Effect of Neurokinin-1 Receptor Antagonists on Experimental Postoperative Adhesion: A Systematic Review and Meta-Analysis with Trial Sequential Analysis of Preclinical Studies.

Background and Objectives: Postoperative adhesions are a major surgical concern. Preclinical studies of neurokinin-1 receptor antagonists (NK-1RAs) have reported inconsistent findings. We conducted a systematic review and meta-analysis with trial sequential analysis (TSA) to evaluate whether NK-1RAs prevent postoperative adhesions. Materials and Methods: We searched MEDLINE (via PubMed), EMBASE (via Ovid), Web of Science, and Google Scholar for animal studies assessing NK-1RAs applied to the surgical site. The primary outcome was macroscopic adhesion score; secondary outcomes were tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) mRNA expression in peritoneal tissue and t-PA activity in peritoneal tissue. Results: Nine studies including 331 animals (162 NK-1RA; 169 control) met the criteria. Macroscopic adhesion scores were significantly lower with NK-1RAs than control (standardized mean difference [SMD] 1.474; 95% confidence interval [CI] 1.030 to 1.918; Pchi2 = 0.001; I2 = 63.8%; τ = 0.619; 95% predictive interval [PrI] 0.133 to 2.815). TSA showed the cumulative Z-curve crossed both the conventional and trial sequential monitoring boundaries for the macroscopic adhesion score. t-PA activity was higher with NK-1RAs (SMD -1.219; 95% CI -2.379 to -0.058; Pchi2 < 0.001; I2 = 77.66%; τ = 1.453; PrI -4.655 to 2.217). There was no evidence of a difference in t-PA or PAI-1 mRNA expression. Conclusions: NK-1RAs reduced postoperative adhesions by macroscopic scoring and increased t-PA activity in preclinical models.