Do Nonsteroidal Anti-Inflammatory Drugs Increase Bleeding Risk After Craniotomy for Brain Surgery? A Systematic Review and Meta-Analysis

BACKGROUND AND OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for pain management in adults undergoing craniotomy for brain surgery, with several randomized clinical trials supporting their efficacy. However, concerns remain about their safety, particularly regarding the risk of postoperative bleeding because of cyclooxygenase inhibition. This study aimed to evaluate whether NSAIDs increase the risk of hemorrhagic complications after craniotomy for brain surgery when compared with non-NSAID approaches or placebo. METHODS: A systematic search was conducted in PubMed, Scopus, Web of Science, and Cochrane databases to identify studies comparing NSAIDs with non-NSAID drugs for postoperative analgesia after craniotomy for brain surgery. End points were (1) all bleeding complications and (2) bleeding complications requiring surgical intervention. Subanalyses focused on randomized controlled trials (RCTs) and patients undergoing tumor resection. Risk ratios (RR) and risk difference (RD) with 95% CI were pooled using a random-effects model, and heterogeneity was assessed with the I 2 statistic. RESULTS: Seven studies (5 RCTs), including 2251 patients (1119 males; median ages ranging from 11 to 55 years), of whom 583 (25.9%) received NSAIDs, met the inclusion criteria. Surgical indications included tumor resection, aneurysm clipping, and microsurgery for brain arteriovenous malformations. No significant differences were observed between NSAID and non-NSAID groups for overall bleeding complications (RR: 1.05; 95% CI: 0.58, 1.93; I 2 = 0%; RD: 0.31%; 95% CI: -1.46%, 0.84%) or bleeding complications requiring surgical intervention (RR: 1.27; 95% CI: 0.51, 3.16; I 2 = 0%; RD: 0.03%; 95% CI: -0.90%, 0.97%). 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 craniotomy for brain surgery, because they do not significantly increase the risk of bleeding complications, including those requiring surgical intervention, compared with non-NSAID analgesics.