Abstract
Background and Objectives: We performed a systematic review and meta-analysis using trial sequential analysis (TSA) to investigate the potential preventive postoperative antiadhesive effects of local anesthetics (LA). Materials and Methods: A comprehensive search was conducted using Ovid-MEDLINE, Ovid-EMBASE, Web of Science, and Google Scholar to identify animal studies that explored the postoperative antiadhesive effect of LA applied in the surgical area. The primary outcome was the macroscopic adhesion score, including adhesion quality, quantity, and total adhesion score, whereas the secondary outcome was the microscopic adhesion score, including adhesion severity, inflammation, and fibrosis. Certainty of evidence was assessed using a GRADE-adapted framework for animal studies. Results: The comprehensive analysis involved 227 rats across 6 animal studies, with 158 rats subjected to LA and the remaining 69 administered a placebo or received no treatment. For macroscopic adhesion score, LA were associated with reductions in the total adhesion score (standardized mean difference (SMD) -1.528; 95% confidence interval (CI) -2.081 to -0.976; I(2) = 30.0%) and adhesion quality (SMD: -0.996; 95% CI -1.906 to -0.085; I(2) = 72.6%), while no significant difference was observed in adhesion quantity (SMD -0.544; 95% CI -1.452 to 0.365; I(2) = 77.6%). For the microscopic adhesion score, LA appeared to reduce adhesion severity (SMD -1.304; 95% CI -1.862 to -0.746; I(2) = 31.7%) and fibrosis (SMD: -2.373; 95% CI -3.400 to -1.346; I(2) = 60.4%), whereas the effect on inflammation was inconsistent. Across all macroscopic outcomes, TSA demonstrated that the accrued sample size was far below the required information size, and the certainty of evidence remained low to very low. Most included studies had unclear or high risks of bias, which reduces confidence in the synthesized estimates. Conclusions: LA may have a potential association with reduced postoperative adhesion formation; however, the certainty of evidence was low to very low, and TSA indicated insufficient required information size to draw firm conclusions.