The effects of locally administered aminophylline in patients undergoing ureteroscopic lithotripsy: a systematic review with exploratory meta-analysis

Aminophylline, a methylxanthine derivative, acts as a smooth muscle relaxant through non-competitive inhibition of phosphodiesterase. It has been suggested to facilitate ureteroscopic lithotripsy by relaxing ureteral smooth muscle. The aim of this systematic review is to assess the available evidence on locally administered aminophylline in patients undergoing ureteroscopic lithotripsy and, where feasible, to perform an exploratory meta-analysis to estimate pooled effects. A systematic search was conducted through November 2025. Three randomized controlled trials (RCTs) met the inclusion criteria. The primary outcome was residual stone proportions (derived from the stone-free rate). Secondary outcomes included operative time, postoperative ureteral stenting, and auxiliary procedures. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB-2) tool. This review was registered with PROSPERO (CRD420251229352). Three RCTs enrolling 310 patients (155 receiving aminophylline and 155 receiving placebo) were included. Local aminophylline was associated with significantly fewer residual stones (RR 0.3; 95% CI: 0.13, 0.69; p = 0.025; I² = 0%) and fewer auxiliary procedures (RR 0.15; 95% CI: 0.06, 0.38; p < 0.001; I² = 0%). Reductions in operative time and postoperative ureteral stenting were observed in the primary analysis; however, these did not remain statistically significant after applying the Hartung–Knapp–Sidik–Jonkman (HKSJ) correction. This exploratory meta-analysis provides preliminary evidence that locally administered aminophylline may reduce residual stone fragments and auxiliary procedures during ureteroscopic lithotripsy. Reductions in operative time and ureteral stenting did not retain statistical significance in sensitivity analyses and should be considered hypothesis-generating. These findings should be interpreted with caution, given the low certainty of the evidence. Adequately powered randomized trials are required to validate these results. https://www.crd.york.ac.uk/prospero/ , identifier CRD420251229352.