Do Non-steroidal Anti-inflammatory Drugs Increase Bleeding Risk After Invasive Brain Surgery? A Systematic Review and Meta-analysis

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for pain management in adults undergoing brain surgery, with several randomized clinical trials supporting their efficacy. However, concerns remain about their safety, particularly regarding the risk of postoperative bleeding due to cyclooxygenase inhibition. This study aims to evaluate whether NSAIDs, when used as postoperative analgesics following brain surgery, are associated with an increased risk of bleeding complications and other adverse effects.

Methods: A systematic search was conducted in PubMed, Scopus, Web of Science, and Cochrane databases to identify studies comparing NSAIDs to non-NSAID drugs for postoperative analgesia in brain surgery patients. The primary endpoints were bleeding complications, including those requiring surgical intervention. Subanalyses focused on randomized controlled trials (RCTs) and patients undergoing tumor resection. Odds ratios (OR) with 95% confidence intervals (CI) were pooled using a random-effects model, and heterogeneity was assessed with the I² statistic.

Results: Eight studies, including 2,313 patients, of whom 611 (26.4%) received NSAIDs, met the inclusion criteria. The cohort included 1,152 males (49.8%), with median ages ranging from 11 to 55 years. Surgical indications included tumor resection, aneurysm clipping, and microsurgery for brain arteriovenous malformations. Seven studies performed craniotomies, while one employed an endonasal transsphenoidal approach. No significant differences were observed between NSAID and non-NSAID groups for overall bleeding complications (OR: 0.91; 95% CI: 0.61–1.34; I² = 0%) or bleeding complications requiring surgical intervention (OR: 1.08; 95% CI: 0.49–2.39; I² = 0%). Similar results were found in the RCT-only and tumor resection subanalyses.

Conclusion : Our findings suggest that NSAIDs are a safe option for postoperative analgesia in patients undergoing brain surgery, as they do not significantly increase the risk of bleeding complications, including those requiring surgical intervention, compared to non-NSAID analgesics.