WO1996035369A1

WO1996035369A1 - Method and apparatus for determination of production and secretion of certain substances in the body and dialyse catheter

Info

Publication number: WO1996035369A1
Application number: PCT/SE1996/000618
Authority: WO
Inventors: Anders Essen-Möller
Original assignee: Synectics Medical Ab
Priority date: 1995-05-10
Filing date: 1996-05-10
Publication date: 1996-11-14
Also published as: AU5709996A; SE513570C2; EP0957746A1; SE9501735L; SE9501735D0

Abstract

A method and apparatus for determining the production of certain substances secreted in the body, for instance such substances as hydrochloric acid, bile salts, pancreas enzymes, pepsins, trypsins, porphyrins, nitrogen oxide and carbon dioxide. A dialyzable calibrating substance (21) is added to body fluid to a known extent, said calibrating substance containing the substance whose production shall be determined; the amount of calibrating substance dialyzed in a dialysis catheter in time is determined, the amount of substance whose production shall be determined dialyzed in the dialysis catheter in time is determined and a quotient (F(t)) between the added and dialyzed quantities of calibrating substance in time is determined and is correlated with a corresponding quotient (G(t)) for the substance whose production shall be determined, so as to determine said production.

Description

METHOD AND APPARATUS FOR DETERMINATION OF PRODUCTION AND SECRETION OF CERTAIN SUBSTANCES IN THE BODY AND DIALYSE CATHETER

The present invention relates to a method of determining production and secretion of certain body substances.

The invention also relates to apparatus for carrying out the method.

The invention also relates to a dialysis catheter.

The ability to determine accurately the amount of hydrochlo¬ ric acid produced per unit of time by the mucous membrane of the stomach would be of extreme value in determining the gastrointestinal functions of an individual. In one known method, a gastric probe is normally used to this end. The gastric probe is connected to an external suction source and the stomach regularly emptied of its content, whereafter the amount of hydrochloric acid present in thee sample is determined by titration. The continual emptying of the stomach, and therewith the substance to be determined referred to in the following as the investigative substance, by natural causes is often not taken into account. The method is also complicated and time-consuming, and the analysis is often carried out under conditions which are abnormal to the patient, eg on an empty stomach and over a limited period of time.

As a result of these difficulties, the production of hydro¬ chloric acid by patients with gastrointestinal problems is often replaced with other function measurements, for instance hydrochloric acid exposure in the stomach over a period of twenty-four hours, the occurrence of bilirubin, the rate at which the stomach is empyied, the motor activity of the oesophagus, stomach and small intestines, etc. These investi¬ gations are often carried out with the aid of a portable data logger, which the patient is able to carry on his/her person over a period of one calendar day for instance, during which time measurement data is collected in an environment normal to the patient. The value of the investigations, however, is restricted by the fact that the total amount of secreted substances cannot readily be determined. An example of the problems related hereto is found in a patient suffering from gastroesophageal reflux, in which gastric juices flow backwards into the oesophagus to an abnormal extent. This may be due to: (1) an incompetent gastroesophageal sphincter, (ii) subdued motor activity of the oesophagus, (iii) reduced stomach emptying rate, (iv) an excessively high hydrochloric acid production, (v) abnormal intestinal motor activity, and so on. For instance, one conceivable case is when impaired intestinal motor activity results in the build-up of a relatively large reservoir of gastric juices in the stomach and is regurgitated into the oesophagus to an abnormal extent, despite the production of hydrochloric acid perhaps being less than normal by virtue of compensatory feedback. The administration of anti-acid pharmaceuticals in this state would be to treat a symptom, whereas a motor stabilizing measure might be preferred, if possible.

The present invention relates to determining the amount of certain substances produced by a patient over a longer period of time and under conditions which are practically normal to the patient. The invention thus has significant advantages.

Thus, the invention relates to a method according to the preamble of the following Claim 1, said method being particu¬ larly characterized by the features set forth in th charac¬ terizing clause of said Claim.

The invention also relates to apparatus according to the preamble of the following Claim 3. The apparatus is charac¬ terized by the features set forth in the characterizing clause of said Claim. The invention also relates to a catheter of the kind defined in the preamble of Claim 10 and having the characteristic features set forth in the characterizing clause of thereof.

The invention will now be described in more detail with reference to an exemplifying embodiment thereof and also with reference to the accompanying drawing, in which

Fig. 1 illustrates schematically a data logger in accor- dance with the invention and in perspective;

Fig. 2 shows the data logger of Fig. 1 as seen obliquely from the right in said Figure;

- Fig. 3 is a principle diagram of one embodiment of an inventive apparatus; and

Fig. 4 illustrates schematically the inventive apparatus applied to and inserted inside a patient.

The inventive apparatus, shown in Fig. 1, includes a data logger 10, for instance a Microdigitrapper, Synectics Medical AB, Stockholm, Sweden, whose function is determined by means of a computer-applied program in accordance with European Patent No. 0 356 603, through the medium of coupling means 10, for instance. The Microdigitrapper includes two pumps 11 and 12, a valve 13, two liquid reservoirs 14 and 15, a titration device 16, and a spectrophotometer 17. Also included are catheter connections 18, 19 and 20 and connec- tions 20', 20", 20"' for different types of sensor for different magnetudes, such as bilirubin assays, with the aid of fiberoptics and sensors for sensing pH, pressure, Egg, Gastric Emptying, Potential Difference, Pco₂, Po₂, etc.

One liquid reservoir 14 is intended to be charged with cali¬ brating substance 21 in known concentration (K), and the other liquid reservoir 15 is intended to be supplied with a dialysis liquid or dialysate 22. A pump 11 functions to pump the calibrating substance 21 at a predetermined, user- adjusted rate out through a catheter connection 18 and into a catheter 23, which opens out in the stomach for instance, preferably so that maximum spreading of gastric juices will be achieved. The other pump 12 functions to pump dialysis liquid 22 through a dialysis lumen at a known rate. The dialysis liquid is arranged to pass into the dialysis lumen 24 through the connection 19, and thereafter pass one side of a dialysis membrane, the other side of which membrane is intended to be in contact with the body fluid that contains the investigative substance to be quantitatively determined, such as hydrochloric acid, and to return to the Microdigit¬ rapper via the connection 20. The dialysis liquid with dialysate is then intended to pass the valve 13, which in the illustrated embodiment is normally intended to create a subpressure for the dialysis liquid and thereby obtain ultrafiltration, although the valve can also be used to create an overpressure. Downstream of the valve, the dialysis liquid is intended to be conveyed to a collecting vessel 25 for later disposal. The dialysis liquid is intended to pass a cuvette-like part 26 immediately prior to said liquid entering the Microdigitrapper via the connection 20. This arrangement can be used for photometric (fluorescence, adsorption, etc.), titration, pH measurements and other measurements. The cuvette-like part 26 is placed in a holder 27 on the Microdigitrapper. The holder 27 forms a supportive base for a photometric measuring device 17, a titration measuring device 16 and a pH-measuring device for determining the dialyzed calibrating substance and for measuring purposes.

The manner in which the inventive apparatus and inventive dialysis catheter operate will be evident essentially from the aforegoing, as will also the inventive method. Thus, a known calibrating substance is added to the investi¬ gative substance (e.g. hydrochloric acid) under controlled conditions. By dialyzing the calibrating substance in a catheter with flowing dialysis liquid and thereafter deter- mining the quantities of the dialyzed calibrating substance and the dialyzed substance (hydrochloric acid) at the same time, it is possible to obtain a time-dependent quotient (t), a quotient in time, between added calibrating substance and dialyzed calibrating substance. F(t) takes into account the speed at which the calibrating substance is eliminated, for instance when the stomach is emptied. The quotient is correlated with a corresponding quotient G(t) for the substance whose production or secretion is to be determined and studied. The correlation can be carried out with the quotients F(t), G(t) made equal to one another. It is conceivable to choose or determine other relationships between the quotients F(t), G(t). The production of said substance in time can be determined from the relationship between the quotients.

It will be evident from the aforegoing that the invention enables, among other things, the production or secreted quantities of certain substances in time to be accurately measured, for instance stomach-contained hydrochloric acid, thereby providing greatly improved diagnostic possibilities, among other things.

Although the invention has been described in the aforegoing with reference to an exemplifying embodiment thereof, it will be understood that other embodiments and minor changes and supplementations are conceivable without departing from the inventive concept.

For instance, in the case of preferred embodiments, there is provided a data logger for ambulatory use and for use as a central unit, etc., although stationary devices are also conceivable for corresponding functions. The production and secretion of hydrochloric acid in the stomach has been mentioned above to exemplify one application of the invention. Naturally, the invention can be applied equally as well in other areas, for instance the urinary bladder.

The invention can also be applied to determine secretion and production of many different substances, such as bile salts, pancreas enzymes, pepsins, trypsins, porphyrins, nitrogen oxide, carbon dioxide, and so on.

Also conceivable is an embodiment in which the cuvette-like part does not form a separate unit, for instance is connected to the catheter.

It will therefore be understood that the invention is not restricted to the aforedescribed exemplifying embodiments thereof and that variations can be made within the scope of the following Claims.

Claims

1. A method of determining the production of certain substances secreted in the body, for instance such substances as hydrochloric acid, bile salts, pancreas enzymes, pepsins, trypsins, porphyrins, nitrogen oxide and carbon dioxide, characterized by

- adding to body fluid a known quantity of dialyzable cali¬ brating substance (21) that contains the substance whose production is to be determined;

- determining the amount of calibrating substance dialyzed in a dialysis catheter in time, for instance photometrically (absorption, fluorescence, etc.);

- determining the amount of investigative substance dialyzed in the dialysis catheter in time; and

- determining a quotient (F(t)) between the added and dialyzed quantities of calibrating substance in time, and correlating said quotient with a corresponding quotient (G(t)) for the investigative substance, so as to determine said production.

2. A method according to Claim 1, characterized in that the quotient (F(t)) is made equal for the calibrating substance and the investigative substance when determining said production.

3. Apparatus for determining the production of certain substances secreted in the body, for instance hydrochloric acid, characterized by means (10, 11, 14, 18, 23) for supplying a predetermined amount of dialyzable calibrating substance (21) to body fluid, wherein the investigative substance contains means (10, 16, 17, 26, 27) for determining the amount of calibrating substance (21) dialyzed in a dialysis catheter in time, for instance photometrically; means (10, 16, 17, 26, 27) for determining investigative substance in the dialysis catheter in time, wherein a quotient (F(t)) between added and dialyzed quantities of calibrating substance (21) in time is intended to be deter¬ mined and correlated with a corresponding quotient (G(t)) for the investigative substance, so as to determine said produc¬ tion or secretion.

4. Apparatus according to Claim 3, characterized in that the quotients (F(t), G(t)) are intended to be made equal when determining said production or secretion.

5. Apparatus according to Claim 3 or Claim 4, characterized by a so-called data logger (10) which forms a central control unit in the production determining process and includes catheter connections (18, 19, 20), a first pump (11) which functions to pump calibrating substance (21) to said body fluid at a predetermined rate, and a second pump (12) which functions to pump dialysis liquid (22) through a dialysis lumen (24) at a predetermined rate, wherein the dialysis liquid is intended to pass one side of a dialysis membrane whose other side is intended to be in contact with said body fluid, and to pass back to the data logger.

6. Apparatus according to Claim 3, 4 or 5, characterized in that the dialysis catheter, preferably in connection to the data logger, is connected to a cuvette-like part (26) intended for measurements on the dialysis liquid (22) that has passed the membrane, wherein said measurements may constitute one or more measurements from the group photomet¬ ric measurement, titration measurement and pH measurement.

7. Apparatus according to Claim 6, characterized in that the cuvette-like part (26) is intended to be mounted in a holder (27) on the data logger.

8. Apparatus according to Claim 7, characterized in that the holder (27) functions to provide support for a photometry measuring device (17), a titration measuring device (16 and a pH measuring device.

9. Apparatus according to Claim 5, 6, 7 or 8, characterized in that the data logger includes connections (20', 20", 20¹'¹) for sensors relating to one or more measuring magni¬ tudes from the group: the occurrence of bilirubin, pH, pressure, EGG, Gastric Emptying, potential difference, Pco₂, Po₂, and so on.

10. A dialysis catheter, characterized by a cuvette-like part (26) for measuring dialysis liquid, for example one or more measurements from the group photometric measurement, titration measurement and pH measurement.