For determining cardiac output, hepatic function and liver
For ophthalmic angiography.
DOSAGE AND ADMINISTRATION
Indicator Dilution Studies
IC-GRE EN™ permits recording
of the indicator dilution curves for both diagnostic and research purpose
independently of fluctuations in oxygen saturation. In the performance of dye
dilution curves, a known amount of dye is usually injected as a single bolus as
rapidly as possible via a cardiac catheter into selected sites in the vascular system.
A recording instrument (oximeter or densitometer) is attached to a needle or
catheter for sampling of t he dye blood mixture from a systemic arterial
Under sterile conditions, the IC-GRE EN™ powder should be
dissolved with the Aqueous Solvent provided for this product, and the solution
used within 6 hours after it is prepared. If a precipitate is present, discard
the solution. The amount of solvent to be used can be calculated from the
dosage form which follows. It is recommended that the syringe used for injection
of the dye be rinsed with this diluent. Isotonic saline should be used to flush
the residual dye from the cardiac catheter into the circulation so as to avoid
hemolysis. With the exception of the rinsing of the dye injection syringe,
saline is used in all other parts of the catheterization procedure.
The usual doses of IC-GREEN™ which have been used for
dilution curves are as follows:
Adults - 5.0 mg
Children - 2.5 mg
Infants - 1.25 mg
These doses of the dye are usually injected in a mL volume.
An average of five dilution curves are required in the performance of a
diagnostic cardiac catheterization. The total dose of dye injected should be
kept below 2 mg/kg.
While sterile water for injection may be used to rinse the syringe, isotonic saline should be used to flush the residual dye from the cardiac catheter into the circulation so as to avoid hemolysis. With the exception of the rinsing of the dye injection syringe, saline should be used in all other parts of the catheterization procedure.
Calibrating Dye Curves
To quantitate the dilution curves, standard dilutions of
IC-GREEN™ in whole blood are made as follows. It is strongly recommended that
the same dye that was used for the injections be used in the preparation of
these standard dilutions. The most concentrated dye solution is made by
accurately diluting 1 mL of the 5 mg/mL dye with 7 mL of distilled water. This
concentration is then successively halved by diluting 4 mL of the previous concentration
with 4 mL of distilled water.
If a 2.5 mg/mL concentration was used for the
dilution curves, 1 mL of the 2.5 mg/mL dye is added to 3 mL of distilled water
to make the most concentrated “standard” solution. This concentration is then
successively halved by diluting 2 mL of the previous concentration with 2 mL of
Then 0.2 mL portions (accurately measured from a calibrated
syringe) of these dye solutions are added to 5 mL aliquots of the subject's
blood, giving final concentrations of the dye in blood beginning with 24.0 mg/liter,
approximately (actual concentration depends on the exact volume of dye added).
This concentration is, of course, successively halved in the succeeding aliquots
of the subject's blood. These aliquots of blood containing known amounts of
dye, as well as a blank sample of which 0.2 mL of saline containing no dye has
been added, are then passed through the detecting instrument and a calibration
curve is constructed from the deflections recorded.
Hepatic Function Studies
Due to its absorption spectrum, changing concentrations
of IC-GREEN™ (indocyanine green for injection) in the blood can be monitored by
ear densitometry or by obtaining blood specimens at timed intervals. The
technique for both methods is as follows.
The patient should be studied in a fasting, basal state. The
patient should be weighed and the dosage calculated on the basis of 0.5 mg/kg
of body weight.
Under sterile conditions, the IC-GREEN™ powder should be
dissolved with the Aqueous Solvent provided. Exactly 5 mL of aqueous solvent
should be added to the 25 mg vial giving 5 mg of dye per mL of solution.
Inject the correct amount of dye into the lumen of an arm
vein as rapidly as possible, without allowing the dye to escape outside the
vein. (If the photometric method is used, prior to injecting IC-GREEN™,
withdraw 6 mL of venous blood from the patient's arm for serum blank and
standard curve construction, and through the same needle, inject the correct
amount of dye.)
Ear oximetry has also been used and makes it
possible to monitor the appearance and disappearance of IC-GREEN™ without
the necessity of withdrawal and spectrophotometric analysis of blood samples
for calibration. An ear densitometer which has a compensatory photo
electric cell to correct for changes in blood volume and hematocrit, and
a detection photocell which registers levels has been described. This
device permits simultaneous measurement of cardiac output, blood volume
and hepatic clearance of IC-GREEN™* and was found to provide a reliable index
of plasma removal kinetics after single injections or continuous intrusions of
ICGREEN™. This technique was employed in newborn infants, healthy adults and in
children and adults with liver disease. The normal subject has a removal rate of
18-24% per minute. Due to the absence of extra hepatic removal, IC-GREEN™ was
found to be ideally suited for serial study of severe chronic liver disease and
to provide a stable measurement of hepatic blood flow. In larger doses,
IC-GREEN™ has proven to be particularly valuable in detecting drug induced
alterations of hepatic function and in the detection of mild liver injury.
Using the ear densitometer, a dosage of 0.5 mg/kg in normal
subjects gives the following clearance pattern.
*Dichromatic earpiece densitometer supplied by The Waters
Company, Rochester, Minnesota.
Determination Using Percentage Retention of Dye
A typical curve obtained by plotting dye concentration versus
optical density is shown opposite. Percent retention can be read from this
If more accurate results are desired, a curve using the
patient's blood and the vial of IC-GREEN™ being used in the determination can
be constructed as follows:
- Take 6 mL of non dye containing venous blood from the
patient's arm. Place in a test tube and allow the blood to clot. The serum is
separated by centrifugation.
- Pipette 1 mL of the serum into a microcuvette.
- Add 1 lambda (λ) of the 5 mg/mL aqueous ICGREEN ™ (sterile
indocyanine green) solution to the serum, giving a dilution of 5 mg/liter, the
standard for 50% retention. (The addition of 2 lambda (λ) of the 5 mg/mL
IC-GREEN™ solution would give 100% retention; however, this concentration
cannot be read on the spectrophotometer.)
- The optical density of this solution is read at 805 nm,
using normal serum as the blank.
- Using graph paper similar to that used in the
illustration, plot the 50% figure obtained in Step 4, and draw a line
connecting this point with the zero coordinates.
A single 20-minute sample (withdrawn from a vein in the
opposite arm to that injected) is allowed to clot, centrifuged and its optical density
is determined at 805 nm using the patient's normal serum as the blank. Dye
concentration is read from the curve above. A single 20-minute sample of serum
in healthy subjects should contain no more than 4% of the initial concentration
of the dye. The use of percentage retention is less accurate than percentage disappearance
rate, but provides reproducible results. Hemolysis does not interfere with a reading.
Determination Using Disappearance Rate of Dye
To calculate the percentage disappearance rate, obtain samples
at 5, 10, 15 and 20 minutes after injecting the dye. Prepare the sample as in
the previous section and measure the optical densities at 805 nm, using the
patient's normal serum as the blank. The ICGREEN™ concentration in each timed
specimen can be determined by using the concentration curve illustrated. Plot
values on semilogarithmic paper.
Specimens containing IC-GREEN™ should be read at the same
temperature since its optical density is influenced by temperature variations.
Percentage disappearance rate in healthy subjects is
18-24% per minute. Normal biological half time is 2.5-3.0 minutes.
Ophthalmic Angiography Studies
The excitation and emission spectra (Figure 1) and the
absorption spectra (Figure 2) of IC-GREEN™ make it useful in ophthalmic
angiography. The peak absorption and emission of IC-GREEN™ lie in a region
(800-850 nm) where transmission of energy by the pigment epithelium is more
efficient than in the region of visible light energy. IC-GREEN™ also has the
property of being nearly 98% bound to blood protein, and therefore, excessive dye
extravasation does not take place in the highly fenestrated choroidal
vasculature. It is, therefore, useful in both absorption and fluorescence
infrared angiography of the choroidal vasculature when using appropriate
filters and film in a fundus camera.
Dosages up to 40 mg IC-GREEN™ dye in 2 mL of aqueous
solvent have been found to give optimal angiograms, depending on the imaging
equipment and technique used. The antecubital vein injected ICGREEN™ dye bolus
should immediately be followed by a 5 mL bolus of normal saline.
Clinically, angiograms of uniformly good quality can be
assured only after taking care to optimize the contributions of all possible
factors such as, patient cooperation and dye injection. The foregoing injection
regimen is designed to provide delivery of a spatially limited dye bolus of
optimal concentration to the choroidal vasculature following intravenous
IC-GREEN™ is supplied in a kit (NDC 17478-701-02) containing
six 25 mg IC-GREEN™ vials and six 10 mL
NDC 17478-701-25 IC-GREEN™ vial. 25 mg fill in 20 mL
NDC 17478-701-10 Aqueous Solvent ampule. 10 mL fill in 10
Store at 20° to 25°C (68° to 77°F).
Manufactured by: Akorn, Inc., Lake Forest, IL 60045. Rev. March 2015