Comparative Efficacy of Perioperative Blood Conservation Agents in Pediatric Cranial Vault Remodeling: A Systematic Review and Network Meta-Analysis

BACKGROUND AND OBJECTIVES: Red blood cell transfusions are commonly required in pediatric cranial vault remodeling (CVR); however, they carry risks and potential complications. This study evaluates the evidence on perioperative blood conservation agents assessing their efficacy in optimizing and reducing transfusion requirements in CVR. METHODS: A systematic review was conducted using PubMed/MEDLINE, Scopus, Embase, Web of Sciences, and Google Scholar according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to assess articles discussing blood conservation agents in pediatric CVR. A network meta-analysis compared the effectiveness of different agents including tranexamic acid (TXA), aminocaproic acid (ACA), aprotinin, erythropoietin (EPO), and iron. RESULTS: Sixteen studies analyzing 1072 patients with a mean age of 15.6 months and weight of 8.78 kg were included. The most reported craniosynostosis subtypes were sagittal (30.2%) and metopic (13.8%). TXA and ACA were independently associated with lower transfusion rates and volumes compared with placebo (ACA: odds ratio [OR], 0.25; 95% CI, 0.08-0.80; TXA: OR, 0.17; 95% CI, 0.07-0.42). Combination therapy with TXA + EPO + iron (OR: 0.004, 95% CI: 0.002-0.10) or ACA + EPO (OR: 0.04, 95% CI: 0.01-0.32) were associated with reductions in transfusion rates. Network meta-analysis ranking revealed TXA + EPO + iron (Surface Under the Cumulative Ranking [SUCRA]: 98.90%) and ACA + EPO (SUCRA: 75.41%) as the most effective treatments for reducing transfusion rates. While TXA was associated with significant reductions in blood loss compared with placebo (standard mean difference: −1.26, 95% CI: −1.97 to −0.56), ACA ranked highest for blood loss reduction (ACA: SUCRA, 84.58% vs TXA: SUCRA, 72.43%). Combination of TXA + EPO + iron was associated with significantly reduced hospital length of stay (standard mean difference: −1.00, 95% CI: −1.71 to −0.29). No treatment significantly affected the duration of surgery, and there were no reported treatment-associated thromboembolic events. CONCLUSION: Our meta-analysis reveals that TXA + ACA reduce red blood cell transfusion rates and volumes, with TXA + EPO + iron and ACA + EPO being most effective. This highlights the superiority of combination therapies and underscores the need for structured multimodal protocols in perioperative blood conservation for pediatric CVR.