JPS618028A - Apparatus for measuring concentration of ion in blood - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a device for measuring or monitoring ion concentration in blood. More specifically, the present invention relates to an intravascularly insertable blood ion concentration measuring device that has particular utility in in-vivo monitoring applications.

(Prior Art) Knowing the concentrations of ionic components in the blood, particularly hydrogen ions, potassium ions, sodium ions, and p-Schlum ions, is clinically extremely important in order to know the quality of the respiration and metabolic abilities of living organisms.

Especially patients undergoing surgery, I (3U inmates, or CCU)
For hospitalized patients receiving infusions, it is strongly desirable to continuously monitor the hydrogen concentration, potassium, sodium, and p-Schlum ion concentration in the blood. Continuous monitoring of the ion concentration in the blood is often carried out using an ion electrode or flame method after blood collection. In addition, sensors using small catheter-type glass electrodes, coated wire electrodes, and FET sensors have been prototyped for this purpose, but they have not yet been put into practical use.

On the other hand, recently, blood has been taken out into an extracorporeal circuit, the blood is brought into contact with the outside of a hollow fiber dialysis membrane provided in the circuit, a monitor solution is flowed inside, and the hydrogen ion concentration in the monitor solution is measured. A device that can measure the pH in blood was announced (Toshiyo Tamura, New Medicine, Vol. 10).
Black 10.23 pages (1983)).

(Problems to be Solved by the Invention) The former continuous monitoring device using an intravascular sensor has the following problems.

(1) In order to insert the sensor itself into a blood vessel, it was necessary to sterilize the sensor, and it was also necessary to make the sensor disposable. I have to say that this is extremely uneconomical.

(2) Once the sensor is placed in a blood vessel, it is impossible to calibrate the sensor with a standard solution. However, since the zero point and sensitivity of any sensor usually change over time (drift), continuous measurement over a long period of time has been impossible.

(3) When a sensor is directly placed in a blood vessel, it is essential to reduce the diameter of the sensor itself in order to minimize the degree of invasiveness in the living body. Currently, FET sensors and coated wire type sensors have been successfully reduced in diameter, but when these two are combined, it is extremely difficult to reduce the diameter.

On the other hand, if the latter method is used, the sensor does not come into direct contact with blood, so the first problem mentioned above is solved. Furthermore, since the sensor is installed outside the body, it is possible to calibrate it as necessary, which also solves the second problem. Furthermore, it seems possible to measure multiple ions simultaneously. Unfortunately, this method has serious drawbacks that cannot be ignored.

The problem is that blood must be taken to a circuit outside the body in order to measure ion concentration. Therefore, although this method may be used to monitor blood ions in an extracorporeal circulation circuit for cardiopulmonary bypass or artificial analysis, it cannot be used to monitor blood ions in the majority of normal critically ill patients who do not require an extracorporeal circulation circuit. The burden on the patient is too great for its use.

As described above, the known devices for the purpose of continuously monitoring the ion concentration in blood each have their own problems, and it seems that they have not been widely used in clinical practice.

(Means for Solving the Problems) The present inventors solved the problems of conventional blood ion monitoring devices and arrived at the present invention as a result of intensive research into a highly practical system. The most important feature of the present invention is the use of a catheter /I/ (hereinafter referred to as ion permeable catheter p) which has an ion permeable function and can be inserted into a blood vessel.

(Function) A carrier solution containing ions at a constant concentration is flowed at a constant flow rate inside a catheter inserted into a blood vessel.
Exchange is performed with blood flowing outside the catheter via an ion-permeable membrane on the outermost side of the catheter. The carrier solution after ion exchange is led to a measurement chamber installed outside the body, and the ion concentration in the carrier solution is measured, thereby indirectly measuring the ion concentration in the blood. By using such an ion permeable catheter, it is possible to continuously monitor ions in the patient's blood without taking the patient's blood to a circuit outside the body.

(Example) Next, the basic configuration of the device of the present invention will be explained with reference to the drawings.

As shown in FIG.
, sensor 10, conduits 6 and 7, and optionally cocks 15 and 16. First, the ion permeable catheter/L/1 consists of an inner tube 2, an outer tube 3 made up of ion permeable glands, a tube body 4 with no ion permeability, and a stopper 5 used to connect the catheter to an indwelling needle, etc. . The tube body 4 without ion permeability has an ion permeable part (
In this case, it is provided to keep the membrane area of the catheter tip (in this case) constant. The injection device 8 delivers the carrier solution 17 at a constant flow rate into the iontophoretic catheter. A sensor 10 is installed in the measurement chamber 9. 11 is a connector, 13 is a lead wire, and 14 is a pin of the connector, which is connected to the monitor. 15 and 16 are cocks for changing the flow path of the carrier solution. For normal measurements, the cock 15 is open;
16 is closed and the carrier solution is passed from the injection device to the stopcock 1.
5. The blood is sent to the inside of the inner tube 2 of the ion permeable catheter via the conduit 6, and after ion exchange with blood is performed outside the inner tube 2, it is sent to the measurement chamber 9 via the conduit 7, and the waste liquid port 12 more discarded. On the other hand, when calibrating the sensor, use cock 1.
5 is closed and 16 is opened to directly feed the carrier solution from the injection device 8 into the measurement chamber 9.

Next, details of the device of the present invention will be explained for each component. First, the ion permeable catheter will be explained. Although several shapes are possible for the ion permeable catheter, the double tube structure shown in FIG. 1 is considered to be the most practical. The outer diameter of the ion-permeable catheter (the outer diameter of the ion-impermeable membrane 4 in FIG. 1) is 1. Qmm or less,
Preferably, Q is 6 mm or less. If it becomes thicker than this, it will cause too much pain to the patient when it is placed in the blood vessel. The most important part of the ion permeable catheter p is the ion permeable membrane 3. First of all, the membrane must be made of a material with high ion permeability. The most preferable materials are cellulose membranes, porous ethylene vinyl alcohol copolymer membranes, hydrophilic acrylic esters such as hydroxyethyl methacrylate (HEMA), hydrophilic membranes such as methacrylic ester polymers, porous acetyl cellulose, and polystyrene. Porous membranes such as μphone, polymethyl methacrylate, etc. The thickness of the film is 10
The thickness is preferably about 100 μm. If the membrane thickness exceeds this range, the ion permeability will decrease and the outer diameter of the entire catheter will increase, which is not preferable. If the thickness is less than 10 μm, the mechanical strength of the film becomes insufficient and pinholes are likely to be formed, which is not preferable. The shorter the length of the ion-permeable membrane tube portion 3, the better from a clinical perspective, but if it is too short, the effective membrane area for ion exchange will be insufficient, so it is practically recommended to use IC7F+ to 5a.
About m is preferable. The inner tube 2 of the ion permeable catheter functions as a tube for delivering the carrier solution to the tip of the catheter, and at the same time functions as a core tube that maintains the shape of the catheter, so it has a certain degree of rigidity. It is necessary that the person has the same gender.

For example, a tube body made of stainless steel, polypropylene, Teflon, polycarbonate, polyethylene, etc. is used. The thinner the wall thickness of the inner tube 2 is, the less the above-mentioned rigidity is maintained. The thinner the wall thickness, the larger the volume of the carrier solution flow path, which increases the residence time of the carrier solution in the catheter and therefore the contact time with the ion permeable membrane, thereby bringing it closer to equilibrium. It is possible to carry out ion exchange. Practically speaking, the wall thickness of the inner tube is preferably 10 μm to 100 μm. The ion-impermeable tube 4 needs to be as thin as possible and have low ion permeability. Materials used include polymeric materials (non-porous) such as polyethylene, polypropylene, Teflon, polyvinyl chloride, nylon, ethylene-vinyl alcohol copolymer, AH-acid cellulose membrane, or metal thin films such as vapor-deposited aluminum films. It will be done.

Next, regarding a liquid injection device, a syringe as shown in FIG. 1 is one example. This naturally requires a device that automatically inserts the syringe piston at a constant speed. It is also possible to use a roller pump instead of a syringe. The injection rate varies depending on the thickness and length of the ion permeable catheter, but is generally a small amount of 0.1 to 5 s+J/hr. Moreover, since temporal fluctuations in the injection rate cause errors in the measured values, it is necessary to keep the fluctuation within ±10%.

It is necessary that the carrier solution conduits 6 and 7 satisfy the following conditions. Firstly, the water vapor permeability is low, and secondly,
The internal volume should be as small as possible. The exchange of ions between the carrier solution and the external atmosphere takes place only in the ion-permeable membrane 3 of the catheter, and must not take place in any other part of the flow path. If the material of the conduit is highly permeable to moisture, evaporation of water into the outside air will cause a change in the ion concentration of the carrier solution. Furthermore, the smaller the internal volume of the carrier solution conduit, the faster the response can be obtained.

Therefore, as the material of the conduit, polyethylene, polypropylene, Teflon, polyvinyl chloride, nylon, ethylene-vinyl alcohol-A/copolymer, cellulose acetate, etc. are used, and the inner diameter thereof is preferably 0.5 mm or less. Similar conditions are required for the measurement chamber 9 as well. In other words, it is necessary that the flow path volume of the carrier solution is small. The measurement chamber 9 is housed in a thermostatic box as required. Various sensors are used as the sensor 10 depending on the type of ion to be measured. For example, electrodes such as glass electrodes, liquid film electrodes, solid film electrodes, FET sensors in which the gate electrode of a field effect transistor (FET) is replaced with an ion-sensitive membrane, ion analyzers using flame method, pH sensors using optical fibers, etc. can be mentioned. Among these, electrode or FET sensors are preferable because continuous measurement is easy and no flame is used.

As the electrode, a glass electrode is preferable for measuring pH1 Na+ ions, and a liquid film electrode with a sensitive substance dissolved in a solvent or polymer matrix is preferable for measuring K+ and Oa++ ions. Various types of electrodes with small measurement chamber volumes have been manufactured for analysis, such as capillary electrodes and flat membrane electrodes.

Similar to electrodes, FET sensors can be made to handle various ions by changing the sensitive film. 1i' :/ evening/L/(
FET pH sensors such as Ta205), Na and K ion sensors that use ion-sensitive glass membranes, K"%Ca+" ion sensors that use polymer membranes containing ion-sensitive substances such as neutral carriers as sensitive membranes, etc. can be mentioned. FET sensors have the characteristics of being small and easy to combine, and are particularly suitable as sensors for use in the present invention.

A reference electrode is required for measurement using an electrode or FET sensor, and a silver-silver chloride electrode or a string electrode is usually used for this, but these do not necessarily need to be housed in the measurement chamber 9. , or may be installed at another location connected to the main electrode by a carrier solution, for example, downstream of the waste liquid 12. Although water itself can be used as the carrier solution, if the concentration of the substance to be measured is close to that of blood, the concentration of the carrier solution after ion exchange will approach the equilibrium value, making it difficult to measure. The error can be reduced.

Therefore, Na and C1- in the carrier solution are 50 to 200
mM.

Good i L (Ha1 (10-150 mM, , Kj,
It is desirable that the amount of Ca++ is 0.1 to 10 mM, preferably 1 to 5 ml.

Making the composition of Na'' and U- close to that of blood equalizes the osmotic pressure of both, reduces the force applied to the ion exchange membrane, and reduces the movement of water between the carrier solution and blood. It is also significant that the pH does not necessarily have to be equal to the pH of blood, but rather that weak electrolyte ions such as organic acids, organic amines, phosphoric acid, etc. It is important not to contain a large amount of boric acid, etc.

(Effects of the Invention) By appropriately combining the sensor and carrier liquid composition described above, it is possible to measure a plurality of ions with one ion permeable catheter using this device. In this case, the sensor It is okay to use a composite one,
Single sensors may be connected in series or in parallel.

Similarly, it is also possible to measure the concentration of chemical substances other than ions by combining the sensor of this device with 02, a CO2 sensor gas sensor, and a substrate sensor such as glucose, urea, or urease. By using the device of the invention, (1) it has become possible to monitor many parameters simultaneously with a very small invasion.

(2) Since ion permeable catheters can be easily sterilized and are extremely inexpensive, continuous monitoring of blood ions can be carried out at a lower cost than when a sensor is inserted directly into a blood vessel.

(3) Since blood is not taken out of the body, there is no need for a large-scale extracorporeal circulation circuit. Therefore, not only is it economical, but precious blood is not wasted, and the amount of heparin administered to prevent blood clots may be minimal, or in some cases, may not need to be administered.

(4) Since the sensor is installed outside the body, it is not disposable. In addition, calibration is possible, and size restrictions are relaxed, making it easy to combine.

[Brief explanation of drawings]

FIG. 1 is a sectional view illustrating the configuration of the apparatus of the present invention. 1...--Ion permeable catheter, 2...
...Inner tube, 3...Ion permeable membrane, 4...Ion impermeable membrane, 5...
-...Plug body, 6,7...Carrier solution conduit, 8...Carrier solution injection device, 9...... Measurement room, 10...
...Sensor, 11...Connector, 1
2... Waste liquid port, 13... Lead wire, 14... Connector pin, 15.
16・・・・・・・・・cock, 17・・・・・・carrier solution, 18・・・・・・blood vessel

Claims (1)

[Scope of Claims] 1. A tube body to be inserted into a blood vessel whose distal end is closed, has an outgoing path and a returning path for a carrier solution inside, and at least a portion of the outermost part is made of an ion-permeable membrane. A carrier solution is supplied into the tube by a liquid injection device connected to the outbound side of the tube through a conduit, and the carrier solution, which has exchanged ions with blood through the ion-permeable membrane, is transferred to the return side of the tube. A device for measuring ion concentration in blood, characterized in that the blood is introduced into a measurement chamber connected by a conduit, and a sensor sensitive to ions in a carrier solution is provided in the measurement chamber. 2. A device for measuring ion concentration in blood, characterized in that the carrier solution supplied in claim 1 contains ions to be measured at a constant concentration.