A note on arterial to venous oxygen saturation as reference for NIRS-determined frontal lobe oxygen saturation in healthy humans

Near infrared spectroscopy (NIRS) offers non-invasive assessment of oxygenation within the human brain (ScO2) by appreciating the different absorption of near infrared light by hemoglobin and oxyhemoglobin (Jobsis, 1977). Since the length the light has passed when traveling from the skin to the cortex and then returning to the skin remains unknown, there is a need to adjust the signal according to an assumed ratio between the arterial vs. venous blood that is appreciated. Apparently, most NIRS devices use a fixed reference ratio between the arterial (25%) and venous contribution (75%) to the signal despite not eligible mismatch (Bickler et al., 2013). This assumption is based on anatomical evidence (Pollard et al., 1996), but might be confounded by changes in cerebral blood volume during, e.g., hypoxia and changes in the arterial carbon dioxide tension (PaCO2) (Ito et al., 2005). A standard reference arterial to venous ratio may therefore not exist for application of NIRS to determine ScO2 in humans. Thus, an estimate of cerebral capillary hemoglobin oxygen saturation (ScapO2) to express cerebral oxygenation is based on 50% jugular and arterial saturations (Gjedde et al., 2005) and has been reported to follow changes in ScO2 (Rasmussen et al., 2007). In this report we made a meta-analysis on published data (Rasmussen et al., 2007; Sørensen et al., 2012, in press) in order to evaluate which ratio between arterial and internal jugular venous hemoglobin saturation that fits best to the concomitant determined ScO2 in healthy humans exposed to a wide range of interventions. Thirty seven subjects [age 27(9) years, height 181(10) cm, mass 79(13) kg, mean (SD)] were catheterized in the right internal jugular vein with the tip of the catheter advanced to the bulb of the vein and with a catheter in the brachial artery of the nondominant arm, while ScO2 was monitored by the Invos Cerebral Oximetry (Covidien, Mansfield, MI). Arterial partial pressure for oxygen and carbon dioxide, and oxygen saturations were measured in the jugular and arterial blood (PaO2; PaCO2; SaO2; SjO2) (ABL-800, Radiometer, Brønshøj, Denmark). The subjects were exposed to hypoxia (FiO2 = 10%; n = 23), inspiration of 100% oxygen (n = 8), atmospheric air (n = 37), hypercapnia (FiCO2 = 5%; n = 8) and asked to hyperventilate (∼2– 3 kPa reduction in PaCO2; n = 32) with separate controls. By linear regression the contribution from arterial and jugular blood to ScO2 was estimated and Rsquared (R2) and root mean square error (RMSE) between ScO2 and the arterial fraction in the reference saturation were calculated (SAS Institute Inc., Cary, NC). Only data points where SjO2 ≤ ScO2 ≤ SaO2 were included. All reference saturations were calculated, e.g., ScapO2 = 0.50 · SaO2 + 0.50 · SjO2. The following equation, 0 = ScO2 – [a · SaO2 + (a − 1) · SjO2], was used to calculate the arterial fraction (a) for which the difference between ScO2 and the reference saturation was zero. SaO2 and SjO2 ranged from 70 to 100% and 33 to 87%, respectively, while ScO2 ranged from 48 to 95%. PaCO2 was manipulated from 1.6 to 6.3 kPa. According to the linear regression analysis, ScO2 demonstrated a correlation to a wide range of ratios between the arterial and venous hemoglobin saturations. The highest RMSE was obtained when it was considered that there was no arterial contribution to ScO2 and the RMSE became gradually lower when the arterial contribution was considered to increase (Figure 1A). The lowest RMSE was observed for a 75% arterial and 25% jugular venous blood contribution to ScO2(RMSE = 2.70; R2 = 0.644; P < 0.0001; Figure 1A). For the oftenused calibration ratio (25% arterial) R2 was 0.505 (P < 0.0001) with a RMSE of 4.233. In contrast, ScapO2 (50% arterial) had a R2 of 0.606 (P < 0.0001; RMSE = 3.276; Figure 1A). Zero was within the 95% confidence interval only with a calculated 40–50% arterial contribution to the reference ratio. When ScO2 was compared with the calibration ratio, the mean difference was zero in 2.9% of the blood samples, whereas it was 10.5% when ScapO2 was used as reference (Figure 1B). This meta-analysis of published data suggests that the optimal reference ratio has a larger arterial contribution than the ratio defined by anatomical models and likely incorporated in most NIRS devices (Pollard et al., 1996; Bickler et al., 2013). The subjects were not only exposed to conditions that changes the venous oxygen saturation, i.e., hyperventilation, but also to conditions known to affect arterial and venous cerebral blood volume and oxygen content without influencing extracerebral blood (Ito et al., 2005). From these interventions, linear regression analysis demonstrated that the correlation between