Bedside Monitoring of Patients with Shock Using a Portable Spatially-resolved Near-infrared Spectroscopy References and Links Study on Shock Monitoring Using a Space-resolved Nirs, " Pibm 2014, Proc. Spie. in Press

Clinical monitoring of shock mainly depends on blood-oxygen-indices obtained from invasive blood sample tests. The central internal jugular central vein oxygenation level (ScvO 2) has been considered as a gold standard indicator for shock prediction. We developed a noninvasive spatially-resolved near-infrared spectroscopy (SR-NIRS) to measure tissue blood oxygen saturation (StO 2) surrounding the region of taking blood sample for the ScvO 2 test in 25 patients with shock. StO 2 values were found to be highly correlated (r = 0.84, p < 0.001) with ScvO 2 levels and the concordance coefficient of 0.80 is high. The results suggest the potential of noninvasive SR-NIRS for bedside shock monitoring. Monitoring the microcirculation in the critically ill patient: current methods and future approaches, " Intensive Care Med. Patients Trial Investigators, " Tissue oxygen saturation predicts the development of organ dysfunction during traumatic shock resuscitation, " J. Can near-infrared spectroscopy identify the severity of shock in trauma patients? " J. Regional tissue oxygenation during hemorrhage: can near infrared spectroscopy be used to monitor blood loss? " Tissue hemoglobin O2 saturation during resuscitation of traumatic shock monitored using near infrared spectrometry, " J. Use of tissue oxygen tension measurements during resuscitation from hemorrhagic shock, " J. Near-infrared spectroscopy measurement of regional tissue oxyhemoglobin saturation during hemorrhagic shock, " A method to determine the adequacy of resuscitation using tissue oxygen monitoring, " J. Tissue oximetry: a comparison of mean values of regional tissue saturation, reproducibility and dynamic range of four NIRS-instruments on the human forearm, " Biomed. Reproducibility of cerebral tissue oxygen saturation measurements by near-infrared spectroscopy in newborn infants, " J. modeling of photon migration in voxelized media, " J. Innov. Visualization of light propagation in visible Chinese human head for functional near-infrared spectroscopy, " J. Three dimensional Monte Carlo code for photon migration through complex heterogeneous media including the adult human head, " Opt. Non-invasive optical monitoring of the newborn piglet brain using continuous-wave and frequency-domain spectroscopy, " Phys. Determination of optical properties and blood oxygenation in tissue using continuous NIR light, " Phys.


Introduction
Shock may result in an acute blood flow reduction, metabolic abnormalities, anaerobic metabolism, cellular and organ dysfunction, and irreversible damage and death if prolonged [1].The shock resulting from inevitable hemorrhage during surgery and traumatic injury is a fatal complication (up to 50% in mortality), frequently leading to early deaths [2,3].Estimation of shock severity is crucial to guide clinicians for making treatment plans and for evaluating therapeutic effects [4].
The widely used clinical method to determine shock severity is to measure blood sample oxygen indices.Various oxygen-related indices were proposed as shock indicators, such as oxygen delivery (DO 2 ), oxygen consumption (VO 2 ), blood lactate, pulse oxygen saturation (SpO 2 ), central venous oxygen saturation (ScvO 2 ), artery oxygen saturation (SaO 2 ), and partial pressure of oxygen (PO 2 ).Among these indicators, only SpO 2 can be detected noninvasively by a finger-sensor.However, finger pulse oximetry works ineffectively during shock because of the poor peripheral blood perfusion in the finger [5].The global indicators of DO 2 and VO 2 may not catch up regional hypoperfusion [6].Blood lactate is not sensitive to pre-existing medical conditions [7].PO 2 has been used for monitoring shock in an uncontrolled study with a small number of patients [4].ScvO 2 [8] and SaO 2 are accepted to be accurate and objective for shock monitoring [9], and ScvO 2 is commonly regarded as a gold standard [8].However, the invasive and intermittent procedures to obtain these acceptable indicators (i.e., PO 2 , ScvO 2 , SaO 2 ) limit the use for continuous shock monitoring.As a result, the clinician may miss the best time window to rescue the patient.Therefore, it's crucial to explore a noninvasive technique to continuously monitor shock.
Shock occurs mostly because of insufficient oxygen to the body.Tissue blood oxygen saturation (StO 2 ) measured at an appropriate region may be a good indicator of shock state [9][10][11].In this study, we investigated the correlations between StO 2 and ScvO 2 , SaO 2 , and PO 2 , and explored the use of StO 2 as an indicator for shock.We have developed a SR-NIRS to monitor StO 2 in the region surrounding the internal jugular vein [16].Two detectors and a 3-wavelengths (735, 805, and 850 nm) integrated LED were integrated into a probe (Fig. 1(a)) [17,18].The LED was controlled by a micro-controller to be "on" or "off" alternatively.Relatively larger source-detector distances (2.4 cm and 2.7 cm) were used to probe deeper tissue property around the internal jugular vein, which located ~1 cm beneath the skin/probe (Fig. 1(b), 1(c), Fig. 2), and thus yielding more sensitive signals for the comparison of StO 2 and ScVO 2 measurements.The diameter of each detector was ~0.6 cm, making it impossible to arrange S-Ds in a linear pattern.Thus they were configured in a shape of triangle.Figure 2(b) shows Monte Carlo Simulation [19][20][21] of NIRS signal sensitivity profile with our probe design, suggesting that the sampling volume of our probe covered the tissue surrounding the central internal jugular vein.The size and depth of the veins in shock patients were determined by ultrasonographs.The thicknesses of skin and fat over the measured population were 0.2 ± 0.04 cm (mean ± standard deviation) measured by a Vernier caliper.

Spatially-resolved NIRS
The calculation of local StO 2 was accomplished by converting from the detected light intensity changes based on the modified Beer-Lambert law [22,23].The following formula describes the relationship between the measured optical density (OD), tissue optical properties, and the source-detector spacing (ρ): Here, ρ 0 is the average of the chosen maximum and minimum source-detector separations in the probe, R app is the spatial dependence of the approximated diffuse reflectance, and 3 ( (1 )) μ is the absorption coefficient, s μ is the scattering coefficient, and g is the anisotropic factor.cal means the calibration control.We then plotted OD changes as a function of ρ and the slope λi of the plotted curve was calculated.The correlation between slope λi and μ aλi was calculated as follows: The relationship between a μ and the concentrations of deoxy-hemoglobin (Hb) and oxyhemoglobin (HbO 2 ) can be described as follows: Here, ε Hbλi and HbO λ ε represents the extinction coefficient of Hb and HbO 2 respectively.

Subjects and experimental protocol
Twenty-five patients with shock were recruited from Xinhua Hospital in Shanghai of China with their written informed consents approved by the ethics committee (Approval No. XHEC-D-2014-005).Patients were 67.3 ± 16.6 years old.StO 2 measurements were performed using our SR-NIRS device in conjunction with other conventional shock monitoring procedures.The StO 2 measurements were carried out either at the end of shock treatment (8 males and 5 females) or one day after (7 males and 5 females).The internal jugular central venous catheterization could not be performed on the former group of patients since the measurement site was still occupied to perform tracheal intubation to obtain respiration-oxygen delivery at that point.

Data collection and analysis
with combinations of the acceptable blood indices, we fit multiple linear regression models.We also test the consistency between StO 2 and ScvO 2 and reported Lin's concordance coefficient [24], which combines a measure of precision and accuracy.A Bland-Altman plot was carried out to visualize the extent of agreement between the indicators.

Results
SpO 2 measurements were not reliable on our patients with shock; almost all showed low invalid values or no readout except one patient had a value 95% which was in the valid range.The comparisons between the StO 2 measured by SR-NIRS and other shock-monitoring clinical measures are shown in Fig. 3, 4 and Table 1.A significant linear relationship was observed (r > 0.843, p < 0.001) between the StO 2 and ScvO 2 (see Fig. 3(a)), with a slope (95% confidence interval) of 0.96 (0.53 to 1.39) (see Fig. 4(a)).Only three data points fell outside 95% confidence level.The Bland-Altman plot (Fig. 4(b)) for these two measurements also demonstrated an agreement, with a mean difference of 4.16% (−6.87% to 15.20%).The concordance coefficient between StO 2 and ScvO 2 of 0.804 is high.Additionally, StO 2 was found to be correlated with SaO 2 (r = 0.501, p = 0.011; see Fig. 3(b)) and PO 2 (r = 0.465, p = 0.019; see Fig. 3(c)) and there were significant regressions between StO 2 and other acceptable blood oxygen indices (Table 1).The corresponding residual analysis showed only two patients had outlier data, also indicating the robust regression relationships.There were no significant differences in StO 2 , SaO 2 and PO 2 between the measures at different days (i.e., the day at treatment versus one day after treatment) (p > 0.16), hence it is not unreasonable to speculate that ScvO 2 might show obscure difference as well.It may contribute to the effective resuscitation on the shocks.

Discussion and conclusion
Continuous monitoring of shock is crucial for clinicians to perform treatment timely and evaluate therapeutic effect so that irreversible injuries can be avoided.However, currently available methodologies for shock monitoring rely on frequent blood sampling with internal jugular central venous catheterization, which is invasive and discontinuous.In this study, we demonstrated that the StO 2 level measured at the tissues surrounding the internal jugular vein by noninvasive SR-NIRS may be a shock indicator.The SR-NIRS used in this study enabled absolute measurement of StO 2 .Data from 25 patients with shock demonstrate significant correlations between StO 2 and the gold standard ScvO 2 as well as other acceptable blood oxygen indices.These results support the use of SR-NIRS as a noninvasive, continuous tool for bedside monitoring of shock.
Our study is the first exploration of the StO 2 measured by NIRS at the region surrounding the internal jugular central vein as a new shock indicator.Previous studies using NIRS to monitor StO 2 in shocks were performed in the peripheral area including finger, deltoid muscle, subcutaneous tissue, and thenar eminence [11,13].However, shock usually results in poor peripheral blood circulation, making peripheral measurements unreliable, as seen in this study with SpO 2 measurements.By contrast, we chose the tissue surrounding internal jugular central veins because the gold standard ScvO 2 sampling is usually taken from this vein [11] and this site roughly belongs to splanchnic circulation which is crucial for shock monitoring.We may also explore other potential sites such as patient's head in the future as cerebral circulation is apparently critical for shock monitoring.
The StO 2 measured by NIRS showed strong correlation and high concordance with the gold standard ScvO 2 , which might be because a portion of the signal ScvO 2 goes into the StO 2 (see Fig. 2(b)) measured in the tissue surrounding the internal jugular central vein.Meanwhile, the StO 2 showed weak correlations with other indicators (i.e., SaO 2 and PO 2 ), indicating that the StO 2 measurement performed closer to the vein for the ScvO 2 test is supper than other places for monitoring shock states.However, the thresholds to separate healthy subjects and shock patients using ScvO 2 and StO 2 have not been established yet, and further investigations including healthy subjects are needed.
In summary, we have demonstrated that NIRS measurements of StO 2 in the internal jugular central venous region provide valuable information for shock monitoring.The NIRSmeasured StO 2 has been verified by comparing to the conventional blood oxygen indices, especially ScvO 2 .SR-NIRS device can be used at the bedside for continuous monitoring of shock, and thus has the potential to become a clinical tool for shock management.

Fig. 2 .
Fig. 2. (a) Ultrasonograph of internal jugular central vein and (b) Monte Carlo simulation of photon paths within the tissues surrounding the veins.

Fig. 3 .Fig. 4 .
Fig. 3.The correlations between StO 2 and conventional blood oxygen indices, represented by scatter plot with least-squares fitted lines added.