Risks of serious adverse events with non-steroidal anti-inflammatory drugs in gastrointestinal surgery: A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly recommended for perioperative opioid-sparing multimodal analgesic treatments. Concerns regarding the potential for serious adverse events (SAEs) associated with perioperative NSAID treatment are especially relevant following gastrointestinal surgery. We assessed the risks of SAEs with perioperative NSAID treatment in patients undergoing gastrointestinal surgery. METHODS: We conducted a systematic review of randomised clinical trials assessing the harmful effects of NSAIDs versus placebo, usual care or no intervention in patients undergoing gastrointestinal surgery. The primary outcome was an incidence of SAEs. We systematically searched for eligible trials in five major databases up to January 2024. We performed risk of bias assessments to account for systematic errors, trial sequential analysis (TSA) to account for the risks of random errors, performed meta-analyses using R and used the Grading of Recommendations Assessment, Development and Evaluation framework to describe the certainty of evidence. RESULTS: We included 22 trials enrolling 1622 patients for our primary analyses. Most trials were at high risk of bias. Meta-analyses (risk ratio 0.78; 95% confidence interval [CI] 0.51-1.19; I2 = 4%; p = .24; very low certainty of evidence) and TSA indicated a lack of information on the effects of NSAIDs compared to placebo on the risks of SAEs. Post-hoc beta-binomial regression sensitivity analyses including trials with zero events showed a reduction in SAEs with NSAIDs versus placebo (odds ratio 0.73; CI 0.54-0.99; p = .042). CONCLUSION: In adult patients undergoing gastrointestinal surgery, there was insufficient information to draw firm conclusions on the effects of NSAIDs on SAEs. The certainty of the evidence was very low.

Risk of serious adverse events associated with non-steroidal anti-inflammatory drugs in orthopaedic surgery. A protocol for a systematic review.

BACKGROUND: Postoperative pain is a common condition following orthopaedic surgeries and causes prolonged hospitalisation, delayed rehabilitation and hamper the quality of life. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective analgesics and anti-inflammatory mediators in the treatment of postoperative pain. The association of NSAIDs with serious adverse events may however keep some clinicians and clinical decision makers from using NSAIDs perioperatively. The evidence regarding the risks of serious adverse events following perioperative use of NSAIDs in orthopaedic surgery is sparse and needs to be assessed in a systematic review. This is a protocol for a systematic review that aims to identify the risks of serious adverse events from perioperative use of NSAIDs in orthopaedic patients. METHODS: Our methodology is based on the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols and the eight-step assessment procedure suggested by Jakobsen and colleagues. We wish to assess if NSAIDs versus placebo, usual care or no intervention, will influence the risks of serious adverse events in patients undergoing orthopaedic surgery. We will include all randomised trials assessing the use of NSAIDs perioperatively. To identify trials we will search the Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cochrane Central Register, Science Citation Index Expanded on Web of Science and BIOSIS. Two authors will screen the literature and extract data. We will use the 'Risk of Bias 2 tool' to assess trials. Extracted data will be analysed using RStudio and Trial Sequential Analysis. We will create a 'Summary of Findings' table in which we will present our primary and secondary outcomes. We will assess the quality of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). DISCUSSION: This systematic review can potentially aid clinicians and clinical decision makers in the use of NSAIDs for treatment of postoperative pain following orthopaedic surgeries.

Risks of serious adverse events associated with non-steroidal anti-inflammatory drugs in gastrointestinal surgery. A protocol for a systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Post-operative pain is frequent following gastrointestinal surgery and may result in prolonged hospitalisation, delayed recovery, and lower quality of life. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective analgesics and recommended by Enhanced Recovery After Surgery guidelines as part of opioid-sparing multimodal treatment. However, perioperative NSAID treatment may be associated with increased risk of harm. We will investigate the risks of serious adverse events associated with perioperative NSAID treatment in patients undergoing gastrointestinal surgery. METHODS: This protocol uses the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We wish to assess the effects of NSAIDs versus placebo, usual care, or no intervention on the incidence of serious adverse in patients undergoing gastrointestinal surgery. We will include all randomised trials. To identify trials, we will search the medical literature analysis and retrieval system online, excerpta medica database, cochrane central register of controlled trials, web of science core collection, and BIOSIS. Two authors will screen the literature and extract data. We will use the 'Risk of Bias 2 tool' to assess the risks of systematic errors. We will perform meta-analyses using R. We will use Trial Sequential Analysis to account for the risks of random errors. We will create a "Summary of Findings"-table in which we will present our primary and secondary outcome results. We will assess the certainty of the evidence using grading of recommendations assessment, development and evaluation. DISCUSSION: This systematic review can potentially elucidate the risks of perioperative NSAID treatment in gastrointestinal surgery and inform the already established non-opioid multimodal pain treatment regimen recommended by enhanced recovery after surgery guidelines.