Non-invasively measuring arterial oxygen tension

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.

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.

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.