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Indocyanine Green (ICG)

Indocyanine green (ICG) is a tricarbocyanine near-infrared (NIR) fluorescent dye that binds rapidly to plasma proteins after IV injection and is cleared almost exclusively by hepatic excretion into bile — with a plasma half-life of 3–4 minutes. When excited by 750–800 nm light, ICG emits at 830 nm — a wavelength that is invisible to the naked eye but visualized by dedicated NIR imaging systems (Firefly, SPY, Rubina, PINPOINT). This combination — rapid plasma binding, rapid clearance, biliary excretion, and NIR emission through several millimeters of tissue — makes ICG the dominant intraoperative fluorophore in GU reconstruction.[1][2]

Pharmacology​

PropertyValue
ClassTricarbocyanine NIR fluorescent dye
Molecular weight775 Da
Plasma half-life3–4 minutes
Protein binding>95% (plasma proteins, primarily albumin)
DistributionRemains intravascular due to protein binding
ClearanceHepatic — excreted into bile; no renal or urinary excretion
Peak excitation~800 nm
Peak emission~830 nm
FDA approval1959 (originally for cardiac output and hepatic function); off-label for most GU applications

Why the pharmacology matters​

  • Rapid plasma half-life means you can give multiple doses per case as anatomy evolves
  • No urinary excretion — ICG given IV does not appear in urine; this is the critical distinction from indigo carmine / methylene blue and is why IV ICG is not useful for ureteral visualization from within the urinary tract. IV ICG can still be used for ureter visualization via peristaltic microvascular flow in the adventitia, but not for visualization of the urinary column itself
  • Biliary excretion — ICG can faintly highlight the biliary tree, which is rarely clinically relevant in GU work but worth knowing

Dosing​

IV dosing (perfusion / lymphatic / adventitial)​

  • 2.5–5 mg IV bolus is the standard adult dose for a single perfusion assessment
  • Reconstitution: 25 mg vial diluted in 10 mL sterile water → 2.5 mg/mL
  • Can be repeated every 5–10 minutes for serial assessments, up to a total daily dose of 2 mg/kg
  • Administered through any peripheral IV — arterial transit to the target organ occurs within 15–45 seconds

Direct instillation dosing​

  • Intraureteral stent coating or retrograde instillation: 2.5 mg in 10 mL saline, injected through a ureteral catheter
  • Intravesical: 25 mg in 50 mL saline for bladder-wall fluorescence
  • Direct tissue injection for lymphatic mapping: 0.5–2 mL of diluted ICG (1.25 mg/mL) submucosally or intradermally around the index site

Iodine allergy warning​

ICG contains sodium iodide (<5%) as a solubilizer. Contraindicated in patients with known iodide allergy. The plasma protein binding means free iodide exposure is minimal, but the warning persists in labeling.

GU Reconstruction Applications​

1. Perfusion assessment​

The original and highest-yield urologic application. IV ICG highlights the arterial perfusion of any tissue — ureteral stump viability, bowel mesentery before urinary diversion, bladder flap vascularity, phalloplasty flap perfusion, omental pedicle viability.

  • Ureter after reimplantation — confirms distal ureteral segment remains perfused after extensive dissection
  • Ileal conduit before anastomosis — verifies the vascular arcade is intact
  • Kidney perfusion during partial nephrectomy — assesses residual parenchymal perfusion after clamp release; identifies poorly perfused territories that may need excision
  • Bladder flap for Boari — confirms viability of the long flap before tubularization
  • Omental flap — verifies the gastroepiploic pedicle is preserved after mobilization[3]
  • Bowel anastomosis in urinary diversion — early identification of poorly perfused anastomotic segments

2. Ureteral identification​

Two distinct techniques — IV vs. intraureteral:

Intraureteral ICG (retrograde):

  • Ureteral catheter placed cystoscopically; 5–10 mL of 2.5 mg/mL ICG solution instilled antegrade up the catheter
  • The urinary column within the ureter fluoresces under NIR imaging
  • Most reliable method for intraoperative ureter localization during robotic pelvic surgery
  • Particularly valuable in fibrotic / reoperative / malignant fields where ureter is hard to identify by dissection alone

IV ICG for ureter:

  • IV injection does not fill the ureter (no urinary excretion)
  • However, the ureter's adventitial vessels fluoresce transiently after IV dose, outlining the ureter's course
  • Less reliable than intraureteral but useful when retrograde access is impractical
  • See also pudexacianinium (ASP-5354) — the IV NIR alternative that does excrete into urine

3. Lymphatic mapping​

  • Pelvic lymph node dissection during radical prostatectomy, cystectomy (within functional-urology scope where it overlaps)
  • Sentinel node mapping in penile cancer (outside primary WARWIKI scope but referenced for completeness)
  • Intradermal / peritumoral ICG injection → lymphatic channels fluoresce → sentinel node identification

4. Vesicourethral / bladder-neck identification (robotic)​

  • Y-V plasty for refractory bladder neck contracture — Firefly ICG visualization of the residual bladder neck in the scarred post-prostatectomy field is a defining technique-enabler. See Y-V plasty.[4]
  • Vesicourethral anastomotic stenosis repair — similar rationale

5. Penile reconstruction​

  • Perfusion assessment after Peyronie's degloving
  • Phalloplasty flap assessment — RFFF, ALT, SCIP perfusion
  • Penile shaft coverage flap viability

6. Fistula localization (emerging)​

Experimental use of intravesical ICG for VVF localization in selected cases; methylene blue remains standard.

NIR Imaging Hardware​

ICG fluorescence requires dedicated imaging:

SystemPlatformWorkflow
FireflyIntuitive da Vinci (Si, Xi, X, SP, 5)Toggle between white-light and NIR modes at the console
SPY / Luna-IRStryker (open + laparoscopic)Handheld NIR imager for open cases
PINPOINTNovadaq/StrykerLaparoscopic NIR video system
IMAGE1 S RubinaKarl StorzLaparoscopic NIR with side-by-side display
Visera Elite IIIOlympusLaparoscopic NIR
FUJIFILM VISERA ELITE / ENDOEYE—Some support NIR

Firefly dominance in robotic reconstruction means ICG is overwhelmingly associated with da Vinci workflows in urology. Open and laparoscopic cases rely on SPY or Rubina.

Technique Pearls​

  • Give the bolus at the right moment — 15–45 seconds from injection to target tissue fluorescence. Coordinate with anesthesia so the bolus is given just before the assessment rather than 5 minutes ahead
  • Don't dose too early in the case — ICG clears in 3–4 minutes; if given before the tissue is fully mobilized, the fluorescence will have washed out
  • Multiple doses are fine — the 2 mg/kg daily ceiling allows 5+ doses in a standard adult case
  • Intraureteral retrograde dosing is more reliable than IV for ureteral course visualization
  • Firefly auto-gain can over-brighten adjacent tissues — toggle the NIR view intermittently to recalibrate
  • Iodide allergy — document preoperatively; use alternatives (methylene blue, pudexacianinium) in documented allergy

Adverse Events​

ICG has an excellent safety profile over 65+ years of clinical use:

  • Anaphylaxis — rare (<1:10,000); more common in iodine-allergic patients
  • Mild reactions — nausea, flushing; rare
  • No renal toxicity — safe in CKD
  • No nephrogenic systemic fibrosis risk (unlike gadolinium)

Relative Cost​

  • ICG is inexpensive ($20–40 per 25 mg vial)
  • NIR hardware is the capital expense — the dye itself is essentially free on a per-case basis
  • Contrast with pudexacianinium, which is substantially more expensive

See Also​

References​

1. Alander JT, Kaartinen I, Laakso A, et al. A review of indocyanine green fluorescent imaging in surgery. Int J Biomed Imaging. 2012;2012:940585. doi:10.1155/2012/940585

2. Reinhart MB, Huntington CR, Blair LJ, Heniford BT, Augenstein VA. Indocyanine green: historical context, current applications, and future considerations. Surg Innov. 2016;23(2):166–75. doi:10.1177/1553350615604053

3. Yang YK, Hsieh ML, Chen SY, Liu CY, Lin PH, Kan HC, Pang ST, Yu KJ. Clinical benefits of indocyanine green fluorescence in robot-assisted partial nephrectomy. Cancers (Basel). 2022;14(12):3032. doi:10.3390/cancers14123032

4. Granieri MA, Weinberg AC, Sun JY, Stifelman MD, Zhao LC. Robotic Y-V plasty for recalcitrant bladder neck contracture. Urology. 2018;117:163–165. doi:10.1016/j.urology.2018.04.017