U.S. patent application number 10/357996 was filed with the patent office on 2003-11-27 for device for assessing perfusion failure in a patient by measurement of blood flow.
Invention is credited to Bisera, Jose, Kimball, Victor E., Tang, Wanchun, Weil, Max Harry.
Application Number | 20030220551 10/357996 |
Document ID | / |
Family ID | 23094111 |
Filed Date | 2003-11-27 |
United States Patent
Application |
20030220551 |
Kind Code |
A1 |
Kimball, Victor E. ; et
al. |
November 27, 2003 |
Device for assessing perfusion failure in a patient by measurement
of blood flow
Abstract
A device is provided for assessing impairment of blood
circulation in a patient, such as that in perfusion failure, by
measurement of blood flow adjacent a mucosal surface accessible by
a mouth or nose and connecting with the gastrointestinal tract or
upper respiratory/digestive tract of a patient. The device includes
a blood-flow sensor adapted to be positioned adjacent a mucosal
surface with a patient's body and measuring blood flow in adjacent
tissue and a PCO.sub.2 sensor adapted to be positioned adjacent the
mucosal surface and measuring PCO.sub.2. In addition a pH sensor
may be used in combination with the blood flow determination. The
invention affords rapid measurement and detection of perfusion
failure.
Inventors: |
Kimball, Victor E.;
(Burnsville, MN) ; Weil, Max Harry; (Northbrook,
IL) ; Tang, Wanchun; (Palm Desert, CA) ;
Bisera, Jose; (Camarillo, CA) |
Correspondence
Address: |
OPPENHEIMER WOLFF & DONNELLY LLP
45 SOUTH SEVENTH STREET, SUITE 3300
MINNEAPOLIS
MN
55402
US
|
Family ID: |
23094111 |
Appl. No.: |
10/357996 |
Filed: |
February 4, 2003 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10357996 |
Feb 4, 2003 |
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09866042 |
May 24, 2001 |
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09866042 |
May 24, 2001 |
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09285409 |
Apr 2, 1999 |
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6258046 |
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09285409 |
Apr 2, 1999 |
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09160224 |
Sep 24, 1998 |
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6216024 |
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09160224 |
Sep 24, 1998 |
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09099293 |
Jun 18, 1998 |
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6055447 |
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09099293 |
Jun 18, 1998 |
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08939591 |
Sep 29, 1997 |
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08939591 |
Sep 29, 1997 |
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08710208 |
Sep 13, 1996 |
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08710208 |
Sep 13, 1996 |
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08498932 |
Jul 6, 1995 |
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5579763 |
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Current U.S.
Class: |
600/345 |
Current CPC
Class: |
A61B 5/0261 20130101;
A61B 5/14539 20130101; A61B 5/1473 20130101; A61B 8/12 20130101;
A61B 5/14542 20130101; A61B 5/42 20130101; A61B 5/682 20130101;
A61B 5/0084 20130101; A61B 5/412 20130101; A61B 8/06 20130101; A61B
5/0071 20130101 |
Class at
Publication: |
600/345 |
International
Class: |
A61B 005/05 |
Claims
What is claimed is:
1. A device for assessing the degree of systemic perfusion in a
patient, the device comprising: a blood-flow sensor, adapted to be
positioned adjacent a mucosal surface within a patient's body and
measuring blood flow in adjacent tissue; a PCO.sub.2 sensor,
adapted to be positioned adjacent the mucosal surface and measuring
PCO.sub.2 in the adjacent tissue; and an indicating means operably
connected to the sensor means, for indicating the measured blood
flow and the measured PCO.sub.2 whereby the degree of systemic
perfusion of the patient may be deduced.
2. The device of claim 1, wherein the mucosal surface is in the
gastrointestinal tract.
3. The device of claim 2, wherein the mucosal surface is in the
esophagus.
4. The device of claim 2, wherein the mucosal surface is in the
stomach.
5. The device of claim 2, wherein the mucosal surface is in the
jejunum.
6. The device of claim 2, wherein the mucosal surface is in the
colon.
7. The device of claim 2, wherein the mucosal surface is in the
rectum.
8. The device of claim 1, wherein the mucosal surface is in the
upper respiratory/digestive tract.
9. The device of claim 8, wherein the mucosal surface is in the
nasal passages.
10. The device of claim 9, wherein the mucosal surface is in the
vestibule of the nasal cavity.
11. The device of claim 9, wherein the mucosal surface is in the
nasal cavity.
12. The device of claim 9, wherein the mucosal surface is in the
middle nasal conchae.
13. The device of claim 9, wherein the mucosal surface is in the
inferior nasal conchae.
14. The device of claim 9, wherein the mucosal surface is in the
choana.
15. The device of claim 9, wherein mucosal surface is in the
pharyngeal opening of the auditory tube.
16. The device of claim 8, wherein the mucosal surface is in the
oral cavity.
17. The device of claim 8, wherein the mucosal surface is in the
pharynx.
18. The device of claim 8, wherein the mucosal surface is in the
oropharyngeal passage.
19. The device of claim 1, wherein the mucosal surface is
accessible by a mouth and connects with the gastrointestinal
tract.
20. The device of claim 1, wherein the mucosal surface is
accessible by a nose and connects with the upper
respiratory/digestive tract.
21. The device of claim 15, wherein the mucosal surface is a
sublingual surface.
22. The device of claim 1, wherein the device further comprises a
positioning means for locating or maintaining the blood flow sensor
at a position in the upper respiratory/digestive tract.
23. The device of claim 22, wherein the positioning means is a
holder adapted to fit within the oral-nasal cavity of the patient
and maintain the blood flow sensor in place adjacent the mucosal
surface.
24. The device of claim 23, wherein the positioning means is a
holder adapted to fit within the mouth of the patient and hold the
blood flow sensor in place adjacent the mucosal surface.
25. The device of claim 23, wherein the holder is adapted to
position the blood flow sensor adjacent a sublingual mucosal
surface.
26. The device of claim 23, wherein the holder is constructed to
fit between the inside of a lip and gum of the patient.
27. The device of claim 23, wherein the positioning means is a
holder adapted to fit within the vestibule of the nasal cavity of
the patient and hold the sensor in place adjacent the mucosal
surface.
28. The device of claim 1, wherein the blood-flow sensor is a
laser-Doppler blood-flow sensor.
29. The device of claim 1, wherein the blood-flow sensor is an
ultrasound-Doppler blood-flow sensor.
30. The device of claim 1, further comprising a pH sensor.
31. The device of claim 1, further including a means for
determining the rate of change of blood flow.
32. The device of claim 31 wherein the determining means comprises
a circuit for generating a signal representing rate-of-change of
blood flow.
33. A device for assessing the degree of systemic perfusion in a
patient, the device comprising: a blood-flow sensor, adapted to be
positioned adjacent a mucosal surface within a patient's body and
measuring blood flow in adjacent tissue; an indicating means
operably connected to the sensor means, for indicating the measured
blood flow whereby the degree of systemic perfusion of the patient
may be deduced; and a sensor holder with an inner portion and an
outer portion, said inner portion shaped to fit in the mouth of a
patient under the patient's tongue, said holder forming at least
one holder passage extending from said outer portion to said inner
portion, wherein the sensor is located within the holder
passage.
34. The device of claim 33, wherein the sensor holder has an upper
surface that supports the tongue of the patient.
35. The device of claim 33, wherein the outer portion has a slot
for receiving the patient's frenulum, and the holder passage has an
inner end lying on one side of said slot.
36. The device of claim 33, wherein at least a portion of the
holder is comprised of an elastomeric material.
37. A device for assessing the degree of systemic perfusion in a
patient, the device comprising: a blood-flow sensor, adapted to be
positioned adjacent a mucosal surface within a patient's body and
measuring blood flow in adjacent tissue; a pH sensor, adapted to be
positioned adjacent the mucosal surface and measuring pH in the
adjacent tissue; and an indicating means operably connected to the
sensor means, for indicating the measured blood flow and the
measured pH whereby the degree of systemic perfusion of the patient
may be deduced.
38. A device for assessing the degree of systemic perfusion in a
patient, the device comprising: a blood-flow sensor, adapted to be
positioned adjacent a mucosal surface accessible by a mouth and
connecting with an upper respiratory/digestive tract in a patient's
body and measuring blood flow in adjacent tissue; an indicating
means operably connected to the sensor means, for indicating the
measured blood flow whereby the degree of systemic perfusion of the
patient may be deduced; and a sensor holder adapted to hold the
blood-flow sensor adjacent the upper respiratory/digestive tract
mucosal surface.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. Ser. No.
09/866,042, filed May 24, 2001, which is a continuation of U.S.
Ser. No. 09/285,409, filed Apr. 2, 1999, issued on Jul. 10, 2001 as
U.S. Pat. No. 6,258,046, which is a continuation-in-part of U.S.
Ser. No. 09/160,224, filed Sep. 24, 1998, issued on Apr. 10, 2001
as U.S. Pat. No. 6,216,024, which is a continuation-in-part of U.S.
Ser. No. 09/099,293, filed Jun. 18, 1998, issued Apr. 25, 2000 as
U.S. Pat. No. 6,055,447, which is a continuation-in-part of U.S.
Ser. No. 08/939,591, filed Sep. 29, 1997, abandoned, which is a
continuation-in-part of U.S. Ser. No. 08/710,208, filed Sep. 13,
1996, abandoned, which is a continuation-in-part of U.S. Ser. No.
08/498,932, filed Jul. 6, 1995, which issued Dec. 3, 1996 as U.S.
Pat. No. 5,579,763.
TECHNICAL FIELD
[0002] The present invention relates generally to methods and
devices for assessing perfusion failure in a patient. More
particularly, the invention relates to assessment of perfusion
failure in a patient by measuring blood flow in a mucosal tissue in
the body of a patient.
BACKGROUND OF THE INVENTION
[0003] Very low blood flow, or low "systemic perfusion," is
typically due to low aortic pressure and can be caused by a number
of factors, including hemorrhage, sepsis and cardiac arrest. The
body responds to such stress by reducing blood flow to the
gastrointestinal tract to spare blood for other, more critical
organs. Thus, when there is a reduced flow of blood from the heart,
the body directs a higher portion of blood to critical organs, such
as the brain, which will not survive long without a continuous
supply of blood, while restricting the flow to less critical
organs, whose survival is not as threatened by a temporary large
reduction in blood flow. For example, blood flow to the splanchnic
vasculature which supplies the stomach and intestines, and also the
esophagus and oral/nasal cavity, is drastically reduced when there
is a reduced blood flow from the heart. For this reason, decreased
blood flow to the splanchnic blood vessels is thus an indication of
perfusion failure in a patient. Physicians commonly take advantage
of this phenomenon by taking CO.sub.2 and pH measurements in the
stomach and intestine to assess perfusion failure.
[0004] Assessment of CO.sub.2 concentration in the less critical
organs, i.e., those organs to which blood flow is reduced during
perfusion failure, has been useful in perfusion assessment. Carbon
dioxide production, which is associated with metabolism, continues
in tissues even during conditions of low blood flow. The
concentration of CO.sub.2 builds-up in tissues experiencing low
blood flow because CO.sub.2 is not rapidly carried away. This
CO.sub.2 build-up (an increase in partial pressure of CO.sub.2
(PCO.sub.2)) in the less critical organs in turn results in a
decrease in pH in nearby tissue. Therefore, perfusion failure is
commonly assessed by measuring pH or PCO.sub.2 at these sites,
especially in the stomach and intestines. For examples of catheters
used to assess pH or PCO.sub.2 in the stomach or intestines, see,
e.g., U.S. Pat. Nos. 3,905,889; 4,016,863; 4,632,119; 4,643,192;
4,981,470; 5,105,812; 5,117,827; 5,174,290; 5,341,803; 5,411,022;
5,423,320; 5,456,251; and 5,788,631.
[0005] The inventors have found that increases in PCO.sub.2 may be
measured throughout the body, including in accessible organs and
tissues fed by splanchnic vessels, and used to assess perfusion
failure. For example, the inventors have found that a useful
measurement of perfusion failure can be obtained by measuring
CO.sub.2 in the upper respiratory/digestive tract. In U.S. Pat. No.
5,579,763, a method is described that can be used to accurately
assess perfusion failure by measuring PCO.sub.2 in the patient's
esophagus, rather than in the less accessible stomach and/or
intestine as previously practiced in the art. Tests showed that
measurements of PCO.sub.2 in the esophagus are closely correlated
with aortic pressure, and, furthermore, that measurements made in
the esophagus are even more closely correlated to aortic pressure
than measurements of CO.sub.2 in the stomach. More recently, in
co-pending, commonly assigned U.S. Ser. No. 09/160,224, the
inventors further showed that PCO.sub.2 measurements in a patient's
mucosal tissues (e.g., mouth, nasal mucosa, and throat) are also
closely correlated to aortic pressure. As disclosed in U.S. Ser.
No. 09/160,224, the CO.sub.2 sensor may be placed at a site within
the oral-nasal cavity (e.g., under the tongue at a site in contact
with the tongue or the floor of the mouth) where it effectively
measures CO.sub.2 in the tissue. Since carbon dioxide can readily
pass through mucosal surfaces, CO.sub.2 generated by metabolic
activity occurring in tissue below the mucosal surface that is not
carried away by blood flow readily migrates through the mucosal
surface, where its build-up provides a good measure of perfusion
failure. Placement of a CO.sub.2 sensor adjacent a mucosal surface
of the upper respiratory/digestive tract thus provides a very good
quantification of perfusion failure at all times, including the
most critical minutes after the onset of perfusion failure when
treatment is likely to be most effective. Thus, mucosal
measurements of tissue perfusion can be used to assess perfusion
failure in patients.
[0006] However, PCO.sub.2 and pH are indirect measures of blood
flow in tissue, being based upon the build-up of metabolites that
result from poor perfusion. In addition, measurements of pH may be
complicated by the presence of saliva, food, or stomach acids.
CO.sub.2 measurements may be affected by ambient CO.sub.2 , and,
since they depend on equilibration with tissue CO.sub.2 levels, are
slow. Thus, there is a need for a more direct method for measuring
blood flow in a tissue, to more accurately assess perfusion failure
and to monitor the effectiveness of methods taken to increase
perfusion, e.g., blood infusion or the like.
BRIEF SUMMARY OF THE INVENTION
[0007] Methods and devices are provided for assessing impairment of
circulatory function in a patient, such as that in perfusion
failure, by measurement of blood flow adjacent a mucosal surface
accessible via the mouth or nose that connects with the GI tract
and/or upper respiratory/digestive tract of a patient. The
perfusion of a tissue is a function of both the velocity of blood
cells flowing through tissue, and of the number of blood cells, so
that the blood flow through tissue is a more direct measurement of
tissue perfusion than pH or CO.sub.2 measurements. Previously, the
belief in the art was that decreased blood flow was a localized
phenomenon during perfusion failure. It has now been discovered
that decreased blood flow, decreased pH and increases in tissue
CO.sub.2 occur throughout the body during perfusion failure, and in
particular occur not only in the stomach, jejunum, colon and
rectum, but also in the esophagus, throat, mouth, nose and
associated areas. Thus, new and useful methods and devices are now
provided, for assessing perfusion failure and perfusion levels in a
patient by measuring blood flow in tissues of the GI tract and/or
of the upper respiratory/digestive tract of a patient.
[0008] In one embodiment, then, a method is provided for assessing
impairment of circulatory function, such as that in perfusion
failure in a patient. The method comprises introducing a blood-flow
sensor adjacent a mucosal surface that is accessible via the mouth
or nose and connects with the GI tract or the upper
respiratory/digestive tract of a patient, measuring blood flow in
the tissue adjacent the sensor, and providing that measurement for
assessment of perfusion failure. Specifically, a blood-flow sensor
is placed adjacent a mucosal surface within a patient's body,
preferably without passing the sensor down through or beyond the
patient's epiglottis, most preferably within the oral or a nasal
cavity of the patient. The blood-flow sensor may be introduced
sublingually to one side of the frenulum. The invasiveness of such
a technique is minimal, being substantially no more than in the use
of an oral thermometer. Alternatively, the blood flow sensor may be
introduced and placed adjacent any mucosal surface accessible via
the mouth or nose including connections to the upper
respiratory/digestive tract or the gastrointestinal tract.
Preferably, the sensor is a laser-Doppler sensor. The output of the
sensor can be detected by a device which electronically converts
the sensor output to provide the blood flow in a form that is
easily understood by persons viewing the display. The device can
optionally further sense the rate of change of blood flow with time
to indicate the patient's condition.
[0009] Accordingly, in another embodiment the invention features a
device for assessing perfusion failure in a patient, where the
device is composed of a laser-Doppler blood-flow sensor means for
measuring blood flow in a tissue, the sensor means being adapted
for lying adjacent a mucosal surface in a patient's body, e.g. in
the upper respiratory/digestive tract of a patient, and measuring
blood flow in vessels in the mucosal tissue; and an indicating
means connected to the sensor means, wherein the indicating means
indicates a degree of perfusion failure of the patient associated
with the detected blood flow. The device may also include a
positioning means for positioning the sensor means adjacent the
mucosal surface. In one embodiment, the "positioning means" is a
holder designed to fit within the mouth of the patient and hold the
sensor in place adjacent the mucosal surface. For example, the
holder may be designed to position the sensor adjacent the tongue
of a patient, or to position the sensor between the inside of a lip
and gum of the patient. Alternatively, the positioning means may be
a holder designed to fit within a nares of the patient and hold the
sensor in place adjacent the mucosal surface. Alternatively, the
positioning means may be adapted to position the sensor adjacent
any mucosal surface that connects to the upper
respiratory/digestive tract or the gastrointestinal tract, which is
accessible via the mouth or nose.
[0010] In a further embodiment the invention features a device for
use with a blood-flow sensor assembly for assessing perfusion
failure of a patient. The device is composed of a sensor holder
with a sublingual holder inner portion shaped to fit in the mouth
of a patient under the patient's tongue, said holder forming at
least one holder passage optionally extending from said holder
outer portion to said sublingual holder portion.
[0011] In a further embodiment the invention comprises measuring
blood flow with a blood-flow sensor and additionally making an
indirect measurement of blood flow by making, e.g., a CO.sub.2
measurement or a pH measurement, or by making all three such kinds
of measurements.
[0012] One advantage of the invention is that perfusion can be
rapidly assessed in a patient, with measurements being made in just
a few seconds.
[0013] Another advantage of the invention is that perfusion can be
assessed in a patient in a minimally invasive manner, and with
minimal discomfort or risk of harm to the patient.
[0014] Another advantage of the invention is that perfusion can be
assessed in a patient without interference in the measurement by
ambient levels of CO.sub.2 and without substantial drift of the
measurement when used in a continuous monitoring application.
[0015] Another advantage of the invention is that perfusion can be
assessed in a patient without interference with the measurement by
the pH of fluids or food near the sensor.
[0016] Another advantage of the invention is that perfusion can be
readily assessed in a patient suffering from perfusion failure
associated with any of a variety of causes, including, but not
limited to physical trauma, infection, hypothermia, cardiogenic
shock (e.g., acute myocardial infarction, aneurysm, or arrhythmia),
obstructive shock (e.g., pulmonary embolism), hypovolemic shock
(e.g., due to hemorrhage or fluid depletion), and distributive
shock (e.g., due to sepsis, exposure to toxins, or anaphylaxis).
The sensitivity of the methods and devices of the invention further
allow for assessment of perfusion across a wide range of perfusion
failure severity, thereby providing a means to accurately monitor
the patient's condition.
[0017] Still another advantage of the invention is that the devices
and methods can be readily adapted for use in alert,
semi-conscious, or unconscious patients, and can be further adapted
for accurate assessment of perfusion in a patient for a period
lasting for only seconds to minutes to hours or days.
[0018] The novel features of the invention are set forth with
particularity in the appended claims. The invention will be best
understood from the following description when read in conjunction
with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] FIG. 1 is a graph showing variation in blood flow in various
tissues with time, during an experiment on rats where blood was
withdrawn to simulate hemorrhage and so induce perfusion failure,
and during reinfusion of blood to allow recovery.
[0020] FIG. 2 is a partial sectional view showing a sensor of the
present invention in place in one of many acceptable positions
within the GI tract of a patient.
[0021] FIG. 3 is an isometric view showing a sensor of the present
invention as it is introduced into the mouth of a patient, for
sublingual placement.
[0022] FIG. 4 is a sectional view of a sensor assembly and holder
constructed in accordance with an embodiment of the invention,
shown lying in a patient's mouth.
[0023] FIG. 5 is an isometric view of the holder of FIG. 4.
[0024] FIG. 6 is a sectional view of a sensor assembly and holder
of another embodiment of the invention, shown holding a sensor
between a lip and teeth of a patient.
[0025] FIG. 7 is a front isometric view of the holder of FIG.
6.
[0026] FIG. 8 is a sectional view of a sensor assembly and holder
of another embodiment of the invention, shown holding a sensor in
the nose of a patient.
DETAILED DESCRIPTION OF THE INVENTION
[0027] Definitions and Nomenclature:
[0028] Before the present devices, apparatus and methods are
disclosed and described, it is to be understood that this invention
is not limited to sensor designs, measurement techniques, or the
like, as such may vary. It is also to be understood that the
terminology used herein is for the purpose of describing particular
embodiments only and is not intended to be limiting.
[0029] It must be noted that, as used in the specification and the
appended claims, the singular forms "a," "an" and "the" include
plural referents unless the context clearly dictates otherwise.
[0030] We define the term "perfusion failure" as used herein to
mean a reduction in blood flow associated with maldistribution of
blood through the circulatory system and a reduction in blood flow
to a less critical tissue(s) and/or organ(s) relative to blood flow
in vital (critical) tissues and organs (e.g., the brain and heart).
In general, "perfusion failure" is meant to encompass reduction in
blood flow associated with a decrease in blood flow significantly
or substantially below that associated with normal perfusion.
[0031] We define the term "measurement" as used herein to refer to
a single measurement or a series of measurements made over time,
and which may be taken continuously or intermittently (e.g., at
selected time intervals).
[0032] We define the term "mucosal surface" as used herein to refer
to a surface of a mucous membrane containing or associated with
mucus secreting glands, and which lines body passages, tubular
structures, and organs, consisting of epithelium, lamina, propria,
and, in the digestive tract, a layer of smooth muscle and
encompasses, for example, the nasal passages (including the nasal
cavity, the middle nasal conchae, the inferior nasal conchae, the
choana, the naso-pharyngeal opening of the auditory tube and the
auditory tube), the oral cavity (including the mouth and spaces
within the mouth such as the sublingual area, the hard palate, the
soft palate, and the gingival surfaces), the pharynx, the
oropharyngeal passage, the esophagus, the stomach, the jejunum, the
colon, and the rectum.
[0033] We define the terms "gastrointestinal tract" and "GI tract"
as used herein to encompass the entire tract from esophagus to
rectum, including, e.g., the esophagus, the stomach, the jejunum,
the colon, and the rectum.
[0034] We define the term "upper respiratory/digestive tract" as
used herein to mean the region of the upper respiratory tract and
digestive tract above the stomach. We define the "upper
respiratory/digestive tract" to encompass the nasal passages
(including the nares (or vestibule of the nasal cavity), the nasal
cavity, middle nasal conchae, inferior nasal conchae, choana, the
naso-pharyngeal opening of the auditory tube, and the auditory
tube), the oral cavity (commonly called the mouth and including the
spaces within the mouth such as the floor (e.g., sublingual area)
and roof of the mouth (e.g., hard palate), the soft palate, the
regions between the lips and gums, and the cheeks and gums), the
pharynx (including the nasopharynx, oropharynx and laryngopharynx)
and oropharyngeal passage (collectively, commonly called the
throat) and the esophagus.
[0035] We define the term "auditory tube" (Eustachian tube) as used
herein to mean the channel through which the tympanic cavity
(middle ear) communicates with the nasopharynx.
[0036] We define the term "nasopharynx" as used herein to mean the
part of the pharynx that lies above the soft palate; anteriorly it
opens into the nasal cavity; inferiorly, it communicates with the
oropharynx via the pharyngeal isthmus; laterally it communicates
with tympanic cavities via auditory tubes.
[0037] We define the term "oral-nasal cavity" as used herein to
mean the region of the upper respiratory/digestive tract
encompassing the nasal passages (including the nares (or vestibule
of the nasal cavity), the nasal cavity, the middle nasal conchae,
the inferior nasal conchae, the choana and the pharyngeal opening
of the auditory tube), the oral cavity (including the mouth and
spaces within the mouth such as the floor (e.g., sublingual area)
and roof of the mouth (e.g., hard palate), the soft palate, the
regions between the lips and gums, and the inner cheeks and gums),
and the pharynx (including the nasopharynx, oropharynx and
laryngopharynx) and oropharyngeal passage (collectively, commonly
called the throat) extending to the top surface of and in the
region of the epiglottis.
[0038] We define the term "sublingual" as used herein to refer to a
region below or beneath the tongue.
[0039] We define the term "adjacent" as used herein (e.g.,
"adjacent the mucosal surface") to mean near or against, e.g., at a
distance from the mucosal surface that allows acceptably accurate
measurement of blood flow by blood-flow sensor.
[0040] We define the term "patient" as used herein to mean a
mammalian subject, preferably a human subject, that has, is
suspected of having, or is or may be susceptible to a condition
associated with low blood flow, and thus perfusion failure.
[0041] The present invention is based on the inventors' discovery
that blood flow decreases throughout the body during perfusion
failure, rather than as only a localized phenomenon as previously
believed in the art. Evidence for this is seen, e.g., in that
tissue CO.sub.2 increases in esophagus and sublingual tissue during
perfusion failure, as disclosed by the inventors in U.S. Ser. No.
09/160,224. Further evidence of this is shown in FIG. 1 where blood
flow in various tissues of experimental animals was measured by the
deposition of small beads measured at autopsy. The methods and
devices of the invention measure blood flow in tissue at a
convenient site within the GI tract or within the upper
respiratory/digestive tract, and are thus performed in a minimally
invasive manner. In general, these measurements are made by placing
a blood-flow sensor such as a laser-Doppler sensor or an ultrasound
Doppler adjacent a mucosal surface at a selected site within the
upper respiratory/digestive tract and using the sensor to measure
blood flow at the selected site. Such measurements may also be made
using imaging techniques such as MRI, optical imaging, angiography
techniques and other methods as would be known to those skilled in
the art.
[0042] As blood flows through tissue, the blood cells and the fluid
blood plasma move at similar rates. Light, as may be provided by a
laser-Doppler blood-flow device, and ultrasound, as may be provided
by an ultrasound-Doppler blood-flow device, can pass through tissue
to illuminate or impinge upon blood cells moving through tissue of
interest. When light or ultrasound reflects off moving blood cells
its frequency is shifted in a velocity-dependent manner, a
phenomenon known as the "Doppler shift." This phenomenon can be
used to measure the velocity of blood cells flowing through the
tissue so illuminated or so subject to ultrasound. In addition, a
laser-Doppler device or ultrasound-Doppler device may be used to
measure the ratio of moving blood cells to the non-moving cells
located in the measurement volume of the sensor. The measurement
volume of tissue in which this measurement is made may be
calculated using scattering theory and the geometry of the
illuminating and collecting sites, or may be measured using
standard calibration techniques; either of which is routinely done
with laser-Doppler devices. The total blood flow may be calculated
from these three parameters: 1) the number of cells within the
measurement volume, 2) the velocity of the moving cells, and 3) the
measurement volume.
[0043] Methods and techniques for using laser-Doppler techniques
and devices to measure blood flow are known in the art, and may be
found in such references as, e.g., U.S. Pat. No. 3,511,227 to
Johnson, U.S. Pat. No. 4,596,254 to Adrian et al., and U.S. Pat.
No. 4,590,948 to Nilsson.
[0044] Methods and techniques for using ultrasound-Doppler
techniques and devices to measure blood flow are known in the art,
and may be found in such references as U.S. Pat. No. 4,324,258 to
Huebscher et al. and U.S. Pat. No. 4,759,374 to Kierney et al.
[0045] Thus, laser-Doppler, ultrasound-Doppler, and other
blood-flow measurement devices can be used to provide direct
measures of blood flow in tissues. The present invention provides
novel methods using such measurements to detect and quantify blood
flow in tissues susceptible to low blood flow effective to detect
perfusion failure in a patient.
[0046] In order to assess perfusion failure in a patient, one first
determines the expected range of blood-flow measurements for
subjects of similar age and health status as the patient. Normal
levels of blood flow may vary with the age of the subject. Health
status may also be an important variable, since, for example, blood
flow in a diabetic subject may differ from that of a subject not
suffering from diabetes. Next, the blood flow in a mucosal tissue
of the patient is determined. The blood-flow value is compared with
the expected value for a normal subject determined in the first
step; patient blood-flow values that are significantly lower than
the normal values indicate perfusion failure. In addition, the
rate-of-change of the patient's blood flow is measured over time
with the blood-flow sensor. Rising values of blood flow indicate
recovery, while declining values of blood flow indicate a worsening
of the patient's condition.
[0047] The correlation of perfusion failure with decreased blood
flow in several bodily tissues, including sublingual blood flow in
particular, as well as the correlation of perfusion recovery and a
corresponding increase in sublingual blood flow as blood volume
recovers, was tested in an animal model that simulates a sudden
loss or shedding of blood, such as might be caused by a gunshot
wound or other severe wound. Perfusion recovery was simulated by
subsequently reperfusing the animals with a blood infusion. Blood
flow in the several tissues was assessed by counting (at autopsy)
the numbers of colored microspheres deposited in various tissues
under the indicated conditions, as described in Hale et al.
(Circulation 78:428-434, 1988). The results are shown in FIG. 1.
Blood flow in a tissue as a percentage of baseline (control) blood
flow is plotted as a function of time during hemorrhage (induced
blood-loss) and reinfusion of blood in an experimental animal. At
the beginning of the test (BL), just prior to the time-point
labeled "0," considerable blood was drawn from an animal that was
previously in good health, the blood being drawn within a period of
a few minutes. Aortic pressure drops rapidly during the first few
minutes of such a test. In a subsequent period of about two hours,
the aortic pressure remained about 40-50% below normal. The graph
shows that tongue and sublingual blood flow decreased to about 35%
during the first hour, showing a more dramatic response than other
tissues. These data show that an decrease in sublingual blood flow
is directly correlated with the effects of blood loss, i.e.
perfusion failure.
[0048] The relationship of sublingual blood flow and recovery of
blood volume (i.e., during perfusion recovery) was tested by
infusing the animal with a blood infusion at 120 minutes. Aortic
pressure rapidly increases during this period; similarly,
sublingual blood flow rapidly recovered.
[0049] In addition to blood flow, as described above, PCO.sub.2 or
pH may also be measured in the animal or patient, at the same time
or shortly before or shortly after such blood-flow measurements are
made, to provide further information useful for assessing perfusion
failure in an animal or a patient. PCO.sub.2 and pH may be measured
using any suitable technique, as will be appreciated by those
skilled in the art.
[0050] For example, PCO.sub.2 may be measured using a CO.sub.2
sensor such as a pH-sensing PCO.sub.2 sensor. Such PCO.sub.2
sensors may have, for example, a membrane that is permeable to
CO.sub.2, and that separates a sodium bicarbonate or carbonic acid
(HCO.sub.3) solution from the environment. A pH sensor in the
device measures the pH of the sodium bicarbonate solution. Two
exemplary CO.sub.2 sensors of this type are manufactured by
Microelectrode, Inc. and Nihon Kohden (ISFET PCO.sub.2 sensor).
[0051] Alternatively, the CO.sub.2 sensor is an optical PCO.sub.2
sensor. Structures, properties, functions, and operational details
of fiber optic chemical sensors can be found in U.S. Pat. Nos.
4,577,109; 4,785,814; and 4,842,783, as well as in Seitz, "Chemical
Sensors Based on Fiber Optics," Anal. Chem. 56(1):16A-34A (1984).
Fiber optic sensors for monitoring CO.sub.2 that may be suitable
for use in the present invention include, but are not limited to,
those described in U.S. Pat. Nos. 4,800,886; 4,892,383; 4,919,891,
5,006,314; 5,098,659; 5,280,548; and 5,330,718. Other exemplary
fiber optic CO.sub.2 sensors are described in Peterson et al.
"Fiber Optic Sensors for Biomedical Applications," Science
224(4645):123-127 (1984) and Vurek et al. "A Fiber Optic PCO.sub.2
Sensor," Annals Biomed. Engineer. 11:499-510 (1983).
[0052] A suitable optical CO.sub.2 sensor is described in U.S. Pat.
No. 5,714,121 ('121) to Alderete et al., which pertains to an
optical CO.sub.2 sensor and method of manufacture thereof; a
preferred sensor system and method of using the aforementioned
optical CO.sub.2 sensor is described in U.S. Pat. No. 5,672,515
('515) to Furlong. In general, the sensor of the '121 patent is
composed of a single optical fiber having a distal tip and a
proximal region for communication with a means for receiving a
signal from the distal tip. Light of a predetermined wavelength is
directed through the optical fiber towards the distal tip, and
emitted fluorescent light returns along the fiber to be detected
and converted to a CO.sub.2 concentration value. A capsule,
composed of a CO.sub.2-permeable silicone material, is arranged
over the distal tip at a predetermined position. The capsule
contains an indicator solution having a suitable pH-sensitive
indicator component, generally a fluorescent dye, and substantially
no air. Examples of fluorescent dyes include without limitation
fluorescein, carboxyfluorescein, seminaphthorhodafluor,
seminaphthofluorescein, naphthofluorescein, 8-hydroxypyrene
1,3,6-trisulfonic acid, trisodium salt ("HPTS") and
dichlorofluorescein, with HPTS particularly preferred. A sealing
means provides a liquid-tight seal and affixes the capsule onto the
distal tip.
[0053] Optical CO.sub.2 sensors are generally used by contacting
the distal end of the sensor with a mucosal surface as described
herein. Light of a predetermined wavelength is directed from an
external source, through the optical fiber, impinging distally on
the encapsulated indicator composition. The intensity of the
emitted fluorescent light returning along the fiber is directly
related to the concentration of CO.sub.2 in the sample, as a result
of the pH-sensitive indicator material present at the fiber tip
(i.e., the pH of the indicator solution is directly related to
CO.sub.2 concentration, as a result of carbonic acid formation).
The emitted light is carried by the optical fiber to a device where
it is detected and converted electronically to a CO.sub.2
concentration value. The sensor may additionally have a reference
dye present in the indicator composition. The intensity of the
light emitted from the reference dye may be used to compensate, via
ratioing, the signal obtained from the indicator. A more preferred
system for determining PCO.sub.2 is described in the '515 patent,
directed to a simultaneous dual excitation/single emission
fluorescent sensing method, wherein light of two different
wavelengths is used to excite a single fluorescent indicator
species, with one of the two wavelengths at the isosbestic point.
The two fluorescence emission signals that result are ratioed to
provide the desired measurement.
[0054] Suitable pH sensors include optical pH sensors as described
in U.S. Pat. Nos. 5,536,783 and 5,607,644 to Olstein et al. Such
optical sensors include a chemical pH sensor means, capable of
responding to changes in pH in nearby tissues and fluids, that is
incorporated into a fiber optic waveguide assembly so as to
interact with the environment into which the pH sensor means is
placed. The sensor may be placed in a patient's body, and more
particularly, may be placed adjacent a mucosal surface in a
patient's body. Typically, the responses of the chemical sensor
cause changes in the optical properties of the chemical
sensor/optical waveguide assembly, so that pH changes near the tip
of the assembly may be monitored and assessed by the user at
another portion of the apparatus, e.g., at a portion of the
apparatus remaining external to the patient's body. For example, as
described in the aforementioned U.S. patents, the pH sensor means
may comprise a fluorescent poly(urethrane) copolymer that
fluoresces in response to irradiation, wherein the fluorescence is
dependent on the pH of the environment being monitored.
[0055] The results of experiments in the animal model, as shown in
FIG. 1, can be extrapolated to represent a human subject suffering
perfusion failure, such as that associated with a gunshot wound or
a severe cut from machinery or a knife. Thus, a patient will suffer
a rapid decrease in aortic pressure during blood loss, until the
outflow of blood is stopped by application of pressure or other
means to stop bleeding. The present invention takes advantage of
the relationship between blood flow (in the GI tract or the upper
respiratory/digestive tract, including in such tissues as
sublingual, tongue, stomach and so forth) and perfusion failure or
perfusion level, to provide methods and devices to assist a
physician or other health care provider in the diagnosis and
treatment of a patient having or susceptible to a condition
associated with perfusion failure.
[0056] For example, although assistance from a paramedic or other
person may be available shortly after the initial primary insult,
it may take thirty minutes or more for the patient to reach a
hospital. This lapse in time may make it difficult to accurately
assess the condition of the patient and the presence and/or
severity of perfusion failure. Measuring and/or monitoring
sublingual blood flow according to the present invention allows the
physician or other healthcare provider to readily detect the level
of blood flow relative to normal, as well as the rate of change of
blood flow. A rapid decrease in blood flow suggests that the
patient has suffered a loss of blood within the last hour or so,
while low blood flow indicates the patient presently suffers from a
low level of aortic pressure and perfusion failure. In this manner
the invention can be used to assess the patient's condition,
allowing for appropriate and rapid selection of an appropriate
therapy.
[0057] The present invention can also be used to monitor the
efficacy of reperfusion or other therapeutic regimen to treat
perfusion failure in the patient. For example, if the physician,
paramedic, or other emergency provider determines that a
transfusion of blood or blood components is indicated, and the
transfusion is successful in rapidly increasing aortic pressure
(such as that illustrated in FIG. 1 from 120 minutes onward), then
this success will be reflected by a rapid recovery in blood flow
(as illustrated in FIG. 1 from 120 minutes onward). FIG. 1 shows
that sublingual blood flow measurements provide a good indication
of the level of perfusion failure.
[0058] In the present invention, the inventors disclose that a
useful measurement of perfusion failure can be obtained by
measuring blood flow anywhere in the GI tract or the upper
respiratory/digestive tract. Although FIG. 2 illustrates the upper
portion of the GI tract, it is to be understood that the invention
may be practiced by placement of a blood-flow sensor adjacent any
mucosal surface accessible by the outh or nose and connecting with
the GI tract or upper respiratory/digestive tract. Accordingly, by
way of illustration, FIG. 2 shows the upper respiratory/digestive
system or tract A of a person, and particularly including the nasal
passage B, the oral cavity C, and the upper portion D of the throat
that extends to the top of the epiglottis E. The upper
respiratory/digestive tract includes, without limitation, the
esophagus F, and the gastrointestinal tract includes, without
limitation, the esophagus F, the esophageal sphincter G, the
stomach H, and the intestines J. Insertion of a catheter 10 with a
blood-flow sensor 12, through the nose or mouth B, C, past the
epiglottis E, and into the esophagus F so that the end 14 of the
catheter with the sensor 12 thereat lies adjacent a mucosal surface
within the esophagus.
[0059] Preferably, the sensor may be positioned in the upper
respiratory/digestive tract A, preferably with the sensor lying
above, at the surface of, or at the epiglottis E so it does not
have to pass by it. More preferably, the sensor is placed at a site
within the oral-nasal cavity, e.g., within the nasal cavity, the
mouth (e.g., under the tongue at a site in contact with the tongue
or the floor of the mouth, between a region of the lip and gum or
the cheek and gum, the roof of the mouth, or the soft palate), or
at a site within the pharynx. Most preferably, the sensor is placed
adjacent a mucosal surface at a site that will avoid the patient's
gag reflex or otherwise minimize discomfort.
[0060] The blood-flow sensor lies adjacent a mucosal surface in the
upper respiratory/digestive tract A, in order that it effectively
measures blood flow in the tissue. Placement of a blood-flow sensor
adjacent a mucosal surface of the upper respiratory/digestive tract
A according to the present invention provides a very good
quantification of perfusion failure at all times, including the
most critical minutes after the onset of perfusion failure when
treatment is likely to be most effective.
[0061] FIG. 3 shows one embodiment of a device or apparatus of the
present invention, wherein a tube 20 containing a blood-flow sensor
22 at its front end, is inserted into the oral cavity and placed
under the tongue T of the patient, preferably to one side of the
frenulum V. After insertion, it might be desirable if the mouth M
of the patient is kept closed around the tube. However, as with
other instruments commonly inserted through the mouth, and as with
a patient in a critical condition, the patient is usually unable to
keep his mouth closed. In such cases the device can be adapted with
a holder as described below.
[0062] As illustrated in FIG. 3, the tube 20 and sensor 22 are part
of an instrument 24 that includes a flexible cable 26 that extends
to a test instrument 30 that typically indicates the blood flow
which provides an indicia of a degree of perfusion failure. While
the tube 20 is substantially rigid, the cable 26 is flexible. The
cable 26 can be made highly flexible for ease of use, instead of
having only the moderate flexibility of a catheter. Usually
catheters require enough flexibility to pass through curved body
passages, but yet must be resistant to column-type collapse in
order to withstand the force applied to the catheter's proximal end
necessary to accomplish insertion of the distal end and movement of
the distal end along the body passage. Since the cable 26 in the
device of FIG. 3 does not have to be pushed, it can have more
flexibility for ease of use. The largely rigid tube 20 preferably
has a length of no more than about one foot (one-third meter),
since a longer length would be cumbersome. Catheters for insertion
through the esophagus into the stomach, generally have a length of
much more than two feet. FIG. 4 shows an example of a sensor 212,
which lies against the sublingual mucosal surface.
[0063] FIG. 5 shows a preferred embodiment of the device of the
invention that is suitable for taking sublingual blood flow
measurements. In this embodiment, sensor assembly instrument 214
may be held in position by a sensor holder 202 that is shaped to
lie primarily in a patient's mouth. The holder 202 forms a holder
passage 204 that extends between the inner and outer portions 202,
226 of the holder. When located in place, the sensor 214 projects
inwardly from the holder and substantially directly contacts the
mucosal surface of the patient. The frame may have an outer end
that lies outside the patient's mouth.
[0064] The holder 202 can serve to prevent discomfort to the
patient. To this end, the sublingual inner portion 226, including
portions 222 and 224, of the holder preferably lies close to the
walls of the mouth on opposite sides of the sensor 214, as well as
above and below the sensor. The upper surface 206 of the holder is
designed so the tongue T can lie on at least its inner portion, to
further provide a seal and to support the tongue to avoid tiring
the patient. The holder 202 can also serve as an aid to prevent
drying of the oral-nasal cavity.
[0065] While the holder is an exemplary and preferred isolating
means for use with the present invention, other isolating means
that serve substantially the same function can be substituted or
used in conjunction with the holder. For example, a sheath can
surround the blood-flow sensor. The sensor and the sheath can be
held in place by a holder similar to that described above, but with
the advantage that the entire device may be of an overall smaller
size (e.g., for placement in the mouth).
[0066] A second purpose of the holder is to substantially fix the
position of the sensor assembly 214 and the sensor 212 so the
sensor is maintained in a proper position and does not move. This
is particularly useful where the patient is incapable of holding
the sensor properly in place due to unconsciousness or some other
reason. A tension coil spring extending between the handle and
holder, can be used to gently urge the sensor 212 inwardly, where
necessary. The holder 202 is preferably formed of an elastomeric
material (Young's modulus of less than 50,000 psi) such as a soft
rubber or soft foam, to avoid high localized pressure on the
patient's mouth that could cause discomfort. In one embodiment, the
sensor is positioned on either side of the frenulum of the tongue.
The rear portion of the holder 226 may be shaped, as with a slot or
bevel, to comfortably receive the frenulum, so the sublingual inner
portion can lie close to the inner end of the sublingual area and
therefore closely around the blood-flow sensor.
[0067] In an alternative embodiment, the sensor can be placed
adjacent any mucosal surface accessible by the mouth or nose and
connecting with any region of the GI tract or upper
respiratory/digestive tract.. For example, in FIG. 6 the sensor 230
can be placed at a gingival mucosal surface W that lies between a
lip X and the teeth Y of the patient. The area at the rear of the
upper or lower lips X, Z is a mucosal surface. FIGS. 6 and 7
illustrate a holder 230 suitable for use at a mucosal surface
adjacent a patient's lips. In this embodiment, holder 230 is
preferably of soft elastomeric material such as an elastomeric
solid or a foam, or even a viscous fluid in a flexible shell. The
holder isolates the mucosal surface area contacted by the sensor
and prevents movement of the sensor.
[0068] In another embodiment, the blood-flow sensor 240 lies
adjacent a mucosal surface area AA in the vestibule of the nasal
cavity of a patient (FIG. 8). A foam plug 242 serves as a holder
that holds the sensor to position it. Only a pair of electrical
wires 244 extend from the sensor through the holder. Where the
blood-flow sensor is a fiber optical sensor, the holder can be
adapted accordingly so that only the optical fiber extends from the
plug.
[0069] In another embodiment, the blood-flow sensor may be placed
adjacent any mucosal surface in the nasal cavity of a patient.
[0070] In another embodiment, the blood-flow sensor may be placed
adjacent any mucosal surface in the middle nasal conchae of a
patient.
[0071] In another embodiment, the blood-flow sensor may be placed
adjacent any mucosal surface in the inferior nasal conchae of a
patient.
[0072] In another embodiment, the blood-flow sensor may be placed
adjacent any mucosal surface in the choana of a patient.
[0073] In another embodiment, the blood-flow sensor may be placed
adjacent any mucosal surface in the pharyngeal opening of the
auditory tube of a patient.
[0074] In another embodiment, the blood-flow sensor may be placed
adjacent any mucosal surface in the pharynx of a patient.
[0075] In another embodiment, the blood-flow sensor may be placed
adjacent any mucosal surface in the oropharyngeal passage of a
patient.
[0076] In another embodiment, the blood-flow sensor may be placed
adjacent a mucosal surface in the stomach of a patient.
[0077] In another embodiment, the blood-flow sensor may be placed
adjacent a mucosal surface in the jejunum of a patient.
[0078] In another embodiment, the blood-flow sensor may be placed
adjacent a mucosal surface in the colon of a patient.
[0079] In another embodiment, the blood-flow sensor may be placed
adjacent a mucosal surface in the rectum of a patient.
[0080] In another embodiment, a PCO.sub.2 sensor may be used in
conjunction with the blood-flow sensor. Alternatively, a pH sensor
may be used in conjunction with the blood-flow sensor. In a further
embodiment, both a pH sensor and a PCO.sub.2 sensor may be used in
conjunction with the blood-flow sensor. The advantages of such a
combination in providing a more robust indication of perfusion
failure will be well understood by those skilled in the art.
[0081] The blood-flow sensor used in the methods and devices of the
invention may be any blood-flow sensor suitable for detection of
blood flow in the manner described herein, such as laser-Doppler
blood-flow sensors, ultrasound-Doppler blood-flow sensors, imaging
sensors and so forth. For example, the preferred blood-flow sensor
is a laser-Doppler blood-flow sensor.
[0082] An exemplary blood-flow sensor of this type is manufactured
by Vasomedics (2963 Yorkton Blvd., St. Paul, Minn. 55117-1064;
(800) 695-2737)). For example, the Laserflo BPM.sup.2 may be used
to provide continuous tissue perfusion data which can be used to
practice the present invention.
[0083] Thus, the invention provides a method and device for
assessing perfusion failure, which methods may be performed
rapidly, with little equipment set-up required, and with minimal or
substantially no invasion, and thus minimal risk of harm to the
patient and an improved probability of patient compliance. The
method generally involves introducing a blood-flow sensor adjacent
any mucosal surface accessible by the mouth or nose and connecting
with the GI tract of a patient, or the upper respiratory/digestive
tract of a patient. Furthermore, the method can be performed so as
to avoid even triggering the gag reflex of the patient by placing
the blood-flow sensor in the upper respiratory/digestive tract at a
position generally above the epiglottis. Measurements of blood flow
are taken while the sensor is held adjacent a mucosal surface in
the upper respiratory/digestive tract, such as a mucosal surface of
the mouth or nose, for example the area under the tongue, an area
between the upper or lower lip and the teeth, or an area in the
nose. A holder may be optionally used to prevent sensor movement
The invention is useful in a variety of settings, such as in triage
in emergency and disaster settings, monitoring in anesthesia,
intensive care, and other acute settings in which patients may have
acute perfusion failure (shock).
[0084] It is to be understood that while the invention has been
described in conjunction with the preferred specific embodiments
thereof, that the foregoing description as well as the examples
which follow are intended to illustrate and not limit the scope of
the invention. Other aspects, advantages and modifications within
the scope of the invention will be apparent to those skilled in the
art to which the invention pertains. All patents, patent
applications, journal articles and other references mentioned
herein are incorporated by reference in their entireties.
* * * * *