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Indocyanine Green (ICG) in Present-Day Surgery
Background and Pharmacology
Indocyanine green is a water-soluble tricarbocyanine dye that was first used in the late 1950s to evaluate liver function, and subsequently found use in cardiology and ophthalmology. It is the only FDA-approved near-infrared (NIR) fluorophore for intraoperative use. Once injected intravenously, it binds strongly to plasma proteins (predominantly albumin), is not metabolized, and is completely eliminated unchanged in bile. Its half-life is short - 3 to 5 minutes - which permits repeated intraoperative evaluations during a single procedure.
ICG absorbs NIR light at approximately 800 nm and emits fluorescence at ~830 nm. A dedicated camera system filters out wavelengths below 820 nm, capturing only the ICG-emitted signal, which is then superimposed on the white-light image. This gives surgeons real-time anatomical or physiological information that is invisible to the naked eye. Its severe reaction rate is extremely low (~0.05%), making it safe for routine intraoperative use.
- Fischer's Mastery of Surgery, 8th ed. (pp. 881-882)
Principle Operating Domains
1. Biliary Anatomy Visualization - Laparoscopic Cholecystectomy
One of the best-established uses of ICG is near-infrared fluorescence cholangiography (NIFC) during laparoscopic cholecystectomy. ICG (2.5 mL of a 25 mg/10 mL solution) is injected intravenously at least 45 minutes before the procedure, allowing time for hepatic excretion into bile. The cystic duct, common hepatic duct, and common bile duct (CBD) then fluoresce brilliantly under NIR light, revealing their anatomy and junctions before any dissection.
A landmark multicenter RCT by Dip et al. randomized 639 patients to white light alone vs. white + NIR light, showing superior extrahepatic bile duct visualization in the NIFC group. Critically, both cases of bile duct injury (BDI) in the trial occurred in the white-light-only group, as did four of five conversions to open surgery. A meta-analysis of eight prospective studies (1,603 NIFC vs. 5,070 non-NIFC cases) found the BDI rate roughly 75% lower with NIFC and the conversion rate ~95% lower. Two separate RCTs confirmed that ICG-based fluorescent cholangiography is as effective as intraoperative X-ray cholangiography for identifying bile duct variations.
- Fischer's Mastery of Surgery, 8th ed. (pp. 889-890); Sabiston Textbook of Surgery (p. 185)
2. Colorectal Surgery - Anastomotic Perfusion Assessment
Ischemia is a primary cause of anastomotic leaks in colorectal surgery. ICG fluorescence angiography provides a real-time map of bowel wall perfusion before and after the anastomosis is formed. The surgeon injects ICG IV (2.5 mL of 25 mg/10 mL), toggles to NIR mode, and within seconds the arterial supply of the bowel segment lights up, identifying areas of poor perfusion where the resection margin can be moved proximally.
The 2025 SAGES guidelines (the most current and comprehensive evidence synthesis available) gave a strong recommendation with moderate certainty for the use of FIGS with ICG in patients undergoing left-sided colorectal anastomosis, based on strong evidence that it reduces anastomotic leak rates. The European Registry EURO-FIGS, analyzing 1,240 patients across 30 hospitals in 8 countries, found that ICG imaging changed the intended resection level in 27% of cases, and 99% of surgeons reported higher confidence in their anastomosis when guided by ICG.
- Fischer's Mastery of Surgery, 8th ed. (p. 884); SAGES 2025 guidelines (PMID 41249539); PMID 41422225
3. Hepatic Surgery - Tumor Detection and Margin Assessment
The liver's intrinsic metabolism of ICG underpins several hepatic applications:
- Preoperative liver function testing: The ICG 15-minute retention rate (ICG-R15) is a standard tool to assess hepatic reserve and functional capacity before major hepatectomy, replacing the older constant-infusion clearance technique because of better tolerance.
- Intraoperative tumor identification: ICG (0.25-0.5 mg/kg) is administered 24 hours or more before surgery. Normal hepatocytes clear ICG into bile, while tumor cells - particularly metastases from colorectal and pancreatic cancer - are unable to accumulate ICG. This creates a sharp "dark spot" contrast against fluorescing liver parenchyma that guides resection margins.
- Differential tumor fluorescence: Hepatocellular carcinoma fluoresces less intensely than surrounding parenchyma, while fibrolamellar carcinoma and cholangiocarcinoma display brighter fluorescence than the hepatic background - enabling pathological differentiation.
- A 2024 systematic review and meta-analysis (PMID 38867212) confirmed that ICG-guided laparoscopic hepatectomy achieves significantly better surgical margin status in liver malignancies.
- Fischer's Mastery of Surgery, 8th ed. (pp. 886-887)
4. Sentinel Lymph Node (SLN) Mapping
ICG is now widely used for intraoperative SLN identification across multiple cancer types, exploiting the fact that ICG injected peritumorally drains through lymphatics to the regional sentinel nodes, which then fluoresce under NIR light (780 nm excitation).
- Breast cancer: ICG identifies sentinel nodes with 95-100% accuracy under infrared light at 780 nm - superior to older methods. It can be used alone or in combination with blue dye (>90% identification), and serves as an alternative when radioisotope (Tc-99m) is unavailable.
- Gastric cancer: ICG is injected submucosally around the primary lesion endoscopically. Within minutes, lymphatic drainage basins and SLNs light up under NIR, guiding lymphadenectomy. This is particularly valuable in laparoscopic/robotic settings where traditional blue dye or radiotracers are impractical.
- Colorectal cancer: A 2024 meta-analysis (PMID 39542857) found ICG fluorescence imaging significantly increases lymph node yield and improves long-term oncologic outcomes in colorectal cancer surgery.
- Gynecologic oncology: SLN mapping with ICG is now standard in endometrial and cervical cancer, with near-universal adoption in robotic-assisted surgery.
- Bailey and Love's Short Practice of Surgery, 28th ed. (pp. 957-958); Fischer's Mastery of Surgery, 8th ed. (p. 827)
5. Esophageal and Foregut Surgery
After esophagectomy, anastomotic leak rates can reach 30%, with ischemia as the dominant cause. ICG perfusion assessment of the gastric pull-up conduit is now routinely performed. After IV injection (2.5 mL of 25 mg/10 mL), the arterial supply of the conduit and esophageal stump can be visualized within 30 seconds under NIR. Studies have suggested that if NIR perfusion is visualized within 60 seconds of injecting ICG, the graft blood supply is likely adequate for anastomosis. "Fluorescence-based enhanced reality" software can quantify time-to-peak fluorescence, adding objective measurement to the assessment.
- Fischer's Mastery of Surgery, 8th ed. (pp. 890-891)
6. Bariatric Surgery
In sleeve gastrectomy, leaks near the esophagogastric (EG) junction are the most feared complication, driven by tenuous blood supply from the left phrenic and left gastric arteries. ICG perfusion assessment during sleeve gastrectomy and gastric bypass identifies areas of inadequate arterial supply before the staple line is completed, potentially allowing the surgeon to adapt the technique. Though current evidence from small series remains limited, the safety and simplicity of the approach make it an attractive adjunct.
- Fischer's Mastery of Surgery, 8th ed. (pp. 892-893)
7. Endocrine Surgery - Parathyroid Identification
Inadvertent devascularization or removal of parathyroid glands during thyroidectomy is a major cause of postoperative hypoparathyroidism. ICG angiography is now used to confirm the viability and perfusion of parathyroid glands in real time. After IV ICG injection, the parathyroid glands (which receive their blood supply from small end-arteries) display robust fluorescence when perfused, and diminished or absent fluorescence when devascularized. This guides the decision to auto-transplant a gland into the sternocleidomastoid muscle. Parathyroid autofluorescence (without exogenous dye) is also exploited but is limited to a few mm depth; ICG offers greater penetration and more dramatic signal.
- Sabiston Textbook of Surgery (pp. 1528-1529)
8. Thoracic Surgery
ICG is used in video-assisted (VATS) and robotic thoracoscopic surgery for:
- Pulmonary nodule localization: Before resection of small or ground-glass pulmonary nodules that are difficult to palpate, ICG is injected endobronchially or percutaneously to mark the target segment, which then fluoresces under NIR and guides the resection plane.
- Intersegmental plane identification: For anatomic segmentectomy, ICG administered intravenously lights up the perfused segment while the target segment to be resected remains dark (or vice versa), precisely delineating the intersegmental boundary.
- Fischer's Mastery of Surgery, 8th ed.; Bailey and Love's, 28th ed. (p. 3007)
9. Urology - Robotic Partial Nephrectomy
ICG is increasingly used in robotic-assisted partial nephrectomy (RAPN) for:
- Selective arterial clamping guidance: After IV ICG injection, the specific renal artery branch supplying the tumor can be identified before selective clamping, preserving perfusion to the remaining kidney. A 2024 meta-analysis (PMID 38000056) confirmed improved perioperative outcomes with ICG-guided selective arterial clamping compared to standard RAPN.
- Tumor margin delineation: Renal cortex and tumor tissue can be differentially fluoresced based on their perfusion characteristics.
- Adrenal surgery: ICG helps with intraperitoneal tumor localization during robotic adrenal procedures.
10. Plastic and Reconstructive Surgery - Flap Perfusion
ICG angiography is a standard tool for intraoperative assessment of:
- Free flap viability: Real-time assessment of arterial inflow and venous outflow in free tissue transfers, allowing early identification of a failing anastomosis before clinical signs develop.
- Perforator mapping: Locating perforator vessels preoperatively or intraoperatively for perforator flap design.
- Pericranial flap viability: Used in head and neck reconstructive surgery and skull base surgery to confirm vascular pedicle integrity.
- Cummings Otolaryngology Head and Neck Surgery (PMID references, p. 3159)
11. Ophthalmology - ICG Angiography
While technically a diagnostic rather than purely surgical use, ICG angiography (ICGA) is performed in the operating room or ophthalmic suite to:
- Evaluate choroidal circulation
- Diagnose polypoidal choroidal vasculopathy, central serous chorioretinopathy, and other macular diseases
- Guide photodynamic therapy targeting
- Kanski's Clinical Ophthalmology, 10th ed. (p. 568-575); The Wills Eye Manual
12. Acute Care and Emergency Surgery
A 2023 systematic review (PMID 37743419) assessed ICG in the acute care setting, highlighting its role in:
- Evaluating bowel ischemia and viability in emergency laparotomy
- Assessing perfusion of stomas and bowel segments
- Identifying the extent of ischemia in vascular emergencies
Technical Considerations
| Parameter | Detail |
|---|
| Excitation wavelength | ~800 nm (NIR) |
| Emission wavelength | ~830 nm |
| Half-life | 3-5 minutes |
| Elimination | Unchanged in bile (hepatic) |
| Severe reaction rate | ~0.05% |
| Typical IV dose | 2.5 mL of 25 mg/10 mL (for perfusion/cholangiography) |
| Hepatic tumor detection dose | 0.25-0.5 mg/kg, administered 24h pre-op |
| Re-dosing | Permitted - short half-life allows multiple intraoperative evaluations |
Modern laparoscopic towers and robotic platforms (including the da Vinci system with Firefly technology) are equipped with built-in NIR capabilities. Newer overlay systems allow white-light and NIR images to be superimposed in real time, maintaining anatomical context without toggling.
Current Evidence Level Summary (SAGES 2025)
| Application | Evidence/Recommendation Strength |
|---|
| Left-sided colorectal anastomosis | Strong recommendation, moderate certainty |
| Laparoscopic cholecystectomy (cholangiography) | Strong evidence, BDI reduction ~75% |
| Hepatic tumor identification | Good evidence from systematic reviews |
| SLN mapping (breast, gynecologic) | Well-established; >95% detection |
| Anastomotic leak prevention (esophageal, bariatric) | Promising; limited RCT evidence |
| Parathyroid identification | Growing evidence; no randomized trial yet |
Key References
- Fischer's Mastery of Surgery, 8th ed. - Chapter 27: Fluorescence-Guided Surgery
- Sabiston Textbook of Surgery - Chapter 11 (Tools section); Chapter on Thyroid Surgery
- Bailey and Love's Short Practice of Surgery, 28th ed. - Chapter 58 (Breast surgery)
- SAGES 2025 Guidelines - PMID 41249539 (strong recommendation for left-sided colorectal anastomosis)
- PMID 38867212 - Meta-analysis: ICG hepatectomy and surgical margin status
- PMID 39542857 - Meta-analysis: ICG lymph node detection in colorectal cancer
- PMID 38000056 - Meta-analysis: ICG-guided selective arterial clamping in partial nephrectomy
- PMID 41422225 - GRADE systematic review: ICG perfusion vs. standard to prevent anastomotic leak