Indocyanine Green (Cardiac) (Monograph)

Drug class: Cardiac Function

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

Introduction

Indocyanine green is a tricarbocyanine dye used for measurement of cardiac output.

Uses for Indocyanine Green (Cardiac)

Indocyanine green is used in the measurement of cardiac output by the indicator-dilution method. It is the dye most frequently used in the measurement of cardiac output because it 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. The concentration of the dye in the blood may be measured using a conventional cuvette densitometer or with an ear densitometer.

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 hepatic function determination and measurement of hepatic blood flow, see Indocyanine Green 36:44.

Indocyanine Green (Cardiac) Dosage and Administration

Reconstitution and Administration

Indocyanine green is administered into the heart or pulmonary artery through a cardiac catheter for determination of cardiac output.

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 calculated dose is usually administered in a volume of 1 mL; therefore, the amount of diluent required varies with the dose to be given. The dye solution should be used within 10 hours after preparation.

Dosage

In the determination of cardiac output, the usual dose of indocyanine green is 5 mg for adults, 2.5 mg for children, and 1.25 mg for infants, diluted, if necessary, with sterile water for injection or 0.9% sodium chloride injection to make a final volume of 1 mL. These doses are repeated periodically to obtain several dilution curves. The manufacturer recommends that the total dose of indocyanine green not exceed 2 mg/kg.

Indocyanine green solution is injected as rapidly as possible into the right atrium, right ventricle, or pulmonary artery through a cardiac catheter. The residual dye should be flushed from the catheter with saline to prevent hemolysis. The measurement of indocyanine green should begin immediately after administration of the dye using either a dichromatic ear densitometer or continuous arterial blood withdrawal and a cuvette densitometer. Cardiac output is calculated using the data derived from the initial peak of the blood level-time curve. Specialized references should be consulted for specific procedures and to determine the most appropriate method of calculation and the interpretation of the results of cardiac output studies.

Cautions for Indocyanine Green (Cardiac)

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 due to 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.

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 1 week following the use of indocyanine green.

Pharmacology

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

Indocyanine Green (Cardiac) 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 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.