What is the Indocyanine Green (ICG) test, how is it performed, and what are its indications, contraindications, and interpretation?

Indocyanine Green (ICG) Test

What is the ICG Test?

The ICG test is a diagnostic procedure that measures hepatic function by assessing the liver's ability to clear indocyanine green dye from the bloodstream, with normal subjects showing an 18-24% per minute clearance rate and less than 4% retention at 15 minutes. 1

ICG is a water-soluble tricarbocyanine dye that binds nearly 98% to plasma proteins (primarily albumin) and is exclusively cleared by the liver without extrahepatic removal, making it an ideal marker for hepatic blood flow and function 1, 2. The dye is excreted into bile without enterohepatic recirculation 1.

How the Test is Performed

Patient Preparation

• The patient must be studied in a fasting, basal state 1
• Calculate dosage at 0.5 mg/kg body weight 1

Administration Technique

• Dissolve 25 mg ICG powder with exactly 5 mL aqueous solvent to create a 5 mg/mL solution 1
• Inject the calculated dose rapidly into an arm vein without allowing extravasation 1

Measurement Methods

Two primary methods exist for measuring ICG clearance:

1. Ear Densitometry (Non-invasive)

• Uses a dichromatic earpiece densitometer with compensatory photoelectric cells 1
• Monitors ICG appearance and disappearance without blood sampling 1, 3
• Permits simultaneous measurement of cardiac output, blood volume, and hepatic clearance 1
• Shows good correlation with blood sampling methods (r = 0.721 for clearance rate, r = 0.944 for 15-minute retention) 3

2. Photometric Blood Sampling Method

• Withdraw blood samples at 5,10,15, and 20 minutes post-injection from the opposite arm 1
• Allow blood to clot and separate serum by centrifugation 1
• Measure optical density at 805 nm wavelength using patient's normal serum as blank 1
• Plot values on semilogarithmic paper to calculate disappearance rate 1

Interpretation

Normal Values for Hepatic Function

• Percentage disappearance rate: 18-24% per minute 1
• Biological half-time: 2.5-3.0 minutes 1
• 15-minute retention (R15): ≤4% of initial concentration 1

Abnormal Values Indicating Hepatic Dysfunction

• ICGR15 above 15-20% indicates impaired hepatic functional reserve 4
• This threshold is considered an indication for volume optimization strategies before major hepatic resection 4, 5
• In liver cirrhosis patients, ICG clearance rate drops to 0.063 ± 0.026 with R15 of 31.6 ± 15.6% 6

Clinical Context Considerations

Several factors can influence ICG test results beyond baseline hepatic function:

• Acute cholestasis can cause marked impairment (75% reduction in clearance) even without liver insufficiency symptoms 7
• Moderate exercise improves ICG clearance in chronic liver disease by increasing hepatic blood flow 6
• Temperature variations affect optical density readings, requiring consistent measurement conditions 1

Indications

Primary Indication: Hepatic Function Assessment

• Preoperative risk stratification before major hepatic resection 4, 5
• Serial monitoring of severe chronic liver disease 1
• Detection of drug-induced hepatic alterations 1
• Evaluation of mild liver injury 1

Surgical Applications

ICG has expanded beyond hepatic function testing to multiple intraoperative visualization applications:

Ureteral Identification During Colorectal Surgery

• Intraureteral ICG (5.0-12.5 mg) enables fluorescent visualization of ureters during laparoscopic/robotic surgery with 98.5% identification rate 8
• Requires cystoscopy, ureteral stenting, and injection into ureteral orifice before surgery 8
• ICG binds to ureteral epithelial proteins and fluoresces under near-infrared laser technology 8

Ophthalmic Angiography

• ICG angiography (up to 40 mg in 2 mL) visualizes choroidal vasculature due to minimal leakage from fenestrated choriocapillaris 9, 1
• Particularly useful for detecting polypoidal choroidal vasculopathy and retinal-choroidal anastomoses 9
• Peak absorption/emission at 800-850 nm allows efficient transmission through pigment epithelium 9, 1

Anastomotic Perfusion Assessment

• ICG fluorescence angiography reduces anastomotic leak rates by 38% (RR 0.62) in left-sided colorectal resections 10
• Prevents one leak per 27 patients treated when baseline leak rate is 10% 10
• Does not prolong operating time 10

Lymph Node Mapping

• Peritumoral ICG injection for sentinel lymph node biopsy shows 79.5% sensitivity with 100% detection of malignant nodes 11
• Safe alternative to technetium lymphoscintigraphy in pediatric and adolescent patients 11, 12

Lung Nodule Localization

• CT-guided transthoracic placement of ICG-soaked coils achieves 100% localization success 13
• Allows delayed surgical resection (median 1 day, up to >24 hours) unlike direct ICG injection 13

Contraindications

Absolute Contraindication

ICG contains sodium iodide and should be used with caution in patients with a history of allergy to iodides 1

Important Safety Considerations

Despite theoretical concerns about iodine content, clinical evidence suggests excellent safety profile:

• In vulvar cancer SLNB studies with 75 patients (66 previously exposed to iodinated contrast, 2 with documented allergy), no ICG-related allergic reactions occurred 12
• Systematic review of 206 patients undergoing SLNB showed no adverse reactions to peritumoral ICG injection 12
• No adverse events reported in 40 pediatric/AYA patients undergoing SLNB with ICG 11

Specific contraindications for alternative dye (methylene blue) include:

• Glucose-6-phosphate dehydrogenase deficiency 8
• Renal impairment 8
• Heinz body hemolytic anemia 8

Adverse Events from Surgical Applications

• Transient hematuria (most common, especially with ureteral stenting) 8
• Ureteral stenosis requiring stent placement (rare) 8
• Prostatic bleeding from instrumentation 8
• Modified technique using ICG injection without ureteric catheter placement reduces hematuria incidence while maintaining reliability 8

Clinical Pearls

For hepatic function testing, ICG retention above 15-20% at 15 minutes should prompt consideration of portal vein embolization or other volume optimization strategies before major hepatectomy 4, 5. The test provides more accurate functional assessment than volumetric measurements alone, as volume serves merely as a surrogate for function 4.

When using ICG for intraoperative tissue visualization, near-infrared fluorescence technology is required for detection 8. The advantages include high tissue contrast, rapid identification, visualization through overlying peritoneum with minimal dissection, and prolonged visualization 8. However, limitations include technology availability, dye cost, and additional operative time for administration 8.