U.S. patent application number 11/891890 was filed with the patent office on 2008-04-17 for measurement of autonomic function.
This patent application is currently assigned to Biographs, LLC. Invention is credited to John Burke.
Application Number | 20080091098 11/891890 |
Document ID | / |
Family ID | 39082694 |
Filed Date | 2008-04-17 |
United States Patent
Application |
20080091098 |
Kind Code |
A1 |
Burke; John |
April 17, 2008 |
Measurement of autonomic function
Abstract
The present invention is an article of manufacture and method
for using same, comprising at least two sensors having a paired
offset potential of below about +/-1.0 mV; and a data gathering
device connected to the sensors capable of measuring the voltage
difference between the sensors. The sensors preferably are AgCl
coated Silver.
Inventors: |
Burke; John; (Bayville,
NY) |
Correspondence
Address: |
Richard Gearhart
4 Ferndale Rd.
Chatham
NJ
07928
US
|
Assignee: |
Biographs, LLC
Stony Brook
NY
|
Family ID: |
39082694 |
Appl. No.: |
11/891890 |
Filed: |
August 14, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60837658 |
Aug 15, 2006 |
|
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|
Current U.S.
Class: |
600/391 |
Current CPC
Class: |
A61B 5/4824 20130101;
A61B 5/6825 20130101; A61B 5/4035 20130101; A61B 5/24 20210101;
A61B 2562/0215 20170801 |
Class at
Publication: |
600/391 |
International
Class: |
A61B 5/0408 20060101
A61B005/0408; A61B 5/04 20060101 A61B005/04 |
Claims
1. An article of manufacture, comprising: at least two sensors
having an offset potential of below about +/-1.0 mV; and a data
gathering device connected to the sensors capable of measuring the
voltage difference between the electrodes.
2. The article of claim 1, wherein at least two of the sensors
possess a sensing side having an AgCl coating on a Silver
substrate
3. The article of claim 1, wherein the offset potential is below
about +/-0.5 mV.
4. The article of claim 1, wherein the offset potential is about
+/-0.01 mV.
5. The article of claim 1, wherein a pre-applied conductive gel is
disposed on the sensing side of the sensors.
6. The article of claim 1, wherein the sensors are connected to a
data gathering device via lead wires across a resistor of 0.5 to
500 k-Ohms.
7. The article of claim 1, wherein the sensors are less than 20 mm
in diameter.
8. The article of claim 1, wherein the sensors are 10 mm in
diameter.
9. The article of claim 1, wherein the sensors are disposable.
10. The article of claim 1, wherein the sensors have an adhesive
collar.
11. A device suitable for detecting a shift in the autonomic
nervous system, comprising: a sensor, wherein said sensor is
utilized with at least one other sensor, and said sensor has an
offset potential of less than 0.5 mV when used with said other
sensor.
12. The device of claim 11, wherein the sensors have an
exposed-to-gel sensing side of silver chloride coated silver.
13. The device of claim 11, wherein the offset potential is below
about +/-0.5 mV.
14. The device of claim 11, wherein the offset potential is about
+/-0.01 mV.
15. The device of claim 11, wherein a conductive gel is pre-applied
to the sensor.
16. The device of claim 11, wherein the sensor is less than 50 mm
in diameter.
17. The device of claim 11, wherein the sensor is less than 20 mm
in diameter.
18. The device of claim 11, wherein the sensor is about 10 mm in
diameter.
19. The device of claim 11, wherein the sensor is disposable.
20. The device of claim 11, wherein the sensor has an adhesive
collar.
21. A method for detecting a shift in the autonomic nervous system,
comprising: affixing at least two sensors having a paired offset
potential of less than 0.5 mV to contralateral sides of an animal
or human; and measuring the voltage difference between said
sensors.
22. The method of claim 21 wherein the voltage differential is
measured continuously.
23. The method of claim 21, wherein the voltage differential is
recorded, displayed or both recorded and displayed by a data
gathering device.
24. The method of claim 21, wherein the voltage differential is
correlated to a Visual Analogue Scale and self-reported pain.
25. The method of claim 21, wherein the method is used to diagnose
conditions of altered ANS function.
26. The method of claim 21, wherein the method is used to ascertain
the effectiveness of medicine.
27. The method of claim 21, wherein the method is used on a
human.
28. The method of claim 21, wherein the method is used on an
animal.
29. The method of claim 21, wherein at least one sensor is affixed
to each hand of a human.
Description
RELATED APPLICATION
[0001] This application is based on provisional application Ser.
No. 60/837,658 filed Aug. 15, 2006.
FIELD OF THE INVENTION
[0002] The invention relates to methods of detecting and
quantifying nociception and pain, and devices and components
related thereto.
BACKGROUND OF THE INVENTION
[0003] The autonomic nervous system (ANS) governs the functioning
of numerous organs in the body of humans and other mammals. Yet
there exists no quick, simple, inexpensive, or reliable test to
measure the full range of autonomic function in an individual, nor
its current state.
[0004] The two major components of the ANS are the sympathetic
nervous system (SNS) and the parasympathetic nervous system (PNS).
Nerves from both usually innervate the organs they control. Thus
organ performance is the result of the interplay of both PNS and
SNS. A measure of either SNS or PNS is not very useful in assessing
the condition of the subject. For example, a subject may have high
PNS tone without being relaxed because its effects are being offset
by high SNS tone. Heart rate, for example, is determined by
interplay between PNS and SNS. Both nerves innervate and affect our
hearts. When a subject's PNS vagal nerves to the heart are cut, its
heart rate rises and remains elevated.
[0005] A novel method is described herein to measure the
moment-to-moment relative dominance of PNS tone (sometimes also
referred to as vagal tone) and SNS tone. The method is inexpensive,
easily understood, consistent, reliable, as well as simple and
quick to administer. It is completely passive and requires no
voltage to be administered to the subject, thus eliminating the
possibility of side effects from the resultant current. It works
well on both humans and animals.
[0006] The method gives a distinctive, "signature" reading for
subjects experiencing any moderate to severe pain that has lasted
for more than a few minutes, both in humans and other mammals.
Therefore, it provides a previously non-existent, objective
description of pain. Currently, all pain is now measured by asking
the subject questions about their pain (i.e., "On a scale of 0-10,
how would you rate your pain?"). This is clearly subjective.
Non-verbal patients cannot be evaluated by these methods. Thus
health care providers are at a loss to measure pain in young
children, advanced dementia adults, some stroke victims and
intubated patients, as well as the rest of the animal kingdom. Prey
species of animals (including horses and sheep) pose a particular
challenge because they are genetically programmed to mask their
pain so as not to become the primary target of a predator. Even
expensive thoroughbred racehorses are often the subject of vigorous
debate by their caretakers regarding their pain status.
Furthermore, a reliable and consistent objective measure of pain
would prove useful to doctors who suspect the patient is
exaggerating or imagining his or her pain, as well as to insurers
who suspect malingering.
[0007] The method described herein works by recording a measurable
physiological correlate of ANS changes, namely the difference in
electrical potential between two sensors placed on the skin.
Similar to the Tarchinoff voltage measure of electrophysiology, it
differs by sensing between sites of similar instead of high to low
sweat gland densities. Skin is innervated by nerves from both the
SNS and PNS, which, respectively, increase and decrease
physiological rates in tissue and organs throughout the body. These
nerves are distributed relatively symmetrically throughout the body
but are not always activated in a symmetrical manner. With pain,
for example, persistent pain from anywhere in the body of moderate
to severe intensity begins to raise blood pressure (BP). This
activates the baroreceptors in the carotid sinus artery. They
trigger an increase in PNS (vagal) tone in an attempt to stop the
BP increase and restore homeostasis. In addition, this process
triggers the release of endorphins, the body's own, natural opioids
which provide partial pain relief. This process is part of what is
known as Descending Nociceptive Inhibitory Control, or DNIC. This
response is mediated primarily by the right cardiac vagal (PNS)
nerve, not the left one. This nerve branches off and innervates
other tissue along the way. The result is slightly slower
physiology on the right side of the body. It has now been found
that this includes the two-skin-site voltage difference effect.
Accordingly, the voltage sensed on the right side of the body, with
respect to the left, drops as PNS tone rises through increased
activation of the right cardiac vagal nerve.
PRIOR ART
[0008] Most Galvanic Skin Reflex measurement has been done by
sensing the Fere effect, so named after its discoverer. This is the
change in the skin's ability to conduct electrical current due to
sweat gland activity. The reason for this method has been due
partly to the relative ease, reliability, and consistency of
measurements. This is due to the relatively large applied voltages
used to measure the Fere effect, in contrast to the small, natural,
body voltages of the Tarchinoff aspect of the GSR. In the case of
the present invention, the magnitude of the voltage difference
between the right and left sites on the body, is often smaller than
the offset voltages of sensors which have been standard in the
industry. Data gathered with high offset sensors would lead to
inconsistent measurements and the conclusion that there was no
useful information to be obtained this way. The invention described
herein overcomes these deficiencies of the prior art methods.
[0009] Two posters have been presented at medical conferences
showing anecdotal reports of such ANS shifts reflected in skin
potential. (Ngeow, et al, Aug. 21-26, 2005), (D'Angelo, May 2006).
This previous work did not use sensors which had been selected for
their low offset potentials. The practitioners presenting these
posters had been unaware of the role of offset potentials in these
types of measurements, and it was not discussed in their posters.
The form of sensor used to obtain the data presented in the posters
has produced a wide and changing variety of offset potentials due
to a combination of factors. One was a lack of consistency in
manufacture. Still another was a lack of consistency in use. These
sensors were of a cup style which required the examiner to fill the
cups above the Ag/AgCl coated sensor surface to the brim of the cup
with conductive gel. If the examiner fails to place the adhesive
collar with its hole directly above the cup, part of the collar
will cover some of the electrode gel, blocking its area of contact
with the skin. This may produce a smaller signal coupled to the
system load resistor. In addition, if the examiner fails to fill
one of the cups completely to the brim, this may introduce a
difference between the area of contact of the two recording
electrodes that also may produce a smaller coupled signal.
Occasionally, good readings can be taken, such as those selected
for the posters, but they cannot be obtained consistently with the
type of sensor methodolgy shown in the posters even with trained
personnel in the time conscious environment of a clinical setting.
The proposed method solves that by using pre-applied gel that has
been spread evenly on each electrode during manufacture, producing
much more consistent readings.
[0010] The present low offset voltage sensors invention can be used
to track the progress of an individual during a series of
treatments or during healing, due to consistent readings obtained
by minute and consistent offset potentials. This cannot be said of
most other types of electrodes.
[0011] Most prior work involving the use of measuring sensors on
the skin in order to chart autonomic changes has been Galvanic Skin
Resistance Work. This also uses electrodes on the hands, but the
purpose and approach is of an entirely different type. In GSRes an
external voltage is applied to the subject's skin through a pair of
sensors and the OSRes unit measures the current.
[0012] Levengood and Gedye in U.S. Pat. No. 6,347,238 utilize some
of the same hardware as the disclosed invention but their method
has great limitations. Levengood teaches electrodes against which
the hand must be pressed neither of which is self-adhesive and both
of which must be pressed against the hand or body by the physical
force of tester or subject. Since the magnitude of the coupled
resistance loaded signal is affected by the area of contact, even
very slight variations in pressure produce artifacts, namely
variations in the recording. If skin surface contact resistances of
the sensor pair, in some manner, tap into a bulk, internal,
electrical field gradient, a voltage polarity reversal may even be
brought about by a difference in physical force being applied to
the left versus right sensor. The self-adhesive sensor employed in
the present invention eliminates this deficiency. Levengood's
method is further limited by its use of solid metals. Virtually all
solid metals form a "half-cell" potential when they are in contact
with a saline solution such as the subject's perspiration. This
well known electrochemical effect need not be further elucidated.
The absolute and imbalance magnitudes of the half-cells for
aluminum, the metal specified in Levengood, are amongst the largest
for solid metals. This artifact can overshadow the small signals
being sought in the two-sensor site voltage measure. At a minimum,
it will affect the numeric reading of the site to site voltage.
AgCl coated Ag sensors of the type employed in the present
invention minimize this effect. Such low offset sensors are not
taught by Levengood.
[0013] Unlike prior art that deals primarily with the Fere effect
and involves active addition of extraneous electrical current to
the skin, the present invention, like Levengood, measures only the
two site voltage measure. Leavengood does not teach the involvement
of the ANS. Accordingly, the occasional false positive cannot be
spotted. Occasionally a subject produces a positive reading despite
being in moderate to severe pain. If ANS indictors such as Heart
Rate and Diastolic Blood Pressure are over 95, the examiner can
take into account that SNS tone is obviously extremely high at the
moment and therefore the reading is unreliable. A chronic pain
patient with pain of 7 on the 0-10 VAS scale could still produce a
positive reading under these conditions. Thus the other cited prior
art does not teach the disclosed method. None of the cited prior
art deals with offset potentials of the sensors used. Without
consideration of offset potentials, the weak two site voltage
difference cannot be measured accurately. Even some commercial
Ag/AgCl sensors possess offset potentials sufficient to seriously
affect the voltage readings of the present method. However, by
utilizing low offset potential electrodes (i.e. below 1.0 mV as in
the disclosed system, (and the lower the offset potential the
better) as described in more detail herein below, the voltage
difference can be measured with consistent accuracy. Selected low
offset potential sensors were not taught in the prior art.
SUMMARY OF THE INVENTION
[0014] The present invention is an article of manufacture and
method for using same, comprising at least two electrodes or
"sensors" having an offset potential of below about +/-1.0 mV; and
a data gathering device connected to the sensors capable of
measuring the voltage differential between the electrodes. The
sensors preferably are AgCl coated Silver.
[0015] It is an object of the invention to teach a device capable
of measuring pain in a subject.
[0016] It is also an object of the invention to detect changes in
the ANS.
[0017] It is a further object of the invention to teach a device
capable of measuring pain that uses low offset potential
sensors.
[0018] It is another object of the invention to teach a device that
senses voltage and does not pass a significant, exploratory current
through the subject.
[0019] It is yet another object of the invention to teach a pain
measuring device that utilizes AgCl coated Ag sensors.
[0020] It is also an object of the invention to teach the use of a
low offset electrode in a pain measuring device.
[0021] It is yet a further object of the invention to teach a
device and method which allows consistent quantifiable measurement
of pain.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] FIG. 1a shows one example of the data gathering device of
the invention, a portable digital data gatherer with numerical LCD
readout.
[0023] FIG. 1 b shows an example of the present invention for use
with animals, wherein the electrodes are applied to identical spots
on contralateral sides of a horse's neck.
[0024] FIG. 2 shows an example of use with humans wherein the
electrodes are applied to the center of the subject's palms.
[0025] FIGS. 3a and b show examples of graphic display of a pain
reading of an animal, on a computer, showing the effects of a known
ANS trigger, namely, the effect of a vacuum cleaner noise in
proximity to a cat.
[0026] FIG. 4 shows epilepsy-like alterations in ANS activity.
[0027] FIGS. 5a-d show dental pain and pain relief in a 51 year old
male human, depicted on a strip chart recorder.
[0028] FIGS. 6a-c show headache pain and pain relief in humans,
depicted on strip chart recorder.
[0029] FIGS. 7a and b show pain and pain relief for horses, as
shown on a strip chart recorder.
[0030] FIGS. 8a and b show the reading of a lame horse before and
after healing (shown on computer generated graph).
[0031] FIGS. 9a and b show sensor offset potentials only measured
by pressing two gelled sensors together gel to gel and connecting
them to a data gathering device.
[0032] FIGS. 10 a and b show the magnitude distortion of subject
readings caused by electrodes with different amounts of offset
potential.
[0033] FIGS. 11a and b show the magnitude of the distortions of the
sensors in the prior art.
[0034] FIGS. 13a-d show the consistency in readings taken with the
AgCl coated Silver sensors of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0035] The present invention is an article of manufacture and
method for using same. Comprising at least two sensors having an
offset potential of below about +/-1.0 mV; and a data-gathering
device connected to the sensors capable of measuring the voltage
differential between the sensors. The sensors preferably are AgCl
coated Silver.
[0036] It is a key feature of the preferred embodiment that low
offset potential sensors are utilized in the present invention. As
mentioned above, low offset potential sensors allow (the low
artifact) detection of the very (small voltages) generated as a
result of SNS and PNS changes in tone. Sensors of the prior art had
higher offset potentials which act as noise artifact and confound
the measurement of the small, desired signal voltages. The offset
potential difference between the sensor pair of the sensors of the
present invention should be below about +/-1.0 mV, and are
preferably below +/-0.5 mV, and most preferably about +/-0.01 mV.
Preferred sensors are model GS-26 from Bio-Medical Corp. (Warren,
Mich.), although any sensors meeting the criteria stated herein
will be sufficient for the purposes of the invention.
[0037] In addition, the sensors of the present invention should
have a coating sufficient to conduct the small voltages due to SNS
& PNS activations but should not create offset potentials of
similar magnitudes. As previously mentioned, aluminum sensors or
other crystal lattices can create a higher offset potential. The
most preferred coating for the sensor is an AgCl coating. The
coating can deposited electrolitically deposited and be of any
thickness, although coatings of higher thicknesses are more durable
and less prone to scratching. Other materials or coatings may be
suitable, such as gold, so long as they achieve the offset
potential requirements of the present invention. The AgCl compound
is most preferred.
[0038] It is also preferable that the sensors be coated with a
conductive gel. The conductive gel is preferably applied by a
mechanical process that allows for the gel to be applied in a
consistent manner, and with a minimum of air bubbles. In most
cases, this will mean that the gel is pre-applied utilizing a
mechanical process at a factory. However, as used herein, the term
pre-applied can refer to any process that allows for a consistent
application of the conductive gel, i.e., a gel that is applied with
a consistent thickness across the sensor and in a manner so that
conductivity is consistent from electrode to electrode. This may
mean that the gel is applied in a manner which creates a minimum of
air bubbles or at least a consistent amount of air bubbles from
sensor to sensor.
[0039] The sensors of the present invention will also most likely
have a means for adhering the sensors to the subject. Any method of
adhering the sensors to the subject is acceptable, as long as it
does not interfere with the ability of the sensor to acquire the
sensor to sensor voltage. For example, the electrodes could be
taped to the subject. In a preferred embodiment, the sensor has a
collar around the outer diameter of the electrode, which has an
adhesive applied thereto. The sensors can be affixed anywhere on
the subject, so long as they are affixed contralaterally in an
identical manner. Preferably, the electrodes are affixed in
identical positions on either side of the body, for example, on the
palms a humans' hands or opposite sides of their neck.
[0040] The size of the electrode depends on the type subject, and
on which body part the sensor is to be attached. The device of the
present invention can be used for either humans or animals. For
humans, a sensor of 50 mm or less is desirable, and if the sensor
is to be attached to the palm of the hand, a sensor of 10 mm is
most desirable. For large animals such as horses, sensors of up to
50 mm or larger may be appropriate. Therefore, it is anticipated
that the size of the sensor will be selected appropriately for the
type of subject as well as the expected place of placement
thereon.
[0041] The data gathering device of the present invention can be
any device suitable for detecting the signals generated during the
measurements. For example, the device can be an analog meter with a
digital readout that simply reports the voltage differentials
between the electrodes. An illustrative example is seen in FIG. 1a.
Or, in the alternative, the data gathering device can be a
stripchart recorder typically used to monitor EKG outputs. The data
gathering device can also have a memory which allows it to record
the data of one or more subjects over a period of time. The data
gathering device can potentially be linked with a computer having
software to maintain and analyze subject data. It can also consist
of an analog dial to display the strength of the reading.
[0042] In preferred embodiments of the present invention, the
examiner uses disposable, low-offset-potential biomedical sensors
(offset of less than 0.5 millivolts) with adhesive collars, a
covering of conductive gel applied at the factory, and an actual
diameter of the sensor of approximately 10 mm, designed for use
with humans. Each subject should be allowed to rest quietly for ten
minutes before the measurement process begins. Preferably, the
subject refrains from coffee or other stimulants for three hours
before the measurement session. The present invention begins with
the placement of the self-adhesive, extremely low-offset-potential
electrodes. On humans this may be advantageously achieved by
placing one sensor in the center of each palm. The same site on the
palm should be used on each hand. See FIG. 2. However, other sites
on the body can be used so long as care is taken to select
identical sites on both left and right sides of the body. An
alcohol swipe of the sites to remove excess skin oils (which can
inhibit conductivity) may be performed prior to electrode
placement. During the measurement process, the subject should be
asked to remain still and relax. Abrasion of the skin can also be
used to obtain still better conductivity. To insure identical
conditions, each palm is preferably treated the same way to (e.g.,
use an identical number of strokes of the alcohol pad or abrasive
on each palm, and use a different side of the pad for each palm).
On short haired animals such as horses this can be achieved by
using other contralateral electrode sites, such as both sides of
the neck, (see FIG. 1b) which may require shaving of the electrode
site and preparation with an alcohol swipe. Alternatively, a
conductive gel may be used to obtain valid readings through a coat
of hair or fur if it is not too thick.
[0043] During readings on humans, the subjects preferably sit
upright, with the backs of their hands resting on the top of their
thighs. Care should be taken to avoid pressure on the wires or the
electrodes. Subjects should then be asked to remain still, close
their eyes, and relax for the duration of the reading. If a
non-digital data gatherer is used, such as a strip chart recorder,
an ear clip ground should be employed. This is in the form of a
silver clip attached to the right ear lobe, with a lead wire that
plugs into the ground input receptacle of the recorder. This ground
wire substantially limits electrical interference by other people
moving around nearby in a busy clinical environment. For animal
subjects and non-verbal humans, the subject should be kept as
stationary as possible. In interpreting results, care should be
taken to spot ANS disruptions caused by impatience or anger on the
part of the subject from frustration or annoyance of being perhaps
restrained for the measurement. It should be noted that a minority
patients, when measured in the afternoon after lunch, have negative
readings when in a pain free state. Patient readings should be
double checked or measurements done in the morning if this
phenomenon occurs for a particular patient.
[0044] To avoid the above problems with restraint, a hand-held
measuring unit with battery-powered data logger can be moved
alongside the individual while they move about. Similarly, subjects
with conditions that only manifest pain during movement (for
example, walking or bending) can be tracked while they move.
Decreases in the values of readings during movement can be taken to
indicate pain that is induced by the movement.
[0045] After preparation of the sensor site with alcohol pads,
special self-adhesive sensors with low offset potential are then
peeled off their sheet and pressed onto the skin at the proper
site. The individuals performing the measurement should run their
thumb firmly around the top surface of the electrode's adhesive
collar and press down on the metal electrode snap itself to assure
that both electrodes are firmly affixed. It is preferred that the
entire gel coated metal sensing surface be in contact with the skin
on both sites on the subject. It is also preferred to treat each
electrode the same way in order to achieve identical conditions on
both contralateral sides. If, after removal of the electrodes, the
examiner wishes to take another measurement, the alcohol swipe
should be repeated to remove any adhesive residue on the skin from
the first measurement.
[0046] Next the lead wires are attached to the electrodes by clips
or snaps. The lead wires are connected across a load resistor of
from 0.5 k to 500 k Ohms, preferably 22 k Ohms, at a data gathering
device such as a chart recorder, digital data logger, or other
device. The voltage difference between the lead wires in series
with the voltage's source resistance (representing the
"resistance-containing" voltage source between the left and right
sides of the body) produces a voltage drop across the load resistor
which then "feeds" the data gathering device. The data gathering
device can produce both numerical values and/or a continuous line
on a volts vs time graph, either or both of which constitute the
reading. The Y-axis displays the resistance-divider modified
voltage of the incoming signal. Increases in voltage or decreases
in voltage-source-resistance between the left and right sides of
the body, will increase the Y value. Sometimes the subject's
reading or "trace" will be a fairly horizontal line on the graph.
Often it will start out high above the Y=0 "baseline" (i.e.
positive numerical values) and then, as the subject relaxes, begin
to move downwards towards the Y=0 baseline. Under normal
circumstances, a trace will occur directly on the Y=0 baseline if
the voltage between the sensors is 0. Usually by the one minute
mark the trace will have stabilized at a "plateau" and remain
relatively steady. If this has not occurred, the measurer may wish
to continue the trace for another minute.
[0047] After 60-120 seconds, the recorder can be switched off. The
reading may now be interpreted. While useful information may be
obtained from the entire trace, the degree to which the trace may
be above or below baseline at the end of the trace should be
observed. The record of the trace may be stored in a paper file or
in a computer. The entire process, from site prep to storing the
recording takes approximately 3-5 minutes and can be performed by a
minimally trained individual. Presence or absence of moderate to
severe pain can usually be confirmed with a glance at the graph to
see whether the subject's trace is above or below Y=0. If it is
below Y=0 (i.e. negative numerical values), the subject can be
assumed to be in moderate to severe pain, unless other confounding
factors are at work (ANS dysfunction, etc.) If the trace is above
Y=0, the subject can be assumed to be pain free or experiencing
pain below a level of 4 on the 0-10 Visual Analogue Scale (VAS), as
has been determined by large numbers of measurements that have been
taken on subjects reporting their pain state on the 0-10 VAS at the
time of measurement.
[0048] This same protocol should be used even when the measurement
is being taken for purposes other than the confirmation of the
presence or absence of significant pain (e.g., searching for
disruptions in ANS balance produced by other causes).
[0049] Lead wires from the electrodes should be connected to the
data gatherer in a pre-determined manner such that lower voltage on
the right hand (vs. the left) will produce a trace below the zero
baseline, or Y=0 and give negative numerical values.
[0050] If analysis of more rapidly changing signals is desired, a
data gatherer with sampling rates faster than 1 per second should
be used along with a commensurate increased bandwidth "anti-alias"
filter. A trace should then be taken while the subject engages in
controlled breathing or Valsalva maneuver or other known vagal
triggers for a minimum of one minute. The data gatherer will record
SNS tone increases in response to inspiration (breathing in) and
PNS tone increases in response to exhalation. On a graphic display,
the difference between the high peaks and the low valleys provide
the lability of that individual's ANS. In a graphic display, or
trace, of a subject's recordings taken during normal breathing for
diagnostic purposes, the distance of traces below the zero baseline
can then be expressed in terms of percentage of total ANS lability.
If the display being used is numerical, adding the absolute values
of the greatest positive voltage readings to the absolute values of
the greatest negative voltage readings will equal the maximum ANS
lability of the individual (e.g., positive 2.0 mV+negative 1.5
mV=3.5 mV total lability). This can allow the investigator to, for
example in the case of pain, estimate how significant the negative
displacement of the trace below Y=0 is for that given individual.
This can be used to account for a decrease in the degree of ANS
lability associated with age, and/or the fact that some individuals
simply have more ANS lability (for example, are more excitable)
than others. Therefore this controlled breathing measurement
procedure allows a quantitative estimate of the subject's condition
to be made without obtaining a prior baseline. The baseline reading
can be obtained during controlled breathing when the subject comes
in for the first visit to obtain treatment or investigation of
their condition. Similar analyses can be performed using other
known clinical vagal triggers such as the Valsalva maneuver.
[0051] When tracking of rapidly changing signals is not required, a
lower rate of sampling (once every second to once every few
seconds) along with a narrower bandwidth anti-alias filter will
provide a smoother, more easily interpreted trace, one that
eliminates much of the moment-to-moment swings caused by
respiration. When faster tracking is desired, the examiner may
advantageously first measure with the fast sampling rate and
broader filter during controlled breathing and save this record.
Next he or she may measure with the slower sampling rate and
narrower filter and take the reading at the 60 second mark to allow
calculation of the sixty second reading as a percentage of total
lability. This observed value can then be compared to established
databases, thus indicating a range of pain levels associated with a
given degree of deflection from the neutral, zero baseline for that
given individual being measured.
[0052] Paper records from a chart recorder can be torn off and
stored in the patient's folder. With computer-linked digital data
recorders, both the numerical readings and the graph can be printed
on paper and inserted in the patient's chart and/or stored
electronically as a file in the computer. Furthermore, such
electronic files can be analyzed by sophisticated statistical
analysis programs, and such files can be e-mailed to a colleague
for consultation if the colleague has the same software installed
on his or her computer.
[0053] If grossly unexpected results are obtained, there may be one
of two problems present. One of the sensors may have adhered to the
subject loosely. If this is suspected, simply repeat the
measurement to confirm. However, if connections seem to be of equal
quality on both sides, then the examiner should remove the sensors
and check their offset potential. Even specially manufactured
low-off set-potential sensors can sometimes have a defective unit
in a batch. Carefully peel off the sensors from the subject and
place them together so that the exposed gelled metal sensing
surfaces (i.e. the gelled surface contacting the skin) of the two
sensors are precisely atop one another. Press them and their
adhesive collars firmly together so that the adhesive collars keep
the gelled surfaces in contact. Connect lead wires to the sensors
and take a reading. Readings obtained should be on the order of
less than 0.2 mV. If readings substantially above this are
obtained, then the offset potential may be grossly affecting the
subject's reading magnitude and the entire measurement process
should be repeated.
[0054] Problems of high offset potential may be due to the nature
of the sensors or the chemical compound coating the sensors. Pure
metals generally form sizeable half-cell potentials. That is,
interaction between the salt water of the subject's perspiration
(always present on the skin to some extent) reacts with the metal
to generate a half-cell voltage. This artifact can overwhelm the
small signals being acquired in the two-sensor-site measure of the
present invention. At a minimum, it will affect the numeric reading
of the site to site voltage. AgCl coated Ag electrodes of the type
employed in the present invention were developed precisely to
counter this effect. These are pure standard metals, such as
silver, but the area in contact with the skin contacting gel is
coated with an electrolytically formed silver-chloride layer. These
have much lower offset potentials than most other sensors. However
the thin coats of AgCl are easily scratched and therefore it is
preferred to use disposable Ag/AgCl sensors in order to insure
consistency of readings.
[0055] However, even Ag/AgCl sensors may have offset potentials on
the order of several millivolts. This is measured by pressing two
sensors together and measuring the effect. The site to site voltage
difference measured without skin abrasion in the present invention
is often less than a millivolt. Thus offset potentials can
overshadow this signal and produce erroneous results. Clearly, the
use of low offset potential electrodes allows meaningful data to be
obtained during the type of measurements that constitute the method
described here.
[0056] There are numerous uses for the present invention including
measuring the effects of various agents on SNS and PSNS tone,
including but not limited to: beta blockers, atropine, scopolamine,
beta-adrenergenic blockade, sedatives, anti-anxiety medications,
analgesics, anesthetics, narcotics, and others. Thus the proposed
method may help in titration of medicines and/or determining the
effectiveness of a particular medication for a given subject. The
method may also help in diagnosing conditions that involve altered
ANS function, including but not limited to: certain types of
hypertension, Parkinson's disease, multiple sclerosis,
Guillain-Barre syndrome, and orthostatic hypertension of the
Shy-Drager type. In some of these disorders, changes in PNS tone
may be useful in quantitating the rate of disease progression
and/or the effect of therapeutic intervention. Identifying changes
in PNS tone may help in identifying fetal and neonatal distress and
identifying those at high risk of sudden infant death syndrome.
EXAMPLES
[0057] For the examples described below the following procedure was
followed: Unless otherwise noted, the examiner used disposable,
low-offset-potential biomedical sensors model GS-26 from
Bio-Medical Corp. (Warren, Mich.), with adhesive collars, having a
covering of conductive gel applied at the factory. When humans were
measured, the subject was allowed to rest quietly for ten minutes
before the measurement process started. A self-adhesive, extremely
low-offset-potential sensor was placed in the center of each palm.
An alcohol swipe of each palm to remove excess skin oils (which can
inhibit conductivity) was performed prior to sensor placement. and
an ear clip ground was employed if other individuals were moving
around a Chart Recorder based data gathering setup. The subject was
asked to remain still and sit upright, with the backs of their
hands resting on the top of their thighs, and to sit in a relaxed
position with their arms limp. When horses were measured, the
horses neck was shaved and the sensors placed on both sides of the
neck, (see FIG. 1b).
[0058] The lead wires were connected at their opposite ends to a
data gathering device. In the case of the data generated for FIGS.
4 to 7, the data gathering device was a recorder available from
Kipp & Zonen, Model BD112, (Delft, Holland). For data generated
for FIGS. 3, and 8-13, the recorder was a Biographs, LLC, PT-05
PainTree.TM.. The device was switched on, and data recorded for a
period of 2-3 minutes. The machine was turned off, the electrodes
removed from the subject, and data interpreted.
Example 1
[0059] FIGS. 3a and b show examples of the graphic display of a
reading on a computer, showing effects of a known ANS trigger.
Specifically, FIG. 3a shows distress in a cat. The sensors were
placed on the cat's paws. The computerized trace shows a rise in
sympathetic tone (upward movement on the Y-axis) known to be
associated with distress in animals caused by proximity of an
operating vacuum cleaner. Vacuum was switched on at 107 seconds
(X-axis) and moved closer until at 140 seconds after measurement
began, the cat fled the device.
[0060] FIG. 3b shows a human doing controlled breathing: Trace
rising and falling (re. Y-axis) illustrates the known ANS effects
of controlled breathing. Inhalation causes a rise in sympathetic
tone (rise in trace on graph) and exhalation causes a rise in
parasympathetic (i.e. vagal) tone (fall in trace). This 41 year old
female human was inhaling for 5 seconds (x-axis), followed by
exhaling for 5 seconds, for approximately one minute. This type of
controlled breathing is a classic medical technique used in the
study of ANS function.
Example 2
[0061] FIG. 4 shows epilepsy-like alterations in ANS activity:
Reading depicted on strip chart recorder is for a 75 year old male
with sporadic, pronounced, and uncontrollable hand tremors. As is
known to happen with some types of epilepsy, the seizure-like
activity occurs at the peak of a rise in sympathetic tone (rise of
trace on Y-axis) and is immediately followed by a strong rise in
parasympathetic tone (shown by a fall in subject's trace on the
Y-axis) as the body attempts to restore homeostasis. This example
depicts how the proposed method may help diagnose non-manifesting
forms of epilepsy, as well as catch epileptic-like activity early
in its development with a subject before it grows into full-blown
seizures. Likewise, such measurements might help the physician
titrate the dosage of seizure medications.
Example 3
[0062] FIGS. 5a-d show dental pain in 51 year old male human,
depicted on strip chart recorder. In FIG. 5a, the subject reports
substantial pain. Trace is well below the X axis, indicating
moderate to severe pain. In FIG. 5b, the same subject is shown 20
minutes after ingestion of oxycodone (1/2 tablet of 5/500TA). Trace
is rising slightly. In FIG. 5c, 70 minutes after oxycodone
ingestion, half of trace is above X-axis. Subject reports
significant pain relief. In FIG. 5d, 180 minutes after oxycodone
ingestion, subject is pain free and trace is completely above
X-axis in 3 separate measurements. Oxycodone is known to take 3
hours to achieve its full effect.
Example 4
[0063] FIGS. 6a-c show headache pain in humans, depicted on strip
chart recorder using methods disclosed in U.S. Pat. No. 6,347,238.
In FIG. 6a, a 35 year old female reports severe headache pain.
Trace of reading is well below X-axis, indicating moderate to
severe pain. FIG. 6b shows the same subject one hour after
ingestion of Excedrin Migraine.RTM. medication. Subject reports
that pain has greatly lessened. Trace is almost back to X-axis. 135
minutes after ingestion of medication, FIG. 6c shows the subject is
pain free and the trace is now well above X axis, indicating a
pain-free state, which agrees with the subjects self-report.
Example 5
[0064] FIGS. 7a and b show pain and Pain Relief in Horses (shown on
strip chart recorder). FIG. 7a shows a 2 year old female horse
suffering post-surgical pain, before prescribed analgesic
injection. FIG. 7b shows the same horse 6-7 minutes after
prescribed analgesic injection. FIGS. 8a and b show a lame horse
before and after healing (shown on computer generated graph). FIG.
8a shows a 3 year old lame male horse with swollen, cut foot. FIG.
8b shows the same horse one week later. Foot healed, lameness
gone.
Example 6
[0065] FIGS. 9a and b show pure offset potentials measured by
pressing two sensor's sensing faces together and connecting them to
the measuring device. There is no connection here to any subject.
FIG. 9a shows that sensors with relatively high offset potential
(0.75 mV) create their own, large traces which decay over time,
adding a changing level of distortion to readings taken on any
subject. Often this voltage potential can exceed the size of the
voltage being measured in a subject. FIG. 9b shows that sensors
with very low offset potential (0.01 mV) add only a minimal and
unchanging distortion, which is much lower than the vast majority
of two-sensor site readings from animal or human subjects.
Example 7
[0066] FIGS. 10a and b show the distortion of subject readings
caused by sensors with different amounts of offset potential.
Subject: 51 year old male human with no pain.
[0067] FIG. 10a shows a human subject in a non-pain state. The
offset potential of the sensors used equals 0.01 mV. FIG. 10b shows
the same human subject, 8 minutes later. The offset potential of
the sensors used equals 5.0 mV. Note added distortion from high
offset potential completely changes the nature of the reading
obtained from subject.
Example 8
[0068] FIGS. 11a and b show the distortions of subject readings
caused by sensors with different amounts of offset potential.
Subject: 3 year old male horse with no known pain. FIG. 11a shows
the horse in a non-pain state. The offset potential of the
electrodes used equals 0.01 mV. FIG. 11b shows the same horse 8
minutes later. The offset potential of the electrodes used equals
4.2 mV. Note how the added distortion of the high offset potential
here has even changed which side of the X=0 baseline the trace
occurs on. In this case, this could have caused a pain-free state
to be mistaken for a painful state.
Example 9
[0069] FIGS. 12a-d shows the inconsistency in four readings taken
with reusable, cup-style, Ag+AgCl mixture sensors. All readings
were taken on same subject just minutes apart (FIG. 12a, 9:15 P.M.;
FIG. 12b, 9:22 P.M.; FIG. 12c 9:39 P.M.; FIG. 12d 9:47 P.M.). Note
great variability. Subject was normal, healthy 54 year old white
male, not in pain, and without ANS dysfunction of any kind. FIGS.
13a-d show the consistency in four readings taken with AgCl coated
Ag sensors of the present method. All readings were taken on same
subject as in FIGS. 12a-d, just minutes apart from one another
(FIG. 13a, 9:54 P.M.; FIG. 13b, 10:01 P.M.; FIG. 13c 10:06 P.M.;
FIG. 13d 10:12 P.M.). Much greater consistency is observed in
readings than among those in FIGS. 12a-d.
[0070] Although this invention has been described with a certain
degree of particularity, it is to be understood that the present
disclosure has been made only by way of illustration and that
numerous changes in the details of construction and arrangement of
parts may be resorted to without departing from the spirit and the
scope of the invention.
* * * * *