Anesth Analg 2007;104:341-346
© 2007 International Anesthesia Research Society
doi: 10.1213/01.ane.0000253508.97551.2e
TECHNOLOGY, COMPUTING, AND SIMULATION
Section Editor:
Jeffrey M. Feldman
Measurements of Optical Pathlength Using Phase-Resolved Spectroscopy in Patients Undergoing Cardiopulmonary Bypass
Kenji Yoshitani, MD*,
Masahiko Kawaguchi, MD
,
Takashi Okuno, MD*,
Tomoko Kanoda, MD*,
Yoshihiko Ohnishi, MD*,
Masakazu Kuro, MD*, and
Mitsunori Nishizawa, BS
From the *Department of Anesthesiology, National Cardiovascular Center, Suita, Osaka; Department of Anesthesiology, Nara Medical University, Kashihara, Nara; and System Engineering, Systems Division, Hamamatsu Photonics K.K. Hamamatus, Shizuoka, Japan.
Address correspondence and reprint requests to Kenji Yoshitani, MD, Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC 27710. Address e-mail to kenji.yoshitani{at}duke.edu.
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Abstract
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BACKGROUND: Near infrared spectroscopy (NIRS) has been used during cardiac surgery to monitor cerebral oxygenation although the validity of this technique has yet to be established. Although optical pathlength included in the algorithm for calculating NIRS values is supposed to be constant, recent evidence has suggested that optical pathlength could be affected by acute hemodilution in animals. We conducted the present study to investigate whether optical pathlength changes during cardiopulmonary bypass (CPB), and whether these changes affect NIRS values in adult patients.
METHODS: Nine patients undergoing elective cardiac surgery with CPB were enrolled in this study. Optical pathlength and cerebral NIRS values (oxyhemoglobin [
O2Hb] and tissue oxygen index) were measured by phase-resolved spectroscopy and NIRO 100, respectively. Optical pathlength, hemoglobin concentration, and NIRS values were measured at the following points: 1) after the induction of anesthesia, 2) 10 min after the start of CPB, 3) 60 min after the start of CPB, and 4) 1 h after CPB. The associations between optical pathlength and other variables were analyzed by Pearson correlation coefficients and multiple regression analysis.
RESULTS: Optical pathlength significantly increased starting at 27.7–30.8 cm at 10 min, and 31.3 cm at 60 min after the start of CPB (P < 0.0001). Hemoglobin concentrations significantly decreased (from 11.2 to 7.1 g/dL at 10 min and 7.7 g/dL at 60 min P < 0.0001). There was a significant correlation (r = 0.55, P < 0.001) between percentage changes in pathlength and hemoglobin concentration. Multiple regression analysis showed that optical pathlength was a significant determinant of O2Hb.
CONCLUSION: The results indicate that optical pathlength can change during CPB and its changes may affect O2Hb.
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Introduction
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Despite recent advances in techniques of anesthesia, cardiopulmonary bypass (CPB) and surgery, cerebral injury remains a major source of morbidity after cardiac surgery (1). Continuous cerebral monitoring during cardiac surgery is used to detect cerebral ischemia and to determine the state of oxygen balance in the brain. Conventional cerebral monitors, such as jugular bulb oximetry, transcranial Doppler, and electroencephalography, have advantages and disadvantages, but there is no generally accepted monitor of cerebral oxygenation. Near infrared spectroscopy (NIRS) is a noninvasive technique that is not costly and can be used continuously in almost any environment. Several investigators have reported the usefulness of NIRS during cardiac surgery (2–5). However, NIRS measurement is still based on some unproven assumptions, and the validity of NIRS values to assess cerebral oxygenation has yet to be confirmed.
In quantitative NIRS measurement, one of the uncertainties is the optical pathlength. Some commercially available cerebral NIRS monitors have used a modified Beer–Lambert (MBL) method to calculate oxyhemoglobin and deoxyhemoglobin concentration (O2Hb and HHb). Although the change in absorbance is directly proportional to the pathlength, the formula includes the assumption that optical pathlength is constant in the commercially available NIRS devices. As a result, an increase or decrease in the pathlength relative to the assumed constant values will introduce error into the calculation (see Appendix). Kurth and Uher (6) demonstrated, in an in vitro brain model and in piglets, that optical pathlength increased during hemodilution and affected NIRS measurement values. In cardiac surgery, the priming volume of the CPB circuit causes acute hemodilution and leads to a reduction in hemoglobin (Hb) concentration. Therefore, the optical pathlength could become longer than before CPB. However, the changes in optical pathlength related to hemodilution during CPB in humans have not been determined. The present study was conducted to test the hypothesis that the optical pathlength changes during CPB in patients undergoing cardiac surgery. The associations between the pathlength and other variables, including Hb concentration and NIRS values, were also investigated.
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METHODS
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After institutional approval, we obtained informed consent from patients undergoing elective cardiac surgery with CPB. Nine patients were enrolled in this study. Patients' characteristics are shown in Table 1.
Anesthetic Management
Anesthesia was induced with fentanyl (10 µg/kg) and propofol (1 mg/kg) and the trachea was intubated with vecuronium 0.2 mg/kg. Anesthesia was maintained with propofol 5 mg · kg–1 ·h –1 and the lungs were mechanically ventilated with an air/oxygen mixture (Fio2 = 0.4). Additional fentanyl was administered as necessary. After induction of anesthesia, a Swan–Ganz catheter (Abbott Opticath 7.5F, North Chicago, IL) was inserted through the right jugular vein and advanced into the pulmonary artery. Routine monitoring equipment included a radial artery catheter for direct arterial blood pressure measurement, a pulse oximeter, and an electrocardiograph. ETco2 tension was measured using a CAPNOMAC multi-gas analyzer (Hewlett-Packard, Andover, MA). The bladder temperature was continuously monitored (Tyco Health Care, Norwalk, CT).
NIRS Measurements
The optical sensor of phase spectroscopy was attached 1 cm above the eyebrow on the right side and the sensor of a NIRO 100 (Hamamatsu Photonics, Hamamatsu, Japan) was placed on the left side (Fig. 1A). NIRO 100 can monitor changes in Hb concentration using a MBL equation (O2Hb and HHb). In addition, NIRO-100 uses the spatially resolved spectrometer that combines the multi-distance measurements of optical attenuation and makes it possible to calculate the absolute concentration of O2Hb and HHb in the tissue. Then, the tissue oxygen index percentage that is, the ratio of oxygenated to total tissue Hb is rapidly calculated.
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Figure 1. The block diagram of the phase-resolved spectroscopy machine to measure the optical pathlength. (A) The schematic layout of the sensor of NIRO 100 and the phase-resolved spectroscopy machine. (B) OCS = Oscillator; MOD = modulator; LD = laser diode; PMT = photomultiplier tube; DEMOD = demodulator. When the emitted modulated near infrared light reaches a detector, the difference of the peak time between emitted and detected light stands for the time that near infrared light takes from the emitter to the detector.
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Methodology of Measuring Optical Pathlength
To measure the optical pathlength, we used a prototype machine of phase-resolved spectroscopy (Hamamatsu Photonics, Hamamatsu, Japan) (7). A block diagram of the optical pathlength meter developed is shown in Figure 1B. A 810-nm laser diode is used as the light source and the light intensity is sinusoidally modulated at 140 MHz by the modulator that is driven by the oscillator. The modulated light is delivered to the patient's head by the fiberoptic bundle with a diameter of 3 mm. The average intensity of the irradiated light is about 1 mW. The light transmitted through the tissue is collected by another fiber with the same diameter and is transmitted to the photomultiplier tube (Hamamatsu Photonics R7400). Signals from the photomultiplier tube and oscillator are fed into the demodulator that measures the phase difference between two signals (df) by means of the homodyne method (8,9). The phase difference signal is transmitted to the PC, where the optical pathlength is calculated and displayed on the screen in real-time (Fig. 1B).
The optical pathlength (L) is calculated from the phase difference by the following formula:
where c is the light velocity in a vacuum, n is the refractive index of tissue and f is the modulation frequency of light (f = 140 MHz). In the calculation, we used n = 1.4 (refractive index of water) because the water content is predominant in human tissues. In case of changing the ratio of water in the tissue by hemodilution, errors in the tissue refractive index would cause a small change only in the magnitude of the estimated pathlength. Therefore, such errors should not influence the measurement of variability in the pathlength, which was the sole purpose of this study. Before conducting the clinical measurements, the system was calibrated by measuring a thin light absorber, which was put between the fibers to set df to 0, or the 0 cm of pathlength.
CPB Management
Before CPB, the bypass machine was primed with crystalloid (lactated Ringer's solution, mannitol, and sodium bicarbonate) and a nonpulsatile pump flow rate was set at 2.8–3.2 L · min–1 · m–2. Extracorporeal ultrafiltration was used to maintain hematocrit values more than 20%. After cross-clamping the ascending aorta, cardioplegia was administered. Blood cardioplegia consisted of a mixture of one part autologous blood to one part potassium-enriched cardioplegia solution [40 mEq KCl and 1.5 mg of diltiazem and 10 mL of acid-citrate-dextrose per liter crystalloid] and was delivered every 20–30 min. A membrane oxygenator and a 40-µm arterial cannula filter were used. Paco2, uncorrected for temperature, was adjusted to normocapnic levels (35–40 mm Hg) by varying fresh gas flow to the membrane oxygenator (
-stat regulation). The target bladder temperature was 28°C–32°C. Metaraminol or norepinephrine infusion was used during CPB to maintain a mean arterial blood pressure of 50–70 mm Hg.
Statistics
Optical pathlength, Hb concentration, cerebral NIRS values, and arterial blood gas were measured at the following four points: 1) after the induction of anesthesia, 2) at 10 min after the start of CPB, 3) at 60 min after the start of CPB, and 4) at 1 h after CPB. Each parameter was analyzed by one-way analysis of variance (ANOVA) with repeated measurements. In addition, the data were compared with optical pathlength values, and cerebral NIRS values. The relationship between optical pathlength and Hb concentration was analyzed using Pearson correlation coefficients. Also, the effects of these factors on optical pathlength and NIRS values were analyzed by multiple regression analysis. P values <0.05 were considered statistically significant.
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RESULTS
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The patient demographic data are shown in Table 1 and the corresponding physiological data are provided in Table 2. Arterial Po2 values at 10 min after the start of CPB were significantly higher than those at the pre-CPB level. Body temperatures were significantly low during CPB when compared with control values. Hb concentrations and O2Hb significantly decreased and optical pathlength significantly increased during CPB (Figs. 2A–D). There was a significant negative correlation between percentage changes in Hb concentrations and that in optical pathlength (r = 0.55, P < 0.001) (Fig. 3). The results of multiple regression analysis are shown in Table 3. Percentage changes in optical pathlength, Paco2, and Pao2 values were significant determinants of O2Hb. Percentage change in Hb concentration was a significant determinant of those in both tissue oxygen index and optical pathlength.
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Figure 2. (A) The time course of changes in pathlength, (B) hemoglobin concentration, (C) tissue oxygen index (TOI), (D) oxyhemoglobin concentration (O2Hb). Measurements were performed at 1) after the induction of anesthesia (pre-CPB), 2) 10 min after the start of CPB (CPB 10 min), 3) 60 min after the start of the CPB (CPB 60 min) and 4) 1 h after CPB (after-CPB) Data are expressed as mean ± sd. *P < 0.05 versus pre-CPB. CPB = Cardiopulmonary bypass.
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Figure 3. The relationship between percentage change in hemoglobin (Hb) concentration and that in pathlength. There was a significant correlation between percentage change in Hb concentration and pathlength (r = 0.55, P < 0.0001).
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DISCUSSION
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The results of the present study show that optical pathlength significantly increased as Hb concentration decreased during CPB. There was a significant negative correlation between percentage changes in optical pathlength and Hb concentrations. Multiple regression analysis showed that optical pathlength was one of the significant determinants for O2Hb values. These results indicate that optical pathlength can change during CPB, and that changes in optical pathlength may affect O2Hb values of NIRS.
In contrast to jugular bulb oxygen saturation and cerebral blood flow measurement, NIRS is a noninvasive continuous measurement of cerebral oxygenation. However, there are factors that can affect NIRS measurements, such as optical pathlength, extracranial blood flow, and thickness of skull (7,10–12). Among these, optical pathlength is one of the most important factors used to calculate NIRS cerebral oxygen saturation. Some commercially available NIRS devices calculate cerebral oxygen saturation using a MBL method. In this calculation, optical pathlength is assumed to be constant. However, previous studies reported that optical pathlength varies among people (7,13). Furthermore, Kurth and Uher (6) reported that optical pathlength increased in hemodilution and there was a significant correlation between optical pathlength and Hb concentration in the experimental model. In hemodilution, as Hb concentration decreases, near infrared light can travel a longer distance because absorbance of near infrared light by Hb decreases. In the present study, we hypothesized that optical pathlength may increase during CPB because priming the CPB circuit without blood causes acute hemodilution. This study showed that optical pathlength increases during CPB when compared with the pre-CPB level, and that there is a significant inverse correlation between percentage changes in optical pathlength and Hb concentration.
Moreover, a lower Hb concentration leads to an increase in optical pathlength, causing an overestimation of O2Hb (Appendix). In this study, multiple regression analysis revealed that optical pathlength is one of the determinants of O2Hb. Although further investigation would be required to determine the effects of changes in optical pathlength during CPB on NIRS values, careful attention should be paid to the interpretation of NIRS data and their changes during CPB.
In addition to Hb concentration, other factors can affect optical pathlength during CPB. Cerebral hypoperfusion during CPB may reduce the amount of regional chromophores, resulting in an increase in optical pathlength. Mutch et al. (14) suggested, using magnetic resonance imaging, that a large proportion of cerebral parenchyma was hypoxic and CPB caused lower splanchnic perfusion (15–17). They also suggested that -stat management can lead to mild hypocarbia and decrease cerebral blood flow. In addition, if regional cerebral blood volume changes during CPB, the amount of chromophore would change and thus affect optical pathlength. However, in this study we did not investigate these variables. Further investigations need to be done to determine the influence of blood flow and CO2 management on NIRS measurement.
There are some limitations to this study. First, the sample size was small because measurement of optical pathlength by phase-resolved spectroscopy is very complicated. It would be beneficial to conduct further studies with a larger sample sizes. Second, there are other methods of measuring optical pathlength, such as time-resolved spectroscopy. It is not presently clear which method is more accurate in calculating optical pathlength. With time-resolved spectroscopy, the results might be different.
In summary, we investigated the changes of optical pathlength during CPB. Optical pathlength increased as Hb concentrations decreased during CPB. There was a significant correlation between percentage changes in optical pathlength and that in Hb concentrations. In addition, optical pathlength was one of the significant determinants of O2Hb by NIRS. Although NIRS is a readily available method to monitor cerebral hemodynamics noninvasively and continuously, the resulting data should be carefully interpreted during CPB, during which Hb concentration can change dramatically.
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APPENDIX: CALCULATION OF THE CHANGE IN OXYHEMOGLOBIN CONCENTRATION USING THE MODIFIED BEER–LAMBERT TECHNIQUE
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The modified Beer–Lambert (MBL) method relates the absorbance of light of a chromophore like hemoglobin to the concentration of the chromophore in the target sample. The MBL method is expressed mathematically as:
where I0 is the light intensity at light emitter, I is the light intensity at light detector, 
(
) is the molar extinction coefficient, C is the change of a substance concentration (O2Hb and HHb), [d] is the optical pathlength (the length of the light travels from the emitter to the detector). A means the change of attenuation rate of light and is in proportion to a variation of substance concentration in a biological tissue. In this calculation, () and [d] are assumed to be constant by most commercially available NIRS monitors.
During hemodilution, the concentration of O2Hb decreases and the light can travel farther before being attenuated. Optical pathlength would therefore increase. And the change of attenuation of light, A would increase because the light that takes the long way without being absorbed can be detected.
If [d] increases 1.5 times as a result of hemodilution, but [d] supposed to be constant, C could be 1.5 times the actual C. In this study, optical pathlength was found to be 1.2 or 1.3 times the control values as a result of CPB. During CPB the change of O2Hb would therefore overestimate the true value by 1.2 or 1.3 times.
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Footnotes
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Accepted for publication October 24, 2006.
Supported, in part, by Hamamatsu Photonics K.K., Shizuoka, Japan.
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Abstract
Introduction
