Indigotindisulfonate Sodium vs Saline for Ureteral Patency After GYN Procedures

Objectives: Indigo carmine (indigotindisulfonate sodium) was the benchmark visualization agent for cystoscopic ureteral patency evaluation, it was in shortage from 2015 until July 2022, when Bludigo (indigotindisulfonate sodium) received FDA approval as a visualization tool for assessing ureteral integrity in adults, reintroducing it to the market.
The trial objective was to determine whether intravenous indigotindisulfonate sodium provides a visualization advantage versus saline during evaluation of ureteral patency during intraoperative cystoscopy for gynecological procedures. Secondary outcomes included safety, time to visualization, impact of dose, and responder analysis.

Methods: This multicenter randomized trial of patients undergoing assessment of ureter patency included a subgroup analysis that evaluated gynecological procedures. The most common surgical procedures were female sterilization (21.2%), hysterectomy (16.9%), and cholecystectomy (13.6%).
Patients first received a 5.0 mL saline injection and were then randomized to receive either 2.5 mL or 5.0 mL of indigotindisulfonate sodium (8 mg/mL). Ten-minute videos were recorded after each injection of 5.0 mL of saline, and the randomized dose of indigotindisulfonate sodium. Independent reviewers, blinded to treatment (saline vs. indigotindisulfonate sodium) and dose (2.5 mL vs. 5.0 mL), scored videos for visualization of ureteral flow using a 5-point conspicuity scale (with 1=no jet and 5=strong jet flow with striking contrast) that was developed and tested. Each ureter was evaluated independently and served as its own control. Subjects with scores ≥ 3 and at least a +1-point difference from saline score were responders. Time to visualization of indigotindisulfonate sodium was recorded, and a responder analysis (Clopper-Pearson exact test) to determine whether indigotindisulfonate sodium significantly improved visualization compared to saline.

Results: There were 42 patients evaluated, with an average age of 40.7 (range 24 to 74). Race and ethnicity were 78.6% White, 16.7%Black/African American, 2.4% Asian, and 2.4% other. 82.7% of patients had an eGFR ≥90 mL/min.
There were 44 ureters evaluated with the 5.0 mL dose of indigotindisulfonate sodium, 40 with the 2.5 mL dose, and 84 with saline. 82.1% of ureters were scored ≥3 on the conspicuity scale following indigotindisulfonate sodium injection; both doses were significantly better than saline for conspicuity (p < 0.0001). Overall, 83.3% of ureters were rated as a responder with indigotindisulfonate sodium. The median time to visualization of blue color was not significantly different (p>0.05), 4.89 minutes for 5.0 mL and 5.63 minutes for 2.5 mL . There were no adverse events related to indigotindisulfonate sodium use.

Conclusions: Intravenous administration of indigotindisulfonate sodium at both 2.5 mL and 5.0 mL doses was significantly better for visualizing ureter patency compared to saline. Indigotindisulfonate sodium was a safe and effective agent for assessing ureteral patency via cystoscopy during gynecologic procedures.