U.S. patent number 3,983,864 [Application Number 05/593,606] was granted by the patent office on 1976-10-05 for method and apparatus for in vivo blood gas analysis.
This patent grant is currently assigned to Airco, Inc.. Invention is credited to Dale A. Brinkman, Wilfried R. Peickert, Ulrich Sielaff.
United States Patent |
3,983,864 |
Sielaff , et al. |
October 5, 1976 |
**Please see images for:
( Certificate of Correction ) ** |
Method and apparatus for in vivo blood gas analysis
Abstract
Method and apparatus for withdrawing and analyzing gases
dissolved in liquid, more specifically, equilibrated blood gas
samples in vivo. A catheter including a semipermeable membrane,
connected to include a volume of carrier gas at atmospheric
pressure, is introduced percutaneousluy into the bloodstream. After
a predetermined period, equilibratin occurs between the blood gases
and the carrier gas. By means of displacement in the volume or
reduction in the pressure, the carrier gas including the
equilibrated gas is then removed from the semipermeable membrane to
another area for analysis. A corresponding volume of carrier gas is
replaced in the semipermeable membrane from an inlet supply.
Inventors: |
Sielaff; Ulrich (McFarland,
WI), Peickert; Wilfried R. (Madison, WI), Brinkman; Dale
A. (Madison, WI) |
Assignee: |
Airco, Inc. (Montvale,
NJ)
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Family
ID: |
27051237 |
Appl.
No.: |
05/593,606 |
Filed: |
July 7, 1975 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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493938 |
Aug 1, 1974 |
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Current U.S.
Class: |
600/364;
604/164.01; 73/863.23; 73/864.81; 436/68; 436/178; 604/27;
604/28 |
Current CPC
Class: |
A61B
5/145 (20130101); A61B 5/14542 (20130101); A61B
5/1473 (20130101); Y10T 436/255 (20150115) |
Current International
Class: |
A61B
5/00 (20060101) |
Field of
Search: |
;128/2G,L,F,E,214.4,348
;421/5R,23R,23.1 ;23/23B,232C |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Med and Biol. Engng., vol. 8, No. 2, pp. 111-128, (1970). .
Journ, of Thoracic and Cardiovascular Surg., vol. 62, No. 6, Dec.
1971, pp. 844-850..
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Primary Examiner: Howell; Kyle L.
Attorney, Agent or Firm: Rathbun; Roger M. Bopp; Edmund W.
Mathews; H. Hume
Parent Case Text
This is a Continuation of application Ser. No. 493,938, filed Aug.
1, 1974, now abandoned.
Claims
We claim:
1. A method of sampling gases dissolved in a liquid comprising the
steps of:
introducing a catheter into the liquid, at least a portion of said
catheter comprising a membrane being permeable to said gases but
substantially impermeable to said liquid, said permeable portion
directly contacting said liquid;
admitting carrier gas at about atmospheric pressure into said
catheter to contact said membrane;
permitting said carrier gas to equilibrate with the gases dissolved
in said liquid whereby said dissolved gases pass into said catheter
through said membrane and are mixed with said carrier gas; and
removing at least a portion of said mixed gases from said
catheter.
2. A method of intermittently sampling and subsequently analyzing
gases dissolved in the bloodstream of a living organism comprising
the steps of:
introducing a member comprising a semipermeable membrane into said
bloodstream, said membrane being permeable to gases but
substantially impermeable to blood;
admitting carrier gas at about atmospheric pressure into said
semipermeable membrane member within the bloodstream;
allowing equilibration between a volume of said carrier gas and
said dissolved blood gases through the lateral walls of said
semipermeable membrane member for a predetermined time;
removing at least a portion of said volume of carrier gas
containing said equilibrated blood gases from said semipermeable
membrane member; and
isolating and analyzing said removed equilibrated gases in said
portion of carrier gas.
3. A method in accordance with claim 2 wherein said carrier gas is
characterized relative to said dissolved blood gases by either a
slow rate of diffusion through said membrane or a low solubility in
blood, or both.
4. The method in accordance with claim 2 wherein said volume of
carrier gas containing said equilibrated blood gases substantially
exceeds the portion analyzed.
5. The method in accordance with claim 4 wherein said volume of
carrier gas including said equilibrated blood gas exceeds the
portion analyzed by at least a factor of ten.
6. The method is accordance with claim 2 in which the steps of
removing and isolating a portion of the volume of said carrier gas
containing said equilibrated gases from the remaining carrier gas
is carried out by first reducing the pressure in means connected to
said membrane member for sampling a discrete portion of said
volume, thereby causing the said portion to move from said member
to said sampling means, connecting said sampling means to a gas
analyzer and subsequently forcing the said portion containing said
equilibrated gases from said sampling means to said gas analyzer by
introducing into said sampling means carrier gas from an auxilliary
source.
7. The method in accordance with claim 6 which comprises the steps
of detecting the peak amount of said equilibrated gas distributed
in said portion of carrier gas as said portion moves from the
membrane member to said sampling means, and actuating valve means
to admit a discreet amount of said portion including said
equilibrated gases to said gas analyzer when said peak is
positioned in said sampling means in a preselected position in
relation to the intake of said gas analyzer.
8. The method in accordance with claim 7 wherein said peak
generates a signal, detecting and utilizing said signal to actuate
said valve means.
9. The method in accordance with claim 7 wherein said carrier gas
is characterized by a thermal conductivity which is substantially
different from that of the blood gas to be measured.
10. The method in accordance with claim 9 wherein helium is
employed as a carrier gas.
11. The method in accordance with claim 9 wherein the space rate of
change to thermal conductivity in said portion of carrier gas
including said equilibrated blood gases is represented by a "bell
shaped" curve, detecting a signal corresponding to the space rate
of change in said thermal conductivity represented by the change in
slope of said curve, and utilizing said signal to actuate said
valve means to receive said portion including said equilibrated
blood gases at a position represented by the flat top portion of
said curve.
12. A device for the sampling of gases dissolved in liquid
characterized by a catheter, a portion of which comprises a
membrane permeable to gas diffusion but substantially impermeable
to diffusion by said liquid, said catheter being designed for
introduction into the liquid to be analyzed, a carrier gas source
connected to the gas permeable membrane portion of said catheter
comprising means to supply carrier gas thereto at substantially
atmospheric pressure, said supply means being adapted to retain a
volume of carrier gas contacting the gas-permeable membrane portion
for a preselected period of time to permit the establishment of an
equilibrium between the carrier gas and said dissolved gases
causing mixing thereof within the catheter, and means connected to
the catheter to remove therefrom at least a portion of the carrier
gas including the mixed equilibrated gases.
13. A system for intermittently sampling and subsequently analyzing
gases dissolved in the blood which comprises in combination:
a catheter comprising intake and exhaust terminals at its proximal
end connected by a continuous passage formed in a semipermeable
membrane member constructed for insertion at the distal end of said
catheter into the bloodstream of a subject to be analyzed, said
membrane being permeable to gases but substantially impermeable to
blood;
a source of carrier gas connected to the intake terminal of said
catheter and comprising means for supplying carrier gas to the
passage formed in said membrane member at about atmospheric
pressure;
means for retaining a volume of said carrier gas in said passage
for a preselected interval to allow equilibration between said
carrier gas and said dissolved blood gases;
means connected to the exhaust terminal of said catheter for
removing said volume of carrier gas including said equilibrated
blood gases from said passage;
means connected to said last-named means for analyzing at least a
portion of said removed equilibrated blood gases.
14. In a system in accordance with claim 13 wherein said means
connected to the exhaust terminal of said catheter for removing
said volume of carrier gas including said equilibrated blood gas
from said passage to said means for analyzing the blood gases
comprises:
an auxilliary source of carrier gas,
pumping means constructed and arranged to induce evacuation and
exhaust cycles in said system,
a gas purging valve connected to said pumping means;
a conduit system including a sampling valve having at least two
positions for transmission therethrough;
during the evacuation cycle of said system: said sampling valve
operable in a first position for connecting the exhaust terminal of
said catheter to said pumping means to receive at least a portion
of said volume of said carrier gas including said equilibrated
blood gas in said sampling valve, and in a second position for
connecting said auxilliary carrier source through said sampling
valve to said means for analyzing said equilibrated blood gas,
whereby said portion is forced into said blood gas analyzing means;
and
during the exhaust cycle of said system: said purging valve
connectable for purging said pumping means of gas in preparation
for the next evacuation cycle.
15. A system in accordance with claim 14 wherein said pumping means
comprises automatic vacuum pumping means, and said system comprises
detecting means connected adjacent one terminal of said sampling
valve and responsive to detect the peak of equilibrated blood gases
in said volume of carrier gas passing from said semipermeable
membrane member to said sampling valve, and to generate a signal in
response to the passage of said peak, and means responsive to said
detecting means and actuated by said signal for operating said
sampling valve to connect said auxilliary carrier source through
said sampling valve to said gas analysis means.
16. A system in accordance with claim 15 wherein the space rate of
change of the thermal conductivity of said volume of equilibrated
blood gas varies as a function of the distribution of dissolved
blood gas therein, and wherein said detecting means is sensitive to
the space rate of change of thermal conductivity in said
volume.
17. A system in accordance with claim 16 wherein said function is a
"bell shaped" curve having a flattened peak, and wherein said
defecting means is responsive to a change of slope of said "bell
shaped" curve to actuate said sampling valve to introduce a portion
of said volume including said equilibrated blood gases represented
by the flat portion of said peak into said means for analyzing
blood gas.
18. A system in accordance with claim 13 wherein said means for
analyzing the blood gases comprises a gas chromatograph.
19. A system in accordance with claim 13 wherein the membrane
member comprising said catheter comprises tubular means constructed
for insertion percutaneously into the blood vessel in a direction
extending along the principal axis thereof and simultaneously
providing a continuous gas permeable conduit in contact with the
blood of said subject between said input and output terminals,
said input and output terminals both the the proximal end of said
tubular means, and
connecting means to said input and output terminals comprising a
housing including input and output gas receptacles respectively
constructed and arranged for connection in circuit relation to said
source of carrier gas at said input receptacle and to said means
for analyzing the blood gases at said output receptacle.
20. The combustion in accordance with claim 19 wherein said
semipermeable tubular membrane member consists essentially of a
polysiloxane polymer.
21. A system in accordance with claim 19 wherein said gas permeable
conduit has a substantially uniform cross-section and permeability
along its length between said terminals.
22. The combination in accordance with claim 19 wherein said
semipermeable tubular membrane member comprises a plurality of
lumens interconnected to provide a continuous uniform gas permeable
conduit between said input and output terminals having a length in
contact with the blood which substantially exceeds the length of
said membrane member.
23. The combination in accordance with claim 22 wherein said
semipermeable tubular membrane member comprises at least two
parallel lumens of substantially uniform cross-section and
permeability forming a gas permeable conduit substantially double
the length of said tubular membrane member and joined together by
connecting means at their distal ends to provide a reversal of gas
flow from one to the other, the proximal ends of said lumens
respectively connected to said input and output terminals.
24. The combination in accordance with claim 22 wherein each of
said lumens has a cross-sectional dimension not exceeding about
0.011 inch and said membrane has an overall cross-sectional
dimension not exceeding about 0.028 inch.
25. The combination in accordance with claim 19 wherein said
membrane member comprises an external membrane tube coaxial with
another tube, said tubes being inter-connected at their distal
ends.
Description
BACKGROUND OF THE INVENTION
The present invention relates to the sampling and analysis of gases
dissolved in liquid, and more specifically to the vivo analysis of
gases dissolved in the blood.
Blood gases have been detected and measured in vivo by a variety of
electronic means. The most successful have been variations of the
polarographic electrode for oxygen and modified pH electrodes for
carbon dioxide. Oxygen, CO.sub.2 and other dissolved blood gases
have also been detected and measured in the prior art on the basis
of their flow rates into an evacuated gas permeable membrane tipped
catheter in contact with the blood. The prior art systems of the
latter type are specifically designed to operate with mass
spectrometers. Blood gases pass through a small membrane area and
are drawn to the mass spectrometer at a rate proportional to their
partial pressures in the blood. The mass spectrometer determines
the relative number of each type of gas molecule passing into the
system and thus, with proper calibration, the partial pressures in
the blood may be indirectly determined.
All of the prior art methods described here rely on the rate of gas
diffusion through a membrane to indicate the partial pressures of
the gases in the blood. In such measurements, a steady state
diffusion rate is reached which is a function of the membrane
thickness, the membrane surface conditions, blood velocity,
temperature, etc., which parameters are either unknown or difficult
to control. The combined effects of these variables on the overall
measuring system can only be overcome by calibrating each system
after it is in place in the artery. It is also known that these
variables may change during the time that a continuous blood gas
measurement is being made. The membrane probes are known to change
position within the blood stream resulting in varied blood flow
conditions which can alter the gas diffusion rates. The membrane
characteristics will also change under the effect of protein
buildup on their surfaces, thus changing the diffusion rates. It is
thus necessary to calibrate such systems frequently during their
use to account for the changes in gas diffusion rates which
naturally occur. Each calibration necessitates the extraction of a
blood sample for gas pressure determination with an in vitro
instrument.
BRIEF DESCRIPTION OF THE INVENTION
Accordingly, it is the principal object of the present invention to
provide for the in vivo sampling of blood gas by a partial pressure
technique which will yield measurements that are more reliable and
accurate than prior art techniques. A more specific object is to
provide a partial pressure blood sampling technique which provides
a gas sample of sufficient volume to be accordingly adapted for
analysis by a gas chromatograph or any other instrument designed to
analyze small gas volumes. Another object of the invention is to
provide a system of the foregoing type, in which the necessity for
calibration is substantially reduced. A further object of the
invention is to provide for partial pressure sampling of blood
gases at substantially atmospheric pressure.
These and other objects are realized, in accordance with the
present invention, in a method and apparatus for intermittently
sampling the gases dissolved in the blood in vivo, employing a
catheter in the form of a highly diffusible double lumen tubular
membrane which is introduced into the bloodstream. Carrier gas from
an inlet supply source is introduced into the membrane at about
atmospheric pressure and allowed to equilibrate for a predetermined
time with the blood gases passing through the diffusible membrane.
The equilibrated gas is then moved to another section of the system
where a portion of it is removed for subsequent analysis. The
equilibrated gases are transported into an analyzer which
preferably takes the form of a gas chromatograph. This is
accomplished by a vacuum means which moves the equilibrated gas
sample from the equilibration region to a sampling valve.
A carrier gas suitable for the present invention is characterized
by either slow rate of diffusion through the selected membrane or
low solubility in blood, or both, relative to the gases to be
measured. Since the diffusion area in the catheter comprises a
long, narrow tube, complete equilibration is only achieved in the
central section. Carrier gas diffusion into the blood gas produces
a "bell shaped" distribution of the diffusing blood gases relative
to the carrier gas.
In accordance with a preferred embodiment of the invention, a
thermal conductivity sensor is interposed into the system to detect
the presence of the equilibrated gas sample just before it moves
into the sampling valve section of the system. For this embodiment,
a pump is used at negative pressure to move the gas to the sampling
region. The pump operates upon the opening of a valve in the
conduit system to draw the equilibrated volume of gas along the
connecting conduit. The thermal conductivity detector is calibrated
to detect passage of the blood gas peak, in response to which it
generates a signal which switches a sampling valve, causing it to
direct a small preselected volume of gas into the gas analyzer. A
continuous flow of gas is simultaneously admitted from an auxiliary
carrier source which serves to drive the equilibrated gas sample
into the analyzer.
In accordance with another feature, the valve at the output
terminal of the catheter is connected to perform a selector
function between the diffusion area, the sampling valve and a
calibration source. When this valve is closed to the catheter
terminal, it may serve to supply a flow of calibrating gas to the
sampling valve and gas analyzer for calibration purposes.
For the purposes of the embodiment including the thermal
conductivity sensor, the carrier gas should have a significantly
different thermal conductivity than any of the gases being measured
in the blood. Helium, for example, allows a blood gas mixture
containing O.sub.2, CO.sub.2, N.sub.2 O, N.sub.2 or anesthetic
vapors to be easily detected by the thermal conductivity detector
adjacent to the sampling valve.
A particular advantage of the techniques and apparatus of the
present invention over prior art systems for in vivo measurement of
dissolved blood gases is that a gas sample of substantially the
same partial pressure as in the blood is made available for
analysis. The system of the present invention operates safely since
carrier gas is transported at substantially below atmospheric
pressure. Moreover, it provides a relatively large volume of blood
gases and is accordingly well adapted for use with the gas
chromatograph type of analyzer, which is simpler and more
economical than the mass spectrometer previously used in
combination with prior art systems employing diffusible membranes.
Further advantages of the system of the present invention are that
it requires less calibration than systems of the prior art; and its
operation is not sensitive to changes in body temperature.
These and other objects, features and advantages will be apparent
to those skilled in the art after a detailed study of the
specification hereinafter with reference to the attached
drawings.
SHORT DESCRIPTION OF THE DRAWING
FIG. 1 is a schematic diagram of the simplest embodiment of a
conduit system in accordance with the present invention operated by
a displacement volume means, including a diffusible membrane
catheter in place in the bloodstream of a subject for measuring
dissolved blood gases.
FIGS. 2A and 2B are respectively a longitudinal section and an
enlarged cross-section of a catheter configuration suitable for the
purposes of the present invention shown in place in a
bloodstream.
FIG. 3 is a plot against time of the percent of equilibration of a
selected blood gas in two selected catheter tips during
equilibration.
FIG. 4 is a schematic diagram of a modification of the system of
FIG. 1, including thermal detecting means for automatically
operating the valve in the sampling area, including a vacuum pump
which replaces the displacement volume means of FIG. 1.
FIG. 5 shows a graphical representation of the distribution of
blood gases in a carrier gas along the length of the catheter
tip.
DETAILED DESCRIPTION OF THE INVENTION
The simplest embodiment of the invention is represented
schematically in FIG. 1. While, for clarity, the components in FIG.
1 are depicted in a configuration which requires manual operation,
it is evident that by application of electronic logic circuitry,
well known in the state of the art, the system can be made to
operate entirely automatically.
Basic to the operation of this system is a suitable catheter 1
which can be inserted through the skin into a blood vessel. A
preferred form for this purpose is disclosed in the companion
application Ser. No. 493,939 filed Aug. 1, 1974 by U. Sielaff and
W. Peickert, now abandoned, and application Ser. No. 611,473, a
Continuation-in-Part thereof, filed Sept. 8, 1975, that part of the
disclosure of which as originally filed being made a part hereof by
reference. The general feature of this design is represented in
simplified form in longitudinal section 2A and enlarged
cross-sectional view in FIG. 2B. The design is discussed in greater
detail in the application of Sielaff and Peickert, supra. It will
be understood that such a catheter may have a variety of
geometries, but must have an inlet and outlet port which
communicate to a tubular membrane area. A continuous path for gas
flow must be available between an inlet terminal and outlet
terminal, both outside of the body (See FIG. 1). The proximal
portion of the catheter 1, outside of the body, is preferably
constructed of a pair of non- or low gas permeable tubes 11, 12 of,
for example, stainless steel, each from 4 to 6 feet in length,
respectively, about 0.013 and 0.022 inch in inner diameter, which
carry gas to and from the distal catheter tip region 10 within the
body. Connecting tubes 11 and 12 are jacketed in a covering tube 14
of polyvinylchloride or the like, of sufficient length to reach
conveniently from a patient measuring site to an instrument, the
components for which are schematically within the dotted line 20
(FIG. 1).
Referring to FIGS. 2A and 2B and a highly gas permeable tubular
membrane 4 of, for example, a silicone polymer or similar non-toxic
highly permeable membrane material, is interposed into the
bloodstream of a living subject through cannula 7. The membrane is
more particularly described in the companion application of U.
Sielaff and W. Peickert, supra. The cannula is of a conventional
commercially available type having hub 7a and a distal end
comprising a plastic tube 7b. The latter accommodates the proximal
end of membrane 4 coaxially guiding it into place in vessel 2,
where it may be retained semi-permanently, even when the plug to
measuring system 20 is disconnected.
The cross-sectional geometry of the membrane 4 may be varied; but
to expose maximum surface area of the membrane in the blood vessel,
a tri-lumen membrane construction is chosen in the embodiment as
shown in the cross-sectional view FIG. 2B. The two larger lumens
4a, 4b are each about 0.011 inch in diameter and are connected by
means of a U-shaped stainless steel or nickel tube 5, thus
permitting a reversal in the direction of gas flow from one lumen
to the second lumen. The small 0.006 inch diameter lumen 4c
accommodates a stainless steel wire 6 of 0.006 inch diameter which
is soldered at its distal end in a smooth joint to the inner curve
of the stainless steel U-shaped tube 5. The wire 6 serves the
purpose of providing proper rigidity to the membrane 4 in the
longitudinal direction, permitting it to be more readily inserted
through the cannula 7. The wall thickness of the membrane 4 is
preferably, for example, 0.002 inch to assure good gas
diffusibility and still provide adequate catheter lumen rigidity. A
membrane exposed length of 5 inches beyond the end of the tubular
portion 7b of cannula 7 provides a combined lumen volume of 16
microliters for gas diffusion. It will be understood that in
substitution for the disclosed U-shaped tube 5, alternative devices
can be employed in order to pass gas between the ends of lumens 4a
and 4b, such as for example, piercing one or more holes in the
webbing between the two.
At their proximal ends the lumens 4a, 4b respectively accommodate a
pair of metal connector tubes 27, 28 which pass through a bore
along the axis of the shank 8a and one arm 8c, of a Y-shaped
adapter plug 8, which may, for example, be molded from acetal
plastic or the like. The tubes 27, 28, which extend from the end of
shank 8a to about 1/8 inch beyond the end of arm 8c are press-fit
into the axial bore, and sealed into position by, for example, a
silicone adhesive. The male connector 8a of the adapter 8, and the
other branch 8b, comprising a female connector are of a form known
in the art as a "Luer taper". The male Luer taper 8a provides a
quick leak-proof connection to the hub 7a of cannula 7. The female
Luer taper 8b communicates via a separate passage with the blood
surrounding the membrane portion 4 inside the cannula 7, thus
providing a port for taking blood samples without disturbing the
catheter.
The connecting tubes 27, 28 are joined beyond the end of adapter
branch 8c to the respective tubular members 11, 12 which are of a
substantially non-diffusible material for gases, such as, for
example, stainless steel.
tubes 11 and 12 in the insulating tubular jacket 14 extend 5 or 6 l
feet beyond the end of adapter 8 terminating in a receptacle and
plug which leads into the blood gas analysis system 20 through down
gas terminal 15 from the carrier gas source 30 and return gas
terminal 16 to the chromatograph analyzer, as will be explained.
Additional features of the catheter are described in more detail in
the companion application of Sielaff and Peickert, supra,
incorporated by reference.
Referring to FIG. 1, the system's operation may be described as
follows: A suitable carrier gas supplied from a conventional gas
supply cylinder 30, which may be pressurized for convenience of
transport and storage, is metered through a conventional
restricting valve 31 to a chamber 26 which is open to atmosphere.
As previously pointed out, the supply gas in the present embodiment
is helium, although it will be understood that alternatively it can
be any gas characterized by slow diffusion or low solubility, or
both, relative to the gases to be measured. The flow into chamber
26 is regulated such that all of the ambient air is expelled from
within, and only pure carrier gas surrounds the inlet of tubing 19,
which leads from the instrument to the catheter inlet port 15.
The conduits of the system are preferably of stainless steel, or
other non-diffusible material having an inner diameter of, say
0.013 inch in the present example. Tubing 19 extends into the inlet
of catheter 1, through connecting tube 12, through diffusing loop
10, back to the measuring portion of the instrument 20 through
non-diffusible tubes 11 and 40 and through sampling valve 50 to a
volume displacement means 34. The pump 34 may take the form of a
conventional syringe having a total volume displacement of
approximately 200 microliters between evacuation and exhaust
positions. As the piston 34a in volume displacement means 34 is
moved from evacuation position 35 to exhaust position 36, a
reduction of pressure therein causes a volume of carrier gas equal
to the pump's displacement to move through the system.
Interposed between conduits 40 and 42 is a sampling valve 50 with a
known specific internal volume between its ports 53 and 54. This
may take the form of any standard internal sample loop
chromatographic sampling valve, well known in the art. In the
present embodiment, the preselected volume between ports 53 and 54
is, say, one microliter. The volume of sampling valve 50 between
ports 53 and 54 should preferably be chosen so that the diffusion
volume in the catheter tip 10 extending between 17 and 18 is at
least about ten times the volume enclosed between ports 53 and 54
in sampling valve 50. This assures that a fully equilibrated
portion of sample gas is injected into gas analyzer 49. The
internal path of sampling valve 50 should have approximately the
same bore as the connecting tubing 40 to minimize gas mixing.
In position I of valve 50, shown in FIG. 1, gas is free to flow
from chamber 26 through catheter 1 and ports 53 and 54 to the
volume displacement pump 34. A second bore between 56 and 55
connects another gas supply source 47 to a gas analyzer 49, which
is flowing continuously. Additionally, a vent valve 38 is
interposed in conduit 42 which may be opened to expell carrier gas
to atmosphere when the volume displacement pump 34 is returned to
position 35.
When sampling valve 50 is rotated through 90.degree. to take
position II, the gas in the tube between 53 and 54 is injected into
the conduit between 56-55, and the dotted channel replaces the
original channel moving to the catheter line.
In the present embodiment the gas analyzer may take the form of a
gas chromatograph of a micro chromatographic type adapted for the
measurement of small volume gas samples of one microliter or
less.
The equilibration and sampling process will operate as follows.
Assuming an initial condition of pure carrier gas throughout the
entire system at time zero, gases within the blood 13 in contact
with the permeable tubular membrane 4 diffuse inwardly at rates
dependent on the membrane permeability, diffusion area and
thickness of the membrane, and the respective partial pressure
gradients. At the same time carrier gas may diffuse out of the
catheter into the blood 13.
The equilibration process is indicated graphically in FIG. 3 which
shows two equilibration curves A and B which may either represent
the conditions of two different catheters, or may represent the
rate of equilibration of the same catheter under different
conditions within the body. The significance of choosing a
sufficiently long equilibration time T is demonstrated by these two
curves. Since both are essentially exponential functions, it can be
seen that, if the equilibration time is picked long enough,
variations in the specific catheter and its diffusing properties,
blood flow, or temperature will have very little effect on the
final equilibrated partial pressure level. Although this technique
sacrifices strictly continuous readout of the blood gas values, if
one allows this equilibration to go on for approximately two minute
intervals, it results in more reliable and accurate measurements
than prior in vivo blood gas measuring systems. An interval of
approximately two minutes is a sufficient time to permit a gas
depleted area near the catheter to become replenished, such that
the sample volume is completely equilibrated with blood gases at
the same conditions as they exist in the blood.
After an appropriate equilibration time, assuming the components to
be in the positions shown in FIG. 1 with the on-off valve 38
closed, the piston is now moved to position 36, which displaces the
gas volume within the system, such that the gas at point 18 moves
to point 23 and the gas at point 17 moves to point 22. The
distribution of blood gas equilibrated within the membrane tip is
shown in FIG. 5. It is evident that the most complete equilibration
is achieved midway between points 17 and 18; and for the most
accurate operation, the displacement volume must be picked so that
the center of the equilibration region is drawn exactly to the
center of the sample valve 50. During the gas drawing phase, the
system undergoes a slight negative pressure condition (of the order
of -10 cm. of water), which is allowed to return to atmospheric
pressure as carrier gas is replenished from chamber 26. After the
gas has been drawn to position 22-23 with sampling valve 50 in
position I, and the pressure is allowed to return to atmospheric
throughout the entire system, sampling valve 50 is rotated ninety
degrees, which places the ports containing the blood gases, into
position II between points 55 and 56 connecting conduits 46 and 48.
Helium from auxiliary supply 47 then flows through conduit 46 and
into valve 50 to inject this known volume of blood gas mixture into
the gas analyzer 49 for subsequent analysis. Valve 38 in output
conduit 42 is then opened to atmosphere, the piston 34a of pump 34
is returned to position 35, and the system is purged of gas in
preparation for the next drawing cycle. Valve 50 is quickly
returned to its original position I between conduits 40 and 42 in
preparation for the next sample arrival.
The following table summarizes the sequence of operations of the
embodiment of FIG. 1:
TABLE I
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Steps Time Operation
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1 2 min. With valve 38 closed, catheter tip 10 equili- brates with
blood gases. 2 10 sec. Valve 50 in position I; sample drawn from
tip of catheter I into sampling valve 50 as pis- ton 34a moves from
35 to 36. 3 1 sec. Valve 50 is switched from position I to position
II to inject sample into gas analy- zer 49. 4 2 sec. Exhaust valve
38 opens; and piston 34a moves from 36 to 35 to purge cylinder 34.
5 (Beginning Vent valve 38 closes in preparation for next of 1)
draw. (Process is repeated).
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An important feature of this system is that the blood gases, once
equilibrated within the catheter tip inside the body, are moved to
an analysis section, and there, before they are injected into the
analyzer 49, are allowed to come to the same total pressure as they
occupied within the body. This greatly simplifies the calibration
process, which is based on the assumption of complete equilibration
in the body.
FIG. 4 shows a modified form of the invention in which the
displacement pump 34 of FIG. 1 is replaced with a continuous vacuum
source 35. This system includes, in addition to the components
disclosed with reference to FIG. 1 of the drawings, a source 61 of
calibrating gas which may be connected by conduit 62 through
three-way valve 60, to tube 40'. In FIG. 4 the primed numbers
represent components which are substantially similar to their like
numbered components described with reference to FIG. 1, and will
not be redescribed.
The vacuum source 35, which can be controlled by an on-off valve 39
in conduit 42', is preferably pumping means of a low power
vibrating type, substantially of a diaphragm form conventionally
used in ornamental fish tanks. Upon opening of valve 39 to conduit
42', source 35 operates to produce a negative pressure of 10-20
centimeters of water in conduit 42', thereby drawing through valve
50' equilibrated gas from the catheter tip 10'.
The principal difference between the present embodiment and that of
FIG. 1 is the use of the thermal detector circuit 70, 71, the
operation of which will be presently explained.
As previously pointed out with reference to FIG. 1, the diffusion
area in catheter 1' is a long narrow tube. Substantially complete
equilibration between the blood gas and the carrier gas is achieved
in only the central section of the diffusion area, between the
points 17' and 18'. If the distribution along the tube of the
diffused gases in the carrier gas were plotted, a "bell" shaped
curve 100 would result which is substantially flat in the center of
the equilibration loop (See FIG. 5). When vacuum source 35
operates, upon the opening of valve 39, the volume of equilibrated
gas which moves along conduit 40' to the sample valve 50' has a
clearly detectable maximum variation of thermal conductivity. As
indicated in FIG. 5, it is desirable that the volume of
equilibrated gas is drawn to such a position with reference to
valve 50' that the degree of equilibration is substantially uniform
between ports 53' and 54'. Thus, the volume sampled would represent
the flat mid-position of curve 100, between points 102 and 103. For
the purposes of this embodiment, helium is preferred for a carrier
gas because its thermal conductivity differs substantially from
that of any of the blood gases to be measured.
The detector element 70 preferably comprises a hot wire type well
known in the art, such as those used for chromatographic analysis,
or other thermally sensitive element, which is interposed into
conduit 40' in a position closely adjacent the input end of the
sampling valve 50'. Because of the physical size of the conduit 40'
into which this is interposed, it is necessarily very small.
The thermally sensitive element 70 responds electrically to the
peak of the equilibrated gas, passing a signal to detector circuit
71. Sensitive element 70 is interposed into pipe 40', close to the
sampling valve 50', preferably to coincide with a position
represented by the area between dotted line 101 and 102 of
diffusion curve 100 of FIG. 5, so that element 71 responds to the
space rate of increase in thermal conductivity of the gas mixture,
just past the peak as represented by the positive slope of curve
100. The received signal in detector circuit 71 actuates an
associated electrical system indicated by the dotted lines 74 for
operating the sampling valve 50' to move the sample loop into the
analyzer circuit.
A particular advantage of the thermal detector embodiment of FIG. 4
is that it works substantially better than the system disclosed in
FIG. 1, because of the great precision required for the draw into
the sampling valve.
The auxiliary carrier gas from source 47' drives the gas in sample
valve 50' through conduit 48' and into the gas analyzer 49', as in
the previous embodiment. The electronic means indicated by dotted
lines 74 are well known in the art and could comprise, for example,
solenoid controls to rotate valve 50' to the desired positions.
A further modification of the circuit of FIG. 4 includes means for
calibrating the operation of the system. This includes a source 61
of calibration gas which is connected through a conduit 62 to valve
60, which leads into the conduit 40'. The valve 60 may be a
three-way valve, so designed that the terminal of catheter 1' can
be closed off while conduit 62 is open to conduit 40'. The
calibration gas, which is preferably a mixture of similar
composition as the blood gases, flows continuously during the
calibration cycle, and is injected into the gas analyzer 49'
through sampling valve 50'.
It will be understood that although the present invention has been
disclosed with reference to specific embodiments for the purposes
of illustration, it is not limited to the specific forms or
components shown and described, but is only limited by the scope of
the appended claims.
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