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Systematic Review and Meta-Analysis of the Association Between Non-Steroidal Anti-Inflammatory Drugs and Operative Bleeding in the Perioperative Period.
Bongiovanni, T, Lancaster, E, Ledesma, Y, Whitaker, E, Steinman, MA, Allen, IE, Auerbach, A, Wick, E
Journal of the American College of Surgeons. 2021;(5):765-790.e1
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Abstract
BACKGROUND It is increasingly recognized that non-opioid analgesia is an important analgesia in the perioperative period. Specifically, NSAIDs (nonsteroidal anti-inflammatory drugs) have been touted as an adjunct, or even replacement, for opioids. However, uptake of NSAIDs has been slow due to concern for side effects, including bleeding. We sought to understand the risk of bleeding caused by NSAIDs in the perioperative period. STUDY DESIGN A physician-librarian team performed a search of electronic databases (MEDLINE, EMBASE), using search terms covering the targeted intervention (use of NSAIDs) and outcomes of interest (surgical complications, bleeding), limited to English language articles of any date. We performed a systematic review and meta-analysis of the data. RESULTS A total of 2,521 articles were screened, and 229 were selected on the basis of title and abstract for detailed assessment. Including reference searching, 74 manuscripts met inclusion criteria spanning years 1987-2019. These studies included 151,031 patients. Studies included 12 types of NSAIDs, the most common being ketorolac, diclofenac, and ibuprofen, over a wide-range of procedures, from otorhinolaryngology (ENT), breast, abdomen, plastics, and more. More than half were randomized control trials. The meta-analyses for hematoma, return to the operating room for bleeding, and blood transfusions showed no difference in risk in any of 3 categories studied between the NSAID vs non-NSAID groups (p = 0.49, p = 0.79, and p = 0.49, respectively). Quality scoring found a wide range of quality, with scores ranging from lowest quality of 12 to highest quality of 25, out of a total of 27 (average = 16). CONCLUSIONS NSAIDs are unlikely to be the cause of postoperative bleeding complications. This literature covers a large number of patients and remains consistent across types of NSAIDs and operations.
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Non-steroidal anti-inflammatory agents and anastomotic leak rates across colorectal cancer operations and anastomotic sites: A systematic review and meta-analysis of anastomosis specific leak rate and confounding factors.
Kastora, SL, Osborne, LL, Jardine, R, Kounidas, G, Carter, B, Myint, PK
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2021;(11):2841-2848
Abstract
BACKGROUND Surgical intervention presents a fundamental therapeutic choice in the management of colorectal malignancies. Complications, the most serious one being anastomotic leak (AL), still have detrimental effects upon patients' morbidity and mortality. We aimed to assess whether NSAIDs, and their sub-categories, increase AL in colonic anastomoses and to identify whether this affects specific anastomotic sites. MATERIALS AND METHODS A systematic search of MEDLINE, Cochrane Library, ClinicalTrials.gov, Web of Science, Science Direct, Google Scholar was conducted between January 1, 1999 till the October 30, 2020. Cohort studies and randomized control trials examining AL events in NSAID-exposed, colorectal cancer patients were included. NSAIDs were grouped according to the 2019 NICE guidelines in non-specific (NS-NSAIDs) and specific COX-2 inhibitors. The primary outcome was AL events in NSAID-exposed patients undergoing operations with either ileocolic, colocolic or colorectal anastomoses. Secondary outcomes included NSAID category-specific AL events and demographic confounding factors increasing AL risk in this patient population. RESULTS Fifteen studies involving 25,395 patients were included in the systematic review and meta-analysis. Of all anastomoses, colocolic anastomoses were found to be statistically more prone to AL events in the NS-NSAID-exposed population [OR 3.24 (95% CI 0.98-10.72), p = 0.054]. Male gender was an independent confounder increasing AL rate regardless of NSAID exposure. CONCLUSION The association between NSAID exposure and AL in oncology patients remains undetermined. Whilst in present work, colocolic anastomoses appear to be more sensitive to AL events, the observed association may be anastomotic site and NSAID-category dependent.
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Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis with a combination of pharmacological agents based on rectal non-steroidal anti-inflammatory drugs: A systematic review and network meta-analysis.
Oh, HC, Kang, H, Park, TY, Choi, GJ, Lehman, GA
Journal of gastroenterology and hepatology. 2021;(6):1403-1413
Abstract
BACKGROUND AND AIMS Rectally administered non-steroidal anti-inflammatory drugs (NSAIDs) are effective but suboptimal in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis or PEP. New trials with the combination of rectal NSAIDs and other pharmacological agents have been conducted. This network meta-analysis (NMA) aimed to determine the relative efficacy of combination regimens and identify an optimal regimen for preventing PEP. METHODS We performed a systematic and comprehensive search to identify and analyze all the randomized controlled studies published until October 15, 2019, examining rectal NSAIDs and their combination with other pharmacological agents for the prevention of PEP. The primary outcome was the frequency of PEP. We conducted an NMA to combine the direct and indirect comparisons of rectal NSAIDs and their combination with other pharmacological agents. RESULTS The NMA included 24 studies evaluating 14 regimens in 11 321 patients. According to predictive interval plot and surface under the cumulative ranking curve values, indomethacin + lactated Ringer's solution, followed by diclofenac + nitrate and indomethacin + normal saline, is the most efficacious combination of pharmacological agents for the overall prevention of PEP. Rectal indomethacin alone is the most efficacious agent for prevention of moderate to severe PEP, and rectal diclofenac is the most useful agent for prevention of PEP among the high-risk group. CONCLUSIONS Rectal indomethacin with intravenous hydration and rectal diclofenac with sublingual nitrate are the most efficacious combination regimens for the overall prevention of PEP.
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Perioperative NSAIDs and Long-Term Outcomes After cancer Surgery: a Systematic Review and Meta-analysis.
Shaji, S, Smith, C, Forget, P
Current oncology reports. 2021;(12):146
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Abstract
PURPOSE OF REVIEW This review investigated the use of perioperative non-steroidal anti-inflammatory drugs (NSAIDs) and long-term outcomes in cancer surgery patients, and whether this is dependent on cancer type, type of NSAID and timing of administration. FINDINGS Perioperative NSAID use was found to be associated with longer disease-free survival (hazard ration, HR = 0.84 (95% CI, 0.73-0.97)) and overall survival (HR = 0.78 (95% CI, 0.64-0.94)). No difference was found between different types of NSAID for disease-free survival, although in overall survival ketorolac use was significant (HR = 0.63 (95% CI, 0.42-0.95)). Analysis on the timing of NSAID administration found no subgroup to be associated with cancer outcomes. The cancer-type analysis found an association with outcomes in breast and ovarian cancers. However, the level of certainty remains very low, mostly due to the heterogeneity and the retrospective nature of most studies. Perioperative NSAID use may be associated with increased disease-free and overall survival after cancer surgery. This may be dependent on the type of cancer and type of NSAID, and further research is needed to support this. These data may inform future prospective trials, which are needed to determine the clinical impact, as well as optimal NSAID regimen.
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A Systematic Review and Meta-Analysis on the Efficacy of Curcumin/Turmeric for the Prevention and Amelioration of Radiotherapy/Radiochemotherapy Induced Oral Mucositis in Head and Neck Cancer Patients.
Dharman, S, G, M, Shanmugasundaram, K, Sampath, RK
Asian Pacific journal of cancer prevention : APJCP. 2021;(6):1671-1684
Abstract
BACKGROUND Oral Mucositis(OM) is an acute debilitating dose limiting toxicity of Radiotherapy/Radiochemotherapy(RT/RCT) in management of Head and Neck Cancer (HNC). Curcumin/Turmeric may reduce OM in patients. AIM: Efficacy of Curcumin/Turmeric for preventing and ameliorating the onset and severity of RT/RCT induced OM was analysed in this review. METHODS A systematic literature search with meta-analysis were performed using Mesh terms in PubMed, Google scholar, Science Direct, Cochrane library and manual searching, articles published from 2010 to April 2021 were included. Clinical trials that studied the efficacy/effects of turmeric / curcumin in management of RT/RCT induced OM in HNC patients were included. Statistical Analysis were done to calculate the pooled Risk ratio at 95%confidence interval with significance at p.
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Comparative Efficacy of 6 Topical Pharmacological Agents for Preventive Interventions of Postoperative Sore Throat After Tracheal Intubation: A Systematic Review and Network Meta-analysis.
Wang, G, Qi, Y, Wu, L, Jiang, G
Anesthesia and analgesia. 2021;(1):58-67
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Abstract
BACKGROUND Topical pharmacological agents typically used to treat postoperative sore throat (POST) after tracheal intubation include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, lidocaine, Glycyrrhiza (licorice), and N-methyl-d-aspartate (NMDA) receptor antagonists (including ketamine and magnesium). However, the optimal prophylactic drug remains elusive. METHODS The literature published before September 8, 2019 was searched on the PubMed, the Embase, the Web of Science, and the Cochrane Library. Randomized controlled trials (RCTs) covering topical prophylactic medications for patients with POST were included. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to assess the quality of evidence. The primary outcome is the risk of POST. Combining both direct and indirect evidence, a network meta-analysis was performed to assess odds ratios (ORs) between the topical pharmacological agents and surface under the cumulative ranking (SUCRA) curve for the treatment-based outcomes. This study is registered with PROSPERO, number CRD42020158985. RESULTS Sixty-two RCTs (at least 73% of which were double blinded) that included a total of 6708 subjects and compared 6 categories of drugs and/or placebos were ultimately enrolled. All preventive interventions except lidocaine were more effective than placebo at the 4 time intervals. Lidocaine (OR: 0.35, 95% credible interval [CrI], 0.16-0.79) has a greater POST preventative intervention effect than the placebo at a time interval of only 2 to 3 hours after surgery. Relative to lidocaine, the risk of POST except 2 to 3 hours was lower for the following treatments: corticosteroids, ketamine, magnesium, NSAIDs, and Glycyrrhiza. The NMDA receptor antagonists studied here included ketamine and magnesium. Magnesium generally demonstrated greater benefit than ketamine at 24 hours postsurgery/extubation (OR: 0.41, 95% CrI, 0.18-0.92). Compared with ketamine, corticosteroids were associated with a reduced risk of POST during the 4 to 6 hours (OR: 0.40, 95% CrI, 0.19-0.83) and 24 hours (OR: 0.34, 95% CrI, 0.16-0.72) time intervals. During the 2 to 3 hours time interval, Glycyrrhiza (OR: 0.38, 95% CrI, 0.15-0.97) was more efficacious than magnesium. CONCLUSIONS Our analysis shows that, among the 6 topical medications studied, lidocaine is not optimal for topical use to prevent POST. Glycyrrhizin, corticosteroids, NSAIDs, and NMDA receptor antagonists (ketamine and magnesium) are associated with a reduced postoperative pharyngeal pain across the 4 postsurgical time intervals studied, all of which can be chosen according to the clinical experience of the anesthesiologists and the patient preferences and are recommended for the reduction of postoperative throat pain.
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Topical Nonsteroidal Anti-inflammatory Drugs for Pain Resulting from Intravitreal Injections: A Meta-Analysis.
Popovic, MM, Muni, RH, Nichani, P, Kertes, PJ
Ophthalmology. Retina. 2020;(5):461-470
Abstract
TOPIC The role of topical nonsteroidal anti-inflammatory drugs (NSAIDs) for the reduction of ocular pain after intravitreal injections (IVIs) has been explored. To provide clarity on the evidence for these agents, the present meta-analysis of randomized controlled trials (RCTs) was undertaken. CLINICAL RELEVANCE No standard of care regimen exists for the management of pain resulting from IVIs. METHODS A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central from inception through July 2019. The RCTs that treated patients with a topical NSAID and assessed postprocedural pain were included. Risk of bias was assessed using the Cochrane guidelines. For all analyses, weighted mean differences (WMDs) with 95% confidence intervals (CIs) were reported. Random effects models were used for all analyses. The primary analysis analyzed pain on a 0- to 10-point visual analog scale. Literature estimates were categorized into the following postprocedure time point groups: 1 hour or less, 1 to 24 hours (although data were available only at 6 hours), and 24 hours or more. A subgroup analysis stratified studies based on agent and preprocedure versus postprocedure administration. RESULTS From 241 results, 9 RCTs and 598 eyes were included. A low to medium risk of bias was found across the included studies. The mean pain score on a 0-to-10 visual analog scale was significantly lower after topical NSAID administration relative to control at 1 hour or less after IVI (WMD, -1.01 units; 95% CI, -1.38 to -0.65; P < 0.001), 6 hours after IVI (WMD, -2.17 units; 95% CI, -2.67 to -1.68; P < 0.001; threshold met for clinical significance, defined as WMD >1.2 units), and more than 24 hours after IVI (WMD, -0.75 units; 95% CI, -1.11 to -0.38; P < 0.001). A greater effect size was seen with administration of NSAIDs before versus after IVI, as well as topical nepafenac relative to ketorolac or diclofenac. DISCUSSION At 6 hours after the procedure, NSAIDs provide a clinically meaningful reduction in pain relative to a control group. The administration of NSAIDs before the procedure, specifically topical nepafenac, was associated with the greatest improvement in pain relative to the control group.
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Efficacy and safety of over-the-counter analgesics for primary dysmenorrhea: A network meta-analysis.
Nie, W, Xu, P, Hao, C, Chen, Y, Yin, Y, Wang, L
Medicine. 2020;(19):e19881
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Abstract
BACKGROUND Primary dysmenorrhea is common and troublesome. The comparative efficacy of over-the-counter analgesics (OTCAs) for dysmenorrhea is unclear. This study was aimed at conducting a network meta-analysis to assess the efficacy and safety of 5 OTCAs - naproxen, ibuprofen,diclofenac, aspirin, and ketoprofen - in patients with primary dysmenorrhea. METHODS The study was registered with PROSPERO (number: CRD42019133556). The search strategy involved a review of PubMed, Embase, Cochrane Library, Web of Science, and CINAHL for relative randomized controlled trials of the 5 analgesics from the date of database establishment to July 2019. The outputs are presented as odds ratios (ORs), their corresponding 95% confidence intervals (CIs), and the surface under the cumulative ranking area (SUCRA) probabilities. RESULTS Thirty-five trials with 4383 participants were included in our study. As for efficacy outcomes, all the included analgesics except aspirin were more effective than placebo in treating dysmenorrhea [naproxen (OR 3.99, 95% CI 2.18-7.30), ibuprofen (OR 10.08, 95% CI 3.29-30.85), diclofenac (OR 11.82, 95% CI 2.66-52.48), and ketoprofen (OR 5.12, 95% CI 1.57-16.69). The OTCAs were superior to the placebo in terms of pain relief in primary dysmenorrhea. Aspirin was less effective than ibuprofen (OR 0.17, 95% CI 0.04-0.73) and diclofenac (OR 1.17, 95% CI 0.02-0.85). The SUCRA curves showed that diclofenac and ibuprofen were the most and second most effective (85.1% and 83.8%, respectively), followed by ketoprofen, naproxen, and aspirin. Regarding safety, there was no significant difference between the 5 OTCAs included and the placebo. Diclofenac versus ibuprofen (OR 4.31, 95% CI 1.18-15.67), ketoprofen versus diclofenac (OR 0.18, 95% CI 0.04-0.78), and ketoprofen versus aspirin (OR 0.41, 95% CI 0.18-0.97) presented statistically significant differences. Ketoprofen and ibuprofen were ranked the best (SUCRA 90.6% and 79.6%), followed by naproxen, aspirin, and diclofenac. CONCLUSION Considering the efficacy and safety, ibuprofen is recommended as the optimal OTCA for primary dysmenorrhea. Further well-designed studies that directly compare these analgesics are needed to support our conclusion.
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The association between nonsteroidal anti-inflammatory drugs and skin cancer: Different responses in American and European populations.
Ma, Y, Yu, P, Lin, S, Li, Q, Fang, Z, Huang, Z
Pharmacological research. 2020;:104499
Abstract
OBJECTIVE To conduct a comprehensive systematic meta-analysis investigating the association of nonsteroidal anti-inflammatory drugs (NSAIDs) and their subtypes with skin cancer (SC) and its subclasses (basal cell carcinoma BCC; squamous cell carcinoma SCC; melanoma; nonmelanoma skin cancer NMSC) in general, American and European populations. METHODS PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure and ClinicalTrials.gov were searched up to 24 February 2019. Pooled effect sizes and 95% confidence intervals were used to estimate associations. RESULTS Results based on 26 original studies including 223,619 cases and 1,398,507 controls showed both NSAIDs and nonselective Cyclooxygenase (COX) inhibitors to be statistically significantly associated with a reduced risk of SC, BCC, SCC and NMSC but not with melanoma. Conversely, no association was observed between selective Cyclooxygenase 2 (COX-2) inhibitors and SC or its subclasses. Further subgroup analysis showed that the results analyzed for American populations were almost the same as those for the general population. For European populations, neither NSAIDs nor its subtypes correlated significantly with susceptibility to SC or its subclasses. CONCLUSIONS The use of NSAIDs might reduce the risk of SC, but many factors including study population, drug subtype, and disease subclass affect the significance of the association.
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Effect of Combined Diclofenac and B Vitamins (Thiamine, Pyridoxine, and Cyanocobalamin) for Low Back Pain Management: Systematic Review and Meta-analysis.
Calderon-Ospina, CA, Nava-Mesa, MO, Arbeláez Ariza, CE
Pain medicine (Malden, Mass.). 2020;(4):766-781
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BACKGROUND Cumulative evidence suggests an analgesic effect of thiamine, pyridoxine, and cyanocobalamin (TPC) in monotherapy, and also when combined with nonsteroidal anti-inflammatory drugs (NSAIDs), particularly diclofenac, in a synergistic manner. The aim of this review was to determine the effects of diclofenac combined with TPC compared with diclofenac monotherapy for low back pain (LBP) management. METHODS We searched for randomized clinical trials on the MEDLINE, EMBASE, LILACS, and Cochrane databases of records of clinical trials, among other sources. We evaluated the risk of bias regarding randomization, allocation concealment, blinding, incomplete outcome data, selective reporting, and other biases. A random-effects meta-analysis to examine patients with acute LBP (N = 1,108 adults) was performed, along with a subsequent sensitivity analysis. RESULTS Five studies in patients with LBP were included in the qualitative synthesis. Four of these studies in acute LBP were included in the first meta-analysis. A sensitivity test based on risk of bias (three moderate- to high-quality studies) found that the combination therapy of diclofenac plus TPC was associated with a significant reduction in the duration of treatment (around 50%) compared with diclofenac monotherapy (odds ratio = 2.23, 95% confidence interval = 1.59 to 3.13, P < 0.00001). We found no differences in the safety profile and patient satisfaction. CONCLUSIONS This meta-analysis demonstrated that combination therapy of diclofenac with TPC might have an analgesic superiority compared with diclofenac monotherapy in acute LBP. However, there is not enough evidence to recommend this therapy in other types of pain due to the scarcity of high-quality studies.