Evaluation of Ureteral Patency in the Post-indigo Carmine Era

Many gynecologic, urologic and pelvic reconstructive surgeries require accurate intra-operative evaluation of ureteral patency. Numerous studies show that cystoscopy detects a greater proportion of bladder and ureteral injuries than visual inspection alone.The rate of ureteral injury in gynecologic surgery ranges from 0.6 to 11% when discovered on routine intraoperative cystoscopy depending on the procedure. In a review by Gilmour et al, the incidence of bladder injury in studies performing routine cystoscopy was 4-fold higher than those studies that did not. Early recognition of injury and repair during the primary surgery most often results in less morbidity for the patient, more successful outcome, and increased ease of repair.

Cystourethroscopy is a surgical procedure in which a fiberoptic endoscope is introduced through the urethra to examine the entire lumen of the urethra and bladder for diseases or abnormalities in a systematic manner.There are numerous indications for diagnostic cystourethroscopy during gynecologic surgery. The most important indications are to rule out cystotomy and intravesical or intraurethral suture or mesh placement, verify bilateral ureteral jets to ensure patency, and evaluate a suspected urine leak during or after laparotomy, laparoscopy or vaginal surgery.

Historically, indigo carmine, indigotindisulfonate sodium has been used to assist with cystourethroscopy. Ureteral function is assessed by visualization of ureteral efflux of blue dye after the intravenous injection of indigo carmine. Indigo carmine has many advantages. These include no known drug interactions or metabolites, easy dosing of 40mg or 5 to 10 cc of 0.8% solution, changing urine to a non-physiologic blue color that eases visualization and the ability to give the medication intravenously immediately prior to the procedure. In patients with normal renal function and adequate hydration, the dye is visible after approximately ten minutes, having a half-life of four to five minutes. Because of its large molecular size, it is largely excreted rather than reabsorbed. There are few contraindications to use of indigo carmine. It should be used with caution in patients with cardiovascular diseases secondary to its mild pressor effect.

The U.S. Food and Drug Administration announced the current shortage of indigotindisulfonate sodium in June 2014. This is due to the inability to obtain the active agent. There are two suppliers of indigo carmine in the United States: Akron and American Regent. Akron has discontinued manufacturing indigo carmine with no plan to resume production. American Regent plans to continue manufacturing indigo carmine based on component availability.

Methylene blue is an alternative to indigo carmine. Like indigo carmine, it can be given intravenously. However, it does have some risks. Methylene blue is variably metabolized to multiple end products but is largely metabolized to leukomethylene, which is colorless and therefore, may not be visualized in the urine. It cannot be used in pregnant patients and those with glucose-6-phosphate dehydrogenase deficiency because of risk of inducing hemolytic anemia. It may also cause methemoglobinemia when given in high doses greater than 7mg/kg. Lastly, methylene blue is a monoamine oxidase inhibitor and can cause serotonin syndrome in patients taking other serotonergic agents.