Indocyanine Green (Hepatic) (Monograph)

Drug class: Liver Function

Medically reviewed by Drugs.com on Dec 23, 2024. Written by ASHP.

Introduction

Indocyanine green, a tricarbocyanine dye is used to test hepatic function and measure hepatic blood flow.

Uses for Indocyanine Green (Hepatic)

Indocyanine green is used as a test of hepatic function and for measurement of hepatic blood flow. The dye is of little value in determining the exact nature of liver disease, but it is useful as a supplement to clinical impression and other indices of hepatic function in determining the functional status of the liver.

In the measurement of hepatic function, indocyanine green appears to be generally about as accurate as sulfobromophthalein sodium (BSP). In recommended doses, BSP may be more sensitive to minor alterations in hepatic function; however, BSP is no longer commercially available in the US for use as a hepatic diagnostic agent. One study has shown that indocyanine green in doses of 5 mg/kg is equally effective in detecting minor hepatic dysfunction. Indocyanine green has several advantages over other dyes: its maximum spectral absorbance occurs at a wavelength where reduced hemoglobin and oxyhemoglobin transmit light equally, it is relatively nontoxic, it can be analyzed in relatively low concentrations, and its analysis is not affected by hemolysis. In addition, it has the advantages over BSP of not undergoing metabolism, enterohepatic circulation, or extrahepatic excretion, and having a plasma disappearance rate curve which is more nearly exponential.

Indocyanine green has also been used to measure plasma volume and regional blood flow and to assess hemodynamics in various organs including the kidneys, eyes, and lungs.

For information on the use of indocyanine green in cardiac output determinations, see Indocyanine Green 36:18.

Indocyanine Green (Hepatic) Dosage and Administration

Reconstitution and Administration

Indocyanine green is administered IV for determination of hepatic function.

Indocyanine green powder for injection should be initially dissolved only with the diluent supplied by the manufacturer, and it has been suggested that the syringe to be used should also be rinsed with this diluent. The drug should be reconstituted according to the manufacturer’s instructions to attain a final concentration of 5 mg/mL. The dye solution should be used within 10 hours after preparation.

Dosage

In the determination of hepatic function, the usual dose of indocyanine green is 0.5 mg/kg, although doses as low as 0.1 mg/kg and as high as 5 mg/kg have been used. It has been reported that doses of 5 mg/kg allow detection of mild hepatic dysfunction not otherwise detectable with indocyanine green.

The patient should be studied in a fasting, basal state. If the photometric method is used, a 6-mL sample of blood is obtained from a vein in the arm for use as a blank, and the dye is injected through the same needle as rapidly as possible without allowing the dye to escape. Disappearance of the dye from the plasma may be measured using a dichromatic ear densitometer, or blood samples may be obtained from a vein of the opposite arm at 5-minute intervals for 15 minutes to determine the percentage disappearance rate (PDR) of the dye. An additional sample should be obtained 20 minutes after injection to determine the percentage retention of the dye. PDRs range from 18–24 in healthy adult males and 24–30 in healthy infants. Specialized references should be consulted for specific procedures, methods of calculating PDR, and interpretation of results of hepatic function studies.

Indocyanine green has been administered IV in the determination of hepatic blood flow. Blood from a peripheral artery and a hepatic vein is sampled, and the hepatic blood flow is calculated using the Fick principle. For specific dosage, procedures, and methods of calculating hepatic blood flow specialized references should be consulted.

Cautions for Indocyanine Green (Hepatic)

Adverse Effects

Indocyanine green appears to have a low incidence of adverse effects. Extravasation of the dye appears to cause no adverse effects, and allergic reactions to the drug are rare. Indocyanine green reportedly has caused diaphoresis, pruritus, and headache in several patients. These reactions were believed to be caused by a direct histamine-releasing effect rather than an allergic reaction. Anaphylactoid reactions, which were immediate (e.g., occurring within 10–120 seconds after administration) and were manifested by vasodilation, dyspnea, acute bronchospasm, laryngospasm, facial edema, flushing, hypotension, cardiac or respiratory arrest, and/or shock, have occurred rarely following administration of indocyanine green. These reactions have occurred even in patients with no history of hypersensitivity to indocyanine green or who have not received the drug previously and are potentially fatal. The reactions do not appear to be immunologic, and the risk of their occurrence may be related to the dose and/or rate of administration, appearing to be higher in patients receiving rapidly injected doses of 0.5 mg/kg or more.

Indocyanine green may cause a transient elevation in serum unconjugated bilirubin, probably because of a competition between the dye and bilirubin for biliary excretion.

Precautions and Contraindications

Because commercially available indocyanine green contains sodium iodide, the drug should be used with caution in patients who have a history of iodide allergy.

Pregnancy

Safe use of indocyanine green during pregnancy has not been established.

Drug Interactions

The half-life of indocyanine green may be decreased in patients who are taking phenobarbital, presumably because of an increase in hepatic dye transport induced by phenobarbital. Other drugs which have been reported to decrease the half-life of indocyanine green include phenylbutazone, primidone, phenytoin, opiate derivatives (in addicts), haloperidol, nitrofurantoin, and sulthiame; however, the importance of the effect of these drugs is not well established.

Administration of probenecid to dogs in doses of 25–100 mg/kg decreases the elimination rate of indocyanine green and the possibility of this occurrence in humans should be considered.

Simultaneous administration of indocyanine green and sulfobromophthalein sodium (BSP) may result in an impairment of hepatic excretion of BSP, particularly in patients with hepatic impairment. The presence of BSP in blood may cause changes in the maximum absorption spectrum of indocyanine green, and simultaneous use of these agents should be avoided.

Laboratory Test Interferences

Because of the sodium iodide present in the commercially available product, administration of indocyanine green has been reported to cause an increase in serum inorganic iodide concentrations and a decrease in radioactive iodide uptake in several patients. Radioactive iodide uptake studies should not be performed for at least a week following the use of indocyanine green.

Pharmacology

The use of indocyanine green in hepatic function determinations is not based on its pharmacologic effects, but on its distribution in the body.

Indocyanine Green (Hepatic) Pharmacokinetics

Following IV administration, indocyanine green is almost completely bound to plasma proteins in the bloodstream, mainly to albumin and α₁ lipoproteins. The drug appears to be distributed in the plasma volume. Indocyanine green is not metabolized, but is taken up by hepatic parenchymal cells. The liver exhibits a maximum rate of uptake (transport maximum; T_m) of about 7.5 mg/minute. The liver has a storage capacity, proportional to the blood concentration, of 70 mg of indocyanine green per mg of dye per dL of plasma. In contrast to sulfobromophthalein sodium, indocyanine green is not taken up by any organ other than the liver. The drug is rapidly excreted unchanged in bile and may color feces green; it does not undergo enterohepatic circulation. The elimination half-life of indocyanine green in healthy adults ranges from about 2.2–3 minutes.

Chemistry and Stability

Chemistry

Indocyanine green is a tricarbocyanine dye. Indocyanine green occurs as an olive-brown, dark green, blue-green, dark blue, or black powder and may have a slight odor. The drug has a maximum infrared absorption peak of 800–810 nm in blood or plasma. Commercially available indocyanine green usually contains about 5% sodium iodide as a contaminant and may not contain more than 9.5% sodium iodide. The drug is soluble in water and practically insoluble in alcohol. Aqueous solutions of indocyanine green have a deep emerald-green color. A 0.5% aqueous solution of the drug has a pH of 5.5–6.5.

Stability

A 0.5% aqueous solution of indocyanine green is stable for about 8 hours after reconstitution; the drug is stable in blood and plasma. Trace amounts of reducing agents used as preservatives cause a marked reduction in the absorption peak of indocyanine green, and the dye should not be used or mixed with preparations (including heparin) containing reducing agents such as bisulfite, metabisulfite, or borohydride.

Indocyanine green has been reported to be incompatible with some commercially available water for injection and should be reconstituted only with the sterile water for injection supplied by the manufacturer which has a pH of 5.5–6.5.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.