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Indigo Carmine

Indigo carmine (indigotindisulfonate sodium) is a blue-violet visible-light dye that was for decades the standard IV agent for intraoperative ureteral identification. Given IV, it is excreted rapidly into the urine, allowing the surgeon to see the ureteral efflux appear blue within 5–10 minutes of injection — confirming ureteral patency and localizing the ureters in the operative field without dissection.[1]

Its clinical role has been substantially diminished by persistent supply shortages since 2014, when the primary U.S. manufacturer discontinued production. The agent has drifted in and out of availability since, driving adoption of methylene blue (for visible-light use) and pudexacianinium (ASP-5354) (for IV NIR use) as functional replacements.

Pharmacology​

PropertyValue
ClassIndigoid disulfonate dye
ColorBlue-violet (visible)
RouteIV
Concentration0.8% solution (8 mg/mL); 5 mL ampoule (40 mg) typical adult dose
Onset5–10 minutes to appear in ureteral efflux
Renal excretionRapid — the defining feature
Duration15–30 minutes of visible ureteral efflux

Why the pharmacology was ideal​

  • Rapid glomerular filtration → visible in ureteral efflux within 5–10 min of IV injection
  • No tissue distribution of clinical concern — concentrated in urine, minimal systemic effect
  • Short-acting — cleared within 30 minutes, allowing repeat dosing if needed
  • Visible under normal OR light — no imaging hardware required

GU Applications (Historical and Current)​

1. Ureteral identification during open and laparoscopic surgery​

  • IV indigo carmine → watch for blue ureteral efflux → ureter identified
  • Gold standard in gynecologic, colorectal, and urologic surgery through 2014
  • Particularly valuable when ureter has been identified but patency is questioned (e.g., after possible thermal injury during pelvic dissection)

2. Cystoscopic ureteral orifice verification​

  • Confirms both ureteral orifices are ejecting urine
  • Useful during stent placement, after instrumentation for stone disease, or after suspected ureteral injury

3. Double-dye testing for urogynecologic fistulas​

  • Oral phenazopyridine (orange urine) + IV indigo carmine (blue urine) + intravesical methylene blue (blue urine)
  • Classical algorithm to distinguish VVF from ureterovaginal fistula
  • Has largely been simplified — phenazopyridine alone for "is the ureter leaking" + methylene blue instillation for "is the bladder leaking"

The Shortage Story​

Indigo carmine became unavailable in the U.S. in 2014 when the primary manufacturer discontinued production due to raw-material sourcing issues. It has drifted in and out of availability since — sporadically produced by compounders, imported under FDA shortage allowances, or simply unavailable for months at a time.[2]

The shortage drove three practice shifts:

  1. Methylene blue became the default visible-light dye for most urinary-tract applications
  2. Low-dose sodium fluorescein was explored as an alternative
  3. Pudexacianinium (ASP-5354) was developed specifically as an NIR replacement for IV ureteral identification, FDA-approved in the mid-2020s

Current status: intermittently available; not a reliable first-line agent. When available, still an option in centers without NIR hardware.

Dosing (when available)​

  • 40 mg IV bolus (5 mL of 0.8% solution)
  • Onset 5–10 minutes; duration 15–30 minutes
  • Can be repeated once per case

Contraindications and Cautions​

  • Hypertension — rare cases of transient BP elevation after IV bolus
  • Iodide allergy — indigo carmine does not contain iodine (distinct from ICG)
  • Pregnancy — limited data; avoided when alternatives available
  • G6PD deficiency — theoretical concern; not a strict contraindication

Historical Role in GU Reconstruction​

For the reconstructive urologist trained before 2014, indigo carmine was the default dye. Contemporary trainees may never have used it. The two legacy applications that still appear in literature:

  • Ureteral reimplantation — confirmation of ureteral orifice placement and patency
  • Ureterolysis / retroperitoneal fibrosis surgery — confirming ureter is open after extensive dissection

Both applications have been replaced by ICG (retrograde) or pudexacianinium (IV NIR) in modern practice at centers with NIR hardware.

See Also​

References​

1. Jeppson PC, Balgobin S, Rahn DD, et al. Comparison of vaginal hand-assisted laparoscopic sacrocolpopexy with robotic-assisted sacrocolpopexy. Obstet Gynecol. 2015;126(4):725–34. doi:10.1097/AOG.0000000000001049

2. Doyle PJ, Lipetskaia L, Duecy E, Buchsbaum G, Wood RW. Sodium fluorescein use during intraoperative cystoscopy. Obstet Gynecol. 2015;125(3):548–550. doi:10.1097/AOG.0000000000000691