KENTA TAKEDA, NOBUKAZU TANAKA, SHINICHI NISHI, and AKIRA ASADA. The Application of the Hemoglobin Saturation Sensor and Indocyanine Green (ICG) for Blood Flow Measurement. Osaka City Medical Journal. 2006, 52, 21-27

The Application of the Hemoglobin Saturation Sensor and Indocyanine Green

(ICG) for Blood Flow Measurement

KENTA TAKEDA, NOBUKAZU TANAKA, SHINICHI NISHI,

and AKIRA ASADA

Citation Osaka City Medical Journal. Issue Date 2006-06

Type Journal Article Textversion Publisher

Right © Osaka City Medical Association. https://osakashi-igakukai.com/.

Placed on: Osaka City University Repository

The Application of the Hemoglobin Saturation Sensor and Indocyanine Green (ICG) for Blood Flow Measurement

KENTA TAKEDA, NOBUKAZU TANAKA, SHINICHI NISHI, and AKIRA ASADA

Department of Anesthesiology and Intensive Care Medicine, Osaka City University, Graduate School of Medicine

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Osaka City Med. J. Vol. 52, 21-27, 2006

Received October 7, 2005; accepted November 22, 2005.Correspondence to: Kenta Takeda, MD.

Department of Anesthesiology and Intensive Care Medicine, Osaka City University, Graduate School ofMedicine, 1-4-3, Asahimachi, Abeno-ku, Osaka 545-8586, JapanTel: +81-6-6645-2186; Fax: +81-6-6645-2489E-mail: ktakeda74@msic.med.osaka-cu.ac.jp

AbstractBackground

The aim in this study is to evaluate a new blood flow measurement applying a hemoglobin

saturation sensor and indocyanine green (ICG) in circuit and animal models.

Methods

1) In the basic study, the blood was mixed in a tube with ICG, and a near-infrared sensor was

placed in this tube. The standard curve of the relationship between ICG concentration and

optical density was obtained. 2) In the circuit model, the blood was circulated by the roller

pump. ICG was injected in this circuit and its concentration was calculated from the change in

optical density at 810 nm. Rate of flow was calculated based on the Fick’s principle. The validity

of this method was evaluated by Bland and Altman analysis. 3) In the animal model, a

hemoglobin saturation sensor was inserted into three anesthetized dogs via the jugular vein, and

iced ICG was injected for calculating cardiac output. Cardiac output was calculated by the same

theory of the circuit model. The validity of this method was also evaluated by Bland and Altman

analysis.

Results

1) A standard curve was drawn from 11 different points (r2＝0.99). 2) The calculated flow rate

correlated well with the actual flow rate (r2＝0.97). 3) The calculated cardiac output correlated

well with results obtained with the thermodilution method.

Conclusions

Application of a hemoglobin saturation sensor and ICG to blood flow measurement was

reliable and useful in both circuit and animal models. This method may be clinically useful for

measurement of blood flow.

Key Words: Hemoglobin saturation sensor; Indocyanine green; Near-infrared light;

Blood flow measurement; Thermodilution method

IntroductionIn critically ill patients, it is important to assess organ perfusion. Inadequate splanchnic

blood flow may cause organ failure (ischemic brain, ischemic heart failure, liver failure or renal

failure etc.) and increase mortality in such patients. Various methods have already been

reported for measurement of blood flow in organ, including thermodilution, lithium dilution,

electromagnetic, blood flowmetry, and Doppler ultrasound technique1-5). We have also reported

the measurement of hepatic blood flow using changes in hemoglobin saturation with a

pulmonary artery catheter inserted in the inferior vena cava in critically ill patients6) and the

measurement of coronary blood flow using lithium dilution in an animal model7). But some

problems were pointed in our previous report. One is the limitation of lithium clinical use in

Japan. Indocyanine green (ICG) as a new indicator that has no limitation in clinical use, was

picked up in this study.

ICG has been used in the dye dilution method to measure cardiac output. The change in

hemoglobin saturation injected by ICG is sometimes experienced in clinical practice. This

phenomenon may result from change in optical density at red and near-infrared wavelengths.

The hemoglobin saturation derived from pulse oximetry (SpO2) is decreased by ICG, because

SpO2 is related to the ratio of absorption optical intensities at 660 nm and 940 nm, and more

decrease is observed at 660 nm than at 940 nm when ICG is administrated8). On the other hand,

mixed venous hemoglobin saturation (SvO2) is increased by ICG, because SvO2 is related to the

ratio of reflection optical intensities at 810 nm and 750 nm, and the optical intensity at 750 nm

is more decrease than at 810 nm when ICG is administrated9). The near-infrared light 810 nm

was peculiar in the reflection absorbance of ICG10,11).

The purpose of this study was to determine whether a new method, involving determination

of the change in optical density at 810 nm induced by ICG injection, is as reliable and accurate

as the usual method. We studied the accuracy and reliability of this new method using circuit

and animal models.

MethodsBasic study

The packed blood for transfusion was mixed in a tube with ICG (0 to 12.5 mg/L). A near

infrared light reflection sensor (flow-directed thermodilution fiberoptic continuous cardiac output

pulmonary artery catheter (Opti-Q, Model 05250901, Abbott Laboratories, North Chicago,

IL60064, USA) was placed in this tube. The SvO2 monitor (OX3-60, Model 05973763, Abbott

Laboratories) connected with this sensor to display reflection optical intensity ratio at three

wavelengths of light: 660 nm, 750 nm, and 810 nm. Hemoglobin oxygen saturation was

calculated based on the Lambert-Beer’s law8). The principle for two different situations, absorbed

and reflected lights, is based on the same energy kinetics. ICG concentration was calculated

from ICG optical density at 810 nm by applying Lambert-Beer’s law using the following below

equation.

ICG optical density ＝ －log (I/I0)

I, ICG reflection intensity; I0, blood reflection intensity

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Takeda et al

The standard curve of the relationship ICG concentration and optical density at 810 nm was

derived for the conversion from optical density to concentration.

Circuit model

The packed blood for transfusion was circulated in a circuit containing a roller pump for the

regulation of flow (50 to 300 mL/min) (Fig. 1). The near-infrared light of 810 nm reflection

sensor was placed in this circuit, and 0.5 mg of ICG with 0.5 mL of saline was injected into the

circuit before the sensor. The same amount of ICG was injected at five times in each flow rate.

The change in ICG optical density was converted to ICG concentration using the equation given

above. The area under the time-ICG concentration curve (AUC) was calculated by the

trapezoidal rule. Flow rate was calculated based on the Fick’s principle12) from the derived AUC

(Calculated Flow Rate). The difference between Calculated Flow Rate and pump flow rate

(Actual Flow Rate) was examined by Bland and Altman analysis13).

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The Hemoglobin Saturation Sensor for Blood Flow Measurement

Scheme of the flow model and ICG concentration curve. The blood for transfusion was circulated ina circuit by a roller pump to regulate flow rate (50 to 300 mL/min). The ICG sensor was placed in this circuit,and 0.5 mg (0.5 mL) of ICG was injected into the circuit passing the sensor.

Figure 1.

Animal model

Following approval by the Institutional Animal Care and Use Committee, three beagle dogs,

one male and two females, weighing 8-10 kg were included in this study. After induction of

anesthesia and tracheal intubation, an 8 Fr of pulmonary artery catheter (Opti-Q) was inserted

via the right or left jugular vein through a 8.5 Fr of sheath (Percutaneous Sheath Introducer Set,

Product No. SI-09875-E, Arrow International, Inc. 2400 Bernville Road Reading, PA 19605

USA). The catheter was placed in the pulmonary artery by using the flow directed method. The

position of the catheter was confirmed by the radio imaging and the pressure waveform. After

the catheter was connected with the continuous cardiac output computer (Q-Vue, Model 052230,

Abbott Laboratories), 5 mg of ICG diluted with 3 mL of iced saline was injected using the

thermodilution method. The change in reflected optical density at near-infrared light 810 nm

was recorded through the SvO2 monitor and the blood flow rate was calculated using the same

theory as for the circuit model. The difference in cardiac output values obtained the

thermodilution method and our new method was examined by Bland and Altman analysis.

ResultsBasic study

A standard curve was drawn from 11 different ICG concentrations and optical densities (Fig.

2). The standard regression line was calculated as below:

ICG concentration (mg/L) ＝ ICG optical density×45.24＋0.05 (r2＝0.99, p＝0.001)

Circuit model

The calculated flow rate by our new method correlated well with the actual flow rate (Fig. 3).

The coefficient of correlation between the calculated and actual flow rates was 0.989. The results

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Takeda et al

Standard curve for ICG in staticstatus.Figure 2.

Correlation between calculatedand actual flow rates in circuit model.Figure 3.

Bland and Altman analysis of flow ratescalculated with our new method and actual flowrates as a gold standard in the circuit model.

Figure 4.

of Bland and Altman analysis between the calculated and actual flow rates are shown in Figure

4. The overall bias was 7.6 mL/min, the upper 95% limit of agreement was 13.8 mL/min and the

lower 95% limit of agreement was 29.0 mL/min.

Animal model

The change in ICG concentration was shown as a large peak in the first circulation and

subsequent small peaks (Fig. 5). The area under the concentration-time curve was calculated by

the Stewart-Hamilton method14), and converted cardiac output. The results of Bland and Altman

analysis are shown in Figure 6. The overall bias was 0.5 L/min, the upper 95% limit of

agreement was 3.1 L/min, and the lower 95% limit of agreement was 2.1 L/min.

DiscussionOne of the reasons why ICG has been used in physiological studies is that concentrations of it

can be determined spectrologically. On the other hand, the pulse oximetry method, which can be

applied to determine the change in optical density in transmitted red and near-infrared light,

has been used for bedside monitoring in worldwide. It has been suspected that the change in

optical density at another wavelength for detecting the intensity of green due to ICG in blood

might be useful for assay of ICG concentration. This principle is applied in the DDG2001

analyzer (Nihon Kohden Corp, Tokyo, Japan), which can measure the changes in optical density

using a finger or a nose probe15,16), and which can be used for bedside estimation of cardiac output

and liver blood flow. However, since the wavelength in near-infrared light was well studied and

stable optical density, we hypothesized that change in optical density in pulse oximetry area

would represent ICG concentration.

A standard curve was needed to convert optical density change in near-infrared light of 810

nm to ICG concentration. A good correlation was found between optical density and ICG

concentration, and conversion from optical density to concentration was performed after this

basic study. After this static conversion, dynamic conversion was performed using the circuit

model and cardiac output measurement. Our new method was verified by Bland and Altman

analysis, with use of the roller pump flow rate for the circuit model and the thermodilution

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The Hemoglobin Saturation Sensor for Blood Flow Measurement

ICG concentration curve in ananimal model.Figure 5. Bland and Altman analysis of the

new method and thermodilution method in ananimal model.

Figure 6.

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Takeda et al

method for the animal model as respective gold standards. The major differences between our

method and the gold standard were not found in both models. However, it will be necessary to

verify our new method for various cardiac outputs, because cardiac output varies considerably in

various clinical situations, such as sepsis with high cardiac output, myocardial infarction.

Two options were considered in examing whether the change in optical density at near-

infrared light revealed change in ICG concentration. One was use of transmitted light in a

finger probe, while the other was use of reflected light in a catheter sensor. A blood vessel sensor

was selected for use in this study, because the transmitted light is affected by peripheral

circulatory change17). Another problem with use of ICG as a marker dye is that ICG is

metabolized slowly in the liver, and accumulates when repeatedly injected. This problem will be

settled by the translocation of the basic line of optical density to apply the calibration.

Moreover, ICG is unstable when dissolved in water18). It is necessary to inject ICG rapidly for

measurement of blood flow rate soon after its dissolution. This may cause anaphylactic shock19).

We have already reported the measurement method of hepatic blood flow using changes in

hemoglobin saturation by the pulmonary artery catheter inserted in the inferior vena cava in

critically ill patients6) and the measurement method of coronary blood flow using lithium dilution

in an animal model7). The former method for measurement of liver blood flow is based on the fact

that the confluent flow is the sum of two previous flows. That is, the subtraction of the

measurement value in two points, before the meeting point of the hepatic vein and after it in the

vena cava, will represent liver blood flow. Our new method in this study can be applied to

measurement of liver or kidney blood flow using the same theory. And the latter method of

measurement of coronary blood flow was based on the fact that a lithium sensor on the tricuspid

valve in the right atrium can detect the lithium concentration peak by the coronary flow before

the peak by the systemic flow. Our new method in this study can also be applied to

measurement of coronary blood flow using the same theory. Critically ill patients are often

monitored mixed venous hemoglobin saturation, especially in septic status following the recent

strategy of SCCM20). Our new method in this study will not require additional catheter

insertions in patients.

In conclusion, we have shown that a new blood flow measurement method applying the

hemoglobin saturation sensor and indocyanine green is reliable and accurate in a circuit model,

and that it can be applied to measurement of cardiac output in an animal model. This method

will be clinically useful for measurement of blood flow in certain organs.

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The Hemoglobin Saturation Sensor for Blood Flow Measurement