JP2008110099A - Method and device for monitoring dialysis of dialytic patient - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an accurate and simple means for monitoring dialysis in a non-invasive manner. <P>SOLUTION: In the method and device for monitoring the dialysis by measuring ammonia concentrations in exhalation of a dialytic patient, an ammonia gas sensor by a crystal oscillator 121 is used. Namely, the gas sensor comprises a plate crystal oscillator 121, a pair of electrodes 122 and 123, and a sensing film 124. By supplying AC between the electrodes with the crystal oscillator 121 in between, the crystal oscillator 121 can be vibrated in a particular number of vibrations. On the surface of the electrode 122, the sensing film 124 is further formed. The sensing film 124 uses a zirconium phosphate film suitable to ammonia absorption. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a method and apparatus for simply and accurately monitoring the dialysis status of a dialysis patient.

  The number of patients requiring dialysis, such as patients with renal failure, is increasing year by year. Dialysis treatment is usually forced to receive dialysis treatment by being restrained in a bed for a predetermined long time, such as three hours a week for four hours. On the other hand, if data that can be used as an index for the appropriate treatment time of each patient can be collected, the patient will not be restrained by the bed as usual, so the burden on the patient and hospital can be reduced. Is meaningful.

Conventionally, the method of grasping the patient's dialysis state has been an invasive method of collecting blood and evaluating renal functions such as serum creatinine, blood urea nitrogen (BUN), and uric acid. In addition, the method of non-invasively grasping the dialysis status during dialysis is only the amount of water removal, but a non-invasive technique without the burden of blood collection is desired.
As a non-invasive technique, recently studied is a method for measuring the ammonia concentration in the oral cavity of a dialysis patient (Non-Patent Documents 1 to 5). Non-patent document 1 describes that the ammonia concentration in the oral cavity of a dialysis patient correlates well with the blood urea nitrogen (BUN) concentration, so that it seems useful for grasping the condition of the dialysis patient. Reference 2 describes that the concentration of ammonia in exhaled breath would be useful for non-invasive diagnosis of patients with chronic renal failure. Furthermore, Non-Patent Document 3 also suggests that the amount of ammonia in the breath will help determine the time required for dialysis.
However, since the amount of exhaled ammonia is very small, in any of these documents, in order to analyze the ammonia in the exhaled air, the exhaled air is once collected in a bag or the like, and the collected exhaled air is ion chromatographed or ionized at atmospheric pressure. A complicated method of analyzing with a large-scale apparatus such as a mass spectrometer (APIMS) is employed.

  On the other hand, Patent Document 1 proposes a method for monitoring the treatment status by continuously flowing respiratory gas over a gas sensor as a monitoring method for grasping the patient's condition. However, this document does not describe monitoring dialysis patients.

Under such circumstances, it is desired to develop a technique that can find an appropriate dialysis time for each patient with a simple and non-invasive technique.
In patients with chronic renal failure, etc., dialysis is essential to sustain life. In order to improve the quality of life (QCL) of the patient, it is better to have a short dialysis time. On the other hand, in order to reduce the complications such as hypertension by sufficiently removing the waste, salt and water in the body fluid. For this reason, longer dialysis time is better. Therefore, it is important to provide a monitoring method and apparatus that can continuously monitor the status of a patient during dialysis treatment and is effective in finding an appropriate dialysis time for each individual patient.
Dialysis Society 30 (11): 1283-1288, 1997 Meikai Univ Dent J 32 (2), 193-198, 2003 PNAS / April 10,2001 / vol.98 / no.8 / 4617-4621 Artificial organ 19 (2), 690-692 (1990) Kidney International, Vol.52 (1997), pp.223-228 Special table 2001-507795 gazette

  An object of the present invention is to provide an accurate and simple means for non-invasively monitoring a dialysis state.

As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that the problem can be solved by using an ammonia gas sensor based on a crystal resonator to measure the oral ammonia concentration.
In other words, if an ammonia gas sensor using a quartz crystal is used, it is possible to accurately measure a small amount of ammonia and monitor the patient's exhalation in real time continuously, and it is also affected by the moisture and ambient temperature in the exhalation. As a result, the present invention has been found. The ammonia gas sensor using a crystal resonator is small and has no burden even if worn by a dialysis patient. Moreover, it turned out that the expiration | expired_air ammonia concentration measured using the ammonia gas sensor by a crystal oscillator has a good correlation with the ammonia concentration by other large gas sensors.
The present invention has been completed based on the above findings and relates to the following invention.

(1) In the method of monitoring dialysis by measuring the concentration of ammonia in the exhaled breath of a dialysis patient, a method using an ammonia gas sensor with a crystal oscillator.
(2) The method according to (1) above, wherein the ammonia gas sensor is a crystal resonator using an adsorption film containing zirconium phosphate.
(3) The method according to (1) or (2) above, wherein the ammonia gas sensor is a sensor that detects ambient temperature and humidity, and performs a correction operation based on the detected temperature and humidity.
(4) A device for monitoring dialysis of a dialysis patient, which includes an ammonia gas sensor using a crystal resonator.
(5) The apparatus according to (4) above, wherein the ammonia gas sensor is a crystal resonator using an adsorption film containing zirconium phosphate.
(6) The apparatus according to (4) or (5), wherein the ammonia gas sensor is a sensor that detects ambient temperature and humidity, and performs a correction operation based on the detected temperature and humidity.

  According to the present invention, the progress of dialysis, dialysis efficiency, and termination of a dialysis patient can be accurately detected by simple means.

Hereinafter, the present invention will be specifically described, but the present invention is not limited thereto.
According to the present invention, it is possible to continuously measure the dialysis efficiency by measuring the ammonia concentration in exhaled breath in real time, thereby not only monitoring the progress of dialysis but also the end of dialysis and / or Alternatively, the dialysis efficiency can be detected. Therefore, in the present invention, monitoring dialysis includes not only monitoring the progress of dialysis but also detecting the end of dialysis and / or dialysis efficiency. Moreover, the ammonia concentration by monitoring of this invention becomes a parameter | index of dialysis efficiency in dialysis medical treatment.
The ammonia gas sensor used for the monitoring of the present invention is based on a crystal resonator. A gas sensor based on a quartz crystal is called a quartz crystal microbalance (QCM), and utilizes the fact that the natural frequency of the quartz crystal changes due to a change in mass attached to an electrode. When a minute amount of material adheres to the crystal resonator electrode by gas adsorption or the like, the minute mass change can be detected as a resonance frequency change by the mass load effect.
In order to detect a small amount of ammonia gas, a sensitive film that adsorbs ammonia gas is formed on the crystal resonator. Zirconium phosphate is preferably used as the sensitive film.

Since exhaled air contains a lot of moisture, it is preferable that the ammonia gas sensor used in the present invention can correct the influence of moisture. Moreover, since there is a temperature variation of the exhaled gas, it is preferable that the effect of the temperature variation can be corrected.
As a gas sensor capable of correcting the influence of such humidity and temperature, the present inventors have previously developed an environmental measurement sensor (utility model registration No. 3094415), but as an ammonia gas sensor for dialysis patients of the present invention, We found that the sensor can be applied.
The sensor is small in palm size, but can measure a very small amount of gas with high accuracy. The sensor detects ambient temperature and humidity and outputs it as an electrical signal, and can correct the ammonia gas concentration by a quartz resonator. When applied to dialysis, the sensor was changed so that dialysis patients can receive dialysis without the pain of noise, such as changing the introduction of exhalation using a silent fan.

A tube is connected to the nasal cavity or oral cavity of a dialysis patient, and the other end of the tube is connected to an ammonia gas sensor using the crystal resonator of the present invention (see FIG. 1). A tube with a diameter of about 5 mm is preferable because it is easy to use.
The tube is condensed by exhalation, but the dew condensation does not affect the ammonia gas concentration measurement of the present invention.

It was found that the measurement value of the ammonia gas concentration in the breath by the quartz crystal resonator of the present invention has a good correlation with the ammonia gas measurement value using another conventional device (see Example 2 described later).
In addition, dialysis patients often eat meals during dialysis. In this case, small fluctuations in ammonia gas concentration due to meals are also detected. Even in this case, it is possible to monitor the dialysis status by knowing the tendency of fluctuations in the overall ammonia concentration (see Example 3 described later).
Furthermore, according to the present invention, since the dialysis status can be continuously monitored, the end of dialysis and the dialysis efficiency can also be detected.
[Example]
In the following, the detection method of the present invention will be specifically described by way of examples, but the present invention is not limited thereto.

<Ammonia gas sensor>
The ammonia gas sensor used in the following examples has the following structure.
FIG. 2 shows a block diagram of the gas sensor. The chamber 110 and the gas detector 120 are illustrated in cross-sectional structure. This gas sensor is roughly composed of a physical function unit 100 and an electrical function unit 200.

Here, the physical function unit 100 is a part composed of physical components including a chamber 110, a gas detector 120, a temperature / humidity detector 130, and a silent fan. In this embodiment, the chamber 110 is a structure that forms a sealed envelope made of metal, and accommodates the gas detector 120 and the temperature / humidity detector 130 therein.
Further, the chamber 110 is provided with an introduction port 111 for introducing exhalation and a discharge port 112 for discharging the introduced exhalation. A silent fan 140 is connected to the introduction port 111. By operating the silent fan 140, exhaled air can be introduced into the chamber 110.

  The gas detector 120 is a component that forms the center of the gas sensor, and includes a crystal resonator 121, a pair of electrodes 122 and 123, and a sensitive film 124, as shown in the cross-sectional structure in the figure. The crystal resonator 121 has a plate shape, and an electrode 122 and an electrode 123 are formed on both surfaces thereof. As described above, when the pair of electrodes 122 and 123 are formed on the mutually opposing surfaces of the crystal resonator 121, the crystal resonator 121 is vibrated at a specific frequency by supplying AC power between both electrodes. be able to. In the illustrated example, a sensitive film 124 is further formed on the surface of one electrode 122. The sensitive film 124 is a zirconium phosphate film suitable for ammonia adsorption.

  In order to produce a sensitive film 124 having good detection sensitivity, tetrabutylammonium hydroxide is added to an α-zirconium phosphate aqueous solution forming a layered crystal to make each layered crystal peel in the solution. A sensitive film 124 having a high adsorption performance for ammonia molecules was obtained by a method of dropping onto 122 and casting.

  On the other hand, the temperature / humidity detector 130 is an element that detects the ambient temperature and humidity and outputs an electrical signal. The temperature / humidity detector 130 is housed in the chamber 110, so that the temperature t and The humidity h can be detected and taken out as an electrical signal.

  In the physical function unit 100, operations necessary for detection are mainly performed due to physical phenomena, whereas in the electrical function unit 200, operations necessary for detection are performed due to electrical phenomena. As shown in the figure, the electrical function unit 200 includes an oscillation circuit 210, a frequency counting circuit 220, and a concentration value calculation circuit 230. The oscillation circuit 210 is an electronic circuit having a function of supplying AC power having a predetermined frequency between the electrodes 122 and 123 to vibrate the crystal resonator 121 at a specific frequency. The frequency counting circuit 220 has a function of counting a unique frequency at which the crystal resonator 121 is oscillating based on the operation of the oscillation circuit 210. The natural vibration frequency of the crystal unit 121 is uniquely determined by physical conditions such as the shape, size, and mass thereof, and the oscillation circuit 210 causes the crystal unit 121 to vibrate at this specific frequency. To generate positive exchanges. The frequency counting circuit 220 is a circuit having a function of counting the frequency of the alternating current generated by the oscillation circuit 210.

  In FIG. 2, the line connecting the oscillation circuit 210 and the electrodes 122 and 123 indicates the actual wiring, but the other lines indicated by arrows indicate the information between the components indicated by each block. The flow is shown.

  The frequency f counted by the frequency counting circuit 220 is given to the concentration value calculation circuit 230. The concentration value calculation circuit 230 is actually a circuit in which a microprocessor is incorporated, and has a function of performing calculation for obtaining the concentration value C of ammonia gas based on the frequency f. The concentration value C thus determined is given to the display 240 and displayed on the screen as a detection result by the gas sensor.

  Since the natural vibration frequency of the crystal unit 121 is uniquely determined by physical conditions such as its shape, size, and mass, when the ammonia gas molecules are adsorbed on the sensitive film 124, the specific vibration frequency is changed. become. It is known that the frequency shift amount changes substantially linearly with respect to the mass increase / decrease amount. Therefore, if the value of the frequency f output from the frequency counting circuit 220 is determined as the frequency reference value f0 in a standard state where no gas is adsorbed on the sensitive film 124, the reference of the frequency f obtained at the time of detection is determined. The shift amount with respect to the value f0 indicates the mass of the gas adsorbed on the sensitive film 124 (that is, the concentration of the gas in the exhaled gas introduced into the chamber 110). The density value calculation circuit 230 performs a calculation for obtaining the density value C from the frequency f based on such a principle.

  However, when the temperature or humidity of the exhaled breath introduced into the chamber 110 changes, it becomes impossible to obtain an accurate measurement value. For example, when the expiratory temperature introduced into the chamber 110 rises, the inherent vibration frequency also changes due to the thermal expansion of the crystal unit 121, so that an error occurs in the measured value due to temperature fluctuation. In addition, the adsorption characteristics between the sensitive membrane and ammonia also vary with temperature. Further, when the humidity of the introduced breath increases, the amount of moisture absorbed by the sensitive membrane 124 also increases, and a phenomenon occurs in which ammonia gas dissolves in this moisture, so that the detected concentration value C is larger than the actual value. Value.

  The gas sensor used in the example reduced the above-described measurement error and increased the measurement accuracy by performing correction using the temperature t and the humidity h detected by the temperature / humidity detector 130. That is, the concentration value calculation circuit 230 performs correction based on the temperature t and the humidity h detected by the temperature / humidity detector 130 when calculating the concentration value C based on the frequency f output from the frequency counting circuit 220. It has a function to perform calculations. Therefore, the density value C output from the density value calculation circuit 230 is an accurate detection value that is not affected by the temperature t and the humidity h.

<Ammonia concentration in dialysis patient exhaled gas 1>
As shown in FIG. 1, a tube was connected to the nasal cavity of a dialysis patient, and the ammonia gas sensor of Example 1 was used to measure the ammonia concentration in the expiration gas of the dialysis patient. Two examples of the results are shown in FIGS. 3 and 4 are different measurement examples by different patients.
3 and 4, the horizontal axis represents the dialysis time, and the vertical axis represents the concentration of ammonia gas in the breath calculated from changes in frequency and humidity. 3 and 4, it can be seen that the dialysis progresses and the concentration of exhaled ammonia gas decreases. In the figure, it seems that there are many concentration plots at the same time, but this is because the horizontal axis (time axis) is compressed, and in the actual monitoring screen, every time The concentration plot is one point.
3 and 4 also show measurement values (white circles) measured by a photoacoustic multi-gas monitor (1412 type / INNOVA Tech Instruments) which is a conventional ammonia gas concentration measuring apparatus. It can be seen that the change in the concentration of exhaled ammonia gas using the quartz crystal resonator of the present invention shows the same tendency as the value measured by the photoacoustic multi-gas monitor.
The photoacoustic multi-gas monitor irradiates the sample gas with infrared light, expands the sample gas by heat generated by light energy absorbed by the sample gas, and generates sound waves by intermittently performing this. It is a monitor that measures the gas contained in the sample by detecting it with a microphone.

<Ammonia concentration in dialysis patient exhaled gas 2>
Using the ammonia gas sensor of Example 1, the ammonia concentration in the exhaled gas of a dialysis patient was measured. In this example, the dialysis patient took a meal during dialysis. Two examples of the results are shown in FIGS.
When eating during dialysis, ammonia concentration may increase temporarily after the meal, but there is no effect on the overall trend, and the progress of dialysis can be monitored by the sensor of the present invention. I understand.

Table 1 shows a comparison between the monitor according to the present invention, a conventional blood sampling measurement, and a detection tube and a photoacoustic multi-gas monitor which are other measurement methods.
The ammonia QCM sensor has the advantage that it is relatively inexpensive, can be made small and can be easily measured, and does not generate waste. Moreover, since it is a continuous measurement, it can be confirmed with certainty that dialysis has been completed, and since the confirmation is always performed during dialysis, useless dialysis time can be reduced.
Furthermore, despite the intake during dialysis, dialysis can be monitored and the end of dialysis can be confirmed, and monitoring can be performed without being affected by fluctuations in ambient humidity and temperature.

The conceptual diagram of the ammonia gas measurement in the expiration of a dialysis patient is shown. The block diagram which shows an ammonia gas sensor. An example of exhaled ammonia gas concentration during dialysis is shown. (Measurement results for patients who do not eat during dialysis) Another example of exhaled ammonia gas concentration during dialysis is shown. (Measurement results for patients who do not eat during dialysis) Another example of exhaled ammonia gas concentration during dialysis is shown. (Measurement results of patients who eat during dialysis) Another example of exhaled ammonia gas concentration during dialysis is shown. (Measurement results of patients who eat during dialysis)

Explanation of symbols

DESCRIPTION OF SYMBOLS 100 ... Physical function part 110 ... Chamber 111 ... Inlet port 112 ... Outlet port 120 ... Gas detector 121 ... Crystal oscillator 122 ... Electrode 123 ... Electrode 124 ... Sensitive film 130 ... Temperature / humidity detector 140 ... Silent fan 200 ... Electricity Functional unit 210 ... oscillation circuit 220 ... frequency counting circuit 230 ... concentration value calculation circuit 240 ... display 250 ... printer C ... concentration value f of detected gas ... measured frequency F ... corrected frequency

Claims (6)

  A method for monitoring dialysis by measuring an exhaled ammonia concentration of a dialysis patient, comprising using an ammonia gas sensor based on a quartz oscillator.   2. The method according to claim 1, wherein the ammonia gas sensor is a crystal resonator using an adsorption film containing zirconium phosphate.   The method according to claim 1 or 2, wherein the ammonia gas sensor is a sensor that detects ambient temperature and humidity and performs a correction operation based on the detected temperature and humidity.   An apparatus for monitoring dialysis of a dialysis patient, comprising an ammonia gas sensor using a crystal resonator.   The apparatus according to claim 4, wherein the ammonia gas sensor is a crystal resonator using an adsorption film containing zirconium phosphate. The apparatus according to claim 4 or 5, wherein the ammonia gas sensor is a sensor that detects ambient temperature and humidity, and performs a correction operation based on the detected temperature and humidity.