Definition, analysis, reporting, and interpretation of perioperative bleeding in randomized controlled trials: a methodological systematic review

BACKGROUND: Perioperative bleeding is a common surgical complication and a frequently used outcome in randomized trials; however, its definition and analysis are not straightforward and have important implications for trial design, statistical power and interpretation of treatment effect. This review aimed to summarize how perioperative bleeding was defined in randomized controlled trials, along with sample size considerations, analytic approaches, and interpretation practices. METHODS: On April 9th, 2025, we systematically searched the CENTRAL database for randomized trials in surgical settings published after January 2024 that evaluated perioperative bleeding as the primary outcome. Two reviewers independently screened and extracted data. Where appropriate, we categorized findings into conceptually similar domains and applied descriptive analysis. RESULTS: We included 115 trials reporting 116 primary bleeding outcomes and identified 36 unique definitions, with assessment periods ranging from intraoperative to more than 30 days postoperatively. Volumetric or gravimetric measures were most common (n = 46 [39.6%]), whereas patient-reported events (n = 5 [4.3%]) and clinical management of blood loss (n = 4 [3.4%]) were rare. Most trials reported a sample size calculation based on the primary outcome (n = 90 [78.3%]), but over one-third lacked effect-size justification (n = 34 [37.8%]). Analyses were predominantly parametric (n = 69 [59.5%]), while a few adjusted for baseline covariates (n = 18 [15.6%]). Interpretation in superiority trials relied mainly on statistical significance (n = 49 [47.6%]). Among noninferiority trials, noninferiority was often claimed without prespecified margins (n = 4 [33.3%]). CONCLUSION: Perioperative bleeding outcomes are defined and analyzed with high inconsistency. Standardized outcome definitions and reporting practices are needed in this field to improve trial comparability and clinical relevance.