Pulse oximetry: fundamentals and technology update

Abstract

Oxygen saturation in the arterial blood (SaO2) provides information on the adequacy of respiratory function. SaO2 can be assessed noninvasively by pulse oximetry, which is based on photoplethysmographic pulses in two wavelengths, generally in the red and infrared regions. The calibration of the measured photoplethysmographic signals is performed empirically for each type of commercial pulse-oximeter sensor, utilizing in vitro measurement of SaO2 in extracted arterial blood by means of co-oximetry. Due to the discrepancy between the measurement of SaO2 by pulse oximetry and the invasive technique, the former is denoted as SpO2. Manufacturers of pulse oximeters generally claim an accuracy of 2%, evaluated by the standard deviation (SD) of the differences between SpO2 and SaO2, measured simultaneously in healthy subjects. However, an SD of 2% reflects an expected error of 4% (two SDs) or more in 5% of the examinations, which is in accordance with an error of 3%–4%, reported in clinical studies. This level of accuracy is sufficient for the detection of a significant decline in respiratory function in patients, and pulse oximetry has been accepted as a reliable technique for that purpose. The accuracy of SpO2 measurement is insufficient in several situations, such as critically ill patients receiving supplemental oxygen, and can be hazardous if it leads to elevated values of oxygen partial pressure in blood. In particular, preterm newborns are vulnerable to retinopathy of prematurity induced by high oxygen concentration in the blood. The low accuracy of SpO2 measurement in critically ill patients and newborns can be attributed to the empirical calibration process, which is performed on healthy volunteers. Other limitations of pulse oximetry include the presence of dyshemoglobins, which has been addressed by multiwavelength pulse oximetry, as well as low perfusion and motion artifacts that are partially rectified by sophisticated algorithms and also by reflection pulse oximetry.

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http://dx.doi.org/10.2147/MDER.S47319
Pulse oximetry: fundamentals and technology
update
Meir Nitzan1
Ayal Romem2
Robert Koppel3
1Department of Physics/Electro-
Optics, Jerusalem College of
Technology, Jerusalem, Israel;
2Pulmonary Institute, Shaare Zedek
Medical Center, Jerusalem, Israel;
3Neonatal/Perinatal Medicine, Cohen
Children’s Medical Center of New
York/North Shore-LIJ Health System,
New Hyde Park, NY, United States
Correspondence: Meir Nitzan
Department of Physics/Electro-Optics,
Jerusalem College of Technology,
21 Havaad Haleumi Street,
Givat Mordechai, PO Box 16031,
Jerusalem 91160, Israel
Tel +972 2 675 1139
Fax +972 2 675 1045
Email nitzan@jct.ac.il
Abstract: Oxygen saturation in the arterial blood (SaO2) provides information on the adequacy
of respiratory function. SaO2 can be assessed noninvasively by pulse oximetry, which is based on
photoplethysmographic pulses in two wavelengths, generally in the red and infrared regions. The
calibration of the measured photoplethysmographic signals is performed empirically for each type
of commercial pulse-oximeter sensor, utilizing in vitro measurement of SaO2 in extracted arterial
blood by means of co-oximetry. Due to the discrepancy between the measurement of SaO2 by
pulse oximetry and the invasive technique, the former is denoted as SpO2. Manufacturers of pulse
oximeters generally claim an accuracy of 2%, evaluated by the standard deviation (SD) of the dif-
ferences between SpO2 and SaO2, measured simultaneously in healthy subjects. However, an SD
of 2% reflects an expected error of 4% (two SDs) or more in 5% of the examinations, which is in
accordance with an error of 3%–4%, reported in clinical studies. This level of accuracy is sufficient
for the detection of a significant decline in respiratory function in patients, and pulse oximetry has
been accepted as a reliable technique for that purpose. The accuracy of SpO2 measurement is insuf-
ficient in several situations, such as critically ill patients receiving supplemental oxygen, and can be
hazardous if it leads to elevated values of oxygen partial pressure in blood. In particular, preterm
newborns are vulnerable to retinopathy of prematurity induced by high oxygen concentration in
the blood. The low accuracy of SpO2 measurement in critically ill patients and newborns can be
attributed to the empirical calibration process, which is performed on healthy volunteers. Other
limitations of pulse oximetry include the presence of dyshemoglobins, which has been addressed
by multiwavelength pulse oximetry, as well as low perfusion and motion artifacts that are partially
rectified by sophisticated algorithms and also by reflection pulse oximetry.
Keywords: oxygen saturation, pulse oximetry, photoplethysmography, arterial blood, venous
blood
Arterial oxygen saturation
The transfer of oxygen from the lungs to the tissue cells is carried out mainly by the
hemoglobin molecules in the red blood cells. The total oxygen content in blood includes
the hemoglobin-bound oxygen (97%–98% of the total oxygen content) and the oxygen
dissolved in plasma. The level of arterial hemoglobin oxygenation is assessed by oxygen
saturation in arterial blood (SaO2), which is the ratio of oxygenated hemoglobin con-
centration [HbO2] to total hemoglobin concentration in the blood ([HbO2] + [Hb]):
SaO2 = [HbO2]/([HbO2] + [Hb]). (1)
SaO2 has the same value throughout the arterial system, since oxygen is extracted
from the blood only in the capillaries. The concentration of dissolved oxygen in arterial
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blood is measured by arterial oxygen partial pressure (PaO2).
SaO2 increases as PaO2 increases in an S-shaped curve, the
dissociation curve, which depends on blood temperature,
acidity level, and the concentration of several substances in
the blood. Typical values of PaO2 for adults at sea level range
between 80 and 100 mmHg and those of SaO2 between 96%
and 98%. Because of the gradual slope of the upper part of the
dissociation curve, a change of PaO2 from 100 to 70 mmHg
under normal conditions only results in a decrease of SaO2
from 97% to 92%. With regard to venous blood, the normal
range of oxygen saturation is 70%–80%, and oxygen partial
pressure varies in the range of 40–50 mmHg.1,2
PaO2 and SaO2 have major clinical and physiological sig-
nificance, since they are dependent on the adequacy of respi-
ratory function and are directly related to the oxygen supply
to the organs. Both PaO2 and SaO2 can be obtained from a
sample of extracted arterial blood: PaO2 can be measured
with an arterial blood gas analyzer and SaO2 by co-oximetry,
which uses the different light absorption spectra for oxygen-
ated and deoxygenated hemoglobin. PaO2 and SaO2 can also
be measured noninvasively. The noninvasive transcutane-
ous PaO2 electrode has low accuracy and requires heating
of the skin to 43°C–44°C.3,4 The noninvasive technique of
pulse oximetry5–7 for the assessment of SaO2 is the subject
of the current review. After describing the fundamentals of
the technique, the review discusses the origins and the level
of inaccuracy in oxygen-saturation measurement by pulse
oximetry, as well as the clinical significance of the error in
SaO2 measurement, particularly in newborns.
Pulse oximetry – the technique
The optical techniques that have been developed for the
assessment of SaO2 are based on the different light-absorption
spectra for HbO2 and Hb. Figure 1 shows the extinction coef-
ficients – the specific absorption constants – of HbO2 and Hb
as a function of wavelength in the visible and near-infrared
regions. The extinction coefficient of each type of hemoglo-
bin is defined as the absorption constant of the hemoglobin
in a sample, divided by the hemoglobin concentration in the
sample. The hemoglobin in blood includes HbO2 of extinc-
tion coefficient εO and Hb of extinction coefficient εD, and the
total extinction coefficient in the arterial blood, ε, is related
to its SaO2 by:
ε = εO SaO2 + εD (1 – SaO2), (2)
so that light-absorption measurements can provide assess-
ment of SaO2.
200
100
1,000
10,000
100,000
1000,000
400
HbO2
Hb
600
Wavelength (nm)
Molar extinction coefficient (cm−1/M)
800 1,000
Figure 1 Absorption spectra of the oxygenated and deoxygenated hemoglobin
molecules.
Notes: In the red and the infrared regions, the absorption is relatively low and
allows accurate measurement of light transmission. Copyright © 1999. Prahl S.
Reproduced from Prahl S. Optical absorption of hemoglobin. 1999. Available from:
http://omlc.ogi.edu/spectra/hemoglobin/index.html. Accessed May 26, 2014.8
Abbreviations: HbO2, oxygenated hemoglobin; Hb, deoxygenated hemoglobin.
Time
Light transmission
DC
Systole
End diastole
AC
Figure 2 The photoplethysmography signal.
Note: DC denotes the pulse baseline and AC the pulse amplitude.
Hemoglobin is the main source for light absorption
in tissue in the red and near-infrared regions, but other
chromophores like melanin and myoglobin can also absorb
light in these regions. Venous blood, with less oxygenated
hemoglobin, also absorbs light in the same spectral region
as that of arterial blood. The need to isolate the contribution
of hemoglobin in arterial blood to total absorption has led
to the development of pulse oximetry.
Pulse oximetry for the assessment of SaO2 is based on
photoplethysmography (PPG), the measurement of light-
absorption increase due to the systolic increase in arterial
blood volume.5,6 The PPG signal is shown in Figure 2. Trans-
mitted light intensity decreases during systole, when blood
is ejected from the left ventricle into the vascular system,
thereby increasing the peripheral arterial blood volume.
The maximal and minimal values of the PPG pulse reflect

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Pulse-oximetry update
light irradiance transmitted through tissue when tissue blood
volume is minimal or maximal, respectively. The PPG ampli-
tude is related to the light absorption in the arterial blood
volume increase during systole.
The technique of pulse oximetry has been described
in several publications.6,9–11 PPG measurement in each
wavelength enables the assessment of the contribution
of arterial blood to the total absorption of light, assum-
ing that the PPG signal reflects changes in arterial blood
volume. The PPG-signal amplitude (generally denoted AC)
divided by its baseline (generally denoted DC) is related
to the maximal blood volume change during systole.12 In
order to measure SaO2, PPG curves in two wavelengths
are recorded, and SaO2 is derived from the ratio of ratios,
R, defined as:
RDC
AC DC
=(/)
(/)
AC 1
2
(3)
Direct determination of SaO2 from PPG measurements
in several wavelengths using the Beer–Lambert law is not
applicable, because light scattering in tissue and blood also
affects attenuation of light in tissue. Light scattering in blood
is due to the difference in the refractive index between red
blood cells and plasma, and light scattering in tissue is attrib-
uted to the difference in refractive index between cellular
organelles and cellular fluid, as well as between intracellular
and extracellular fluids.13,14 Scattering results in the escape
of light from tissue in various directions, and also increases
the path length of light in tissue, thereby increasing the prob-
ability for absorption in the blood. In order to determine the
value of SaO2 for blood in tissue from light-transmission
measurements, the contribution of light absorption to the
total attenuation must be isolated.
In commercial pulse oximeters, the two wavelengths are
chosen in the red and infrared regions, where the difference
in light absorption between the two wavelengths is relatively
large. However, the scattering constant and the optical path
length differ significantly between the red and infrared
wavelengths, and consequently the relationship between the
physiological parameter SaO2 and the measured parameter R
cannot be derived directly from physical and physiological
considerations of light absorption in HbO2 and Hb, based
on the Beer–Lambert law. The relationship between R and
SaO2 is determined experimentally for each type of commer-
cial pulse oximeter sensor by calibration:6,7 R is measured
in several healthy volunteers simultaneously with in vitro
measurement of SaO2 in extracted arterial blood by means of
co-oximetry. The formula relating R to SaO2 is determined
by proposing a mathematical relationship, such as:
SaOkk
kkR
R
2
12
34
=−
−
(4)
and obtaining the values of the constant ki for the specific
pulse oximeter by best-fit analysis of the measured para meters
in the calibration process.
Empirical calibration is based on the assumption that
the relationship between the measured parameter R and the
physiological parameter SaO2 is not influenced by intersub-
ject variability in the circulatory system. However, a change
in the optical path length, if not equivalent in the red and
infrared wavelengths, can change the relationship between
R and SaO2.15,16 If the red–infrared path-length ratio changes
between different subjects, in particular between the healthy
subjects on whose fingers the empirical calibration was
performed and the patients on whose fingers the clinical
examination was carried out, inaccuracy in SaO2 measure-
ment could be expected. The SaO2 value measured by pulse
oximetry is denoted as SpO2, and its deviations from the SaO2
value directly measured in extracted blood are discussed.
The accuracy of pulse oximetry
The accuracy of a pulse oximeter is evaluated by the differ-
ences between SpO2, the oxygen-saturation values measured
by the pulse oximeter, and SaO2, measured by co-oximetry
in extracted blood, the gold standard.17 Most manufacturers
of pulse oximeters claim an accuracy of 2%, which is the
standard deviation (SD) of the differences between SpO2
and SaO2. A standard deviation of 2% is associated with an
expected error of 4% (two SDs) or more among 5% of the
examinations (assuming that the distribution curve of the
differences between SpO2 and SaO2 has normal distribution,
the area under the curve at a distance greater than two SDs
from the mean is 5% of the total area). In clinical studies,
it was found that the accuracy for a single measurement of
SpO2 is 3%–4% and for monitoring SpO2 in a specific patient
2%–3%.17,18 Considering the fact that the relevant clinical
range of SaO2, including most sick patients, is 80%–100%,
an error of 3%–4% could be of major significance. Despite
this low accuracy, pulse oximetry enables the detection of an
abrupt drop of SpO2 by 3%–4% in patients during anesthesia
or in an intensive care unit. It is accepted that a significant
decrease in SpO2 value obtained by the available commercial
pulse oximeters is a reliable parameter for the detection of
significant deterioration in respiratory function.

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Nitzan et al
It should be known, however, that the accuracy of SpO2
measurement is not equivalent to that of invasive SaO2
measurement. In intensive care units, where inadequate
oxygen supply to vital organs may be particularly harm-
ful, maintaining a minimum SpO2 level of 94% or 96% in
mechanically ventilated patients has been proposed, in order
to ensure a minimal SaO2 value of 90%.19,20 In a study on
critically ill patients21 the correlation between spontaneous
changes in SpO2 and in SaO2 was found to be relatively low
(r=0.6, r2=0.37), leading the authors to conclude that changes
in SpO2 do not reliably predict equivalent changes in SaO2
in the critically ill.
As was explained earlier, inaccuracy in SpO2 measure-
ment in critically ill patients is to be expected, because the
empirical calibration of pulse oximeters is based on examina-
tions on healthy volunteers and is not necessarily applicable
to critically ill patients. The discrepancy between healthy
volunteers examined during the empirical calibration process
and patients is further accentuated in neonates.22 The devia-
tion of SpO2 from SaO2 is even greater at saturations below
70%–80%,11,23–26 because ethical restrictions prevent manufac-
turers from reducing SaO2 below 80% during the calibration
process. The inaccuracy associated with the co-oximetry itself
(upon which the calibration process is based) is an additional
contributing factor to the error in SpO2 measurement.17
The accuracy of SpO2 measurement can be of great sig-
nificance for critically ill patients undergoing oxygen therapy.
Lately, evidence has accumulated to support the need for pre-
cise control of arterial oxygenation in order to avoid hyperox-
emia and the ill effects of oxygen toxicity associated with it.27
The detection of hyperoxemia in these patients is especially
problematic, because the dissociation curve is almost flat in
the high SaO2 range, ie, greater than 95%, and thus relatively
small changes in SaO2 are associated with large changes in
PaO2. The limited ability of pulse oximetry to accurately deter-
mine the level of excess oxygenation is particularly important
for preterm newborns receiving supplemental oxygen, due to
their vulnerability to retinopathy of prematurity, induced by
high PaO2 in arterial blood. The significance of accurate SpO2
measurement was demonstrated in three studies – SUPPORT
(Surfactant, Positive Pressure, and Oxygenation Randomized
Trial), BOOST (Benefits Of Oxygen Saturation Targeting) II,
and COT (Canadian Oxygen Trial) – where 4,911 preterm
newborns receiving oxygen supplementation were random-
ized to either a low (85%–89%) or high (91%–95%) SpO2
value.28 Increased risk of mortality was noted in the first group,
while an increased incidence of retinopathy of prematurity was
found in the second group. The authors of the meta-analysis
of those studies28 recommended that SpO2 should be targeted
at 90%–95% in infants with gestational age ,28 weeks.
Some authors29–31 suggest that pulse oximetry should not be
the sole means for monitoring oxygenation in the neonatal
intensive care unit.
An additional source for inaccuracy in SpO2 measurement
in newborns is fetal hemoglobin, which can constitute 95%
of total hemoglobin and is slightly different from that of adult
hemoglobin. The maximal expected error due to fetal hemo-
globin in neonates was estimated by Mendelson and Kent32 to
be 3% (using theoretical simulations), and this error should be
added to other sources of inaccuracy in SpO2 measurement in
neonates. Experimental examinations showed a 4% effect of
fetal hemoglobin on neonatal pulse oximetry.33,34
Pulse oximetry for the detection
of congenital heart diseases in neonates
Pulse oximetry has also been proposed as a newborn-
screening test for the detection of critical congenital heart dis-
ease (CCHD), defined as CHD requiring surgery or catheter
intervention in the first year of life.35 This application of pulse
oximetry is distinctive, because it provides an assessment of
cardiac physiology, while the usual aim of SpO2 measurement
is the evaluation of respiratory function. Early detection of
neonates with ductal-dependent CCHD is important, because
their survival depends on the patency of the ductus arterio-
sus to ensure adequate pulmonary and systemic blood flow.
Since the majority of infants with CCHD have some degree
of hypoxemia during the newborn period,35 pulse oximetry
has been recommended as a screening test for the detec-
tion of neonatal CCHD before discharge, prior to the onset
of symptoms. Though postnatal echocardiography is well
established as the gold standard for diagnosing congenital
heart diseases, it has significant limitations as a screening
tool, mainly because of its cost and lack of availability of
trained personnel to perform the examinations.36
The effectiveness of pulse-oximetry screening has been
demonstrated in multiple international clinical trials. In a
study in the UK,36 more than 2 0,000 neonates were examined
in the right hand and either foot. Saturation of ,95% in either
limb or a difference of .2% between the limb readings was
taken as abnormal. In this study, pulse oximetry had a sen-
sitivity of 75% for critical cases and a specificity of 99.16%.
Similar criteria were suggested by the American Academy
of Pediatrics:37 saturation of $95% in either limb with a
difference of #3% between the upper and lower limbs was
taken as normal. In a systematic review and meta-analysis,38
the authors selected studies that assessed the accuracy of

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Pulse-oximetry update
pulse oximetry for the detection of CCHD in asymptomatic
newborns, and found high specificity (99.9%) with moderate
sensitivity (76.5%).
Limitations of pulse oximetry
and technological update
Dyshemoglobins and multiwavelength
pulse oximetry
Apart from HbO2 and Hb, adult blood may contain
dyshemoglobin: hemoglobin derivatives, which are not func-
tional because they are not able to reversibly bind oxygen
molecules at physiological levels of PaO2 in blood. The most
important dyshemoglobins are methemoglobin (MetHb) and
carboxyhemoglobin (COHb), which are commonly present in
low concentrations in normal subjects. Increased concentra-
tion of dyshemoglobin molecules in blood (such as in CO
poisoning) can reduce the effectiveness of tissue oxygenation.
Functional SaO2 is defined as the percentage of HbO2 relative
to the sum of HbO2 and Hb, while fractional SaO2 is defined
as the percentage of HbO2 relative to the total of four variants
of hemoglobin.39 At low concentrations of dyshemoglobins,
the distinction between these two parameters is of negligible
significance because of the small difference between them;
at high-enough levels, both functional and fractional readings
can be compromised.30,40 A change of COHb concentration by
1% changes the pulse-oximetry reading by about 1%.22
Conventional pulse oximeters that utilize two wave-
lengths of light for the assessment of oxygen saturation are
based on the assumption that HbO2 and Hb are the only
absorbers of light in these two wavelengths in the blood.
Since MetHb and COHb absorb light in the wavelengths
used in pulse oximetry,22,40 an error in SpO2 measurement
is expected in the presence of these dyshemoglobins. Some
manufacturers have developed pulse oximeters that use more
than two light wavelengths, thereby enabling estimation of
blood levels of COHb and MetHb (as well as total hemo-
globin concentration). The accuracy of these measurements
has been studied in healthy volunteers and among patients
with suspected CO poisoning in emergency departments.
Some studies showed accurate measurement of COHb and
MetHb,22,40–42 while others43,44 claim that pulse co-oximetry
cannot replace standard blood COHb measurement, though
it could be used as a first-line screening test.
Low perfusion and reection
pulse oximetry
In transmission pulse oximetry, light is detected after being
transmitted through an organ, and is therefore limited to
fingertips and earlobes. The blood flow to the fingertips and
earlobes is greater than what is required by tissue metabolism,
due to their role in heat transfer, and under normal conditions
their PPG pulses have a high signal-to-noise ratio. However,
these organs are under intensive regulation by the autonomic
nervous system, and in cases of low surrounding tempera-
ture or low cardiac output, their arteries are constricted in
order to reduce heat dissipation or to maintain sufficient
blood supply to the critical core organs: the heart, brain, and
kidneys. In such cases, the PPG signal decreases, reducing
pulse-oximeter accuracy. Reflection pulse oximetry, in which
the light sources and the photodetector are located on the
same surface of the skin, can be applied on any accessible
site, and is thus of advantage in low peripheral perfusion
conditions.45,46
The main site used for reflection pulse-oximetry mea-
surement is the forehead. Studies in which a forehead sensor
and a digit sensor were compared to SaO2 measurements by
co-oximetry showed conflicting results. In measurements
on well-perfused pediatric patients, the forehead sensor was
found to be as accurate as the digit sensor.47 Comparison of
forehead and digit sensors in critically ill surgical/trauma
patients at risk for decreased peripheral perfusion showed
lower bias between SpO2 and SaO2 for the forehead sensor,48
and similar results were found in patients with low cardiac
index.49 Contradictory results showing inferior accuracy of
reflective oximetry were found in a study on adults with
acute respiratory distress syndrome during a high positive
end-expiratory pressure recruitment maneuver.50
Some companies suggest reflection pulse oximeters for
the finger. The advantage of reflection finger-pulse oximeters
is their low power consumption, since the distance between
the light sources and the detector can be shortened, resulting
in lower light absorption. Reflection pulse oximeters were
also suggested in accessible internal structures, such as the
esophagus,11,51,52 pharynx, and trachea.53,54 Researchers claim
that measurements at these sites are more reliable in condi-
tions of low peripheral perfusion.
Low perfusion induced by vasoconstriction, which
results in a decreased PPG signal, is also associated with an
increase in SpO2 value.55–57 Local hyperthermia resulted in a
significant decrease in SpO2, while during local hypothermia
SpO2 increased.56 A similar effect was found following
administration of propofol/nitrous oxide anesthesia, leading
to alteration of peripheral vascular tone and concomitant
changes in skin temperature.55 The observed increase in SpO2
probably reflects decreased transmission of arterial pulsations
to venous blood in the finger,55 but it can also be speculated

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Nitzan et al
that the effect is related to the calibration process. Changes
in scattering parameters due to changes in microcirculation
can interfere with the relationship between the measured
parameter R and SaO2 (Equation 4), which was obtained in
healthy subjects under normal thermal conditions.
Calibration
In a former section we described the empirical calibration
required for the determination of the relationship between
R and SaO2, which should be determined experimentally for
each specific type of pulse-oximeter sensor: R and SaO2 in
extracted arterial blood are measured simultaneously in sev-
eral healthy persons, each with several values of SaO2. The
relationship between R and SaO2 (in the form of Equation 4)
is obtained by best-fit analysis of R and SaO2 values, mea-
sured in the calibration process. We hypothesized that the
calibration process, which is based on statistical grounds, is
responsible, at least partly, for the discrepancy between the
pulse-oximetry output, SpO2, and SaO2.
Several techniques have been proposed to obviate the
need for calibration. Reddy et al58 suggested a method based
on a mathematical model for the attenuation of light passing
through the soft tissue, bone, and blood of a finger. Based on
the model, SpO2 is derived from the amplitudes and slopes
of the PPG pulses in red and infrared and the extinction
coefficients for HbO2 and Hb. Examinations performed on
healthy volunteers and patients showed agreement with a
commercial pulse oximeter. Another calibration-free method
based on frequency-modulated near-infrared spectroscopy
(NIRS) was suggested.14,59 However, both techniques are
based on mathematical models that match tissue circulation
only in approximate terms.
As explained earlier, the relationship between R and
SaO2 cannot be derived by analyzing the PPG signals in two
wavelengths in red and infrared (using the Beer–Lambert law
and the different absorption spectra in HbO2 and Hb), because
of the difference in light scattering between wavelengths in
red and infrared. If the two wavelengths are close enough to
each other so that the difference between their path-lengths
can be neglected, it is possible to analytically derive the
relationship between the ratio R and SaO2:6,9,60
SaOR
R
dd
dd
2
12
02 2101
=−
−+−
εε
εε εε()()
(5)
where εo and εd are the extinction coefficient values for HbO2
and Hb, respectively. The indices 1 and 2 refer to the two
wavelengths. The form of Equation 5 is similar to that of
Equation 4, but the coefficients of R are known: the extinc-
tion coefficient values were measured in hemolyzed extracted
blood by several research groups.61–64
Equation 5 enables the derivation of SaO2 from the
measured parameter R and the values of the extinction
coefficients with no need for calibration. This was shown
by Nitzan et al,60 using two infrared light-emitting diodes
with emission spectra that peaked at wavelengths of 7 67 and
811 nm. The SaO2 values, using Equation 5, were in the range
of 90%–100%, while SpO2 values obtained by commercial
pulse oximeters (using red and infrared light and calibration)
were 96%–98%. Higher accuracy was achieved in another
study,65 in which the light-emitting diodes were replaced
by infrared laser diodes with narrow-emission spectra, and
the PPG pulses were analyzed by an improved technique.
The SpO2 values measured by the two infrared wavelengths
were in the range 9 5.3%–100.5%, and the difference between
them and a commercial pulse oximeter for each examinee was
2% or less. The results of these preliminary studies provided
proof of concept, but further development would be needed
to make the technique clinically practical.
A similar calibration-free method based on three
wavelengths in the infrared range was also suggested by the
same group.16 The use of three adjacent wavelengths obviates
the need for the assumption that the difference between the
path lengths of the two wavelengths can be neglected, but
the method has yet to be tested and validated.
Apart from being at an early stage of development,
based on analysis of the Beer–Lambert Law, calibration-
free techniques are not free of flaws. A common problem in
calibration-free techniques is the need for accurate values of
hemoglobin extinction coefficients in order to derive SaO2
from the PPG pulse parameters (such as R). The extinction
coefficients values for HbO2 and Hb can be found in the
literature61–64 for the wavelengths in the visible and infrared
regions, but the discrepancy between the different sources
is significant when aiming for accuracy of about 1%. This
subject was treated by Kim and Liu64 with respect to NIRS
measurements. It should be emphasized that a lack of accu-
rate values of hemoglobin extinction coefficients does not
affect the available technique of pulse oximetry, which is
based on calibration.
Motion-artifact reduction
and other technical achievements
Motion artifacts can reduce the reliability of SaO2 measure-
ment, and are mainly important in pediatric patients and for
monitoring during exercise and activities of daily living.

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Pulse-oximetry update
Several companies have developed techniques for the
elimination of motion artifacts in pulse oximeters, and
since the subject has been reviewed and discussed in sev-
eral articles,7,30,66,67 it is not discussed in this review. Motion
rejection is generally achieved using various algorithms for
differentiation between pure PPG signals and those contami-
nated by motion noise, but also through the introduction of
improved hardware. Advances in PPG-signal analysis that
are not related to pulse oximetry, such as the perfusion index
and PPG variability, are also beyond the scope of the current
review (see Cannesson and Talke).68
Venous blood oxygen saturation
Venous blood oxygen saturation (SvO2) has physiological
and clinical diagnostic significance, because a low SvO2 value
in a specific tissue combined with a normal SaO2 value indi-
cates reduced blood flow to that tissue, and the arteriovenous
oxygen–saturation difference (SaO2–SvO2) is related to the
balance of oxygen supply and demand in the tissue.
Similar to the measurement of SaO2, pulse oximetry
can also be used for the measurement of SvO2, utilizing
the difference in light-absorption spectra for HbO2 and Hb.
The isolation of light absorption in venous blood can be
achieved by measuring the change in light absorption (in two
wavelengths) following change in venous blood volume,
induced either spontaneously or manually. However, in
venous pulse oximetry, the scattering effect cannot be dealt
with by in vitro calibration as in arterial pulse oximetry.
While in vitro calibration can be performed in extracted
arterial blood, because oxygen saturation has the same value
in the whole arterial system, calibration by extracted venous
blood cannot be applied to SvO2 measurement, since blood
extracted from a specific large vein does not necessarily have
the same oxygen-saturation value as that of small veins in the
tissue site, where oximetry measurement is performed.16,60
Some researchers have utilized respiratory blood volume
changes, assuming that these changes are venous in origin.
SvO2 was derived from these changes based on previously
derived empirical calibration for SaO2. Walton et al69 used
an esophageal reflectance pulse-oximetry probe in cardiac
surgery patients undergoing positive pressure ventilation,
and Thiele et al70 used a reflectance pulse-oximetry probe
placed directly over three veins in volunteers. Both mea-
sured the absorbance curves of red and infrared light, and
extracted blood volume changes in respiratory frequency by
frequency-domain or time-domain analysis. Some algorithms
yielded saturations around 80%, which is within the venous
oxygen-saturation physiological range.
Another technique used for isolating the absorption effect
from the combined effects of absorption and scattering of
light during its pass through the tissue is NIRS, a noninvasive
optical technique for the determination of the concentrations
of Hb and HbO2 and oxygen saturation in tissue. NIRS is
based on the measurement of light transmission through the
tissue at several wavelengths and derivation of the absorp-
tion constant at those wavelengths. The elimination of the
scattering effects is done by means of several techniques,
such as time-resolved spectroscopy and frequency-domain
spectroscopy.13,14 In order to derive tissue oxygen saturation
by NIRS, these techniques are supported by a mathemati-
cal model, such as the semi-infinite homogeneous model.
Since the matching of the model to the examined tissue that
is generally heterogeneous is not perfect, the results show
significant errors when applied to measurements on living
tissue.13,71–73
In order to isolate venous blood from arterial blood, NIRS
was used together with venous occlusion by a pressure cuff74,75
or by hand.76,77 NIRS was also combined with measurements
of oscillatory blood volume changes induced by spontaneous
respiration78,79 or during mechanical ventilation,80 assuming
that the oscillatory components of blood volume changes at
the breathing rate are mostly of venous origin.
Venous occlusion by a pressure cuff to increase venous
blood volume was also used with measurements of light
transmission in two adjacent wavelengths60 for the assessment
of SvO2. The technique is based on the assumption of similar
path-length values for the two wavelengths, and is a modifica-
tion of the calibration-free pulse oximetry for the measure-
ment of SaO2 described in the section “Calibration”.
Conclusion
Pulse oximetry has been shown to be a useful noninvasive
tool for evaluation of the respiratory system since its intro-
duction about 30 years ago. Since that time, significant
technological advances in commercially available pulse
oximeters have been achieved, enabling better diagnosis and
monitoring of patients. The great success of pulse oximetry
masks the fact that it is still burdened by an inherent potential
error of 3%–4% in measurements carried out on critically ill
patients and preterm newborns. It seems that the inaccuracy
problem is inherent in the current technology, and significant
improvement in accuracy can be achieved only through a
fundamental modification of pulse oximetry. In the current
review, we hypothesized that at least partly, the low level of
accuracy in pulse oximetry can be attributed to the empirical
calibration that is essential for the execution of conventional

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Nitzan et al
pulse oximetry. It is possible that calibration-free pulse oxi-
metry can provide SaO2 measurements of higher accuracy,
but there is no evidence to support this at present.
Disclosure
The authors report no conflicts of interest in this work.
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