Aminophylline as an Adjunct to Ureteroscopic Lithotripsy: A Systematic Review of Local and Intravenous Use

Aminophylline, a non-selective phosphodiesterase inhibitor with smooth muscle relaxant effects, is established in pulmonary medicine but has not been systematically reviewed as an adjunct in ureteroscopic lithotripsy. This review assesses its efficacy and safety when administered either intravesically or intravenously.

PubMed, Cochrane Library, EBSCO, and Google Scholar were searched to June 2025. Eligible studies were Randomized Controlled Trials (RCTs) or semi-experimental trials assessing aminophylline during ureteroscopic lithotripsy. Outcomes included Stone-Free Rate (SFR), operative time, ureteral access, stent requirement, pain, hematuria, Catheter-Related Bladder Discomfort (CRBD), and adverse events. Risk of bias was assessed with RoB 2.0 for RCTs and ROBINS-I for non-RCTs.

Eight studies (596 patients) were included. Intravesical aminophylline consistently improved ureteral access and reduced operative time; Lubana et al. showed higher success (82% vs 44%, p = 0.002) and less stenting (38% vs 68%, p = 0.011). Shabayek and Saafan reported reductions in intraureteral pressure, hematuria, and pain. Intravenous aminophylline showed mixed results: Barzegarnajad found higher SFR (97.6% vs 84%), Ghadyan reported lower procedural success but less stenting, while Rehab et al. observed reduced CRBD (26% vs 59%, p = 0.025) and analgesic use. Adverse events were mild and transient.

Evidence is limited by small samples, heterogeneous designs, and variable definitions of “success.” Effect sizes may vary with stone size, location, and lithotripsy modality. Sensitivity analysis was not feasible, lowering certainty.

Aminophylline may be a safe, low-cost adjunct to ureteroscopic lithotripsy, enhancing access, reducing operative time, and lowering morbidity. However, evidence remains low-certainty and hypothesis-generating, warranting larger multicenter RCTs.