JPH0370491B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a device for measuring or monitoring gas concentration (or partial pressure) in blood. More particularly, the present invention relates to an intravascularly insertable device for measuring gas concentration in blood, which has particular utility in in-vivo monitoring applications.

Knowing the concentration of gaseous components such as oxygen and carbon dioxide in the blood is extremely important in clinical tests in order to know the quality of the respiratory and metabolic functions of living organisms. Conventionally, the main method used to measure the concentration (or partial pressure) of gaseous components in blood is to draw blood, especially blood from arteries, and directly measure it, but this method does not allow for continuous measurement over time. The question was what was possible and what could be given to the patient. Particularly in the case of premature infants and newborns, the procedure is extremely invasive due to frequent blood sampling, making it extremely difficult to carry out. For this reason, transcutaneous measurement methods have conventionally been mainly used to continuously measure the concentration of gaseous components in blood over time. For example, this method measures the oxygen concentration in the blood by measuring the partial pressure of oxygen in the blood that diffuses to the skin surface using an electrode that applies polarography, or measures the amount of hemoglobin combined with oxygen in the blood through the skin. It is determined by measuring absorbance. However, these methods can only be applied to specific substances, and cannot be applied to other substances, and the equipment used therefor is often expensive. Furthermore, the measurement accuracy was insufficient due to the pessimistic measurement method. For this reason, the concentration of gaseous components in the blood can be accurately and continuously measured with minimal invasion to control the infusion, anesthesia, and breathing of critically ill patients in ICUs, CCUs, etc., patients undergoing surgery, premature infants, and newborns. It is desired to develop a device for measuring gas concentration in blood that can be used to measure gas concentrations in blood.

As a device for monitoring the concentration of chemical substances in blood, the present inventors have already inserted a catheter into a blood vessel, placed a sensor in the catheter, and constantly supplied infusion fluid into the catheter. Unexamined Japanese Patent Publication 1983 (1983) developed a device for measuring chemical substances in blood by suctioning blood into the chamber.
-Suggested in No. 76639. With this device, ions such as K ⁺ , Na ⁺ , Cl ^- , Ca ⁺⁺ and substrates such as glucose and urea in the blood can be detected in the blood with very little invasion by using corresponding sensors. It is possible to measure chemicals continuously. In addition, with this device, the sensor is in contact with the infusion when not measuring, so it is possible to constantly calibrate with the infusion, which has the excellent effect of always obtaining correct values even if there is a sensor zero point or sensitivity drift. However, although this device can measure ions, etc. in blood, it is difficult to measure gas components in blood.

The present inventors have arrived at the present invention as a result of intensive studies to measure the concentration of gaseous components in blood using the above device.

That is, the present invention installs a gas partial pressure sensor in a measurement chamber connected to a catheter inserted into a blood vessel, and comprises a laminate of a metal foil and an organic polymer film with the measurement chamber. An infusion solution containing a certain concentration of gas components is supplied into the measurement chamber by connecting the transfusion reservoir, which can be flat, with a conduit, and blood is sucked into the catheter and the measurement chamber as appropriate by means of sucking the infusion solution in the measurement chamber. A device for measuring a gas concentration in blood is characterized in that at least a detection part of the gas partial pressure sensor is configured to come into contact with blood.

One of the features of the present invention is that an infusion solution containing a gas component at a constant concentration is supplied into a measurement chamber so that the infusion solution is constantly in contact with the sensor sensitive part. These features made it possible for the first time to continuously measure gas concentrations in blood, and the sensor could be calibrated while the catheter was inserted into the blood vessel, eliminating the possibility of some zero point or sensitivity drift in the sensor. can always be measured. Another feature of the present invention is the provision of means for appropriately sucking blood into the measurement chamber. Due to this feature, blood is sucked into the measurement chamber only during measurement, and since the sensor is normally used as an infusion, stable measurement is possible without the attachment of blood clots to the sensor. Another advantage is that there is no loss of blood because blood is sucked into the measurement chamber only during measurement and returned to the blood vessel after measurement.

Next, one embodiment of the device of the present invention will be described with reference to the drawings. As shown in FIG. 1, the device of the present invention includes a catheter 1 inserted into a blood vessel 12, a sensor 2 installed in a measurement chamber 3 connected to the catheter 1, and a sensor 2 for measuring the concentration of a gas component. an infusion reservoir 11 containing a liquid containing a concentrated gas component;
It is comprised of a conduit 9 that connects the infusion reservoir and the measurement chamber 3, and a suction means (a roller pump 22 is used in FIG. 1) that sucks blood into the measurement chamber. 8 is a stopper for inserting the sensor 2 into the catheter, 15 is a measurement circuit, 10 is a drop chamber, and 16 is the skin.

In the device of the present invention, it is important to keep the gas concentration of the infusion constant during monitoring. As such a method, there is a method in which an infusion solution with a certain gas concentration is prepared in advance and the infusion solution is supplied to a catheter using the device shown in FIG. In this case, the gas in the infusion reservoir will not escape through the container during measurement or storage, and the gas concentration in the infusion will not change due to the liquid level in the infusion reservoir falling during measurement and reducing the pressure in the infusion reservoir. It is necessary to devise such a method. In such a method, (A) a bag-like container is used as an infusion reservoir, which is partially or entirely gas-impermeable and which is easily deformed by external pressure. (B) Use metal or glass containers that do not deform under pressure. In this case, it is necessary to actively prevent pressure reduction inside the container due to the infusion during measurement. For example, as shown in FIG. 2a, an exhaust pipe 14 that opens into the space above the liquid level in the container and a gas supply pipe 25 that opens below the liquid level are attached to the infusion reservoir 11, and the gas supply pipe 25 is used for sterilization. Filter 13
or the gas supply pipe 1 that opens below the liquid level of the infusion reservoir 11 as shown in Figure 2b.
A liquid reservoir is created by connecting one end of 7 to the upper space of a sealed container 18 containing water, connecting a gas pipe below the water surface of the container via a sterilizing filter 13, and further attaching an exhaust pipe 19 to the upper part of the container. It is necessary to constantly supply gas at a constant concentration in excess of the amount reduced by the infusion to 11, and to exhaust the excess gas from the exhaust pipe to maintain the gas concentration of the infusion stored in the reservoir at a constant level.

(c) As shown in FIG. 3, the conduit 9 connecting the infusion reservoir 11 and the catheter 1 or the measurement chamber 3 is a hollow fiber, flat membrane, or tube-shaped membrane that is permeable to gas. In this case, for example, a silicone membrane or a Teflon porous membrane 20 is housed in the casing 21 to form an infusion chamber and a gas chamber within the casing via the membrane, and a gas saturated with water at a constant concentration is continuously supplied to the gas chamber. A gas partial pressure equalization device 32 can be used. FIG. 3a shows a silicon tube 20 housed in a casing 21 having a gas inlet 23 and an outlet 24 and an infusion inlet 25 and an outlet 26, and both ends of the hollow fibers are connected to the infusion inlet and outlet in a fluid-tight manner. Fig. 3b shows an example in which both ends are adhesively fixed with a resin, and a silicon hollow fiber having an opening at the end is inserted into a cylindrical case having a gas inlet 23 and an outlet 24. and an infusion inlet 25 and an outlet 2 at both ends of the case.
This is an example in which a cap with 6 is attached. The device of the present invention requires only a very small amount of infusion;
A small-sized gas partial pressure balancing device can easily obtain an infusion containing a gas partial pressure equal to the outside gas partial pressure.

Of the above methods (A), (B), and (C) for supplying an infusion with a certain concentration of gas dissolved in it, both (B) and (C) require a standard gas cylinder to be brought to the measurement site. , operation becomes complicated. In method (A), even if the amount of constant gas infusion decreases, the gas partial pressure inside the container does not change because the container deforms and contracts due to atmospheric pressure. Therefore, not only is it not necessary to bring a standard gas cylinder to the measurement site, but also a gas reinforcing device or a gas partial pressure balancing device is not required, which simplifies the system. It is also easy to operate. First of all, the infusion reservoir used in method (A) must have sufficiently low gas permeability. A constant gas infusion solution is sealed in this infusion reservoir container at the factory, and it is necessary that the gas concentration in the infusion solution remains unchanged during long-term storage. In order to satisfy these conditions, it is necessary to use a gas-impermeable material for the container. Second, the infusion reservoir needs to have enough flexibility to be deformed by atmospheric pressure. When using the same materials, increasing the thickness of the container wall reduces gas permeability, but at the expense of flexibility. It is difficult to create an infusion reservoir that satisfies both flexibility and gas impermeability using only ordinary organic polymer materials. Polyvinyl alcohol and ethylene-vinyl alcohol copolymer are known to have the lowest gas permeability among polymer materials, but even if a laminate film with one layer of these polymer membranes is used, the above-mentioned problems will occur. It is difficult to obtain a container that satisfies both conditions. For example 40μ
A container made of a three-layer laminate consisting of a layer of ethylene-vinyl alcohol copolymer with a thickness of However, after being stored at 37°C for 30 days, the carbon dioxide gas sealed together with water in this container will be reduced to 1/100 of the time when it was sealed.
It will decrease to.

As a result of various studies, it has become clear that a laminate of metal foil and organic polymer film is the best material for containers that satisfies both flexibility and gas impermeability. Various metals such as aluminum, chromium, nickel, copper, and molybdenum can be used, but aluminum is preferred because of its cost and ease of manufacture. The thickness of the metal foil is preferably 0.01 to 100μ. If the thickness is less than 0.01μ, the gas impermeability will be insufficient, and if the thickness is more than 100μ, the flexibility will be insufficient. Such a metal foil may be made by a conventional method, or may be formed on a polymer film for lamination by vapor deposition or sputtering. As the polymer membrane used for lamination, various materials such as polyethylene, polypropylene, polyester, polyamide, polyvinyl chloride, etc. can be used. The laminate of metal and polymer film usually has a three-layer structure of polymer film/metal film/polymer film. The overall thickness of the laminate should be designed to maintain flexibility, but is usually on the order of 30 to 1000 microns.

A known sensor can be used as the gas partial pressure sensor used in the present invention. Examples of this sensor include a polarographic oxygen sensor, a carbon dioxide electrode based on the Severinghaus method, and an ammonia electrode. In order to reduce the impact of the invasion on the patient and to reduce the amount of blood that is refluxed, it is necessary to downsize the catheter and/or the measurement chamber. Therefore, the smaller the sensor, the better. In that sense, the polarographic oxygen sensor and gas partial pressure sensor using FET are preferable. In particular, the gas sensor proposed by the applicant in Japanese Patent Laid-Open No. 56-2546 is small and highly accurate, and is therefore preferable as a sensor for use in the present invention. In addition to sensors that measure specific gas concentrations, precision gas sensors, such as oxygen and carbon dioxide sensors, can also be inserted into the catheter. In this case, there is an advantage that the gas concentrations of multiple components can be measured at the same time, and the range of application can be expanded. In addition to gas partial pressure sensors,
It is also possible to use ion electrodes such as H ⁺ , Na ⁺ , K ⁺ , Ca ⁺⁺ , Cl ^{- and} sensors such as glucose and urea in combination. However, while gas sensors are used integrally with a reference electrode, ion sensors and the like require a separate reference electrode. In this case, the reference electrode may be electrically connected to the ion sensor through an electrolytic liquid such as an infusion solution. The reference electrode can therefore be provided within the infusion conduit or catheter. In order to downsize the sensor section, it is preferable to integrate the reference electrode with the sensor.

In addition, the catheter insertion method for these sensors is the first one, even if it is not directly inserted into the catheter.
It may be inserted into a measurement chamber connected to the rear end of the catheter as shown.

In the device of the invention, blood is flowed back into the catheter or measurement chamber housing the sensor;
When one measurement is completed, the blood is pumped back into the living body by infusion. At this time, if a blood clot forms on the surface of the sensor, the response speed of the sensor becomes slow and the sensitivity decreases. Therefore, it is extremely important to prevent thrombus formation on the sensor surface when putting the device of the present invention into practical use. The present inventors conducted a detailed study on the formation of blood clots on the sensor surface, and found that the vector connecting the infusion inlet and outlet of the measurement chamber housing the sensor (hereinafter referred to as the infusion flow vector) and the gas flow vector It has been found that when the angle (θ) formed by the long axis direction of the pressure sensor is between 0 and 45 degrees, there is less thrombus formation. The definition of the angle θ will be explained using figures. In Figure 4, 2
A book sensor 31 is attached to the tip of a sensor support rod 37 and housed in a measurement chamber container 33. 34 is an inlet for infusion fluid and is connected to a pump and an infusion bag. 35 is an infusion outlet leading to the patient's blood vessel. This is a plug for fixing the sensor support rod to the measurement chamber container. In FIG. 4, the vector AB connecting the infusion inlet A and the infusion outlet B is the infusion flow belt, and the long axis direction of the sensor is the direction CD. The angle formed by these two is the angle shown by θ in the figure. It is clear in FIG. 4 that θ is less than 45°. In FIG. 5, 41 is a sensor, 42 is a measuring chamber container, and 43 and 44 are an inlet and an outlet for infusion, respectively. In this case, it can be seen that the infusion flow vector AB intersects with the long axis direction CD of the sensor at 90°. The present inventors investigated the structure of the measurement chamber container, the arrangement of the sensor within the measurement chamber, and the ease of thrombus formation, and found that the angle between the direction of infusion or blood flow and the long axis direction of the sensor We found that this is an important factor governing thrombus formation. That is, when the infusion flow vector and the long axis direction of the sensor are perpendicular to each other as shown in FIG. 5, thrombus is most likely to be generated around the sensor. On the other hand, as shown in FIG. 4, when the angle between the infusion flow vector and the long axis direction of the sensor is less than 45 degrees, thrombi are less likely to form.

In FIG. 1, an infusion conduit 9 and a catheter 1
Although known materials can be used, these materials need to have appropriate gas barrier properties so that the concentration of gas components in the infusion does not change before reaching the sensor section. The material and the thickness of the tube wall can be selected depending on the type of gas to be measured, but polyvinyl chloride tubes, nylon tubes, or silicon tubes with inner thickness are usually preferably used.

When measuring chemical substances such as ions at the same time as gas partial pressure, if the infusion solution contains a certain concentration of gas and its ionic species, it is possible to calibrate many types of sensors using one type of infusion solution. be able to. One type of infusion is sufficient to calibrate only the zero point of the sensor, but if two-point calibration of the zero point and sensitivity is required, two types of infusion with different concentrations of each component should be prepared and calibrated sequentially. It is necessary to perform sensor calibration with separate infusions.

A pump is usually used as a means for supplying infusion fluid to the catheter or measurement chamber. FIG. 1 shows an example using a roller pump. In such a pump, by arranging the roller 30 eccentrically, as the pump 22 rotates, blood is suctioned in the area where the roller 30 is installed and infusion is performed in the area where the roller is not installed, so that measurement can be performed automatically. There are advantages. Further, the roller pump may be rotated in forward and reverse directions as appropriate using a microcomputer.

In the apparatus of the present invention, it is desirable that the measurement chamber in which the gas partial pressure sensor is installed be maintained at a constant temperature. The sensitivity and zero point of ordinary gas partial pressure sensors and ion sensors change sensitively depending on temperature. Furthermore, the partial pressure of gases in blood and the activity of ions themselves change with temperature. Therefore, gas partial pressure and ionic activity in blood are usually measured at around 37°C. In this device as well, it is desirable to perform measurements while maintaining the temperature of the measurement chamber at around 37°C. For this reason, it is desirable to house the measurement chamber in a thermostatic box.

As described above, the device for measuring gas concentration in blood of the present invention has the following features: (1) Blood is sucked only during measurement and returned into the blood vessel after measurement, so there is little blood loss.

(2) Since infusion is usually used, stable measurements are possible without the attachment of blood clots to the sensor.

(3) Since the sensor is alternately contacted with the transfusion agent and blood, it is possible to perform calibration using the infusion agent and check for sensor drift.

(4) High safety because no electrical circuit is inserted into the body.

By using the device of the present invention, stable monitoring of gaseous components in blood with little blood loss became possible.

[Brief explanation of drawings]

The figure shows an embodiment of the device of the present invention,
FIG. 1 is a partial sectional view of the device of the present invention. FIGS. 2 and 3 are explanatory diagrams showing an example of a device for making the partial pressure of gas in an infusion constant. FIGS. 4 and 5 are explanatory diagrams showing examples of the arrangement of sensors in the measurement chamber.

Claims (1)

[Claims] 1 A gas partial pressure sensor is installed in a measurement chamber connected to a catheter inserted into a blood vessel, and the measurement chamber is composed of a laminate of metal foil and an organic polymer film, and is deformed by atmospheric pressure. A conduit is connected to the infusion reservoir to be obtained, and an infusion containing a gas component at a certain concentration is supplied into the measurement chamber, and blood is appropriately sucked into the catheter and the measurement chamber by a means for sucking the infusion in the measurement chamber. , a device for measuring gas concentration in blood, characterized in that at least a detection part of the gas partial pressure sensor is configured to come into contact with blood.