APPARATUS FOR EXTRACORPOREAL BLOOD TREATMENT AND A CONTROL METHOD THEREFOR

Abstract

An apparatus is described for extracorporeal blood treatment, comprising a treatment unit, an extracorporeal blood circuit and a fluid evacuation line. The apparatus comprises a control unit connected to a pressure sensor and configured to move a blood pump, generating a variable flow with a constant component equal to a desired blood flow value and a variable component having a nil mean value; the variable flow generates, in the expansion chamber, a pressure progression that is variable over time with a pressure component oscillating about a mean value. The control unit receives a plurality of values over a period of time comprising a plurality of oscillations of the pressure about the mean value, calculates a control value representative of the oscillating pressure component, and then determines the verification or not of a condition of variation of the blood level in the expansion chamber.

Claims

1-15. (canceled)

16. A method for reducing the risk of infusion of gas microbubbles in a patient, the method comprising: moving a first actuator to generate a variable flow comprising a constant flow component of a desired flow value and a variable flow component oscillating about the constant flow component, the variable flow component having a substantially nil average value, the variable flow component generating in an expansion chamber a pressure progression that is variable in time, the pressure progression comprising a pressure component oscillating about a mean value; receiving from at least one sensor associated with the expansion chamber and configured to sense pressure values internally of the expansion chamber, a plurality of pressure values for a time period comprising a plurality of pressure oscillations about the mean value, the pressure values being measured at successive time instants; calculating, as a function of the pressure values, a control value that is representative of the oscillating pressure component; comparing the control value representing the oscillating pressure component with a reference threshold; and determining, following the comparison, the occurrence or not of a condition of variation of a level in the expansion chamber.

17. The method of claim 16, wherein the condition of level variation in the expansion chamber occurs when the control value representing the oscillating pressure component is lower than the reference threshold.

18. The method of claim 16, wherein the calculated control value representing the oscillating pressure component is a statistical indicator.

19. The method of claim 18, wherein the statistical indicator is a dispersion index describing a quantitative statistical distribution of the measured pressure values, the control value being an indicative measurement of distance of the pressure values from a central value.

20. The method of claim 16, wherein the control value representing the oscillating pressure component is a function of a statistical variance of the measured pressure values.

21. The method of claim 20, wherein comparing the control value with the reference threshold includes comparing the statistical variance of the measured pressure values with the reference threshold.

22. The method of claim 20, wherein the statistical variance of the measured pressure values is calculated on a plurality n of measured pressure values, n being greater than 6.

23. The method of claim 16, wherein the reference threshold is a variable threshold, the method including updating the reference threshold in real time during a treatment time at each pressure measurement.

24. The method of claim 16, wherein the reference threshold is a variable threshold according to at least one of: a specific probability of generation of a set false alarm; the oscillating pressure component; a dispersion index describing a quantitative statistical distribution of the measured pressure values; an indicative measurement of the distance of the pressure values from a central value; a standard deviation of the measured pressure values; a confidence interval of a Student probability distribution; a confidence interval of a Student probability distribution with n1 degrees of freedom corresponding to a type I error ; a mean of a variance of the measured pressure values; or a mean of a variance of the measured pressure values at a start of a treatment time.

25. The method of claim 24, wherein the type I error is calculated through of the following relation:
=1.sup.Kn{square root over (1P.sub.fa)} wherein Kn is a number of measurements carried out during a treatment time, and P.sub.fa is a set probability of detecting an erroneous change in blood level in the expansion chamber during the treatment time.

26. The method of claim 16, wherein the reference threshold is defined
T.sub.h=VarP.sub.reft* wherein VarP.sub.ref is a mean of a variance of a number n of initial pressure values measured at a start of treatment, to is a confidence interval of a Student probability distribution with n1 degrees of freedom corresponding to a type I error , and is a standard deviation of a pressure variance calculated on a number n of sampled pressure data.

27. The method of claim 16, wherein the expansion chamber is provided with an apparatus for extracorporeal blood treatment, the apparatus comprising: at least one treatment unit having at least a first chamber and at least a second chamber separated from one another by a semipermeable membrane; at least one blood removal line connected to an inlet port of the first chamber and predisposed to remove blood from a patient; at least one blood return line connected to an outlet port of the first chamber and predisposed to return treated blood to the patient; the expansion chamber placed at least in one of the blood removal line and the blood return line, the expansion chamber configured to contain a predetermined quantity of gas in an upper portion and a predetermined quantity of blood at a predetermined level in a lower portion, the blood removal line, the blood return line, the first chamber and the expansion chamber being part of an extracorporeal blood circuit; and the first actuator being a blood pump operating in the extracorporeal blood circuit to move the blood in the circuit.

28. The method of claim 27, wherein the expansion chamber is an arterial expansion chamber located on the blood removal line, the blood pump being located downstream of the arterial expansion chamber along a blood transit direction.

29. The method of claim 27, wherein the expansion chamber is a venous expansion chamber located on the blood return line.

30. The method of claim 27, wherein the steps of moving, receiving, calculating, comparing and determining are carried out in relation both to an arterial expansion chamber located on the blood removal line and to a venous expansion chamber located on the blood return line.

31. The method of claim 27, wherein the pressure sensor is located at the portion of the expansion chamber arranged to contain the gas.

32. The method of claim 27, wherein the expansion chamber includes an inlet for the blood in fluid connection with the extracorporeal circuit and an outlet for the blood in fluid connection with the extracorporeal circuit, the method including receiving blood in the inlet to the expansion chamber and causing blood to flow out of the outlet from the expansion chamber, the inlet and the outlet being positioned at a base portion of the expansion chamber arranged to face downwardly and be occupied by the blood.

33. The method of claim 27, wherein the expansion chamber includes a ventilation opening and the apparatus further comprises at least an actuator operating on the ventilation opening, the method including allowing a passage of gas from or towards the expansion chamber, the actuator selectively inhibiting or enabling the passage of gas, the ventilation opening being positioned at an upper portion of the expansion chamber arranged, in use, to face upwardly.

34. The method of claim 33, further including commanding the actuator to enable passage of gas to exit from the ventilation opening when a blood level in the expansion chamber is below a predetermined threshold.

35. The method of claim 27, further including commanding at least the blood pump to reduce or stop the blood flow in the extracorporeal blood circuit and substantially stop the passage of fluid through the semipermeable membrane of the treatment unit when a blood level in the expansion chamber is below a predetermined threshold.

36. The method of claim 27, which is carried out by a control unit of the apparatus for extracorporeal blood treatment.

37. The method of claim 16, further including comparing the control value with at least a maximum admissible value and a minimum admissible value to determine whether the control value is within a correct functioning interval, and signaling a malfunction when the control value falls outside of the correct functioning interval.

Description

DESCRIPTION OF THE DRAWINGS

[0062] Some drawings are provided by way of non-limiting example, related to aspects of the invention.

[0063] In particular:

[0064] FIG. 1 schematically illustrates a blood treatment apparatus, according to the invention;

[0065] FIG. 2 is a flow diagram illustrating a control procedure according to an aspect of the invention, performable by the control unit of an apparatus for example of the type shown in FIG. 1;

[0066] FIG. 3 is a flow diagram which illustrates the calculation of the variable reference threshold;

[0067] FIG. 4 is a time diagram which shows the progression of the pressure in the arterial expansion chamber in three different conditions: a first condition of standard blood level (case a), a second average blood level condition (case b) and a third condition with substantially empty chamber or low blood level (case c);

[0068] FIG. 5 shows the progression in the arterial chamber in the third condition of FIG. 4 and in a larger-scale view;

[0069] FIG. 6 is a time diagram which shows three progressions of the average arterial pressure in the arterial expansion chamber in the three respective conditions of FIG. 4;

[0070] FIG. 7 is a time diagram which shows three progressions of the variance in arterial pressure in the arterial expansion chamber in the three respective conditions of FIG. 4;

[0071] FIG. 8 shows a detail of the progression of the variance of the arterial pressure in the expansion chamber and also illustrates the variable threshold value in a situation of absence of alarm;

[0072] FIG. 9 shows a detail of the progression of the variance of the arterial pressure in the expansion chamber and also illustrates the variable threshold value in a situation where an alarm is present; and

[0073] FIG. 10 shows a detail of the expansion chambers with the standard blood level (case a), average blood level (case b) and low blood level (case c) in the arterial chamber.

DETAILED DESCRIPTION

[0074] With reference to the accompanying drawings, 1 denotes in an apparatus for the extracorporeal treatment of blood.

[0075] The apparatus 1 comprises an extracorporeal circuit arranged to extract blood from the cardiovascular system of a subject, for example a patient P, and return the treated blood to the patient.

[0076] Below some possible examples are described relating to the general structure of the apparatus 1: in particular some configurations of the extracorporeal blood circuit are described, as well as the infusion lines, if present, in which a replacement fluid circulates, any dialysis line in which a dialysis fluid circulates, and the waste fluid discharge line.

[0077] With reference to FIG. 1, the apparatus for the extracorporeal treatment of blood comprises at least a treatment unit 2, for example a hemofilter, a hemodiafilter, a plasmafilter, a dialysis filter, a membrane oxygenator or other units also suitable for processing the blood taken from the patient, having at least a first chamber and at least a second chamber 3 and 4 separated from one another by a semipermeable membrane 5. A blood removal line 6 is connected to an inlet port 11a of the first chamber 3 and is predisposed, in operative conditions of connection to a patient, to remove blood from a vascular access inserted, for example in a fistula on the patient. A blood return line 7 connected to an outlet port 11b of the first chamber is predisposed to receive the treated blood from the treatment unit and to return the treated blood to a further vascular access also connected to the fistula of the patient. Note that the configuration of the vascular access may be of any nature: for example, a catheter, a port implanted in the patient, a cannula, a needle, and so on.

[0078] As can be seen in FIG. 1, the apparatus 1 comprises at least a first actuator, in the present example a blood pump 9, which operates at a blood removal line such as to facilitate the movement of the blood removed from the patient from the first end 33 of the removal line 6 connected to the patient P to the first chamber 3; the blood pump 9 is, for example, an active peristaltic pump, as shown in FIGS. 1 and 2, on a respective tube section 6a and able, when moved in a clockwise direction, to move a flow of blood along the removal line towards the first chamber 3 (see the arrows indicating the flow along this line).

[0079] It should be noted that for the purposes of the present description and the appended claims, the terms upstream and downstream may be used with reference to the relative positions assumed by components belonging to or operating on the extracorporeal circuit. These terms are to be understood with reference to a blood flow direction from the first end 33 of the removal line 6 connected to the patient P towards the first chamber 3 and then towards the second end 34 of the return line 7 connected to the vascular access of the patient P.

[0080] In the example of FIG. 1, the extracorporeal circuit comprises at least an expansion chamber 11 acting on the arterial blood removal line 6 from the patient P and arranged upstream with respect to the first chamber 3 and upstream with respect to the blood pump 9.

[0081] This chamber 11 receives the blood directly from the patient and accumulates a set amount that will remain substantially constant throughout the treatment.

[0082] The extracorporeal circuit also comprises at least a venous expansion chamber 12 which operates on the venous blood return line 7, downstream of the first chamber 3 and upstream of the vascular access that returns the blood to the patient P.

[0083] At least a pressure sensor 13 is configured to detect at least a parameter relating to the pressure of the fluid present in the arterial expansion chamber 11 and a pressure sensor 14 is configured to detect at least a parameter relating to the pressure of the fluid present in the venous expansion chamber 12.

[0084] In general, the sensors 13, 14 are configured to emit a respective signal corresponding to a measured value of the parameter, then forwarding it to a control unit 21 each time a measurement is carried out in successive moments of time t.sub.j. Note that it is possible to perform the detection of the pressure parameter also in close proximity of the arterial or venous expansion chambers 11, 12, for example through of a transducer located either in the section of pipe between the expansion chamber 11 and the arterial blood pump 9, or in the stretch of piping between the expansion chamber 11 and the arterial vascular access to the patient P, or in the section of pipe between the expansion chamber 12 and the venous return vascular access to the patient P or in the section of pipe between the first chamber 3 and the venous expansion chamber 12.

[0085] In any case, in a possible proper positioning of the pressure sensors 13, 14, the pressure sensors 13, 14 are directly active in the corresponding expansion chamber 11, 12 at an upper portion thereof where normally (in use) a gas (air) is housed.

[0086] It should be noted in fact that the arterial and the venous expansion chambers 11, 12 are generally arranged in use and during treatment to accommodate a predetermined amount of gas in an upper portion and a predetermined amount of blood at a predetermined level in a lower portion thereof.

[0087] Each of the expansion chambers 11, 12 has an inlet 11a, 12a for the blood that is in fluid connection respectively with a first part of removal line 6 connected to the vascular access of the patient P and with a return line portion downstream the treatment unit 2.

[0088] The chambers 11 receive blood entering through the inlets 11a, 12a. In general, the inlets 11a, 12a may be positioned at a base portion of the corresponding expansion chamber arranged, in use, to be directed downwards and in particular always occupied by blood.

[0089] In an embodiment the inlets may be connected to a respective channel internal of the arterial and venous expansion chambers 11, 12 which has an outlet in the chamber itself at a height with respect to the base.

[0090] Each of the arterial and venous expansion chambers also includes a respective outlet 11b; 12b for the blood in fluid connection with the extracorporeal circuit 8, which causes, in use, the flow of blood in outlet from the chambers. The outlets 11b, 12b are also positioned at a base portion of the respective expansion chamber 11, 12 arranged, in use, to be directed downwards and in particular always occupied by blood.

[0091] The portion of the removal line 6 which connects the outlet 11b of the arterial expansion chamber 11 to the first chamber 3 of the treatment unit 2 comprises a pump section 6a which is engaged by the peristaltic pump 9 such as, through squeezing the same tract of tube, to move the blood in the extracorporeal circuit.

[0092] A particular type of peristaltic pump 9 may be provided with two squeezing bodies (rollers) that act on the pump portion 6a twice for each rotation of the blood pump 9.

[0093] The venous chamber 12 also internally houses a venous filter 35 which separates the outlet 12b from the remaining volume of the chamber 12. The venous filter 35 helps avoiding air bubbles reaching the patient since bigger bubbles are broken and the generated small air bubbles trapped in the venous chamber.

[0094] Each of the expansion chambers 11, 12 has also a ventilation opening 15, 16 configured to allow, in use, a passage of gas into or from the expansion chamber 11, 12 itself, for example to or from the external environment.

[0095] The apparatus further comprises at least an actuator 17; 18 for each chamber 11, 12 operating on the ventilation opening 15; 16 (for example a piping connected thereto) for selectively inhibiting or enabling the passage of gas. The ventilation opening 15; 16 is in particular positioned at an upper portion of the expansion chamber 11, 12 intended, in use, to be facing upward, and even more in particular intended to be always occupied by the gas.

[0096] The actuator 17; 18 may be an air pump or even a simple clamp (or other obturator) or may be controlled (or not) by a control unit 21 for allowing gas venting should it be required.

[0097] Each of the arterial and venous expansion chamber 11, 12 may also possibly include a further access 23, 24 (service access) for receiving further fluids, medicaments or other substances in the chamber.

[0098] In relation to the set level of blood in the arterial and venous expansion chambers 11, 12, it should be noted that in general this level should be within a range of depths between a minimum value and a maximum value (possibly and in general the minimum value and a maximum value of the venous chamber 12 are different from the maximum and minimum levels of the arterial expansion chamber). Within these blood level values in the chamber it may be assumed that the equipment is working in a safe state: below, or above the minimum and maximum levels, and particularly during treatment, problems of various natures may arise, which will be more precisely described in the following.

[0099] Not least, it should also be noted out that at least one and generally both the arterial and venous expansion chambers 11, 12 have a constant containment volume, i.e. the chambers, in detail, are made of a rigid and substantially non-deformable material.

[0100] The apparatus 1 further comprises a first fluid flow intercept organ 20 operating on the removal line 6 upstream of the blood pump 9 and the arterial expansion chamber 11 and at least a second fluid flow intercept organ 22 operating in the return line 7 of the blood to the patient downstream of the venous expansion chamber 12. The intercept organs 20, 22, for example each constituted by a respective clamp controlled by the control unit 21, are arranged in the vicinity of the ends 33, 34 of the respective lines connectable to the patient P.

[0101] The apparatus may also include an air-bubble sensor 19 connected to the control unit 21 and capable of generating a signal that, if above a threshold, determines the generation of a closing command of the intercept member 22 and shuts down the blood pump 9. In particular the device 19 is located on the blood return line 7, and still more in particular downstream of the venous expansion chamber 12 along the blood flow direction in the extracorporeal circuit.

[0102] In practice, the blood removal line 6, the arterial expansion chamber 11, the first chamber 3 of the treatment unit, the return line 7 of the blood to the patient and the venous expansion chamber 12 are part of an extracorporeal blood circuit 8, which, during use of the apparatus 1, provides for the circulation of blood externally of the body of the patient undergoing treatment.

[0103] The apparatus 1 further comprises at least a fluid evacuation line 10 connected with an outlet port of the second chamber 4 such as to receive at least a filtered fluid through the semipermeable membrane 5.

[0104] The evacuation line receives the waste fluid coming from the second chamber of the unit 2, for example, comprising used dialysis liquid and/or ultrafiltered liquid through the membrane 5.

[0105] The evacuation line 10 leads to a receiving element 27, for example consisting of a collection bag or a drainage pipe for the waste fluid. One or more dialysate pumps 28 may operate on the evacuation line 10: for example in the accompanying drawings a pump 28 active on the line 10 is provided. Note that the structure of the evacuation line may also be different to the one illustrated (as long as it may properly drain the fluid exiting from the second chamber 4): for example the evacuation line 10 may comprise a single line as shown in the accompanying figures or a main drainage line and an ultrafiltration line branching from the main discharge line and provided with a respective pump (solution not shown).

[0106] In the example of FIG. 1, a dialysis line 25 is also present, for supplying a fresh treatment fluid in inlet to the second chamber 4: the presence of this line is not strictly necessary since, in the absence of the line 25, the apparatus is still able to perform treatments such as ultrafiltration, hemofiltration or plasmafiltration. In the case in which the dialysis line 25 is present, a fluid intercept organ 26 may be used to selectively allow or inhibit fluid passage through the dialysis line 25, depending on whether or not a purification by diffusive effect is to be performed inside the treatment unit.

[0107] The dialysis line 25, if present, is typically equipped with dialysis pump 29 and is able to receive a fresh fluid from a module 30, for example a bag or a section of on-line preparation of dialysis fluid, and to send such a fluid in inlet into the second chamber 4. Finally, the apparatus 1 may comprise one or more infusion lines of a replacement fluid: for example an infusion line 31 may be provided connected to the removal line 6 and/ or an infusion line 32 connected to the blood return line 7. The pre- and/or post-infusion lines 31, 32 may be supplied by suitable bags or directly by the fresh dialysis fluid prepared on-line.

[0108] These lines are only schematically represented in the accompanying figures.

[0109] The apparatus is also provided with at least a control unit 21.

[0110] The control unit 21 may comprise one or more digital modules, for example of the microprocessor type, or one or more analog modules, or a suitable combination of digital and analog.

[0111] As illustrated in the example of FIG. 1, the control unit 21 is connected with the blood pump 9 and/or with the dialysate pump 28 and/or with the dialysis pump 29, as well as with the pressure sensors 13, 14 of the arterial and venous expansion chambers 11, 12 and optionally, if present, with auxiliary pressure sensors. In addition the control unit may be connected to the fluid intercept organs 20, 22 and, if present, 25.

[0112] The control unit 21 is also in communication with the bubble detection device 19, with the module 30 (if the preparation is on-line) and possibly with the actuators 17, 18 on the ventilation lines 15 and 16.

[0113] The control unit 21 is configured or programmed to perform the procedures described below. If the control unit is of the programmable type, this unit is connected with a data carrier for storing instructions that, when performed by the control unit, carry out the procedures described below. The data carrier may comprise a mass storage, for example, optical or magnetic, a re-programmable memory (EPROM, FLASH) or a memory of another type.

[0114] In general, before start of treatment, the apparatus 1 is subjected to a priming procedure controlled by the control unit 21.

[0115] In particular, prior to treatment, a saline solution is fed into the extracorporeal circuit to wash and remove any air and residual particles.

[0116] At the end of this procedure, a set level of saline at the working pressure is established in the arterial and venous expansion chambers 11, 12.

[0117] Once the patient is connected to the equipment via the vascular access, the control unit 21 is configured to move at least the blood pump 9 at the beginning of a treatment to create, in the expansion chambers 11, 12, a corresponding set blood level in the lower portion, while confining a complementary quantity of gas in the upper portion.

[0118] The treatment at this point continues for the duration T.sub.tot required in order to appropriately treat the blood taken from the patient P.

[0119] Throughout the treatment the blood level in the arterial and venous expansion chambers 11, 12 continuously changes (although by small amounts) at least as a result of the fact that the control unit 21 moves the blood pump 9 to generate a variable flow of blood comprising a constant flow component equal to a desired blood flow value and a variable flow component at substantially zero average value. This is due in particular to the fact that the blood pump is peristaltic in nature and therefore produces a non-constant flow of blood in the circuit, as it is related to the successive squeezing actions of the pump section 6a by the roller/rollers associated to the pump rotor.

[0120] In other words, the hydraulic head of the treated fluid is given by a constriction which runs along the tube. In the described example, the pump 9 is constituted by a rotor to which two (or more rollers) are applied, which rotate to squeeze the tube and cause the advancement of the fluid.

[0121] Alternatively linear peristaltic pumps may be used (for example, finger pumps) or also other actuators capable of generating a pulsating movement in the blood, i.e. a non-constant flow, but oscillating about an average flow value.

[0122] Alternatively the control unit might control the pump to generate the pulsating movement in the blood in order to use other kinds of pumps which do not have the pressure variations inherently generated.

[0123] Consequently the variable blood flow generates in the expansion chamber (both arterial 11 and venous 12) a pressure trend that is time-variable P(t) comprising a pressure component P(t) oscillating about an average value P.sub.avg.

[0124] An example of the pressure trend in an arterial chamber is shown in FIG. 5 where, the measurements performed by the pressure sensor 13 over a short time interval are represented.

[0125] This graph shows the average pressure P.sub.avg and the oscillatory behaviour (non-symmetrical, but at a substantially zero mean value) of the pressure P(t) may clearly be observed, i.e. the oscillating component of the pressure.

[0126] The control unit 21 is programmed to receive, from the pressure sensors 13, 14 located in the respective chambers, a plurality of pressure values P.sub.j for a period of time T (typically coinciding with the treatment period).

[0127] For the purposes of the implementation of the present invention, the minimum time period T.sub.min, for which the detected pressure data P.sub.j are used, comprises at least one and in particular a plurality of oscillations of the pressure about the average value P.sub.avg; in particular, time periods of 7 oscillations are used for each control value calculation (described in the following).

[0128] Obviously the pressure values P.sub.j are measured in discrete and successive time instants t.sub.j. The sampling timing may be constant, depending on the type of pressure sensor used and possibly other parameters of apparatus operation.

[0129] The underlying principle implemented by the control unit 21, and described below in detail, is to use the pressure component P.sub.j measured at various instants t.sub.j in order to assess the level variations of blood in the expansion chamber; also verification may be made of the permanence at a set level or in any case a safety level that substantially ensures the absence of air invasion into the removal and/or return lines 6, 7.

[0130] In other terms, by filtering the level of the pressure signal of the constant value component P.sub.avg, and using only the oscillating pressure signal, a monitoring of the permanence of the blood level in the expansion chamber at levels considered safe.

[0131] By observing in particular FIG. 4, three distinct progressions over time of the pressure signals P.sub.j detected in the arterial chamber 11 are represented in three different blood level situations: a first standard level situation, a second average level and a third minimumor a non-safelevel situation (all illustrated in FIG. 4).

[0132] As can qualitatively be noted, the three pressure signals differ from one another and by performing an appropriate analysis thereon it is possible to determine whether or not a condition of variation of the blood level is established in any (including both) of the expansion chambers 11 and 12.

[0133] In particular the applicant has surprisingly found that the oscillating component of the pressure P(t) is alone usable for the above-described verification.

[0134] For this purpose, the control unit 21 is generally set up to calculate, according to the pressure values P.sub.j received from one of the respective pressure sensors 13, 14, a control value (called VarP) which is representative of the oscillating pressure component P(t). This control value VarP representing the oscillating pressure component P(t) is compared with a reference threshold T.sub.h and, following the comparison, a verification is made as to whether there occurs an appreciable variation in the blood level in the respective expansion chamber 11, 12.

[0135] FIG. 5 shows how, on a variation of the blood level in the arterial expansion chamber 11, both the constant pressure component P.sub.avg, and the oscillating pressure component P(t) change.

[0136] FIG. 6 in particular illustrates the variation in the average pressure component P.sub.avg in the three cases of different level of FIG. 4.

[0137] Returning to FIG. 4, it may be seen how the maximum and minimum values of P(t) in the three conditions vary, in particular by reducing the maximum amplitude P.sub.max of pressure oscillation P(t) (i.e. the different between the maximum peak P.sub.max and the minimum P.sub.min of each single oscillation) from the standard level situation to the minimum, or safety, level.

[0138] In these terms, the control value VarP might be, for example, the maximum amplitude P.sub.max between the maximum peak P.sub.max (or minimum peak P.sub.min) and the average pressure P.sub.avg of each single oscillation (or a proportional value thereto) or, alternatively, a statistical variable of the value such as for example an average of the maximum amplitudes P.sub.max of a number of contiguous oscillations (not necessarily, but in particular, consecutive) of pressure.

[0139] The applicant has however observed that this type of absolute control value (i.e. a value linked to the absolute measurements of maximum and minimum pressure subtracted from one another to eliminate the average pressure component), though offering a clear indication of level variation, and being able therefore to be used as an indicator, is susceptible to improvement in an auxiliary aspect of the invention.

[0140] Indeed the measurement of the peak pressure values P.sub.max and P.sub.min involves the onset of problems of calculation (that may be overcome). It is clear that it is necessary, firstly, to determine which are the maximum and minimum points in situations of oscillating pressure and with measured pressure values that are discrete (each time interval t.sub.j) and further the measurement is obviously subject to noise and errors of detection, which set a problem to take into account.

[0141] In this situation the use of a calculated control value VarP (representing the oscillating pressure component P(t)) which is a statistical indicator appears to simplify the analysis.

[0142] In particular, the use of a statistical indicator that is an index of dispersion summarily describing a quantitative statistical distribution of the measure pressure values P.sub.j is more proper; in particular the control value is an indicative measurement of the distance of the pressure values P.sub.j from a central value, for example, identified with the average value P.sub.avg of the pressure or the median value of the pressure.

[0143] By operating in this way it becomes irrelevant to establish what are the maxima and minima of the pressure detected in the window of time established for the analysis, as substantially each measured value P.sub.j contributes to determining the control value VarP (it might be decided to discard some measured pressure values, for example, as clearly erroneousgreater than or less than P.sub.max-admissible or less than P.sub.min-admissibleor not to consider all the values measured on the basis of other calculation optimization logics).

[0144] In the case now described VarP, representing the oscillating pressure component P(t) is a function of the statistical variance of the measured pressure values P.sub.j and in detail coincides with the statistical variance.

[0145] Alternatively, other indicators may be used, such as the standard quadratic deviation, field or interval of variation, absolute standard deviation, standard deviation, median absolute deviation, interquartile deviation, Poisson dispersion index.

[0146] In relation to the step of comparison, the control unit 21 determines the verification of the condition of variation of the blood level in the expansion chamber 11 or 12 when the control value VarP representing the oscillating pressure component P(t) is lower than the reference threshold T.sub.h.

[0147] In detail (and as mentioned), in the formulation used, but not limitedly, the control unit 21 performs the step of comparing the statistical variance VarP of the measured pressure values P.sub.j with the reference threshold T.sub.h determining in particular whether VarP is lower or not than the threshold T.sub.h.

[0148] As can in fact be understood from an analysis of the graph of FIG. 7, which represents, over time, the trends of the pressure variance VarP over time of the three conditions of standard level, median level and minimum level (or level of non-safety), in general the statistical indicator of dispersion (pure number) diminishes when the fluid level in the expansion chamber falls.

[0149] Thus a value of the statistical indicator which is lower than a threshold T.sub.h is a reliable index of minimum (or non-safety) level (or in any case an index of necessary attention on the part of the specialised personnel).

[0150] Obviously the statistical indicator related to the control value (and particularly the statistical variance VarP of the measured pressure values P.sub.j) is calculated on a plurality n of measured pressure values P.sub.j; in particular, n is greater than 6 and still more in particular n is at least equal to 10 with the purpose of eliminating the noise effects in the measurement. The value of n by way of example selected is 13.

[0151] In a further (but secondary) aspect, the reference threshold T.sub.h is a variable threshold, and in particular the reference threshold is updated in realtime during the treatment time, for example at each pressure measurement P.sub.j.

[0152] The calculation of a variable threshold T.sub.h enables setting, as setting parameter, a specific probability of false alarm P.sub.fa and having the threshold T.sub.h such as to guarantee respect of the probability in each step of determining the occurrence of a condition of appreciable variation in the blood level in the expansion chamber 11, 12.

[0153] For this purpose it is provided (even though other possibilities of variable threshold calculation exist) to calculate the probability a of a type I error through of the following relation:

=1.sup.Kn{square root over (1P.sub.fa)}

in which:

[0154] K.sub.n=number of measurements carried out during a treatment time (T.sub.tot);

[0155] P.sub.fa=set probability of detecting an erroneous change in blood level in the expansion chamber during a treatment time (T.sub.tot).

[0156] At this point the variable reference threshold (Th) is defined by the following function:

T.sub.h=VarP.sub.reft*

in which:

[0157] VarPref is the mean of the variance of a number n of initial pressure values (Pj) measured at start of treatment;

[0158] t is the confidence interval of a Student distribution of probability with n1 degrees of freedom corresponding to the error a of type I;

[0159] is the standard deviation of the pressure variance calculated on a number n of sampled pressure data (Pj).

[0160] Thus, the reference threshold T.sub.h is a variable threshold according to one of more of the following variables: the oscillating pressure component P(t), a dispersion index summarily describing a quantitative statistical distribution of the measured pressure values Pj, the standard deviation of the pressure values measured P.sub.j, the confidence interval t of a Student probability distribution, in particular with n1 degrees of freedom corresponding to an error of type I, the average Var.sub.Pref of the variance VarP of the pressure values measured P.sub.j, in particular at the start of treatment time.

[0161] Where the control unit 21 establishes that the apparatus is in a condition of variation of blood level in any one of the expansion chambers 11, 12, through the comparison, an alarm situation is generated at least signalled by an acoustic and/or visual warning, so as to attract the attention of an operator who may verify the effective blood level and possibly correct the potentially dangerous situation.

[0162] In particular FIG. 8 illustrates the progression of the statistical variance of pressure VarP at treatment instants and also the variable threshold T.sub.h in the corresponding instants, evidencing the variable progression over time of both. In FIG. 8 the pressure variance is never below the threshold and thus there is no alarm generation.

[0163] FIG. 9 illustrates the same variables as a function of the time, in a situation in which the variance is for some time instants below the threshold and the apparatus therefore generates an alarm.

[0164] In more evolved apparatus the control unit 21 may be programmed such that in a case that a predetermined number of conditions of variation in the blood level in the expansion chamber 11, 12 obtains (or even one situation only), it commands the respective actuator 17, 18 in the chamber in which the problem has occurred such as to enable passage of gas through the ventilation opening 15, 16, re-establishing the correct blood level in the chamber.

[0165] In particular, since in general a low blood level occurs, the control unit commands the actuator 17, 18 to enable passage of gas in exit from the ventilation opening 15, 16.

[0166] In addition to or alternatively the control unit 21, in the event of a verification of a predetermined number of conditions of variance in the blood level in the arterial expansion chamber and/or venous chamber 11, 12, may command actuators that are at least active on the extracorporeal blood circuit 8 to place the patient in a situation of safety.

[0167] For example, the control unit 21 may command at least the blood pump 9 to reduce or zero the blood flow in the extracorporeal blood circuit 8 and substantially annul the passage of fluid through the semipermeable membrane 5 of the treatment unit 2 (if present).

[0168] Lastly the control unit 21 may also perform a consistency check of the detected and calculated values. In particular the control unit 21 may be programmed to compare the control value VarP calculated with at least one maximum admissible value VarP.sub.max and a minimum admissible value VarP.sub.min such as to determine whether the control value is within a correct functioning interval VarPVarP.sub.max; VarPVarP.sub.min and to signal a malfunction in the event that the control value is not within the correct functioning value. In addition (or alternatively), the consistency check may be performed on the single measured pressure values P.sub.j by verifying whether a plurality thereof is out of a reasonable functioning range.

[0169] Indeed, the pressure sensor of the expansion chamber is substantially the only component of the apparatus (apart from the control unit) that is used for performing the verification function and the analyses mentioned above have the main aim of verifying a fault or a discrepancy that might invalidate the detection.

[0170] It is clear that the control unit 21 is programmed to perform the above-described steps in relation to the arterial expansion chamber 11 located on the blood return line 6 and/or in relation to the venous expansion chamber 12 located on the blood return line 7.

[0171] In particular, the use of this analysis in relation to the arterial chamber is proposed as usually the expansion chambers upstream of the treatment unit 2 are not provided with level sensors and/or other pre-unit safety systems 2 and therefore air that might enter the collecting line 6 is arranged to reach the treatment unit and be transformed into plurality of micro-bubbles thereby, thus becoming more difficult to detect downstream in the return line 7.

[0172] Obviously the described methodology is usable on each expansion chamber which might be present on the extracorporeal circuit (in addition to or in replacement for the described expansion chambers).

[0173] While the invention has been described in connection with what is presently considered to be the most practical and preferred embodiment, it is to be understood that the invention is not to be limited to the disclosed embodiment, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and the scope of the appended claims.