Investigating spectroscopic measurement of sublingual veins and tissue to estimate central venous oxygen saturation

Abstract

BACKGROUND:

Venous oxygen saturation reflects venous oxygenation status and can be used to assess treatment and prognosis in critically ill patients. A novel method that can measure central venous oxygen saturation (ScvO ${}_{2}$ ) non-invasively may be beneficial and has the potential to change the management routine of critically ill patients.

OBJECTIVE:

The study aims to evaluate the potential of sublingual venous oxygen saturation (SsvO ${}_{2}$ ) to be used in the estimation of ScvO ${}_{2}$ .

METHODS:

We have developed two different approaches to calculate SsvO ${}_{2}$ . In the first one, near-infrared spectroscopy (NIRS) measurements were performed directly on the sublingual veins. In the second approach, NIRS spectra were acquired from the sublingual tissue apart from the sublingual veins, and arterial oxygen saturation was measured using a pulse oximeter on the fingertip.

RESULTS:

Twenty-six healthy subjects were included in the study. In the first and second approaches, average SsvO ${}_{2}$ values were 75.0% $\pm$ 1.8 and 75.8% $\pm$ 2.1, respectively. The results of the two different approaches were close to each other and similar to ScvO ${}_{2}$ of healthy persons ( $>$ 70%).

CONCLUSION:

Oxygen saturation of sublingual veins has the potential to be used in intensive care units, non-invasively and in real-time, to estimate ScvO ${}_{2}$ .

Keywords

Sublingual veins venous oxygen saturation near-infrared spectroscopy tissue oxygen saturation

1. Introduction

Oxygen is essential for life, and it is carried to the cell by a particular protein called hemoglobin. Four oxygen molecules binned hemoglobin is called oxyhemoglobin, and otherwise called deoxyhemoglobin. Oxygen saturation is defined as the ratio of the oxyhemoglobin concentration to total hemoglobin concentration. Absorption and reflectance spectrum of oxy- and deoxyhemoglobin is different, and this makes it possible to estimate oxygen saturation by measuring reflectance intensity at two different wavelengths [1].

Oxygen saturation can be measured on different parts of the body to evaluate the body physiology. Arterial oxygen saturation (SaO ${}_{2}$ ) is a vital parameter, and it is generally measured on the fingertip or earlobe. Tissue oxygen saturation (StO ${}_{2}$ ) is the oxygen saturation of a regional tissue consist of arteries, veins, and capillaries. Venous oxygen saturation is measured in the pulmonary artery, and it is defined as mixed venous oxygen saturation (SvO ${}_{2}$ ). Venous oxygen saturation can also be measured in the internal jugular or subclavian vein and described as central venous oxygen saturation (ScvO ${}_{2}$ ). With the decreased use of pulmonary artery catheterization, central venous oxygen saturation has become a surrogate for mixed venous oxygen saturation [2].

Central venous oxygen saturation is a marker of oxygen consumption of the body, and it shows the balance between oxygen supply and demand. It varies in different study populations but generally accepted as 70%–89% in healthy persons and decreases in critical diseases like sepsis [2, 3, 4, 5, 6, 7]. Measurement of the central venous oxygen saturation requires catheterization, recurrent blood sampling, and blood gas analysis. Catheterization is an invasive procedure and requires constant care.

Visible and near-infrared spectroscopy (NIRS) is widely used in the diagnosis of diseases related to hemodynamic changes and has promising results [8, 9, 10]. In the literature, several groups have developed different spectroscopic techniques to measure venous oxygen saturation on different parts of body regions non-invasively and in real-time [11, 12, 13]. However, there is no standard method or body region for non-invasive spectroscopic venous oxygen saturation measurements. In the present study, oxygen saturation of sublingual veins and tissue was measured using NIRS, and its usability in ScvO ${}_{2}$ prediction has been investigated on a healthy population. If validated in subsequent studies on patient groups with a central venous catheter, this technic could lead to a large reduction in the need for invasive procedures such as catheterization and general health expenditures. If this method is accepted in the clinical routine, it will benefit both patient, physician, and public health.

The main objective of the present study was to measure the sublingual venous oxygen saturations by NIRS in a healthy population and compare the results with literature knowledge of central venous oxygen saturations. Our second aim was to describe our spectroscopic sublingual venous oxygen saturation measurement procedure and guide the studies to be carried out on this promising subject.

2. Material and methods

2.1 Study design and population

The study was conducted at the Biomedical Optic Research Unit of the Medical School of Akdeniz University, Antalya, Turkey, between April 2019 and January 2020. The study was approved by the Akdeniz University Institutional Review Board. All procedures performed with human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from each participant included in the present study.

In total 26 healthy volunteers over 18 years old were recruited regardless of gender. Their mean age (mean $\pm$ SD) and body mass index score was 31.5 $\pm$ 6.2 years and 23.9 $\pm$ 3.6 respectively. Nine (34.6%) of the participants were female. All of the participants were Caucasian. None of the participants had a disease that may alter the arterial, venous or tissue oxygen saturation such as hypertension, diabetes mellitus, or atherosclerosis.

2.2 Public involvement

Public involvement was ensured in the study at several stages including the design, participant recruitment and measurement. Feedbacks were collected from the participants about the recruitment and measurements process. These feedbacks are important for the comfort of patients who will be involved in future studies.

2.3 Spectroscopic system

The spectroscopic system consists of a miniature USB spectrometer (USB200; Ocean Optics, FL, USA), a fiber-optic probe (Back reflection probe; Ocean Optics, FL, USA), a halogen white light source (HD200; Ocean Optics, FL, USA) and a computer with ocean optic software. The fiber optic probe had seven fibers with 400 $\mu$ m diameter. One of the fibers is in the middle and surrounded by the other six. The six surrounding fibers are connected to the light source to deliver the light to the tissue. The central fiber is connected to the spectrometer and collects the light reflected from the tissue. A schematic illustration of the spectroscopic system is provided (Fig. 1).

Figure 1.

Schematic illustration of the spectroscopic system.

Near-infrared spectroscopy measurements were calibrated using a diffuse reflectance standard (WS-1-SL; Ocean Optics, FL, USA) and standard calibration formula [14].

2.4 Measurements

Systolic blood pressure, diastolic blood pressure, heart rate, and SaO ${}_{2}$ values of all patients were measured by a specialist physician. Participants were not allowed to drink tea or coffee and smoke within thirty minutes before the measurement. Before the measurements, all participants were taken to the measurement room and rested in the supine position for 15 minutes.

After the measurement of vital parameters, spectroscopic measurements were performed. During the measurement, the probe was gently placed on the relevant body region, and participants were requested not to move. Throughout the measurement process, the probe was held perpendicular to the relevant area. For all participants, measurements were obtained from the sublingual vein, sublingual tissue, and anterior side of the left earlobe. The localization of the sublingual vein is determined by direct visualization while the subject was holding the tongue upward. The left side of the sublingual area was used for spectroscopic measurement. Measurements in the sublingual area are shown (Fig. 2). While taking the NIRS measurement of sublingual tissue, care was taken to place the tip of the probe at least 10 mm far from the sublingual venous structures to avoid its contribution (Fig. 2). Ten near-infrared spectra were obtained from each measurement region and averaged.

Figure 2.

a. Direct visualization of the sublingual area b. Spectroscopic measurement of the sublingual vein c. Spectroscopic measurement of the sublingual tissue.

2.5 Calculation of the tissue oxygen saturation

The absorption of the light at 760 and 790 nm wavelengths by water, melanin, and fat is relatively low compared to the absorption of oxyhemoglobin and deoxyhemoglobin. The light scattering decreases with increased wavelengths, but it does not change significantly between 760 and 790 nm wavelengths. Hence, attenuation of the back-reflected light from the tissue at both wavelengths strongly depends on the absorption of oxyhemoglobin and deoxyhemoglobin in the tissues. To calculate tissue oxygen saturation, we used a method that we developed in a previous study [9]. In this method, the ratio (R) of diffuse reflectance light intensity (I) at 760 and 790 nm from spectra measured from the tissue is determined (R $=$ I ${}_{760}$ /I ${}_{790}$ ). R values were used in the formula derived from previous studies, and tissue oxygen saturation was calculated for all subjects and spectroscopic measurement regions, tissue oxygen saturations were calculated using this method Matlab R2015a (The MathWorks Inc., Natick, MA, USA) software was used to visualize reflectance spectra and calculate tissue oxygen saturations.

2.6 Estimation of sublingual venous oxygen saturation

In estimating of sublingual venous oxygen saturation, two different (direct and indirect) approaches were used. In the direct approach, it is assumed that the tissue oxygen saturation that is measured from the sublingual venous area represents the oxygen saturation of the sublingual veins In the indirect approach, sublingual venous oxygen saturation is estimated using the sublingual tissue oxygen saturation (StO ${}_{2}$ ) obtained from NIRS measurements and arterial oxygen saturation (SaO ${}_{2}$ ) measured with a pulse oximeter. In the indirect approach, the following equation is used to obtain sublingual venous oxygen saturation (SsvO ${}_{2}$ ) [15]:

$\displaystyle\text{StO}_{2}=0.25\ast\text{SaO}_{2}+0.75\ast\text{SvO}_{2}$ (1)

2.7 Statistical analysis

Descriptive statistics such as frequency distribution, mean and standard deviations were used to describe data. The Shapiro-Wilk test was used to analyze the distribution of continuous variables. Paired t-test was used for the analysis of normally distributed variables. All tests were performed with a $P$ -value of $<$ 0.05 considered statistically significant. Statistical analyses were performed using SPSS software version 20.0 (IBM Corp., Armonk, NY, USA) GraphPad Prism software version 7 (GraphPad Software, USA).

3. Results

Demographic data and vital parameter results are presented at Table 1. In Fig. 3, three corrected reflectance spectra obtained from different regions of a participant are shown.

Table 1
Demographic data of the study population

Age (years)	31.5 $\pm$ 6.2
Gender (M/F)	17/9
Body Mass İndex (kg/m ${}^{2}$ )	23.9 $\pm$ 3.6
Systolic B. P. (mmHg)	118.0 $\pm$ 7.0
Diastolic B. P. (mmHg)	77.0 $\pm$ 6.1
Heart rate (bpm)	82.7 $\pm$ 13.0
SaO ${}_{2}$ (%)	98.8 $\pm$ 1.1

Data are presented as means $\pm$ SDs.

Figure 3.

Corrected reflectance spectra of the sublingual vein, sublingual tissue, and earlobe of a subject.

The mean StO ${}_{2}$ value of the sublingual venous area, sublingual tissue, and earlobe of all participants were 75.0% $\pm$ 1.8, 81.5% $\pm$ 1.5, 82.1% $\pm$ 1.0, respectively (Fig. 4). There was a statistically significant difference between the StO ${}_{2}$ of the sublingual venous area and both sublingual tissue or earlobe ( $p<$ 0.001 for both). On the other hand, the difference between the sublingual tissue and earlobe was not statistically significant ( $p>$ 0.05).

Figure 4.

Mean tissue oxygen saturations for different body regions ( ${}^{*}p<$ 0.001 versus StO2 value of sublingual vein).

Mean SsvO ${}_{2}$ was measured as 75.0% $\pm$ 1.8, in the direct approach and calculated using Eq. (1) as 75,8 % $\pm$ 2.1 in the indirect approach. No statistically significant difference was seen between the two methods ( $p=$ 0.10). The results of the two different approaches were compared with the Bland-Altman plot (Fig. 5). Mean difference (bias), lower and upper limits were $-$ 0.7%, $-$ 4.8%, and 3.4%, respectively. All of the data points are located within limits.

Figure 5.

Bland-Altman analysis of the two different approaches for calculating sublingual venous oxygen saturation. The continuous line represents bias ( $-$ 0.7%) and the dashed lines represent negative and positive limits of agreement ( $-$ 4.9% and 3.5%, respectively).

4. Discussion

In the present study, we measured StO ${}_{2}$ values at three different body regions. Two of them were lingual areas, and the other was the earlobe as a control region. We determined a control region in StO ${}_{2}$ measurement to demonstrate the consistency of our measurement method. We chose the earlobe as a control region because it is an easy region to work at and a common region for the oxygen saturation measurements. The mean tissue oxygen saturations at sublingual tissue and earlobe were very similar (81.5% $\pm$ 1.5 and 82.1% $\pm$ 1.0, respectively) and consistent with our StO ${}_{2}$ knowledge [9, 16, 17]. On the other hand, it was statistically significantly lower at the sublingual venous area (75.0% $\pm$ 1.8; $p<$ 0.001 for both regions). In Fig. 3, depression about 760 nm at the spectrum obtained from the sublingual venous area, is clearly seen. The absorption peak of the deoxyhemoglobin is responsible for this depression, and these results support that we were able to measure sublingual venous oxygen saturation. We also examined the agreement between the two approaches used in the present study, and the Bland-Altman plot showed acceptable agreement.

In 2012, Colin et al. conducted a study with patients with severe sepsis and septic shock [11]. In this study, they measured StO ${}_{2}$ at the level of the thenar, masseter, and deltoid muscles using InSpectra StO ${}_{2}$ Tissue Oxygenation Monitor (Hutchinson Technology Inc., Arnhem, The Netherlands) and other hemodynamic parameters, including ScvO ${}_{2}$ . They observed some degree of correlation between ScvO ${}_{2}$ values and StO ${}_{2}$ values for all three measurement areas. Their results also showed that the masseter StO ${}_{2}$ values in the first 6 hours of resuscitation could identify patients with severe sepsis and central venous oxygen saturation $>$ 70%. In 2013, they conducted a randomized, non-blinded study about the prognostic value of StO ${}_{2}$ in patients with sepsis. They tried to add StO ${}_{2}$ target (StO ${}_{2}$ $>$ 80% on at least two muscles) to the Surviving Sepsis Campaign recommendations, but the results showed no clear trend for or against targeting StO ${}_{2}$ [18].

In another study, the thenar StO ${}_{2}$ value of patients with severe sepsis is measured by NIRS to investigate the correlation of thenar StO ${}_{2}$ with reference ScvO ${}_{2}$ values in forty patients [19]. When they divided patients into two groups as ScvO ${}_{2}$ higher and lower than 70%, there was a statistically significant difference between the StO ${}_{2}$ values of groups. However, the correlation between the thenar StO ${}_{2}$ and ScvO ${}_{2}$ was weak (Pearson correlation coefficient – $r=$ 0.39).

In 2012, Colquhoun tried to estimate the jugular venous oxygen saturation non-invasively using near-infrared spectroscopy and transcutaneous venous oximetry in forty patients undergoing cardiac surgery [20]. Correlation between the jugular venous oxygen saturation and transcutaneous venous oximetry measurements were not statistically significant. On the other hand, there was a statistically significant correlation between ScvO ${}_{2}$ and StO ${}_{2}$ values of jugular venous area ( $r^{2}=$ 0.28; $p=$ 0.03). In a similar study, the NIRS method was used to calculate StO ${}_{2}$ values in the internal jugular venous area [12]. In the study, they compared the StO ${}_{2}$ values with reference ScvO ${}_{2}$ values in 13 patients who have a central venous catheter. While measuring the StO ${}_{2}$ values, ultrasonography guidance was used to place the probe on the internal jugular vein. They found a good correlation between StO ${}_{2}$ and ScvO ${}_{2}$ values ( $r=$ 0.906). This technic may also be suitable for continuous monitoring.

As seen in the literature, NIRS is used in the non-invasive estimation of central venous oxygen saturation. Different body regions, devices, and methods are used, and still, there is no standard method yet. In the present study, we aimed to evaluate the potential of sublingual veins and tissue to be used in the estimation of ScvO ${}_{2}$ . We chose the sublingual veins and tissue because gastrointestinal mucosa is shown to be very sensitive to hypoxia [21, 22]. Sublingual capnography is a method by which the partial carbon dioxide pressure in the sublingual mucosa is measured. It evaluates the balance between perfusion and metabolism in the sublingual area. The correlation between sublingual and gastric mucosal partial carbon dioxide pressure and their prognostic value in the management of critically ill patients was also shown [23].

In the present study, the measured StO ${}_{2}$ of the sublingual veins may slightly be different than its actual value due to some connective tissue above the sublingual veins, which may affect the NIRS measurement. However, this connective tissue is not so thick, and the total volume from which reflectance spectrum measurement is obtained is occupied mostly by venous blood. Unlike other veins, sublingual veins are relatively superficial and the active surface area of the probe (1.5 mm ${}^{2}$ ) is small enough to measure within a small volume. The source and detector separation (400 $\mu$ m) of our probe provides a penetration depth of a few millimeters [24, 25].

Our study has some limitations. NIRS measurement on the sublingual venous area is neither comfortable for the patient nor practical for physicians. During the acquisition, variation of the pressure applied to the sublingual veins may dramatically affect the results. In future studies, we will make a special probe to solve the problem, and it will enable us to measure StO ${}_{2}$ on sublingual veins and tissue simultaneously. Another limitation is that our study population consisted of healthy persons. The results were in line with the literature for healthy individuals, but to fully understand the clinical value of the method, it is necessary to conduct studies with patients with abnormal saturation values. Finally, our results should be confirmed with a criticality ill patient population with central venous catheters.

5. Conclusion

In the present study, we showed that the NIRS method offers a non-invasive oxygen saturation measurement technic for sublingual veins and tissue. With future studies investigating this topic, it may be possible to estimate central venous oxygen saturation only by accessing sublingual area. Such a method that allows us to measure or estimate the ScvO ${}_{2}$ non-invasively and continuously can dramatically change the clinical management routine of critically ill patients. It may benefit both healthcare professionals and patients by reducing the need for invasive procedures such as central catheterization.

Data availability

The data used and analyzed in the present study is available from the corresponding author on reasonable request.

Funding

This work was supported by Akdeniz University Scientific Research Units, Antalya Turkey, under project number 2014.01.0103.001.

Footnotes

Conflict of interest

The authors do not have any conflicts of interest to declare.

References

Yoshiya

Shimada

Tanaka

. Spectrophotometric monitoring of arterial oxygen saturation in the fingertip. Med Biol Eng Comput. 1980; 18(1): 27-32.

Walley

. Use of central venous oxygen saturation to guide therapy. Am J Respir Crit Care Med. 2011; 184(5): 514-20. doi: 10.1164/rccm.201010-1584CI.

Tanczos

Molnar

. The oxygen supply-demand balance: a monitoring challenge. Best Pract Res Clin Anaesthesiol. 2013; 27(2): 201-7. doi: 10.1016/j.bpa.2013.06.001.

Pope

Jones

Gaieski

, et al. Multicenter study of central venous oxygen saturation (ScvO(2)) as a predictor of mortality in patients with sepsis. Ann Emerg Med. 2010; 55(1): 40-46 e1. doi: 10.1016/j.annemergmed.2009.08.014.

Angus

Barnato

Bell

, et al. A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators. Intensive Care Med. 2015; 41(9): 1549-60. doi: 10.1007/s00134-015-3822-1.

Schorr

Dellinger

. The Surviving Sepsis Campaign: past, present and future. Trends Mol Med. 2014; 20(4): 192-4. doi: 10.1016/j.molmed.2014.02.001.

Barrier

. Summary of the 2016 International Surviving Sepsis Campaign: A Clinician’s Guide. Crit Care Nurs Clin North Am. 2018; 30(3): 311-21. doi: 10.1016/j.cnc.2018.04.001.

Non-invasive near-infrared hemoglobin spectroscopy for in vivo monitoring of tumor oxygenation and response to oxygen modifiers. BiOS’97, Part of Photonics West; 1997. International Society for Optics and Photonics.

Sircan-Kucuksayan

Uyuklu

Canpolat

. Diffuse reflectance spectroscopy for the measurement of tissue oxygen saturation. Physiol Meas. 2015; 36(12): 2461-9. doi: 10.1088/0967-3334/36/12/2461.

10.

Kagaya

Miyamoto

. A systematic review of near-infrared spectroscopy in flap monitoring: Current basic and clinical evidence and prospects. J Plast Reconstr Aesthet Surg. 2018; 71(2): 246-57. doi: 10.1016/j.bjps.2017.10.020.

11.

Colin

Nardi

Polito

, et al. Masseter tissue oxygen saturation predicts normal central venous oxygen saturation during early goal-directed therapy and predicts mortality in patients with severe sepsis. Crit Care Med. 2012; 40(2): 435-40. doi: 10.1097/CCM.0b013e3182329645.

12.

Ruan

Ren

, et al. Monitoring tissue blood oxygen saturation in the internal jugular venous area using near infrared spectroscopy. Genet Mol Res. 2015; 14(1): 2920-8. doi: 10.4238/2015.March.31.23.

13.

Samraj

Kerrigan

Mejia

, et al. Thenar Muscle Oxygen Saturation Levels: A Surrogate for Central Venous Oxygen Saturation? Clin Pediatr (Phila). 2019; 58(5): 528-33. doi: 10.1177/0009922819832094.

14.

Karakas

Sircan-Kucuksayan

Elpek

, et al. Investigating viability of intestine using spectroscopy: a pilot study. J Surg Res. 2014; 191(1): 91-8. doi: 10.1016/j.jss.2014.03.052.

15.

Yang

Zhang

, et al. Monitoring angiogenesis using a human compatible calibration for broadband near-infrared spectroscopy. BIOMEDO. 2013; 18(1): 016011-11. doi: 10.1117/1.JBO.18.1.016011.

16.

Cai

Zhang

, et al. Evaluation of near infrared spectroscopy in monitoring postoperative regional tissue oxygen saturation for fibular flaps. J Plast Reconstr Aesthet Surg. 2008; 61(3): 289-96. doi: 10.1016/j.bjps.2007.10.047.

17.

Villringer

Planck

Hock

, et al. Near infrared spectroscopy (NIRS): a new tool to study hemodynamic changes during activation of brain function in human adults. Neurosci Lett. 1993; 154(1-2): 101-4.

18.

Nardi

Polito

Aboab

, et al. StO(2) guided early resuscitation in subjects with severe sepsis or septic shock: a pilot randomised trial. J Clin Monit Comput. 2013; 27(3): 215-21. doi: 10.1007/s10877-013-9432-y.

19.

Mesquida

Masip

Gili

, et al. Thenar oxygen saturation measured by near infrared spectroscopy as a non-invasive predictor of low central venous oxygen saturation in septic patients. Intensive Care Med. 2009; 35(6): 1106-9. doi: 10.1007/s00134-009-1410-y.

20.

Colquhoun

Tucker-Schwartz

Durieux

, et al. Non-invasive estimation of jugular venous oxygen saturation: a comparison between near infrared spectroscopy and transcutaneous venous oximetry. J Clin Monit Comput. 2012; 26(2): 91-8. doi: 10.1007/s10877-012-9338-0.

21.

Chapman

Mythen

Webb

, et al. Report from the meeting: Gastrointestinal Tonometry: State of the Art. 22nd-23rd May 1998, London, UK. Intensive Care Med. 2000; 26(5): 613-22.

22.

Veenstra

Ince

Boerma

. Direct markers of organ perfusion to guide fluid therapy: when to start, when to stop. Best Pract Res Clin Anaesthesiol. 2014; 28(3): 217-26. doi: 10.1016/j.bpa.2014.06.002.

23.

Marik

Bankov

. Sublingual capnometry versus traditional markers of tissue oxygenation in critically ill patients. Crit Care Med. 2003; 31(3): 818-22. doi: 10.1097/01.CCM.0000054862.74829.EA.

24.

Bashkatov

Genina

Kochubey

, et al. Optical properties of human stomach mucosa in the spectral range from 400 to 2000 nm: prognosis for gastroenterology. Medical Laser Application. 2007; 22(2): 95-104.

25.

Zhang

Salo

Kim

, et al. Penetration depth of photons in biological tissues from hyperspectral imaging in shortwave infrared in transmission and reflection geometries. J Biomed Opt. 2016; 21(12): 126006. doi: 10.1117/1.JBO.21.12.126006.

Investigating spectroscopic measurement of sublingual veins and tissue to estimate central venous oxygen saturation

Abstract

BACKGROUND:

OBJECTIVE:

METHODS:

RESULTS:

CONCLUSION:

Keywords

1. Introduction

2. Material and methods

2.1 Study design and population

2.2 Public involvement

2.3 Spectroscopic system

2.6 Estimation of sublingual venous oxygen saturation

3. Results

Table 1 Demographic data of the study population

5. Conclusion

Data availability

Funding

Footnotes

Conflict of interest

References

Table 1
Demographic data of the study population