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IEEE Press, 2000.
PULSE OXIMETRY
YITZHAK MENDELSON
Worcester Polytechnic Institute
Worcester, MA
1. OXYGEN TRANSPORT IN BLOOD
Oxygen is vital to the function and survival of every cell in
the body so the viability of many tissues is critically de-
pendent on continuous delivery of an adequate oxygen
2924 PULSE OXIMETRY
supply. Without adequate oxygen supply, irreversible
cell damage can occur rapidly. Therefore, accurate mea-
surement of oxygen and other gases in blood can provide
valuable information concerning the efficiency of the
circulatory and respiratory system. Various diagnostic
measurements are available to assist the clinician in the
determination of patient oxygenation and to protect pa-
tients against life-threatening and often unpredictable
hypoxic conditions. These methods commonly assess pul-
monary gas exchange, the adequacy of alveolar ventila-
tion, blood gas transport, and tissue oxygenation.
Oxygen is transported in the blood in two distinct
states. Only about 2% of O2 carried in blood is physically
dissolved in the plasma because O2 is not soluble in water.
This quantity is proportional to the O2 tension or partial
pressure (pO2). The quantity of dissolved O2 in blood is
relatively small and is not sufficient to sustain normal
body activity. Therefore, to increase the oxygen-carrying
capacity of blood, under normal physiological conditions,
nearly 98% of the O2 transported in the arterial blood is
combined with hemoglobin (Hb), the respiratory pigment
present inside the red blood cells.
When Hb is combined with O2 in a reversible chemical
reaction, it is oxidized and forms oxyhemoglobin (HbO2).
Oxyhemoglobin saturation (SO2) represents the relative
concentration of HbO2 that is bound to oxygen in a given
quantity of blood, which is expressed as a percent of
the total concentration of reduced Hb and HbO2. This
quantity is commonly referred to as functional oxygen
saturation and is defined as
½HbO2 
Oxyhemoglobin Saturationð%Þ ¼  100:
½Hb þ ½HbO2 
After one molecule of Hb combines with one oxygen mole-
cule, the affinity of the Hb molecule to combine with more
oxygen molecules is greater and continues to increase as
more oxygen molecules are combined. This unique binding
property results in a sigmoid-shaped oxyhemoglobin disso-
ciation curve (ODC) that relates the pO2 and SO2 in blood.
2. CLINICAL MOTIVATION
Arterial pO2 and SO2, which are both good indicators to
assess the adequacy of O2 transport in blood, are related
by the ODC. However, each variable has a different phys-
iological meaning. Arterial pO2 determines the efficiency
of alveolar ventilation. On the other hand, arterial SO2,
which accounts for most O2 carried by the arterial blood, is
an important clinical parameter because it helps to assess
how well the arterial blood is oxygenated. It should be
kept in mind that pO2 or SO2 are both important in the
assessment of the patient’s oxygenation status. Although
it is possible to determine SO2 from pO2 or vice versa
based on the ODC, large errors may result unless the pH,
temperature, the partial pressure of CO2 (pCO2), and the
2,3-diphosphoglycerate (2,3-DPG) level in the blood are
also measured simultaneously. All of the above factors
play an important role in controlling the affinity of Hb for
O2 and thus can lead to considerable displacement of the
ODC. In clinical applications in which it is important to
detect fast-changing physiological conditions that may
lead to hypoxemia, it is preferred to measure arterial
SO2 directly rather than to measure pO2 and then calcu-
late SO2 based on the ODC. On the other hand, when
hyperoxia is a clinical concern, pO2 monitoring is more
appropriate than measurement of SO2.
Traditionally, blood oxygen levels have been measured
by invasive sampling, either through an indwelling arte-
rial catheter or by arterial puncture, and analyzed in a
clinical laboratory with a bench-top blood gas analyzer.
Central clinical ‘‘stat’’ laboratories can provide accurate
measurements of multiple respiratory and metabolic
variables from small blood samples. However, this prac-
tice presents significant drawbacks in critical care
medicine particularly because blood gas values may
change rapidly in certain clinical situations, particularly
in patients with unstable respiratory or cardiopulmonary
conditions, and the prolonged delay time between sample
acquisition and the receipt of laboratory results. In neo-
natal applications, for example, frequent blood sampling
can cause significant blood loss especially for very small
premature infants even if micro-blood samples are used
for analysis. Furthermore, blood gas values are available
only intermittently and, therefore, indicate the status
of the patient only at the time the blood samples were
drawn. The inevitable delay and lack of continuous infor-
mation can lead to potential diagnostic errors particularly
in critically ill patients in whom rapid, and often life-
threatening, cardiopulmonary changes can occur during
short periods of time.
The increasing cost of health care today makes the use
of noninvasive oxygen monitoring attractive because in-
stantaneous changes in blood oxygenation can be recog-
nized and adequately corrected for before irreversible
tissue damage occurs. Furthermore, continuous monitor-
ing also provides real-time trending information to assist
the clinician in assessing the response to therapeutic in-
terventions without the time, risk, and high cost associ-
ated with clinical laboratory analysis.
Noninvasive transcutaneous measurement of pO2 has
been available since the early 1970s (1). The principle is
based on O2 diffusion through the skin and the concept of
oxygen polarography using a Clark-type electrode. Be-
cause O2 diffusion through the stratum corneum is nor-
mally too low to obtain measurable pO2 at the skin
surface, the sensor contains a small heating element to
induce hyperemia and speed O2 diffusion through the
skin. Therefore, the position of the electrode must be
changed frequently to avoid skin burns. Additionally, be-
cause polarography is based on an electrochemical reac-
tion, before it is applied to the skin, the sensor must first
be calibrated in vitro with a known gas mixture.
The principal application of transcutaneous pO2 moni-
toring has been limited to newborn infants because of
the relatively thick layer of the epidermis at birth. In
adults, the greater skin thickness prevents accurate and
reproducible measurement of arterial pO2. Besides this dif-
ference and other practical concerns as noted above, trans-
cutaneous pO2 measurements are slower and more
complicated compared with pulse oximetry. For example,

10
Extinction coefficient
1 MetHb
0.1
HbCO
0.01
600 700 800 900
Wavelength (nm)
Figure 1. Optical absorption spectra of Hb, HbO2, MetHb, and
HbCO in the visible and near-infrared regions of the spectrum.
after a transcutaneous pO2 electrode is applied to the skin,
it takes about 5–10 minutes to establish a stable and accu-
rate reading. For these reasons, transcutaneous pO2 mea-
surements remained popular in neonatal applications until
the early 1980s when pulse oximetry was first introduced
into clinical practice. Soon after its introduction, the
popularity of pulse oximetry rose rapidly, whereas the pop-
ularity of transcutaneous pO2 monitoring has gradually
declined.
3. PRINCIPLE OF BLOOD OXIMETRY
3.1. Optical Spectra of Blood
The basic concept of oxygen saturation measurement (ox-
imetry) dates back to Robert Boyle who, in 1700, first ob-
served that blood can change its color when exposed to air.
Early methods that were developed to estimate the rela-
tive amount of O2 in blood are based on the observation
that the characteristic color of deoxygenated Hb is dark
red, whereas when Hb is chemically combined with O2 to
form HbO2 has a distinctly bright red color.
Optical oximetry relies on the significant difference in
the optical absorption of Hb and HbO2 in the visible part of
the spectrum, as illustrated in Fig. 1. Optical methods for
measuring SO2 are based on light absorption by blood at
two specific wavelengths: l1, where there is a large differ-
ence in light absorption between Hb and HbO2 (e.g.,
660 nm); and a second wavelength, l2, which can be an
isobestic wavelength (a wavelength at which the absorp-
tion of Hb and HbO2 are equal, e.g., 805 nm) or a different
wavelength in the near infrared region of the spectrum
between 880 and 940 nm, where the absorption of Hb is
slightly smaller compared with HbO2.
3.2. Calculation of Oxygen Saturation
The absorption of light at a specific wavelength by a ho-
mogeneous substance in a solution contained inside a par-
allel-wall optically transparent holder (optical cuvette)
can be accurately determined with the Beer–Lambert
law. Accordingly, the fraction of radiant energy absorbed
PULSE OXIMETRY 2925
by a substance can be related to its concentration using
the basic relationship
It ¼ Io  10
ecd ;
where It is the intensity of the transmitted light, Io is the
HbO2
intensity of the incident light, e is the extinction coefficient
(or molar absorptivity, which represent the fraction of
Hb light absorbed at a specific wavelength) of the sample,
c is the concentration of the sample, and d corresponds to
the light path length through the sample. This relation-
ship requires monochromatic (i.e., single wavelength) in-
cident light and collimated (i.e., parallel beams) light
1000 transmission through the sample. In other words, the
sample does not scatter any light. In addition, it is as-
sumed that the incident light intensity is equal to the sum
of the light intensities transmitted and absorbed by the
sample. It must be noted also that if the incident light is
scatters by the sample, the effective pathlength of the
transmitted light through the sample is increased, and
thus, the Beer–Lambert law is no longer valid.
Assuming for simplicity that a thoroughly mixed hem-
olyzed blood sample (i.e., blood in which the red blood cell
membrane has been ruptured and destroyed) consists of a
two-component homogeneous mixture composed of only Hb
and HbO2, the light absorption by this homogenous mixture
is equal to the sum of light absorption by Hb and HbO2.
Therefore, it is possible to derive two independent algebraic
equations to describe the absorption of the mixture using
two distinct wavelengths. This set of equations can be then
be solved simultaneously to find the concentration of each
component in the mixture. Using the two equations de-
scribed above, SO2 can be determined from the relationship
ODðl1 Þ
SO2 ¼ A
B ;
ODðl2 Þ
where A and B are functions of the specific extinction coef-
ficients of Hb and HbO2 and OD is defined as the optical
density [i.e., log10(Io/It)] of the substance. In other words,
SO2 can be determined by measuring the incident and
transmitted light intensities of a homogenous sample solu-
tion containing an unknown concentration of Hb and HbO2.
This concept is the underlying principle used by conven-
tional bench-top clinical CO-oximeters to measure SO2 and
other hemoglobin derivatives in blood.
4. HISTORY OF NONINVASIVE OXIMETRY
Since the early 1930s, considerable efforts have been made
to develop noninvasive optical techniques for accurate
measurements of arterial oxygen saturation (2). Matthes
(3,4) developed the first noninvasive oximeter using two
wavelengths of light. However, the need to compensate for
large changes in tissue thickness, unknown blood content,
and variations in skin color among different individuals
was recognized early on as a practical obstacle in achiev-
ing accurate calibration.
Early application of the Beer–Lambert law to noninva-
sive measurement of arterial SO2 began by Millikan et al. (5)
2926 PULSE OXIMETRY
and Wood and Geraci (6) during World War II because of the
need to monitor and protect pilots flying at high altitudes in
unpressurized cockpits from losing consciousness. This de-
vice essentially used the earlobe as an optical cuvette
containing blood. However, the ear tissue contains non-
hemolyzed whole blood, and hence, the transilluminated
light undergoes partial reflection and multiple scattering by
tissue and blood. Furthermore, besides arterial blood, the
ear lobe also contains venous blood and other nonblood sub-
stances that interact with the light. Consequently, initial
attempts to measure SO2 noninvasively required a zero-
point calibration by subtracting the light attenuated by the
bloodless tissue and skin from the total amount of light
transmitted through the ear. The zero-point calibration was
accomplished by compressing the ear using an ear probe
equipped with a transparent pressure capsule that was ini-
tially inflated to a pressure that exceeds the arterial blood
pressure, thus rendering the ear pinna almost bloodless.
After the initial baseline transmission of light through the
bloodless ear was measured, the pressure in the capsule was
released and a second measurement through the uncom-
pressed ear was taken. SO2 was then determined based on
the difference between these two readings. Although this
approach was the first significant step toward an accurate
and absolute noninvasive measurement of SO2, it was not
successful mainly because of poor reproducibility and the
complicated calibration process involved. The other techni-
cal challenge that contributed to significant errors was the
inability to distinguish between the light absorbed by arte-
rial and venous blood because oxygen saturation of venous
blood is lower than arterial blood and depends on local phys-
iological conditions.
The first widely used commercial ear oximeter, which
was considered the forerunner of pulse oximetry, was de-
veloped by the Hewlett-Packard (H-P) company in the
early 1970s (7). Briefly, a high-intensity tungsten lamp
was used to generate a broad spectrum of light. Eight
narrow-band optical interference filters were mounted on
a rotating wheel that intercepted the light path sequen-
tially to provide a source of monochromatic wavelength
selection. These filtered light beam pulses entered a fiber-
optic cable that carried it to the ear. A second fiber-optic
cable carried the light pulses transmitted across the ear-
lobe back to the instrument for detection and analysis. To
measure arterial SO2, the ear probe was positioned across
the ear pinna and a temperature-controlled heater within
the ear probe maintained the tissue at a temperature of
411C, which caused an increase in local blood flow through
the ear that essentially ‘‘arterializes’’ the blood.
The H-P ear oximeter measured arterial SO2 by com-
paring the intensity of light transmitted through the ear
at eight selective wavelengths within the 650–1050 nm
spectral region. These wavelengths were selected because
the light in this spectral range is least attenuated by tis-
sues. Wavelengths outside of this range are heavily ab-
sorbed either by blood or by water. The design of the
H-P ear oximeter assumed that the ear pinna acts as a
fixed path length optical cuvette. The method then as-
sumed that a homogenous mixture of eight independent
light absorbers can adequately represent the bulk optical
properties of the ear pinna, including variations in tissue
thickness and skin pigmentation. Thus, to determine ar-
terial SO2, a computer inside the oximeter had to solve
eight algebraic equations simultaneously. These equa-
tions, which were originally derived based on Beer–Lam-
bert law, are similar to the relationship describing the
optical absorption of a two-component mixture. However,
because the exact optical extinction coefficients of the dif-
ferent light absorbers in the tissue including light scat-
tering by the ear pinna were unknown, a brute force
approach was taken by empirically deriving a set of char-
acteristic extinction coefficients based on data obtained
from human volunteers.
Although the H-P ear oximeter became popular within
pulmonary medicine, its major disadvantages were the
need to heat the skin to arterialize the blood, the heavy
weight of the fiber-optic cable, and the large size of the ear
probe (approximately 10  10 cm), which limited the ap-
plication of this oximeter to adult patients. Manufacturing
of the H-P ear oximeter, which was the prominent fore-
runner to the pulse oximeter, stopped in the early 1980s.
5. THEORY OF PULSE OXIMETRY
Noninvasive monitoring of arterial oxygen saturation by
pulse oximetry (SpO2) was first adopted by anesthesiolo-
gists in the early 1980s in an effort to optimize patient
safety. The goal of this technology was to identify as early
as possible unrecognized episodes of hypoxemia (insuffi-
cient blood oxygenation) that often resulted in irreversible
tissue damage and costly malpractice insurance claims.
During the past decade, pulse oximetry has become a rap-
idly growing practice in many fields of clinical medicine,
including subacute and long-term care. Whether used as a
safety guard or as a diagnostic tool, this new modality is
widely acknowledged to be one of the most important
technological advances in patient monitoring. The most
important advantage of pulse oximetry is the capability to
provide continuous, safe, and cost-effective monitoring of
blood oxygenation noninvasively at the patient bedside. It
is particularly useful when a patient is unstable and sub-
ject to rapid or unpredictable oxygen desaturation. Pulse
oximeters are easy to use, require no user calibration, and
provide virtually maintenance-free operation.
The history and principle of pulse oximetry has been
reviewed extensively in several books and manuscripts
(8–15). This breakthrough idea came about in the 1970s
when Takuo Aoyagi was researching how to measure car-
diac output noninvasively based on a dye dilution washout
curve using light transmission through the ear based on
Wood and Geraci’s method (16–18). While performing ex-
periments on animals, he noted that arterial pulsations
caused fluctuations in light transmission that interfered
with measurements of changes in dye concentration over
time. These arterial pulsations made it difficult to achieve
accurate cardiac output measurements. Realizing that the
minute pulsations (i.e., modulation) in the transmitted
light are sensitive to SO2, and therefore can neatly cir-
cumvent many problems of earlier nonpulsatile oximetry,
Aoyagi’s discovery quickly spurred the commercialization
of the first clinically useful noninvasive pulse oximeter.

Arterial pulse
Residual arterial
blood
Light absorption
Venous blood
Bloodless tissue
Time
Figure 2. Variations in light attenuation by tissue illustrating
the rhythmic effect of arterial pulsation. The arterial pulse cor-
responds to the AC component of the PPG waveform. The DC
component corresponds to the total absorption by the residual
arterial blood present in the vascular bed during diastole, the ve-
nous blood and bloodless tissue components.
Pulse oximetry exploits the time-variant photo-
plethysmographic (PPG) signal that is produced by
changes in arterial blood volume and changes in the ori-
entations of red blood cell associated with cardiac contrac-
tion and relaxation, as illustrated in Fig. 2. The technique
also assumes that venous blood does not pulsate and that
the amplitude of the arterial PPG pulse measured around
660 nm is sensitive to changes in arterial SO2. Taking
these assumptions into consideration, SpO2 can be derived
by analyzing only the changes in the amplitude of the
pulsatile red and infrared PPGs measured in the visible
and near-infrared region of the spectrum.
The unique advantage of this PPG-based noninvasive
approach is that only two wavelengths are required to de-
termine SpO2, which greatly simplifies the configuration
of the optical sensor. Furthermore, the pulsatile portion of
the PPG signal, which is related to the inflow of arterial
blood into the cutaneous vascular tissue, is used to sepa-
rate the arterial blood from all other absorbing substances
present in the illuminating path. Thus, light absorbed by
the skin, which depends on skin color and the composition
of subcutaneous tissues, as well as on the optical absorp-
tion by venous blood, remains constant during the cardiac
cycle and therefore can be ignored. Additionally, rendering
the tissue bloodless during the calibration process and the
need to heat the tissue to ‘‘arterialize’’ the blood, which
were essential in earlier models of nonpulsatile oximeters,
are no longer necessary.
Practically, tissue absorption can vary widely between
individuals and probe locations. Furthermore, transmit-
ted light intensities depend on detector sensitivity and
incident light intensities. Therefore, a normalization (i.e.,
scaling) process is commonly employed in which the pulsa-
tile (alternating current, or AC) component of the red and
infrared PPGs measured by a photodetector, which results
from the influx of arterial blood and expansion of the cu-
taneous vascular bed, is divided by the corresponding
PULSE OXIMETRY 2927
nonpulsatile (direct current, or DC) component of the
PPG that is characteristic of the background light ab-
sorbed by the tissue, the residual nonpulsatile arterial
blood present in the vascular bed during diastole, and ve-
nous blood. This effective scaling yields a normalized AC/
DC ratio for both the red and the infrared PPGs. The ratio
of these two normalized AC/DC ratios, which is largely
independent of the incident light intensity, is denoted by
R and is equal to
ACR =DCR
R¼ ;
ACIR =DCIR
where ACR is the pulsatile red component, ACIR is the
pulsatile infrared component, DCR is the nonpulsatile red
component, and DCIR is the nonpulsatile infrared compo-
nent of the corresponding PPGs. It is this adjusted R ratio
that the pulse oximeter uses to compute SpO2.
5.1. Calibration of Pulse Oximeters
Precalibration of a pulse oximeter by the manufacturer
must be performed empirically by calculating the ratios of
the normalized AC/DC signals obtained from the red and
infrared PPGs during a stepwise hypoxic study. The cal-
ibration data are normally acquired from 10–20 healthy
young adult volunteers breathing hypoxic gas mixtures to
induce hypoxemia. During the study, data measured by
the pulse oximeter are compared simultaneously with
SaO2 values obtained from an indwelling radial artery
catheter and analyzed in vitro by a standard multiwave-
length CO-oximeter. The data collected are later used to
determine specific calibration coefficients and create a
look-up table that is permanently programmed into the
oximeter for converting optical measurements to SpO2
values. This method of calibration can be lengthy and
costly, but it must be conducted by each pulse oximeter
manufacturer to gain U.S. Food and Drug Administration
(FDA) approval.
Because of this empirical calibration, different brands of
pulse oximeters may display different values depending on
the internal calibration of the oximeter. A typical calibra-
tion relationship between the normalized R ratio and the
arterial SpO2 is shown in Fig. 3. This calibration can be
described for example by the mathematical relationship (19)
k1 þ k2 R
SpO2 ¼ ;
k3 þ k4 R
or the data can be fitted by a polynomial relationship of the
form (9)
SpO2 ¼ AR2 þ BR þ C:
The values of the different coefficients in these equations
(k1–k4 and A, B, C) are determined by empirical calibration.
Note that at about 85% SpO2, the amount of light absorbed
by the Hb and HbO2 is relatively equal and, therefore, the
normalized amplitudes of the red and infrared signals are
equal (i.e., R ¼ 1:0). Because the optical properties of blood
are similar among different individuals, individual instru-
ment calibration is not required in the field.
2928 PULSE OXIMETRY
100
90
80
% Oxygen saturation
70
60
50
40
30
20
10
0 compact, and significantly less expensive design that elim-
0 1.0 2.0 3.0
Normalized R ratio
Figure 3. Empirical relationship between arterial oxygen satu-
ration and the normalized R ratio.
The decision of what should be considered a ‘‘safe’’ low-
level SO2 for calibrating pulse oximeters on healthy vol-
unteers remains controversial. Typically, most manufac-
turers perform in vivo calibrations by varying the inspired
O2 concentrations to yield arterial SO2 values between
70% and 100%. However, pulse oximeters are capable of
measuring SpO2 values lower than 70%. Occasionally,
even during clinical calibration studies designed to en-
sure that SO2 levels remain above 70%, a few arterial SO2
values can fall below 70%, although the number of data
points in this range is generally too small to be included in
the calibration data set. Therefore, manufacturers typi-
cally prefer to extrapolate the calibration curves to deter-
mine SpO2 values below 70%.
In general, the accuracy of most noninvasive pulse oxi-
meters is acceptable for a wide range of clinical applica-
tions. Under normal operating conditions, the accuracy of
pulse oximeters compared with a CO-oximeter is typically
within þ /
2–3% in the arterial SO2 range between 70%
and 100% (20–24). Below 70%, the accuracy normally de-
teriorates considerably.
5.2. Pulse Oximeter Sensors
The sensor of the original pulse oximeter as described by
Yoshiya et al. and manufactured by Minolta in Japan (18)
(a)
Figure 4. A typical disposable transmission-type finger sensor of
a pulse oximeter (a) taped to a subject’s finger (b).
was based on a bulky fiber-optic cable that was used as a
split optical guide to conduct light from a quartz halogen
lamp to the measurement site and to conduct the light
transmitted through the finger back to a photodetector
(PD). The light source and PD were both housed inside the
oximeter. Narrow optical band pass filters in combination
with a mechanical chopper were used to properly select
the red and infrared wavelengths and to synchronize the
detection of the transmitted light with the measurements
made by the PD.
An improved design of a noninvasive pulse oximeter
probe was introduced in the United States by BIOX and
Nellcor in the early 1980s based on a much simpler, more
4.0 5.0
inated the need for a fiber-optic cable and other bulky op-
tical components. It included readily available solid-state
components that also allowed manufacturers to signifi-
cantly reduce the overall size and weight of the probe. A
typical pulse oximeter probe comprises of a single highly
sensitive silicon PD and a pair of small, but bright, red and
infrared light emitting diodes (LEDs) mounted inside a
small and light-weight probe. Additionally, using LEDs
reduced significantly the amount of power consumption
and eliminated the amount of heat generated by the in-
candescent light source in previous designs.
Most manufacturers of pulse oximeters offer different
types of disposable and reusable sensors that are suitable
for neonatal, pediatrics, and adult applications. In trans-
mission-type sensors, the LEDs and PD are placed on op-
posite sides across a pulsating arterial bed. The most
popular sensor configurations are flexible bandage-type
disposable sensors (Fig. 4) or reusable finger clip-on type
probes (Fig. 5). Some manufacturers also offer earlobe clip
and nose-bridge type sensors.
In certain clinical situations in which transmission
sensors cannot be used, it is possible to use reflectance-
type sensors. The feasibility to use reflected light rather
than transillumination to measure SpO2 was first intro-
duced by Mendelson et al. in the early 1980s (25,26). Re-
flectance sensors use similar optical components as
transmission sensors except that the LEDs and PD are
mounted adjacent to one another, as illustrated in Fig. 6.
The most compelling reason for developing reflectance-
type sensors is the ability to measure SpO2 from alterna-
tive body locations such as the head. For instance, a re-
flectance sensor can be used in perinatology to monitor a
fetus during delivery. Forehead reflectance sensors have
also been advocated to guard against acute changes in
hypoxemia, particularly in patients with poor peripheral
circulation, because it can be manifested in the head more
rapidly than in the extremities (27–30). Clinical studies
(b)
Figure 5. A typical reusable transmittance-type pulse oximeter
probe.

Figure 6. A typical reflectance-type pulse oximeter probe.
found that the lag time to detect hypoxemia in the finger-
tips during peripheral vasoconstriction can be longer by
about 90 seconds compared with the forehead. These stud-
ies also confirmed that transmission sensors mounted on
the fingertip are the slowest to respond to changes in SpO2
because the fingertips are more affected by thermoregula-
tory vasoconstriction than the forehead.
Pulse oximeters store the unique calibration curves that
are used to convert optical readings to SpO2 values inside
the monitor. This approach can limit the manufacturer’s
ability to introduce new sensor designs that might require
different calibration choices. To overcome this limitation, a
new line of pulse oximeter probes (OxiMax) that includes a
digital memory chip was recently introduced by Nellcor
(31). The memory chip is imbedded within each sensor and
contains all calibration and operating characteristics for
that individual probe, which enables the monitor to oper-
ate accurately with a more diverse range of sensors.
Pulse oximetry is typically used in hospitals, although
several products and research efforts are focused on devel-
oping more portable and wearable pulse oximeters with
unique sensor configurations. Some efforts are also di-
rected toward the development of units that are more suit-
able for long-term ambulatory applications. Nonin Medical
(Plymouth, MN) managed to condense and integrate the
electronics of a pulse oximeter together with a transmis-
sion-type sensor into a unique finger clip probe, creating
the smallest self-contained finger pulse oximeter called the
Onyx. The Onyx pulse oximeter weighs only 2 ounces,
measures 1.3  1.3  2.2 inches, and is powered by two
AAA batteries providing continuous use for up to 18 hours.
Rhee et al. (32,33) developed a miniaturized wireless
pulse oximeter sensor worn by the subject as a finger base
ring. The isolated ring configuration separates the sensor
unit from the rest of the ring body that is much heavier
than the optical sensor unit alone. The separation is
achieved by using two concentric rings that are mechan-
ically decoupled. The inner ring contains a pair of red and
infrared LEDs and a PD configured as a reflectance mode
sensor, whereas the outer ring comprises the rest of the
pulse oximeter circuitry including a battery and a radio-
frequency transmitter. A thin and flexible cable connects
the two rings. Forces from mechanical contacts with the
outer ring are therefore isolated from the optical sensor.
This efficient double-ring design has the potential of min-
imizing the influence of external forces and therefore of
reducing the effects of motion artifacts.
The design of a reflectance-mode pulse oximeter de-
pends on the ability to fabricate a sensor that has im-
proved sensitivity and can detect sufficiently strong PPGs
from various locations on the body combined with sophis-
ticated digital signal algorithms to process the relatively
weak and often noisy signals. Commercial pulse oximeter
PULSE OXIMETRY 2929
sensors employ a single PD element, typically with an ac-
tive area of about 12–15 mm2. Normally, a relatively small
PD chip is adequate for measuring strong transmission
PPGs because most of the light emitted from the LEDs is
diffused by the skin and subcutaneous tissues predomi-
nantly in a forward-scattering direction. However, in re-
flection mode, only a small fraction of the incident light is
backscattered by the tissues. Additionally, the backscat-
tered light intensity reaching the skin surface is normally
distributed over an area larger than 15 mm2. Typically,
the backscattered light is spread concentrically around
the LEDs, but its intensity is inversely proportional to the
square distance from the location of the LEDs.
To improve the signal-to-noise ratio (SNR) and reliabil-
ity of reflection pulse oximeters, several sensor geometries
have been described based on a radial arrangement of a
larger area PD or multiple LEDs. For example, Mendelson
et al. (34–36) and Konig et al. (37) designed a reflectance
sensor prototype consisting of multiple discrete PDs or a
single annular-shaped PD mounted symmetrically around
a pair of red and infrared LEDs. Takatani et al. (38,39)
described a different sensor configuration to increase
the amount of incident light based on ten LEDs that
were arranged symmetrically around a single PD chip.
5.3. Sensor Attachment
Several locations on the body, such as the fingertips and
earlobes, are suitable for monitoring SpO2 with transmis-
sion sensors in adults. The most popular sites in adults are
the fingertips because these locations are convenient to
use and a good PPG signal can be quickly obtained. On
neonates and pediatric patients, the toes, ankles, or wrists
can be used as alternative monitoring sites. Because light
is highly scattered in tissues, other locations on the skin
that are not accessible to conventional transillumination,
such as the forehead or the temple region, can be moni-
tored using reflectance sensors. These sensors are typi-
cally attached to the skin using a double-sided adhesive
tape. A headband can be used to hold the reflectance sen-
sor in place and to minimize ambient light interferences.
5.4. Instrumentation
Hardware implementation of pulse oximeters varies
widely among different manufacturers. In general, a mi-
croprocessor is used to generate a sequence of digital time-
multiplexing pulses to synchronously drive the red and
infrared LEDs such that only one LED is turned on at a
time. Typically, this is accomplished by sequencing the red
and infrared LED on and off, which allows an interval
when both LEDs are turned off to detect changes in am-
bient background light. These digital switching pulses are
also used to demultiplex the red and infrared signals be-
cause light is detected by a single PD. Narrow-width
switching pulses also help to increase the peak illuminat-
ing intensity of the LEDs without the risk of exceeding the
maximum rated average power dissipation that can dam-
age the LEDs. Depending on the particular design, addi-
tional sample-and-hold circuits are sometimes used to
separate the composite signals measured by the PD into
two different analog channels corresponding to the red
2930 PULSE OXIMETRY
and infrared PPGs. The demultiplexed PPG signals can
then be amplified and high-pass filtered individually to
separate the AC and DC components of each PPG wave-
form before it is further digitized by an analog-to-digital
converter (ADC). In some pulse oximeters, the composite
PPG measured by the PD is digitized directly by an ADC,
which considerably simplifies the amount of preprocessing
hardware used, although this approach requires a higher
bit resolution ADC (typically 14–16 bits or more) to
achieve adequate SNR. Some manufacturers use auto-
matic gain control (AGC) either to adjust the light inten-
sity of each LED or to change the gain of the photodiode
amplification. This process is performed to ensure that the
AC and DC levels of the PPGs signals always remain
within a predetermined range. This feature is important
to maximize the amplitude of the analog signal before it is
digitized by the ADC and to compensate for variations in
skin color and tissue properties.
Besides SpO2, most pulse oximeters also provide sev-
eral other displays. Most pulse oximeters, other than
handheld devices typically used for spot-checking, com-
monly include analog or digital bar graph-type displays
in the form of a horizontally scrolling arterial waveform
resembling a blood pressure pulse, or a vertical moving
bar corresponding to the relative amplitude of the arterial
pulse (Fig. 7). These important features enable the clini-
cian to assess in real time the quality and reliability of the
measurement. For example, the amplitude, shape, and
stability of the arterial waveform can often be used as an
indication of motion artifacts or adequate perfusion con-
ditions when erratic SpO2 or HR values are displayed,
particularly in monitoring compromised patients. Simi-
larly, if the patient’s heart rate displayed by the pulse oxi-
meter differs considerably from the actual heart rate,
which often is available as an independent measurement
if the patient is also connected to an electrocardiogram
(ECG) monitor, the SpO2 values displayed by the pulse
oximeter should be questioned.
The software used in pulse oximeters typically per-
forms several important functions. Depending on the
hardware features implemented in a particular pulse oxi-
meter model, the software usually controls the sequencing
of the LEDs and may perform digital filtering to separate
Figure 7. The Nellcor Model N595 pulse oximeter (Courtesy of
Nellcor Puritan Bennett, Inc. Pleasanton, CA). (This figure is avail-
able in full color at http://www.mrw.interscience.wiley.com/ebe.)
the AC and DC components of the PPG waveforms. Addi-
tionally, dedicated software algorithms are commonly
employed to implement digital filtering, improve the
SNR by averaging multiple measurements for AGC, dis-
play different diagnostic or warning information to keep
the user informed, and implement various user-selected
SpO2 and HR alarm settings.
5.5. Signal Processing
There are no standard methods for processing the PPG
waveforms and improving the SNR in pulse oximetry. Sig-
nal processing algorithms used by manufacturers for com-
puting and relating the R ratios to SpO2 and for
measuring heart rate are proprietary information and
therefore protected by patent laws. Review of the patent
literature can reveal some signal processing algorithms
used by manufacturers. Typically, these algorithms range
from simple digital filtering and time-domain analysis
based on a weighted moving average technique to more
sophisticated frequency-domain processing, including
nonlinear filtering, autocorrelation, adaptive filtering,
and feature extractions, to name a few. Rusch et al. (40)
compared several digital signal processing algorithms
based on frequency-domain analysis and found that
computation of SpO2 by fast fourier transform (FFT) or
discrete cosine transform were as accurate as weighted
moving average algorithms.
Because pulse oximeters use the pulsatile signal of the
PPG, several time-domain approaches can be used to de-
rive the R ratios and compute the patient’s HR. Addition-
ally, the response time of a pulse oximeter depends on the
number of data points averaged before the readings are
displayed. Some methods use the peak-to-trough ampli-
tudes of the pulsatile red and infrared components to de-
termine the AC components at each wavelength. However,
this simplified approach has a deleterious effect on the
time response of the pulse oximeter to acute changes in
SpO2 because the readings depend on the patient’s heart
rate, and more importantly, new raw signals are available
for averaging only once every heart beat. An improved
approach is based on averaging many incremental
changes along the steep slope of the PPG pulse. This ap-
proach results in many more data points between succes-
sive heart beats and, consequently, leads to a shorter
instrument response time. In addition, averaging more
data points improves the accuracy and stability of the
values displayed. Because the AC component of each PPG
signal is a bipolar waveform, in the time domain, it is rel-
atively simple to measure the duration of each heart beat
using a simple zero-crossing algorithm.
An alternative approach for processing the PPG signals
is based on a frequency-domain approach. Accordingly, the
composite red and infrared PPG signals (before the DC
and AC components are separated) are first processed by
an FFT algorithm. The FFT spectra for each PPG signal
are then processed by a separate algorithm to identify
the amplitude and frequency of the dominant peaks. Typ-
ically, the amplitude of the zero-frequency peak corre-
sponds to the value of the DC component. Likewise, the
amplitude of the highest spectral peak residing between

1 and 3 Hz (i.e., 60 to 180 beats per minute), which coin-
cides with the subject’s HR, corresponds to the amplitude
of the AC component.
Several methods are typically employed to improve the
accuracy of pulse oximeters, especially in clinical situa-
tions involving motion artifacts. The primary motivation
is the reduction in the occurrence of false alarms. The most
common method to reduce the effect of motion artifacts is
by digital signal processing and averaging of consecutive
measurements over a fixed number of seconds before the
final reading is displayed. However, this approach can
slow the response time of the pulse oximeter to alert cli-
nicians when abrupt changes in hypoxemia occur. There-
fore, many brands permit the user to select the averaging
time depending on the user needs.
Some manufacturers used the R-wave of the patient’s
ECG to synchronize with the optical measurements,
which thereby improved the detection of noisy pulsatile
signals by enhancing the SNR using multiple time-aver-
aged signals (41,42). The disadvantage of this approach is
that it relies on the availability of a separate ECG monitor.
Other techniques use a priori assumptions about specific
feature recognition in a typical PPG waveform and simply
suppress the readings when excessive motion artifacts
corrupt the basic template features of the detected
PPGs. However, because even small artifacts can severely
distort the temporal features of the PPG, this approach
tends to discard potentially useful data, and timeouts
are common.
In 1989, the Masimo Corporation introduced a different
signal extraction technology based on an adaptive filtering
approach (43,44). This approach, which is used to improve
the SNR in signals corrupted with overlapping frequency
noise bands, recognizes that during patient motion, in ad-
dition to a noisy arterial pulse, the venous blood compo-
nent is also susceptible to perturbations caused by
dynamic redistribution attributed to gravity or external
pressure and therefore represents a significant source of
interdependent noise. Because a pulse oximeter assumes
that the AC component of the PPG is caused by arterial
pulsation, venous perturbations during movement can
cause significant errors and lead to false alarms. The
method attempts to estimate the magnitude of this noise
and cancel its contribution from the PPG during patient
movement by an adaptive noise cancellation approach.
The Masimo approach, which is based on a proprietary
statistical signal processing algorithm termed Discrete
Saturation Transform (DST), builds a reference signal
from the incoming red and infrared PPGs for each
percent of SpO2 value. This reference is passed through
the adaptive filter to cancel the correlated frequencies be-
tween the reference and the corrupted PPG signal.
Additional signal processing methods to improve the
performance of pulse oximeters by reducing the sensitivity
to motion artifacts are being developed by the manufac-
turers and independent investigators. Hayes and Smith
(45,46) proposed that a nonlinear PPG artifact reduction
method can be used to significantly reduce the effect of
changes in the probe coupling, with an electronic process-
ing algorithm based on inversion of a physical artifact
model. Deterministic removal of the modeled artifact is
PULSE OXIMETRY 2931
achieved with an additional (i.e., third) measurement
channel with an illuminating wavelength that exhibits
contrasting anatomical absorption characteristics. Co-
etzee and Elghazzawi (47) described a different noise re-
duction algorithm that first detects relatively clean PPG
sections from which the HR is estimated. Then, the HR
value is used to construct a synthetic reference signal that
matches an idealized pulse signal. An adaptive filter con-
tinuously processes the sensor signals, reconstructing sig-
nals in a linear subspace defined by the reference signal. A
projective subspace algorithm is then applied to find SpO2.
6. PERFORMANCE LIMITATIONS OF PULSE OXIMETRY
Certain clinical situations and confounding factors can in-
terfere with the proper acquisition of reliable data and
the interpretation of pulse oximeter readings. The most
common cause of interruptions in the continuous readings
of a pulse oximeter (called ‘‘dropouts’’) seems to be from
motion artifacts and low peripheral blood perfusion. Cli-
nicians must understand these shortcomings so that er-
roneous readings can be properly identified.
6.1. Low Peripheral Vascular Perfusion
Because pulse oximeters rely on adequate arterial pulsa-
tion, significant reduction in peripheral vascular pulsa-
tion, most notably from systemic hypotension, local
vasoconstriction, hypothermia, hypovolemia, and during
cardiopulmonary bypass, can produce a signal too small to
be processed reliably by a pulse oximeter (48–51). In cer-
tain situations, locally applied vasodilating agents or gen-
tle warming of the skin by covering the sensor with a cloth
can be used to enhance the pulsatile signal. In general,
however, pulse oximeters become more susceptible to
motion artifacts under conditions of low peripheral perfu-
sion. When the oximeter cannot detect adequate pulsatile
signals, a ‘‘low perfusion’’ or similar type of diagnostic
message is usually displayed by the oximeter to alert the
user of possible peripheral blood perfusion problems.
6.2. Motion Artifacts
Pulse oximeters must detect a pulsatile signal that is nor-
mally a very small fraction (typically about 1–3%) of the
nonpulsatile component in the PPG. Therefore, any tran-
sient motion of the sensor relative to the skin that is usu-
ally accompanied by changes in the optical coupling
between the probe and the illuminated tissue can cause
significant artifacts. Because these transient artifacts can
sometimes mimic a normal heart beat, erroneous readings
may be displayed if the instrument cannot differentiate
between pulsations that are from motion artifacts and
normal arterial pulsations.
Pulse oximeters were originally used by anesthesiolo-
gists in the operating room on motionless patients. Soon
after, this technology was adopted for use in the intensive
care unit and general wards, where patients can be free to
move around or may become restless. In these circum-
stances, the tolerance of pulse oximeters to motion arti-
facts emerged as one of the most challenging technical
2932 PULSE OXIMETRY
problems to solve. In fact, motion artifacts have been cited
by clinicians as the most common cause of false alarms,
loss of signal, and inaccurate readings in a pulse oximeter.
The high frequency of false alarms associated with motion
artifacts often leads to unsettling tendencies among clini-
cians, especially in a busy hospital ward, to ignore or even
turn off pulse oximeter alarms and thereby compromise
patient safety.
Motion artifacts, such as during shivering or seizure
activity, are usually recognized by false or erratic heart
rate displays or by distorted PPG waveforms. Several clin-
ical studies compared how different brands of pulse oxi-
meters respond to motion artifacts under various
conditions (52–54). It is important to keep in mind, how-
ever, that the interpretations of clinical comparison stud-
ies to evaluate the performance of different pulse
oximeters can depend on the pulse oximeter model used
and the particular revision of the software algorithms.
6.3. Venous Pulsations
Another potential problem with pulse oximeter measure-
ments are artifacts induced by venous pulsations.
As the veins become engorged with blood, the venous
blood pulsates at the same frequency as the arterial blood.
Because pulse oximeters rely on the presence of a pulsatile
signal, and SO2 of venous blood is lower than arterial
blood, some pulsatile red component in the PPG signal
may actually contain venous blood of lower SO2 mixed
with the higher SO2 normally present in the arterial
blood. Therefore, increased venous pulsations interfere
with the measurements, which results in artificially low
SpO2 readings.
Sometimes, if sensors are applied too snugly in an at-
tempt to reduce motion artifacts, they can lead to venous
pulsation and even necrosis. Other situations leading to
venous pulsations may be attributed, for example, to right
heart failure, tricuspid regurgitation, high airway pres-
sures, VALSALVA maneuvers, and changes in body posi-
tion such as during certain surgical procedures when the
patient is placed in a Trendelenberg position (upper body
and head tilted downward by 30–40 degrees) causing ve-
nous blood pooling in the head.
6.4. Effect of Fetal Hb
At birth, fetal hemoglobin constitutes 60% to 95% of the
total Hb in blood of both preterm and term newborns.
Therefore, one of the concerns clinicians may have relates
to the interpretation of pulse oximeter readings in new-
borns because pulse oximeters are calibrated on adult pa-
tients. However, several studies have shown that the
difference in the optical absorption of adult and fetal Hb
is insignificantly small to affect the clinical accuracy of
pulse oximetry (19,55,56).
6.5. Interference from Electrosurgical Units (ESUs) and
Ambient Light
The energy produced by incandescent and quartz-halogen
light sources has spectral components in the visible and
near-infrared wavelength regions, which also overlap with
the wavelengths common in pulse oximetry. Several re-
ports suggest that the readings of pulse oximeters may be
affected by high-frequency radio interference from ESUs
and direct exposure to high-intensity light sources such as
infrared, xenon, and fluorescent lamps (57–59), although a
controlled study conducted by Fluck et al. (60) concluded
that the effect of ambient light on the accuracy of pulse
oximeters is statistically and clinically insignificant. Some
manufacturers of pulse oximeters try to minimize the ef-
fect of stray light by taking intermittent optical back-
ground readings when the LEDs in the sensor are turned
off and subtracting these readings from measurements
taken by the PD when the two LEDs are switched on. Ad-
ditionally, room light flickering from fluorescent lights can
be greatly reduced by sequencing the LEDs at a switching
frequency that is an integer multiple of the power line
frequency. Wrapping the sensor with an opaque material
can continue to reduce these light interferences.
6.6. Interpretation of Pulse Oximeter Readings
When comparing pulse oximeter readings to standard in
vitro CO-oximetry, which are widely used as a reference
for calibrating pulse oximeters, it is important to under-
stand the principal differences between these two mea-
surements. For example, some bench-top CO-oximeters
use four distinct wavelengths between 500 and 600 nm to
measure total Hb, HbO2, HbCO, and methemoglobinemia
(MetHb) in a given sample of blood. Hence, the value of
HbO2 reported by a CO-oximeter is commonly referred to
as fractional oxyhemoglobin. Numerically, it is equal to
the concentration of HbO2 expressed as a percentage of
the total of all active and inactive forms of Hb with respect
to their O2 binding capability. Therefore, it is normally
defined using the relationship
½HbO2 
HbO2 ¼  100%:
½Hb þ ½HbO2  þ ½HbCO þ ½MetHb
In contrast to a CO-oximeter, pulse oximeters perform op-
tical measurements using only two wavelengths. Conse-
quently, a pulse oximeter cannot distinguish between the
relative concentrations of each type of Hb derivative pres-
ent in the blood because it is calibrated to display func-
tional oxyhemoglobin saturation as defined above.
The presence of significant amounts of dysfunctional
hemoglobins (i.e., hemoglobin derivatives that are not ca-
pable of reversibly binding with O2), such as HbCO and
MetHb, can confuse the interpretation of the readings by a
pulse oximeter. Therefore, clinicians must recognize the
above-mentioned differences in interpreting pulse oxi-
meter readings.
As noted in Fig. 1, in the red region around 660 nm, Hb
and MetHb have similar extinction coefficients, whereas
in the near-infrared region, MetHb absorbs considerable
more light compared with Hb and HbO2. MetHb is formed
when the iron in Hb is oxidized from the ferrous (Fe þ þ ) to
the ferric (Fe þ þ þ ) state. Normally, MetHb is present in
the blood in relatively low concentrations (o1%), and thus
its effect on a pulse oximeter is virtually insignificant.
However, clinical studies have shown that MetHb levels

may be high congenitally or various medications, most
notably sulfa and sodium nitroprusside, can increase in
the amount of MetHb in the blood and produce erroneous
low readings by a pulse oximeter (61). This effect is pre-
dictable from the optical absorption property of MetHb
shown in Fig. 1 because an increase in the concentration of
MetHb tends to drive the R ratio toward unity and a cor-
responding SpO2 value of 85%.
HbCO, which is a normal product of Hb catabolism in
the body and is formed when carbon monoxide (CO) com-
bines with Hb, readily competes with Hb for O2 binding
sites. The quantity of HbCO in the blood of nonsmoking
subjects is typically below 2%, although it can be higher
depending on local environmental conditions. In smokers
(or smoke inhalation victims), however, the level of HbCO
may rise above 10%. As shown in Fig. 1, the absorption of
HbCO in the near-infrared region is very small, and for
wavelengths greater than 920 nm, it is practically negli-
gible. On the contrary, the optical absorption of HbCO in
the red region of the spectrum is similar to HbO2, which
gives the blood a ‘‘cherry red’’ color. Thus, as expected from
Fig. 1, a two-wavelength pulse oximeter interprets HbCO
as HbO2. Clinical studies confirmed that elevated levels of
HbCO lead to a falsely high SpO2 readings (62–64).
Because pulse oximetry is based on the principle of
light absorption, nail polish or radiographic dyes intro-
duced into the blood stream intravenously can adversely
affect the readings of a pulse oximeter. For example, meth-
ylene blue, which is commonly used as an antidote in the
treatment of an elevated level of MetHb, has a high ab-
sorbance peak around 670 nm, and this wavelength closely
coincides with the 660 nm wavelength used in pulse oxi-
metry. Clinical studies found that methylene blue can
cause spuriously low SpO2 readings (65–67).
7. CLINICAL APPLICATIONS
Since the invention of pulse oximetry in the mid-1970s,
the technology has rapidly spread and became an invalu-
able monitoring tool in many clinical settings. Monitoring
O2 concentration in the inspired air has long been a stan-
dard procedure to confirm that hypoxic gas concentrations
are not delivered inadvertently to the patient during an-
esthesia well before pulse oximeters became available.
Shortly after pulse oximetry was introduced, in 1986, it
was recommended as a standard of care for basic intraop-
erative monitoring by the American Society of Anesthesi-
ologists (68). In 1988, the Society for Critical Care
Medicine adopted a similar recommendation that pulse
oximetry be used to monitor patients undergoing oxygen
therapy. Continuous monitoring of pulse oximetry is now a
de facto standard of care for virtually all cases that require
intensive or critical care management.
The popularity of pulse oximetry stems from the prem-
ise that pulse oximetry is capable of early detection of
changes in a patient’s condition, which therefore allows
rapid intervention that could prevent adverse conse-
quences. To date, pulse oximetry has been widely used in
various clinical applications including surgery, critical
care, hypoxemia screening, and exercise; during patient
PULSE OXIMETRY 2933
transport from the operating room to the recovery room; in
emergency medicine; and more recently in ambulatory
applications (69–88).
7.1. Neonatal and Pediatric Pulse Oximetry
Hyperoxia in premature neonates is associated with an
increased risk of developing retinopathy of prematurity or
chronic lung disease because the oxyhemoglobin dissocia-
tion curve is flattened at oxygen saturation values above
90%, and errors of only a few percent in SpO2 measure-
ments could easily represent a large and significant error
in estimating the oxygen tension value. Therefore, sup-
plemental oxygen delivery to premature infants must be
closely controlled to obtain optimal tissue oxygenation
while minimizing potential serious side effects associated
with hyper- or hypoxemia.
Although several studies demonstrated that the infor-
mation obtained from a pulse oximeter can be used as a
feedback signal in a closed-loop controller algorithm to
automatically adjust the inspired oxygen fraction during
the administration of supplemental oxygen (89–92), the
main utility of pulse oximetry in neonatology remains the
prevention of hypoxia rather than hyperoxia.
Pulse oximetry has also been used as an apnea monitor
at home for infants and children at risk for sudden infant
death syndrome and to check the adequacy of supplemen-
tal oxygen therapy in patients with chronic obstructive
pulmonary disease. However, the expense and frequent
false alarms from motion artifacts have limited the wide
use of pulse oximeters for these specific applications.
7.2. Retinal Oximetry
Attempts to measure the oxygen saturation within the ret-
inal vasculature noninvasively dates back to the 1950s
(93). This interest was motivated by the idea that measur-
ing oxygen saturation in blood supplying the retinal arter-
ies can be used to infer how much oxygen is supplied to
cerebral tissues because the ophthalmic artery that sup-
plies oxygen to the retina is also a branch of the internal
carotid artery that supplies blood to the brain. A retinal
oximeter has also been suggested as a noninvasive tech-
nique that may be used to identify cerebral bleeding before
changes in vital signs and to provide a reliable index of
oxygen delivery during shock resuscitation of trauma vic-
tims. Additionally, measurement of retinal oxygen utiliza-
tion may provide clinical information about the metabolic
state of the retina. If the ocular blood flow and oxygen sat-
uration of the arterioles and venules in the retina are
known, the information can be used to diagnose and study
retinal metabolic function in different disease states such
as diabetic retinopathy and macular degeneration.
Retinal oximetry exploits the unique transparency of
the ocular media that enables reflectance measurements
from the retinal fundus by shining light through the pupil.
The incident light impinging on the retina interacts with
the blood, the vessel wall, and the pigmented epithelium
background. Consequently, some light reflected and back-
scattered from the retina does not interact with the
blood. In addition, the relationship between the different
components of the reflected light depends on path length,
2934 PULSE OXIMETRY
hematocrit, and blood flow. Moreover, the absolute amount
of light reflected from the retina is wavelength dependent
and can vary depending on the reflectance from surface
and deeper tissue components (94).
Numerous techniques have been employed to develop a
retinal oximeter with various degrees of success. Most
methods are based on digital images acquired at two
wavelengths (569 and 600 nm) (95), three wavelengths
(558, 569, and 586 nm) (96), and four wavelengths (488,
635, 670, and 830 nm) (97). de Kock et al. (98) developed
an in vitro system to simulate the retinal circulation and
ocular optics based on a dual-wavelength (660 and
940 nm) reflectance pulse oximeter and found that it can
detect changes in retinal SpO2 based on data from the in
vitro model. Despite these efforts, because there are mul-
tiple variables that affect the absolute intensity of the re-
flected light that is used to calculate oxygen saturation in
the retina, the method is used as a research tool, but a
clinical useful device that provides accurate reading with-
out the need for in vivo calibration is not yet available.
7.3. Esophageal Pulse Oximetry
Because transmission or reflection-type sensors that mea-
sure SpO2 from the skin rely on adequate peripheral per-
fusion at the measurement site, they can fail to provide
accurate readings in patients with compromised periph-
eral pulsatile circulation. Such clinical situations occur,
for example, in states of hypovolemia, hypothermia, or
vasoconstriction. Several studies investigated the alterna-
tive use of a reflectance-type sensor mounted inside a spe-
cially modified esophageal probe to monitor SpO2 from
core organs within the mediastinum in patients undergo-
ing prolonged cardiothoracic bypass surgery and in the
intensive care unit. The idea is based on the contention
that the use of a more central monitoring site such as the
esophagus increases the likelihood of obtaining more reli-
able measurements because it is a better perfused organ
than the extremities during periods of poor peripheral
perfusion (99–101).
7.4. Fetal Pulse Oximetry
Electronic fetal heart rate (FHR) monitoring is used rou-
tinely in labor as a standard for intrapartum assessment
of fetal well-being. Although it is considered to be a sen-
sitive technique and can identify a fetus with a normal
tracing as being uncompromised, the diagnostic value of
FHR monitoring as an indirect measure of fetal oxygen-
ation and acid-base balance is limited and is open for in-
terpretation. In clinical situations in which FHR tracing is
reassuring, the method has a predictive value of almost
99% on the well-being of the fetus. However, an abnormal
FHR has a positive predictive value of only 50% and there-
fore exhibits relatively poor specificity in detecting fetal
compromise (102).
Several approaches to fetal assessment have been de-
veloped with various degrees of success in an attempt to
resolve the lack of specificity associated with electronic
FHR monitoring as an indication of fetal distress during
labor. For example, blood sampling from the fetal scalp to
determine fetal blood pH has been employed to assist in
fetal assessment of acid–base balance and, thus indirectly,
the adequacy of oxygenation. However, fetal scalp sam-
pling has drawbacks because it is an invasive procedure,
requires operator’s skill, and provides information about
the fetal acid–base balance only at the time of sampling.
Therefore, this method has not been universally or rou-
tinely adopted by obstetricians.
The potential application of reflectance pulse oximetry
to fetal monitoring during labor has been demonstrated by
several groups since the early 1990s (103–105). The main
objective was to detect early signs of hypoxia and perform
trend monitoring in the fetus soon after the cervix is dilated
and the amniotic membranes are ruptured. This technology
is viewed as an adjunct to electronic FHR monitoring in the
presence of a nonreassuring fetal HR pattern to help ob-
stetricians determine whether the fetus is receiving enough
oxygen so that a Caesarian section can be avoided.
Several early designs of fetal pulse oximeters were
based on attempts to affix the sensor to the presenting
part of the fetus scalp. Different methods were proposed,
including tissue adhesive, vacuum cups, inflatable bal-
loons, and a spiral needle used in the attachment of a
scalp ECG electrode. However, these fixation methods
failed to achieve satisfactory results. Nellcor, Inc. has de-
veloped a unique fetal pulse oximeter probe that over-
comes this problem. The disposable probe contains the red
and infrared LEDs and the PD assembly for measuring the
fetal PPG signals and two contact electrodes to determine
through changes in impedance measurements if the optical
components are contacting the tissue. These components
are mounted inside a smooth and pliable housing with a
flexible curved tip acting as a fulcrum as shown in Fig. 8.
The sensor is attached to a handle with a removable stylet.
Because the sensor cannot be observed during application,
directional markings on the sensor’s handle are used to
orient the optical components toward the fetus face, and
depth markings aid the obstetrician in positioning the sen-
sor against the skin. The probe can be used only on fetuses
in vertex (head down position) presentation. It is inserted
transvaginally into the mother’s uterus once the maternal
membranes have ruptured. Normal uterine forces coupled
with the special design of the probe hold it in place against
the cheek or temple of the fetus for the duration of the la-
bor and delivery as illustrated in Fig. 9.
In addition to the problems associated with pulse ox-
imetry, as was previously discussed, fetal pulse oximetry
also poses unique and additional challenges. In particular,
sensor design and monitoring site are important factors
that can compromise its performance as a diagnostic tool
of fetal hypoxia and may lead to adverse outcomes. The
SNR in fetal SpO2 monitoring is significantly smaller com-
pared with conventional pulse oximetry, which is primar-
ily because of the smaller PPG amplitudes obtained from
the sensor application site. Additionally, motion artifact
during contractions caused by fetal and maternal move-
ments present significant technical challenges. A multi-
center study (106) found also that there is a relatively high
incidence of signal dropout that may be attributed to fetal
scalp congestion (edema), vernix, site and probe applica-
tion, and movement artifacts. The study found that reli-
able readings can only be obtained 60–70% of the time.

Sensor's fulcrum tip
Contact
electrodes
Optical
components
and contacts
(a)
(c)
Figure 8. The Nellcor Model N-400 fetal pulse oximeter and the special probe developed to mon-
itor SpO2 from the fetal cheek (Courtesy of Nellcor Puritan Bennett, Inc. Pleasanton, CA). (This
figure is available in full color at http://www.mrw.interscience.wiley.com/ebe.)
Despite these limitations, the FDA approved the mar-
keting of the Nellcor fetal oximeter in 2000. However, the
American College of Obstetricians and Gynecologists has
so far not endorsed the adoption of fetal pulse oximetry as
a standard for routine intrapartum use citing concerns
that ‘‘its introduction could further escalate the cost of
medical care without necessarily improving clinical out-
come’’ (107). The recommendation was based on insuffi-
cient clinical studies to show that the use of fetal pulse
oximetry cuts the rate of Caesarian section deliveries. De-
spite continued efforts to evaluate the utility of this tech-
nology in randomized clinical trials conducted by the NIH
and the manufacturer, several recent opinions remain
Figure 9. Resting location of the Nellcor fetal pulse oximeter
probe (Courtesy of Nellcor Puritan Bennett, Inc. Pleasanton, CA).
PULSE OXIMETRY 2935
LEDs
735 nm and 890 nm
Photodetector
(b)
controversial and contradicting whether this technology
is ready for routine clinical practice (108–111).
7.5. Combining Pulse Oximetry and Transcutaneous pCO2
Measurement
In addition to measuring arterial oxygen saturation, it is
frequently also necessary to determine the pCO2 in arte-
rial blood to determine CO2 elimination and assess more
accurately the respiratory status of the patient.
Gisiger et al. (112) and Eberhard et al. (113) developed
a miniaturized combined sensor for simultaneous moni-
toring of SpO2 and transcutaneous pCO2 in pediatric and
adult patients during surgery. The combined sensor is at-
tached to the earlobe by a low-pressure clip. The transcu-
taneous CO2 sensor is based on a potentiometric
measurement by a Stow–Severinghaus-type electrode
(114,115), which determines the pH of an electrolyte layer
separated from the skin by a permeable transparent mem-
brane. A change of pH is proportional to the logarithm of a
pCO2 change. The other part of this sensor comprises the
optical components of a pulse oximeter sensor, although
the signal measured by the photodiode originates both
from transmission as well as from reflection of light from a
reflective element mounted at the opposite side of the ear-
lobe clip. A small heater is imbedded in the housing to
raise the temperature of the earlobe to 421C to achieve
local arterialization of the cutaneous tissue underneath
the sensor that is normally required for accurate transcu-
taneous pCO2 measurement. This approach can also be
advantageous for enhancing SpO2 monitoring by increas-
ing blood flow during periods of low peripheral perfusion
and thereby the strength of the PPG signals (116).
7.6. Noninvasive Blood Pressure Measurement by Pulse
Oximetry
Because the PPG waveform corresponds remarkably well
to the blood pressure waveform and is displayed on many
2936 PULSE OXIMETRY
pulse oximeters, several studies for alternative measure-
ment of blood pressure noninvasively using a pulse oxi-
meter have been reported (117–120). The method requires
both devices to be placed on the same extremity and the
blood pressure cuff positioned proximal to the location of
the pulse oximeter probe. The technique is based on noting
the disappearance and/or reappearance of the PPG wave-
form during the inflation and deflation of the blood pres-
sure cuff. The technique might be useful in patients for
whom standard oscillometric blood pressure measure-
ments are not reliable or obtainable, such as those with
very low blood pressure. However, the main shortcoming
of this approach is that only systolic blood pressure can be
measured and the oximetric determination is subjective.
7.7. Pulse Oximetry Waveform Interpretations
In addition to the dependence of the PPG amplitude and
frequency on oxygen saturation and HR, the morphology
of the PPG contains spectral information that can be use-
ful for clinical interpretation of various physiological con-
ditions and cardiovascular diseases (121,122). Therefore,
in addition to SpO2 and HR information, several manu-
facturers typically display the AC component of the infra-
red PPG waveform because it does not depend on
variations in SO2. Normally, the variable DC baseline of
the PPG is removed, and autoscaling and autocentering
routines are used to ensure that the amplitude of the AC
waveform is maximized and remains on the display
screen. Some manufacturers include an option to turn off
these automatic functions.
Early investigations recognized that the AC waveform
of the PPG correlates to changes in sympathetic tone of
the peripheral blood vessels and thus can change dramat-
ically with cardiovascular shock and sedation (123–126).
For example, episodes of increased sympathetic tone, such
as vasoconstriction attributed to pharmacologic agents or
physiologic conditions elicited by cold temperatures, cause
the amplitude of the AC component to decrease. Likewise,
with vasodilation, the amplitude is increased. This infor-
mation can be useful for an anesthesiologist to follow sym-
pathetic tone and sympathetic response to surgical
stimulation. Other investigators showed that normal re-
spiratory activity can also affect the amplitude of the PPG
waveform. For example, it was noted that during sponta-
neous breathing, an 8–10 peripheral pulse trace shows a
slow phasic respiratory wave that modulates the envelope
of the AC components of the PPG. These low-frequency
modulations of the PPG signal are directly related to the
pressure and volume of the air contained in the lungs
(127,128). Nakajima et al. (129) have demonstrated ways
of isolating these low-frequency components using digital
filters. The resulting waveforms are representative of a
subject’s breathing pattern.
8. PULSE OXIMETER SIMULATORS
Although pulse oximeters are precalibrated in vivo by
their manufacturer using human subjects, the many pulse
oximeters available on the market increased the demand
for a simple and cost-effective way to test whether a pulse
oximeter performs according to the manufacturer’s func-
tional specifications. In the quest to produce reliable and
reproducible pulse oximeter simulators, various methods
have been employed based on mechanical pumping of
blood through an artificial finger model or nonblood de-
vices that incorporate optical or mechanical means to sim-
ulate the properties of blood pulsation through a human
finger (130).
Several manufacturers of medical testing equipment
(e.g., Metron, DNI Nevada, and Bio-Tek Instruments) de-
veloped nonblood optoelectronic simulators for testing the
performance of different pulse oximeters in vitro over a
wide range of oxygen saturation and heart rate values.
Some of these devices include simulations of different pa-
tient conditions that can be encountered in the clinical
setting, such as the response to weak and noisy PPGs.
These simulators were developed for field testing of pulse
oximeter models from specific manufacturers and there-
fore are not universal. Typical testing may involve simu-
lations of the electronic signals generated by the PD to test
the electronic processing circuitry in the pulse oximeter or
testing the optical sensor separately to identify broken
wires. It is important to realize that these simulators are
only used to test the functional capability of the pulse oxi-
meter relative to its original factory settings and are not
intended to test the absolute accuracy of the pulse oxi-
meter or the validity of the algorithms used by the man-
ufacturer for calibrating their pulse oximeters.
Several in vitro tissue phantoms using blood were pro-
posed for evaluating different physiological parameters or
physical factors that can affect the accuracy of a pulse oxi-
meter. These artificial tissue phantoms attempt to simu-
late the optical absorption and scattering properties of
biological tissues using nonhemolyzed blood. Such models
can be useful because deliberately desaturating human
subjects is a contentious issue mainly because of the asso-
ciated risks that subjects may suffer irreversible brain
damage breathing hypoxic gas mixtures, which can lead
to inaccurate readings at low levels of SpO2. Moreover, it is
sometimes unethical or impractical for example to accu-
rately study in vivo the effect of certain physiological pa-
rameters, such as elevated levels of CO, MetHb, or certain
intravenous dyes; the effect of variations in hematocrit; or
changes in blood flow conditions. Mendelson and Kent
(131) developed a circulating blood phantom of a finger to
investigate the effect of HbCO on the accuracy of a pulse
oximeter. Likewise, de Kock and Tarassenko (132), Vegfors
et al. (133), and Reynolds et al. (134) used a similar in vitro
approach to investigate the effects of hematocrit, blood
flow, blood volume, and degree of pulsatility on the nor-
malized R ratio that is used in calibrating a pulse oximeter.
A noncirculating tissue model that requires a smaller
amount of blood was described by Volgyesi et al. (135).
8.1. In vitro Calibration and Verification
A novel prototype device was proposed for standardized
and universal calibration of a pulse oximeter in vitro
based on a database of time-resolved raw optical trans-
mission spectra that was previously recorded from human
fingers during the calibration studies of pulse oximeters

(136–139). The in vitro calibration process is simulated by
playing back the stored optical transmission spectra that
were recorded in vivo for different arterial SO2 values by
means of a special artificial finger calibrator that has op-
tical scattering properties similar to real human fingers
and a specially designed tissue spectrometer. In contrast
with in vitro simulation models of a human finger, this in
vitro spectrophotometric method is based on data recorded
in vivo from real human subjects and therefore bear the
basic interaction between a pulse oximeter and a human
finger. These data can be played back to test the accuracy
and calibration procedure of any pulse oximeter. It can
also be used to investigate how the pulse oximeter re-
sponds to rapid changes in oxygen saturation and motion
interferences.
8.2. Future Trends
Pulse oximetry has elegantly combined the principles of
photoplethysmography and spectrophotometry to mea-
sure noninvasively the oxygen saturation of arterial blood.
The method has been widely welcomed by many practi-
tioners and undoubtedly serves as an important tool used
by clinicians to assess the status of patient oxygenation.
Pressure on manufacturers to overcome several short-
comings and improve the performance of pulse oximeters
has led to improvement and expansion of the technology in
an attempt to satisfy diverse clinical requirements. De-
spite almost two decades of significant technological
achievements, the scope of pulse oximetry is still expand-
ing. Improvements in performance of pulse oximeters, es-
pecially the most troublesome need to reduce the
occurrence of false alarm rates and provide more reliable
measurements under conditions of low peripheral perfu-
sion, continue to be made as new digital signal processing
hardware and more advanced software algorithms are
being developed by different manufacturers.
Future trends include improvements in performance by
developing more advanced digital signal processing algo-
rithms, more flexible and intelligent alarm settings, and
the combination of pulse oximeters with other monitoring
signals. Additional efforts are also underway to integrate
wireless telemetry with pulse oximetry and expand its use
in ambulatory monitoring, in ambulances, during helicop-
ter transport, and at home. Wearable pulse oximeters are
also being developed for civilian and military applications
by first responders and soldiers during routine training
and combat applications.
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