours compared with control untreated cultures. Our findings suggest a potential use of the COX-2 inhibitor, Parecoxib, as the therapy for keloids.

[Parecoxib sodium down-regulates CXCL8-CXCR1/2 to improve inflammatory microenvironment and promote patient recovery following laparoscopic radical resection of rectal cancer].

OBJECTIVE: To study the effect of parecoxib sodium on tumor microenvironment in patients undergoing laparoscopic radical resection of rectal cancer. METHODS: Sixty patients undergoing laparoscopic surgery for radical rectal cancer resection were randomized into test group and control group (n=30). The patients in test control group received intravenous injections of 40 mg parecoxib sodium at the time of anesthesia induction, immediately after and at 12 h after the surgery, and those in the control group were injected with an equal volume of physiological saline at the same time points. Plasma levels of IL-6, TNF-α, and CXCL8 of the patients were measured using ELISA, and expressions of CXCL8, CXCR1, and CXCR2 in the peripheral blood mononuclear cells (PBMCs) were detected with Western blotting. Postoperative VAS scores and gastrointestinal reactions and disease regression at 6 months after the operation were recorded. RESULTS: Compared with the control patients, the patients in the test group showed significantly reduced plasma levels of IL-6, TNF-α, and CXCL8 (P < 0.05) and milder elevations of CXCL8, CXCR1, and CXCR2 proteins in PBMCs (P < 0.05) with significantly lower VAS scores at 12 h and 24 h after the operation (P < 0.05) and lower postoperative incidence of adverse gastrointestinal reactions (P < 0.05). At 6 months after the operation, the number of patients with metastasis or tumor recurrence was significantly smaller in the test group than in the control group (P>0.05). CONCLUSION: Parecoxib sodium can improve the inflammatory microenvironment to promote patient recovery after laparoscopic radical resection of rectal cancer possibly through a mechanism that down-regulates CXCL8-CXCR1/2 expressions in the PBMCs.

Risk factors of chronic kidney disease in cisplatin-based hyperthermia intraperitoneal chemotherapy.

PURPOSE: Cisplatin is commonly prescribed in hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancy. Acute kidney injury (AKI) is regarded as a common complication after HIPEC combined with cytoreductive surgery (CRS). However, post-HIPEC chronic kidney disease (CKD) is scarce and less investigated. This study aims to investigate the incidence of CKD following cisplatin-based HIPEC and to analyse the associated risk factors. MATERIALS AND METHODS: From January 2016 to August 2021, a total of 55 patients treated with CRS and cisplatin-based HIPEC for peritoneal carcinomatosis were categorized retrospectively into groups, with and without CKD. Demographics, comorbidity, surgery, postoperative management, and complications were collected to evaluate risk factors for cisplatin-based HIPEC-related CKD. Univariate and multivariate analyses were conducted to confirm the correlation between different variables and CKD occurrence. RESULTS: Of the 55 patients, 24 (43.6%) patients developed AKI and 17 (70.8%) patients of these AKI patients progressed to CKD. Multivariate regression analysis identified intraoperative use of parecoxib (Odds Ratio (OR) = 4.39) and intraoperative maximum temperature > 38.5°C (OR = 6.40) as major risk factors for cisplatin-based HIPEC-related CKD occurrence. Though type II diabetes mellitus and intraoperative complications were the independent risk factors of AKI following cisplatin-based HIPEC, but they were not shown in CKD analysis. CONCLUSION: Intraoperative use of parecoxib during cisplatin-based HIPEC emerged as a significant risk factor for postoperative CKD. Clinicians should exercise caution in prescribing parecoxib during HIPEC procedures. Additionally, maintaining intraoperative body temperature below 38.5°C might be crucial to mitigate the risk of CKD development. This study underscores the importance of identifying and preventing specific risk factors to improve long-term renal outcomes in patients undergoing cisplatin-based HIPEC.

Parecoxib sodium attenuates acute lung injury following burns by regulating M1/M2 macrophage polarization through the TLR4/NF-κB pathway.

High temperature-induced burn injury often leads to an excessive inflammatory cascade resulting in multiple organ dysfunction syndrome, such as acute lung injury (ALI), in addition to skin tissue damage. As a specific COX2 inhibitor, parecoxib sodium suppresses the inflammatory response during burn injury. The effect of parecoxib sodium on ALI induced by burn injury and the associated molecular mechanism still need to be investigated. The role of parecoxib sodium in burn injury-induced ALI through the TLR4/NF-κB pathway was explored in the present study. A burn-induced ALI mouse model was constructed, and M1/M2 macrophages in lung tissue and markers involved in the TLR4/NF-κB signalling pathway were evaluated in bronchoalveolar lavage fluid (BALF) and MH-S mouse alveolar macrophages in vitro. The results indicated that parecoxib sodium attenuated lung injury after burn injury, decreased iNOS and TNF-α expression, increased IL-10 expression in BALF, and regulated the CD86-and CD206-mediated polarization of M1/M2 macrophages in lung tissue along with MH-S mouse alveolar macrophages. The effect of parecoxib sodium might be reversed by a TLR4 agonist. Overall, the results suggested that parecoxib sodium can regulate the polarization of M1/M2 macrophages through the TLR4/NF-κB pathway to attenuate ALI induced by skin burns.

Superior analgesic efficacy of preemptive low-dose ketorolac compared with parecoxib after total knee arthroplasty: A retrospective propensity score matching study.

BACKGROUND: Total knee arthroplasty (TKA) is a routine orthopedic procedure often associated with significant postoperative pain. Efficient pain management is paramount for patient recovery, with nonsteroidal anti-inflammatory drugs (NSAIDs) being a common choice. Nevertheless, the specific NSAID and its dosing regimen can have varying impacts on outcomes. METHODS: In this retrospective cohort study spanning from January 2016 to December 2020, we analyzed patients who underwent TKA. These patients were divided into two groups: one receiving preemptive low-dose ketorolac (15 mg) followed by 15 mg every 6 h for 48 h, and the other receiving parecoxib (40 mg) every 12 h for the same duration. We assessed pain scores, opioid consumption, and monitored adverse events. RESULTS: Our findings reveal that ketorolac yielded superior results compared to parecoxib. Specifically, patients receiving ketorolac reported significantly lower Visual Numeric Rating Scale (VNRS) scores at 8- and 20-h post-surgery. This trend was further confirmed by linear mixed models (p = .0084). Additionally, ketorolac was associated with reduced opioid consumption during the initial 24 h. Importantly, the rates of adverse events were comparable between the two groups. CONCLUSION: The utilization of preemptive low-dose ketorolac demonstrates promising potential in bolstering pain control within the initial 24 h post-TKA, potentially reducing the need for opioids. However, further exploration is required to thoroughly assess its prolonged analgesic effects and safety across various surgical contexts. These investigations could provide invaluable insights for optimizing pain management protocols.

The value of preemptive analgesia in older adult patients undergoing laparoscopic hepatectomy / 中国基层医药

Objective:To investigate the efficacy and value of preemptive analgesia in older adult patients undergoing laparoscopic hepatectomy.Methods:A total of 150 older adult patients with liver cancer, who underwent laparoscopic hepatectomy at The 2 nd Affiliated Hospital of Wenzhou Medical University between July 2019 and April 2020, were randomly assigned to two groups: a control group ( n = 75) and an observation group ( n = 75) using the random number table method. The control group received postoperative analgesia with parecoxib sodium, while the observation group received preemptive analgesia with parecoxib sodium. A comparative analysis was conducted between the control and observation groups in terms of the Numerical Rating Scale (NRS) scores at 8, 12, and 24 hours postoperatively, postoperative recovery, length of hospital stay, and overall cost. Results:There were no statistically significant differences in operation time, dosage of Sufentanil 24 hours postoperatively, or the total and effective usage counts of patient-controlled intravenous analgesia with Sufentanil between the control and observation groups (both P > 0.05). However, the NRS scores of the observation group were significantly lower than those of the control group at 8, 12, and 24 hours postoperatively. Specifically, the NRS scores of the observation group were (4.38 ± 1.24) points, (3.41 ± 0.19) points, and (2.90 ± 0.17) points, respectively, while those of the control group were (5.24 ± 1.01) points, (4.65 ± 1.24) points, and (3.32 ± 1.00) points, respectively ( t = 4.66, 8.56, 3.59, all P < 0.001). Patients in the observation group exhibited significantly more frequent off-bed activities [(2.62 ± 1.24) times], a notably longer cumulative duration of off-bed activities [(1.36 ± 0.20) hours], and a significantly shorter duration of first anal exhaust [(13.50 ± 1.27) hours] compared with those in the control group [(1.06 ± 0.12) times, (0.36 ± 0.09) hours, (20.10 ± 2.16) hours, t = -10.84, -39.49, 22.81, all P < 0.001]. Furthermore, the observation group demonstrated a shorter postoperative hospital stay [(8.90 ± 1.34) days], lower hospitalization costs [(55.8 ± 2.1) thousand yuan], and higher patient satisfaction scores [(88.98 ± 5.64) points] compared with the control group [(11.15 ± 1.29) days, (59.4 ± 6.2) thousand yuan, (72.16 ± 3.26) points, t = 10.48, 4.76, -22.36, all P < 0.001]. Conclusion:The implementation of preemptive analgesia intervention among older adult patients undergoing laparoscopic hepatectomy effectively enhances analgesic outcomes, accelerates postoperative recovery, reduces hospitalization duration, and markedly decreases hospitalization costs.

Efficacy and safety of parecoxib and flurbiprofen axetil for perioperative analgesia in children: a network meta-analysis.

Objective: The aim of this study was to systematically review the efficacy and safety of parecoxib and flurbiprofen axetil for perioperative analgesia in children through Bayesian network meta-analysis. Methods: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, VIP, and Wanfang Data databases on 18 July 2022 to obtain randomized controlled trials comparing perioperative parecoxib or flurbiprofen with placebo or standard treatment for pediatric analgesia. The outcomes were the postoperative pain score and the incidence of adverse events. The Gemtc package of R-4.0.3 and Stata 17.0 were used for Bayesian network meta-analysis. Results: We retrieved 942 articles and 49 randomized controlled trials involving 3,657 patients who met the inclusion criteria. Compared with children who received placebo treatment, those who received flurbiprofen axetil had lower pain sores at each time point within 24 h postoperatively, and those who received parecoxib had lower pain sores at each time point within 12 h postoperatively. Compared with children who received tramadol treatment, both the children who received flurbiprofen axetil or parecoxib had lower pain scores at 8 h postoperatively. The ranking results demonstrated that flurbiprofen axetil had significant superiority in reducing pain scores at 2, 4, and 12 h postoperatively, and parecoxib had significant superiority in reducing pain scores at 0, 0.5, 1, 6, 8, and 24 h postoperatively. In terms of safety, compared with children who received placebo, those who received flurbiprofen axetil or parecoxib had a lower incidence of total adverse events and postoperative agitation. Compared with tramadol, flurbiprofen axetil and parecoxib both significantly reduced the incidence of total adverse events and postoperative nausea and vomiting. Compared with flurbiprofen axetil or fentanyl, parecoxib significantly reduced the incidence of postoperative nausea and vomiting. The ranking results showed that parecoxib was advantageous in decreasing the incidence of total adverse events and postoperative nausea and vomiting. Conclusion: Flurbiprofen axetil was most effective at reducing pain scores at 2, 4, and 12 h postoperatively. Parecoxib had an advantage in terms of reducing pain scores at 0, 0.5, 1, 6, 8, and 24 h postoperatively, as well as the incidence of total adverse events and postoperative nausea and vomiting. Systematic trial registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=348886, PROSPERO (CRD42022348886).

The Efficacy and Safety of Parecoxib Multimodal Preemptive Analgesia in Artificial Joint Replacement: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Postoperative pain after artificial joint replacement is intense and remains an unsolved problem. Some studies have shown that parecoxib can provide better analgesia in postoperative multimodal analgesia, however, doubts arise about whether its multimodal preemptive analgesia can reduce postoperative pain. OBJECTIVES: The purpose of this systematic review and meta-analysis was to evaluate the impact of preoperative injection of parecoxib on postoperative pain in patients undergoing artificial joint replacement. STUDY DESIGN: Systematic review and meta-analysis. SETTING: Embase, PubMed, Cochrane Library, CNKI, VIP, Wangfang databases were searched to identify relevant randomized controlled trials. The last search was in May 2022. METHODS: Randomized controlled trials of efficacy and adverse reactions of intra-operative and postoperative injection of parecoxib in artificial joint replacement were collected. The primary outcome was postoperative visual analog scale scores and the secondary outcomes included cumulative postoperative opioid consumption and incidence of adverse reactions. Using the Cochrane systematic review method to screen the studies, evaluate the quality of the included studies, and extract feature information, RevMan 5.4 software performs a meta-analysis of the corresponding research indicators. RESULTS: In total, nine studies were involved in the meta-analysis with 667 patients. The trial and control group were given the same dose of parecoxib or placebo at the same time point before and after surgery. The results showed that compared with the control group, the trial group is associated with substantially reduced visual analog scale scores in 24, 48 h at rest (P < 0.05), visual analog scale scores in 24, 48, 72 h at movement (P < 0.05), dose of opioid need in trial group is notably lower than that in control group (P < 0.05), but shows no obvious effect on visual analog scale scores in 72 h at rest, and adverse events (P > 0.05). LIMITATIONS: The major limitation of this meta-analysis relates to some low-quality studies. CONCLUSIONS: Our results support parecoxib multimodal preemptive analgesia in reducing postoperative acute pain in hip and knee replacement patients, and reduces cumulative opioid consumption without increasing the risk of adverse drug events. Its multimodal preemptive analgesia is safe and effective in hip and knee replacement. PROSPERO REGISTRATION: CRD42022379672.

Multimodal Analgesia with Local Wound Infiltration and Intravenous Parecoxib for Thyroidectomy.

Background and objective: Adequate postoperative pain control is an important component to enhance recovery. Multimodal analgesia with various pain control techniques has been widely used to alleviate postoperative pain. The use of either wound infiltration or a superficial cervical plexus block has been reported to be effective for pain management after thyroid surgery. The present study evaluated the effect of multimodal analgesia using lidocaine wound infiltration combined with intravenous parecoxib for patients monitored after thyroidectomy. Materials and Methods: A total of 101 patients with a multimodal analgesia protocol being monitored after thyroidectomy were enrolled. After the induction of anesthesia, multimodal analgesia was performed through wound infiltration of 1% lidocaine and epinephrine at a ratio of 1:200,000 (5 µg/mL) combined 40 mg intravenous parecoxib before skin excision. Patients were divided into two groups for this retrospective analysis based on the injection dose of lidocaine they received. Patients in Group I (the control, n = 52) received a 5 mL injection solution, while those in Group II (the study, n = 49) received a 10 mL dosage in a time-sequential manner, in accordance with a previous clinical trial. The primary outcome was measuring postoperative pain intensity at rest, as well as during motion and coughing, which was measured at the postoperative anesthetic care unit (PACU) and on the first day after the operation (POD 1) in the ward. Pain intensity was assessed using a numerical rating scale (NRS). The secondary outcomes were postoperative adverse events including anesthetic-related side effects, as well as airway and pulmonary complications. Results: Most of the patients reported no pain or mild pain during the observation period. The patients in Group II had a lower pain intensity during motion than Group I (NRS 1.47 ± 0.89 vs. 1.85 ± 0.96, p = 0.043) when measured at the postoperative anesthetic care unit. Pain intensity during coughing was also significantly lower in the study group than in the control group (NRS 1.61 ± 0.95 vs. 1.96 ± 0.79, p = 0.049) when measured at the postoperative anesthetic care unit. There were no severe adverse events in either of the groups. Only one patient (1.9%) in Group I experienced temporary vocal palsy. Conclusions: The use of lidocaine with an equal volume of intravenous parecoxib provided comparable analgesia with minimal adverse events when monitoring thyroidectomy.

Comparison of pharmacokinetic profiles in hypoalbuminemia and healthy rats after parecoxib sodium injection by LC-MS/MS.

Background: Valdecoxib is an active metabolite of parecoxib that has a high binding rate with plasma protein. Hypoalbuminemia may affect the pharmacokinetics process of valdecoxib. Method & results: A rapid LC-MS/MS method was applied to assay parecoxib and valdecoxib in hypoalbuminemia and healthy rats. Hypoalbuminemia rat models were established by intravenous injection of doxorubicin. The maximum plasma concentration and area under the curve values of valdecoxib in control and model groups were 744.04 ± 128.24 ng/ml, 152,727.87 ± 39,131.36 ng/ml·min and 234.25 ± 77.36 ng/ml, 29,032.42 ± 5116.62 ng/ml·min after 7.2 mg/kg parecoxib sodium injection and 371.95 ± 64.12 ng/ml, 62,218.25 ± 6876.93 ng/ml·min and 153.41 ± 33.17 ng/ml, 18,245.62 ± 868.53 ng/ml·min after 3.6 mg/kg parecoxib sodium injection, respectively. Conclusion: Hypoalbuminemia increases clearance and reduces the plasma concentration of valdecoxib in rats.

The effect of parecoxib sodium on postoperative delirium in elderly patients with hip arthroplasty.

Objective: This study aimed to clarify the effect of parecoxib sodium on the occurrence of postoperative delirium and to investigate its possible mechanism. Methods: A total of 80 patients who underwent elective hip arthroplasty in our hospital between December 2020 and December 2021 were selected and randomly divided into two groups: a parecoxib sodium group (group P, n = 40) and a control group (group C, n = 40). Patients in group P were intravenously injected with 40 mg of parecoxib sodium 30 min before anesthesia and at the end of the surgery. Patients in group C were intravenously injected with the same volume of normal saline at the same time points. The primary endpoint was the incidence of POD, and the secondary endpoints were the levels of inflammatory factors (tumor necrosis factor- α [TNF-α], interleukin [IL]-1ß, IL-6, and IL-10), nerve injury-related factors (brain-derived neurotrophic factor [BDNF], S-100ß protein, neuron-specific enolase [NSE], and neurofilament light chain [NfL]), and antioxidant factors (heme oxygenase-1 [HO-1]), as well as the Visual Analogue Scale (VAS) and Confusion Assessment Method-Chinese Reversion (CAM-CR) scores. Results: The incidence of POD was 10% in group P and 27.5% in group C. Intergroup comparison revealed that the levels of TNF-α, IL-1ß, S-100ß, NfL, and NSE were lower, and BDNF was higher, in group P than in group C at each postoperative time point. The levels of IL-6 were lower, and the levels of IL-10 and HO-1 were higher, in group P than in group C at 1 h and 1 day postoperatively (p < 0.05). Three days after surgery, the differences in the levels of IL-6, IL-10, and HO-1 were not statistically significant between the two groups (p > 0.05). The VAS and CAM-CR scores were lower at each postoperative time point in group P than in group C (p < 0.05). Conclusion: Parecoxib sodium could reduce postoperative pain, decrease the plasma levels of inflammatory and nerve injury-related factors, upregulate HO-1 levels, and reduce the incidence of POD. The results of this study suggest that parecoxib sodium may reduce the occurrence of POD through the effects of anti-inflammation, analgesia, and antioxidants.

Parecoxib attenuates inflammation injury in septic H9c2 cells by regulating the MAPK signaling pathway.

Parecoxib, a non-steroidal anti-inflammatory drug, has been reported to possess protective effects against sepsis. However, its detailed role and underlying mechanisms in septic cardiomyopathy remain unclear. Therefore, the goal of the present study was to clarify the function and to investigate the mechanisms of parecoxib in lipopolysaccharide (LPS)-treated H9c2 rat cardiomyocytes. TNF-α, IL-1ß and IL-6 expression levels in parecoxib-treated H9c2 cells stimulated with LPS were assessed using ELISA. Parecoxib-treated H9c2 cells stimulated with LPS were tested for viability using the Cell Counting Kit-8 assay. Western blotting analysis and 5-ethynyl-2'-deoxyuridine were used to evaluate cell proliferation. Apoptosis was assessed using TUNEL and western blotting. To assess the protein expression of the MAPK signaling pathway, western blotting was performed. The data showed that parecoxib significantly and dose-dependently reduced the inflammatory responses of LPS-treated H9c2 cells. Parecoxib also significantly and dose-dependently increased the proliferation and inhibited the apoptosis of LPS-treated H9c2 cells. In addition, parecoxib significantly suppressed the activation of the MAPK (p38, JNK and ERK) signaling pathway. The current study indicated that parecoxib could be a viable therapeutic option for septic cardiomyopathy.