U.S. patent number RE29,703 [Application Number 05/668,867] was granted by the patent office on 1978-07-18 for non-invasively measuring arterial oxygen tension.
This patent grant is currently assigned to The Regents of The University of California. Invention is credited to Irving Fatt.
United States Patent |
RE29,703 |
Fatt |
July 18, 1978 |
Non-invasively measuring arterial oxygen tension
Abstract
Oxygen tension is measured in the palpebral conjuctiva and is
converted to arterial oxygen tension by applying a conversion
factor thereto. A polarographic oxygen sensor on the outer surface
of a scleral contact member is employed, and the current passed is
read and converted, or read in terms of a special calibration.
Inventors: |
Fatt; Irving (Berkeley,
CA) |
Assignee: |
The Regents of The University of
California (Berkeley, CA)
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Family
ID: |
23723184 |
Appl.
No.: |
05/668,867 |
Filed: |
March 22, 1976 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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273422 |
Jul 20, 1972 |
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Reissue of: |
434191 |
Jan 17, 1974 |
03893444 |
Jul 8, 1975 |
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Current U.S.
Class: |
600/356;
204/403.06; 204/415; 205/778; 205/782.5 |
Current CPC
Class: |
A61B
5/14542 (20130101); A61B 5/1477 (20130101); A61B
5/1495 (20130101); G01N 27/48 (20130101) |
Current International
Class: |
A61B
5/00 (20060101); G01N 27/48 (20060101); A61B
005/00 () |
Field of
Search: |
;128/2L,2E,2.1E
;204/195B |
Other References
walton, D. M. et al., 8th ISA-Biomed. Sciences Instr. Symposium,
May 1970, pp. 155-158. .
Krause, A. C. et al., Amer. Journ. of Opthalmology, vol. 42, 1956,
pp. 764-769. .
Ingvar, D. H. et al., Acta Physiol. Scand., 1960, 48, pp. 373-374.
.
Kwan, M. et al., Anesthesiology, vol. 35, No. 3, Sep. 1971, pp.
309-314..
|
Primary Examiner: Howell; Kyle L.
Attorney, Agent or Firm: Owen, Wickersham & Erickson
Government Interests
The invention described herein was made in the course of a grant
from the Department of Health, Education and Welfare.
Parent Case Text
CROSS-REFERENCE TO RELATED APPLICATION
This application is a continuation-in-part of application Ser. No.
273,422 filed July 20, 1972, now abandoned.
Claims
I claim:
1. A method for non-invasively determining continuous arterial
oxygen tension of a patient, comprising the steps of
a. non-invasively measuring the palpebral conjunctival oxygen
tension,
b. multiplying said tension by a constant dependent upon the
relationship between the oxygen tension of the palpebral
conjunctiva and the arterial oxygen tension of the patient, and
c. subtracting a second constant also dependent upon said
relationship.
2. The method of claim 1 wherein said measuring, multiplying and
subtracting are carried out substantially simultaneously and
continuously.
3. A method for non-invasively and continuously determining
continuous arterial oxygen tension of a patient, comprising the
steps of
a. continuously non-invasively measuring the palpebral conjunctival
oxygen to provide readings thereof; and
b. continuously converting the readings to values in terms of the
relation of palpebral conjunctival readings to arterial
conditions.
4. The method of claim 3 wherein the measurements are continuously
recorded.
5. A method for non-invasively determining continuous arterial
oxygen tension of a patient, comprising the steps of
1. securing an oxygen-sensing electrode assembly to the outer
surface of a scleral contact lens member,
2. emplacing said contact lens member between the cornea of the
patient's eye and the palpebral conjunctiva of his eyelid,
3. applying voltage to said electrode assembly,
4. reading the current passed, and
5. calibrating said current in terms of the oxygen tension modified
by factors corresponding to the relation between the slope and
origin of the arterial oxygen tension to palpebral conjunctival
oxygen tension.
6. The method of claim 5 wherein steps (3) and (4) are done
continuously.
7. The method of claim 6 wherein the calibrated reading is
continuously recorded.
8. Apparatus for non-invasively determining arterial oxygen tension
of a patient, comprising
a. means to abut the surface of palpebral conjunctiva for detecting
the oxygen tension thereof,
b. means for reading the value of the detected tension while
multiplying this value by a constant dependent upon the type of
patient and upon the relationship between oxygen tension of the
palpebral conjunctiva and the arterial tension of the type of
patient while subtracting a second constant also dependent on said
relationship.
9. The apparatus of claim 8 wherein said means (a) comprise a
membrane polarographic oxygen sensor.
10. Apparatus for non-invasively determining continuous arterial
oxygen tension of a patient, comprising
a. means to abut the surface of palpebral conjunctiva for
continuously detecting the oxygen tension thereof,
b. means for continuously indicating the value of the detected
tension while multiplying this value by a first constant dependent
upon the relationship between the oxygen tension of the palpebral
conjunctiva and the arterial oxygen tension of the patient, and
while continuously subtracting therefrom a second constant also
dependent on said relationship, and
c. means for continuously displaying the results of (b).
11. Apparatus for non-invasively determining continuous arterial
oxygen tension of a patient, comprising
1. a scleral contact lens member having an oxygen-sensing electrode
assembly secured to said lens member and sensing at the outer
surface thereof, so that said contact lens member can be placed
between the cornea of the patient's eye and his eyelid,
2. means for applying voltage to said electrode,
3. means for reading the current passed, and
4. means calibrating said reading in terms of the oxygen tension as
modified by factors corresponding to the relation between the slope
and origin of the arterial oxygen tension to palpebral conjunctival
oxygen tension.
12. The apparatus of claim 11 wherein said gas-sensing electrode
assembly is a membrane polarographic electrode assembly. .Iadd. 13.
Apparatus for non-invasively indicating continuous arterial oxygen
tension of a patient, comprising
1. a scleral contact lens member having an oxygen-sensing electrode
assembly secured to said lens member and sensing at the outer
surface thereof, so that said contact lens member can be placed
between the cornea of the patient's eye and his eyelid,
2. means for applying voltage to said electrode,
3. means for sensing the current passed, and
4. means indicating said sensed current in relation to the oxygen
tension as modified by factors corresponding to the relation
between the slope and origin of the arterial oxygen tension to
palpebral conjunctival oxygen tension. .Iaddend..Iadd. 14. A method
for non-invasively indicating continuous arterial oxygen tension of
a patient, comprising the steps of
1. securing an oxygen-sensing electrode assembly to the outer
surface of a scleral contact lens member,
2. emplacing said contact lens member between the cornea of the
patient's eye and the palpebral conjunctiva of his eyelid,
3. applying voltage to said electrode assembly,
4. sensing the current passed, and
5. indicating said sensed current in terms of the oxygen tension
modified by factors corresponding to the relation between the slope
and origin of the arterial oxygen tension to palpebral conjunctival
oxygen tension. .Iaddend.
Description
BACKGROUND OF THE INVENTION
This invention relates to non-invasive and continuous measurement
of arterial oxygen tension.
Arterial oxygen tension or partial pressure and its changes are
phenomena with great significance in several fields of medicine,
including anesthesiology, treatment of respiratory diseases, and
treatment of prematurely born infants. It is very valuable to know
exactly what this tension is and to know it continuously and
currently. Invasive techniques, such as the analysis of blood
samples may overly weaken the patient and in any event cannot give
either current or continuous knowledge. The best and quickest
analysis of a blood sample consumes several minutes, especially
where the laboratory and the patient are a few minutes apart; it
can never provide continuous monitoring.
Attempts to predict or determine arterial oxygen tension indirectly
from measured tissue oxygen tension have not heretofore yielded any
clinically useful methods. When polarographic oxygen sensors are
pressed against tissues, such as the skin, the mucous membranes of
the mouth, the cornea, or the bulbar conjunctiva, there is no
finite steady-state oxygen tension; instead, the recorded oxygen
tension falls rapidly to zero. Even after several years of research
and development the non-invasive oximeter, which measures
oxyhemoglobin saturation rather than oxygen tension, is still not
widely used as a monitoring device. In particular, it does not help
monitor hyperoxic states.
The present invention is capable of continuously monitoring
arterial oxygen tension. It can measure arterial oxygen tension in
both hyperoxic and hypoxic states and is not limited by the 100%
saturation of hemoglobin as is the oximeter.
The invention enables an anesthetist to observe the instant effect
of decreasing and increasing inspired oxygen tension and
ventilation.
When ventilation is assisted in chronic and acute respiratory
disease, there is need for evaluating the state of respiration; in
addition to data such as tidal volume, blood oxygen tension
provided by the present invention can be helpful.
A third immediate area of great usefulness of the present invention
is in the premature nursery. For example, isolette oxygen tensions
can be adjusted by feedback from a device embodying the invention,
chronic palpebral conjunctival electrode taped under one eyelid.
Either continuous or sporadic non-invasive, non-blood loss
evaluation of arterial PO.sub.2 can be made.
In the area of chronic lung disease a chest internist can use the
invention as a diagnostic tool when correlated with certain simple
spirometer measurements. In many instances, the non-invasive nature
of the test of the present invention is more acceptable on an
out-patient basis than arterial puncture.
In the diagnosis and evaluation of shock this invention is capable
of greater sensitivity than a sphygmomanometer. The organism tries
to maintain its blood pressure and arterial oxygen tension;
however, tissue perfusion and oxygenation, especially to
non-critical areas, may be affected very easily.
SUMMARY OF THE INVENTION
This invention rests on my discovery that arterial oxygen tension
can be determined by determining the oxygen tension of the
palpebral conjunctiva. These two tensions are not the same, nor can
a time factor be completely disregarded, but they are so closely
related that, for example, by multiplying the palpebral
conjunctival oxygen tension by a constant that depends on the type
of organism and then subtracting a second constant, the arterial
oxygen tension is obtained. Only a short delay time is involved,
for the palpebral conjunctival oxygen tension adjusts quickly to
any change in arterial oxygen tension.
This discovery has been described in a published paper by Marcus
Kwan and Irving Fatt entitled "A Noninvasive Method of Continuous
Arterial Oxygen Tension Estimation from Measured Palpebral
Conjunctival Oxygen Tension", printed in Vol. 35, No. 3, of
Anesthesiology, September 1971, pages 309-314.
The palpebral conjunctiva is a very specialized tissue. The
avascular cornea of the open eye obtains almost all of its oxygen
from the atmosphere. When the eye is closed, about a third of the
oxygen needed by the cornea comes from the aqueous humor, and about
two-thirds from the conjunctival capillaries. The vessels of the
palpebral conjunctiva are so close to the conjunctival epithelium
that they are clearly visible. The mucous membrane epithelium
overlying these vessels is only two to four cell layers thick, and
appears to have a very low oxygen consumption rate. The palpebral
conjunctiva, therefore, is an easily accessible capillary bed not
covered by a thick layer of oxygen-consuming tissue.
A suitable polarographic oxygen sensor, such as an electrode
assembly, is mounted on a scleral contact lens or lens segment and
used to measure palpebral conjunctival tissue gas tensions either
continuously or sporadically, as desired. The palpebral conjunctiva
supplies oxygen, for example, to the cornea when the eyelids are
shut, thus providing a unique opportunity to separate,
atraumatically, a capillary bed with a high oxygen tension from its
oxygen-consuming tissue.
BRIEF DESCRIPTION OF THE DRAWINGS
In the drawings:
FIG. 1 is a view in cross-section of a portion of an eye and upper
eyelid with an electrode-carrying scleral contact lens installed,
according to the principles of the invention.
FIG. 2 is a view in side elevation of a scleral contact lens
incorporating an oxygen-sensing electrode in accordance with the
invention.
FIG. 3 is a fragmentary view in section of a portion of the
assembly of FIG. 2.
FIG. 4 is a circuit diagram for a gas electrode circuit.
FIG. 5 is a tracing of palpebral conjunctival oxygen tension over a
period of time, with various changes in oxygen ratio in the gas
being breathed.
FIG. 6 is a graph showing a typical relationship between palpebral
conjunctival oxygen tension and arterial oxygen tension, plotting
oxygen tension in torrs against inspired oxygen tension in
torrs.
FIG. 7 is a graph of mean arterial oxygen tension versus mean
palpebral conjunctival oxygen tension at a series of inspired
oxygen tensions.
DESCRIPTION OF A PREFERRED EMBODIMENT
FIG. 1 shows an eye 10 having an eyelid 11 with a palpebral
conjunctiva 12. The eye 10 has a cornea 13. According to the
present invention, the oxygen tension of the palpebral conjunctiva
is to be sensed and measured. This is done by inserting a scleral
contact lens 15 over the cornea 13, the lens 15 having an inner
surface 16 in contact or partial contact with the cornea 13 and an
outer surface 17 in contact with the palpebral conjunctiva 12.
As shown in FIGS. 2 and 3 this contact lens 15 is provided with at
least one sensor 20, which may comprise a Clark polarographic
oxygen electrode sensor, having a silver anode 21 and a small
platinum cathode 22 embedded in plastic 23 and covered by a thin
film or membrane 24 of material such as 12.mu. polyethylene. The
sensor 20 may be secured to the outer surface 17.
The sensor 20 has leads 25 and 26. As shown in FIG. 4, the lead 25
from the anode 21 may be grounded and pass to a suitable
microammeter 27 and to a recorder 28. The lead 26 from the cathode
22 may go to a voltage divider 30 comprising two resistors 31 and
32, and a power source 33, such as a 1.35 volt cell may be
converted to opposite ends of the voltage divider 30, which is
connected by a lead 34 to the ammeter 27. Other types of circuits
may be used.
Continuous measurements of palpebral conjunctival oxygen tensions
have been obtained by such a membrane-covered (polyethylene,
12.mu.) polarographic electrode 20 with a platinum cathode 22 that
was 25.mu. in diameter mounted eccentrically on a scleral contact
lens 15. The site of attachment was chosen so that the electrode 20
would abut directly on the tarsal portion of the palpebral
conjunctiva 12, where the epithelial tissue is firmly stretched
over a supporting structure of dense connective tissue and where
the epithelium would normally be in contact with the cornea 13 when
the eye 10 is closed. One particular electrode or sensor 20 in the
finished state produced a small protuberance (2.0 to 2.5 mm at the
most) of the lid 11 above the normal curvature of the eye 10
covered by the scleral contact lens 15.
The electronic circuitry for the conjunctival electrode may
comprise primarily a Hewlett-Packard microammeter 27 and a Heathkit
.[.sevo-recorder.]. .Iadd.servo-recorder .Iaddend.28. Between the
cathode 22 and the silver anode 21, a potential of 0.75 volts was
applied by the cell 33. In this system currents of 2 to 3 nanoamps
were recorded for 150 torr oxygen. To check correlation, arterial
oxygen tension measurements were also done on blood samples taken
from the femoral artery and passed over a standard Clark
polarographic oxygen sensor in a constant-temperature cuvette. A
Beckman Model 160 gas analyzer was used for readout. Blood pressure
was monitored via a catheter in the femoral artery and a Model P2-
1251 Wiancko pressure transducer.
The contact-lens electrode 20 was calibrated at
35.degree.-36.degree. C. The temperature under the eyelid 11,
measured by a small polyethylene thermistor probe, remained in the
range of 37.0.degree. to 36.4.degree. C. during a four-hour
experiment. The arterial electrode was calibrated and maintained at
39.degree. C. Water-saturated pure nitrogen and water-saturated air
were used as standards.
In animal tests, eight adult New Zealand White rabbits were
anesthetized with 40 to 50 mg/kg of sodium pentobarbital of 2.0
g/kg of urethane in divided doses so that the corneal reflexes were
lost. Tracheostomies were performed, and the rabbits allowed to
respire at their own rates and depths. A polyethylene cannula was
placed in a femoral artery and threaded into the distal aorta to
take arterial samples and monitor blood pressure.
The scleral contact-lens 15 with the oxygen electrode 20 was then
positioned in the eye of the rabbit and the lid sutured shut.
Sutures were used for these tests because tape would not stick to
the hairy rabbit eyelids; in one rabbit, however, tape was
sufficient to hold the electrode in place. The palpebral
conjunctival oxygen tensions were recorded continuously with the
rabbits inspiring various mixtures of oxygen, prepared by mixing
100 per cent oxygen and 100 per cent nitrogen through two
flowmeters, two feet of tubing and a rebreathing bag. In some
experiments, at each inspired oxygen tension an arterial blood
sample was taken and its oxygen tension measured after the
conjunctival oxygen tension had become stable. Recalibration at the
termination of the experiment showed that the contact-lens
electrode 20 was stable after five hours.
As shown graphically in FIG. 5, within one-half to two minutes
after changing the composition of the inspired oxygen mixture, a
maximal and steady-state tissue oxygen tension was found. Stable
repeatable tissue oxygen tensions varying from 35 to 520 torr were
obtained continuously over a three to five-hour period in each of
eight experiments for a range 10 to 100 per cent inspired oxygen.
No variation in electrode current was caused by the mechanical
pressures generated by the eyelids over the electrode face.
Movement of the contact-lens electrode under the lid for distances
of 5 to 6 mm resulted in transient changes in current, but the
oxygen tension recorded returned to the preceding stable reading
once the movement stopped. Thus, the time delay between breathing
and palpebral conjuctival oxygen tension is quite brief, and the
delay with respect to arterial oxygen is even shorter.
When the rabbits were breathing room air, palpebral conjuctival
oxygen tensions of 50 to 100 torr were obtained. On the basis of
oxygen-hemoglobin dissociation data in the rabbit, the expected
arterial oxygen tension would be 75 to 80 torr at 95 percent
saturation. The experimental results for both tissue and arterial
oxygen tensions (see FIG. 6) are in good agreement with this
expectation for respiration of room air. Mean conjuctival-tissue
PO.sub.2 was 70 .+-. 13.3 torr, and mean arterial PO.sub.2 93 .+-.
13.4 torr when room air was inspired. Charleton, Read, and Read (in
Journal of Applied Physiology, Volume 18, No. 6, pages 1247-1251,
1963) reported that intraarterial oxygen tensions measured by a
microelectrode in man varied from 70 to 127 torr (mean 84 torr)
during respiration of air at rest; with voluntary hyper-ventilation
of 712 torr oxygen, arterial oxygen tensions varied from 610 to 656
torr (mean 637 torr).
The steady-state palpebral conjuctival oxygen tensions recorded and
the arterial oxygen tensions are shown in FIG. 6 as functions of a
wide range of inspired oxygen tensions.
One mounted membrane-covered electrode 20 protruded 2.0-2.5 mm
vertically from the carrier lens 15 and with an O-ring 35 in place
produced a 6-7 mm circular, horizontal protuberance. Fine insulated
wire leads 26 and 25 connect the electrode 20 to the battery box
which provides the polarizing voltage. The polyethylene-covered
cathode 22 and anode 21 thus are insulated from the body and should
not add to the microcurrents involved in EKG monitoring or the
macrocurrents from electrocautery. The battery box is connected to
the microammeter 27 and recorder 28 which may rest on a cart or
other support close to the subject's head. These instruments 27 and
28 are suitably calibrated, as described below. A calibrating setup
including a constant temperature bath, and small tanks of gas may
also be included in this space.
Operator skills required are essentially the same as those required
for anyone making arterial blood gas measurements.
Human trials have employed an electrode 20 mounted on a corneal
contact lens 15. In normovolemic, normotensive, anesthetized
patients, the same type of correlation exists between palpebral
conjunctival PO.sub.2 and arterial PO.sub.2 as in the rabbit.
Standard deviations are even smaller, perhaps because of the much
better control of perfusion, ventilation and anesthesia.
The estimating equation (arterial PO.sub.2 = 34.4+0.91 .times.
inspired PO.sub.2) for arterial PO.sub.2 as a function of inspired
PO.sub.2 is represented by the upper solid line in FIG. 6 and has a
correlation coefficient, r, of 0.98. One standard deviation of the
.[.estimated arterial Po.sub.2,.]. .Iadd.estimated arterial
PO.sub.2 .Iaddend. for the entire line is 30 torr. The lower solid
line in FIG. 6 represents the estimating equation (tissue PO.sub.2
= 17.8 + 0.40 .times. inspired PO.sub.2) for tissue PO.sub.2 as a
function of inspired PO.sub.2, r is 0.67, and one standard
deviation for the entire line is 68 torr. The two lines in FIG. 6
show that the palpebral conjunctival oxygen tension as measured in
this system can give an approximation of the arterial oxygen
tension.
The relationship between .[.palpegral.]. .Iadd.palpebral
.Iaddend.conjunctival and arterial .[.oxyten.]. .Iadd.oxygen
.Iaddend.tensions for any given inspired oxygen tension is given by
the equation: arterial PO.sub.2 = 2.3 .times. palpebral
conjunctival PO.sub.2 -- 75 torr. Arterial PO.sub.2 can be
estimated from a measured tissue PO.sub.2 graphically, if desired.
For any inspired PO.sub.2 a correction factor can be added to the
measured palpebral conjunctival tissue PO.sub.2 to give an estimate
of arterial PO.sub.2. FIG. 7 is a graph of the mean arterial
PO.sub.2 versus the mean conjunctival PO.sub.2 at each inspired
oxygen tension, and again reflects the linear correlation between
the two. Part of the deviation from a theoretical 1:1 correlation
indicates the extent of oxygen consumption by the tissue between
sensor and the capillaries; the rest is probably due to relative
decreases in local blood flow at higher oxygen tensions.
The ammeter 27 and recorder 28 are preferably calibrated to read
arterial PO.sub.2 directly by an appropriate readout scale to
provide the multiplier constant of the above equation, while the
location of the zero point provides the subtraction constant. This
calibration thereby multiplies the detected tension by the
indicated constant while also subtracting a second constant. The
spread of the calibration points thus accomplishes multiplication,
and the location of zero therein effects subtraction -- in just the
same manner as any ammeter (e.g., a galvanometer) may be calibrated
to read in terms of amperes, milliamperes, or microamperes and may
be calibrated to read in terms of current above any predetermined
level. Here the ammeter 27 and recorder 28 may be calibrated either
in terms of palpebral oxygen tension or in terms of arterial oxygen
tension.
This system is apparently capable of monitoring hypoxic and
hyperoxic states, and gives an estimate of arterial oxygen tension
in normotensive, normovolemic animals. The conjunctival electrode,
which is not limited by the 100 percent saturation of hemoglobin,
can be very useful as a means of detecting hyperoxia in premature
infant nurseries and acute pulmonary .[.case centers..]. .Iadd.care
centers. .Iaddend.The monitoring system of this invention may show
a characteristic dependence of tissue oxygen tension on local blood
flow, which could make the palpebral conjunctival electrode useful
as a signal of impending shock. This technique has the additional
advantage of being non-invasive and relatively atraumatic. No gross
corneal damage was noted in the rabbits, and scleral contact lenses
have been in human use for years.
Because of the rapid response (minutes), the stability (hours), and
the steady-state nature at a given oxygen tension, this
conjunctival monitoring system is well suited to use as an aid in
the continuous monitoring of the levels of oxygenation of patients
during anesthesia and intensive respiratory care. The palpebral
conjunctiva is supplied by the internal carotid artery via branches
of the ophthalmic artery, and thus may be preferentially perfused
over other cutaneous areas during minimal hypovolemia. Preliminary
studies show that for animals in shock the palpebral conjunctival
oxygen tension has a more complex relationship to the arterial
oxygen tension. Once the exact relationship is better understood,
this monitoring device will have further clinical use.
Thus, this invention is adapted to human use as a non-invasive,
continuous method for monitoring arterial oxygen tensions.
To those skilled in the art to which this invention relates, many
changes in construction and widely differing embodiments and
applications of the invention will suggest themselves without
departing from the spirit and scope of the invention. The
disclosures and the description herein are purely illustrative and
are not intended to be in any sense limiting.
* * * * *