MXPA01003936A - Method and device for measuring access flow - Google Patents

Abstract

An arterial needle removes blood from the access to an extracorporeal circuit comprising a dialyzer and a venous needle returns the blood to the access site. Blood passes along one side of the membrane of the dialyzer and dialysis fluid along the other side. The concentration (Cd norm and Cd rev) of urea in the dialysate emitted from the dialyzer is measured with the needles in the normal position and in a reversed position. The access flow rate before the arterial needle is calculated according to the formula:Cd norm / Cd rev=1 + Keff/Qa in which Keff is the effective clearance of the dialyzer and Qa is the access flow rate.

Description

METHOD AND DEVICE FOR MEASURING ACCESS FLOW FIELD OF THE INVENTION The present invention relates to a method and a device for measuring the speed of blood flow in a blood access. Blood is drawn from the body of a mammal to an extracorporeal blood circuit through an access of blood, via needles or a catheter.

ANTECEDENTS OF THE TECHNIQUE There are several types of treatments in which blood is drawn into an extracorporeal blood circuit. Such treatments involve, for example, hemodialysis, hemofiltration, hemodiafiltration, plasmapheresis, separation of blood components, oxygenation of the blood, etc. Normally, blood is removed from a blood vessel at an access site and returned to the same blood vessel or other location in the body.

In hemodialysis and similar treatments, an access site is commonly created surgically in the nature of a fistula. The needles for blood are Ref: 128519 inserted in the area of the fistula. Blood is removed from the fistula via an arterial needle and blood is returned to the fistula via a venous needle.

A common method for generating a permanent access site with the ability to provide a high blood flow and that is operational for several years and even ten years, is the provision of an arterial-venous fistula. This is produced by operatively connecting the radial artery to a cephalic vein at the level of the forearm. The venous limb of the fistula thickens over the course of several months, allowing repeated insertion of dialysis needles.

An alternative to arterial-venous fistula is the arterial-venous graft, in which a connection is generated, for example, from the radial artery in the wrist to the basilic vein. The connection is made with a graft tube made of autogenous saphenous vein or polytetrafluoroethylene (PTF ?, Teflon). The needles are inserted into the graft.

A third method for accessing blood is to use a silicon dual-cavity catheter surgically implanted in one of the large veins. t-J á ..! Additional methods find use in specific situations, such as a needleless arterial-venous graft consisting of a T-tube coupled with a standard PTFE graft. The T tube is implanted in the skin. The vascular access is obtained either by unscrewing a plastic plug or by puncturing one of the walls of said tube T with a needle. Other methods are also known.

During hemodialysis, it is desirable to obtain a constant blood flow rate of 150-500 ml / min or even higher, and the access site must be prepared to supply such flow rates. The blood flow in an AV fistula is often 800 ml / min or greater, allowing the delivery of a blood velocity in the desired range.

In the absence of sufficient positive blood flow, the extracorporeal circuit blood pump will take some of the already treated blood that enters the fistula via the venous needle, called access or fistula recirculation, resulting in poor treatment results.

The most common cause of a poor flow with AV fistulas is partial obstruction of the venous limbus due to fibrosis. secondary by multiple punctures in the vein. In addition, stenosis causes a reduction in access flow.

When there is a problem with the access flow, it has been found that the access flow rate often shows a long stable time period with a reduced but sufficient access flow, followed by a short period of a few weeks with a flow of markedly reduced access leading to recirculation and finally access failure. By constantly monitoring the evolution of the access flow during consecutive treatment sessions, it is possible to detect imminent access flow problems.

Several methods have been suggested for monitoring recirculation and access flow. Many of these methods involve the injection of a marker substance into the blood, and the resulting recirculation is detected. The methods usually involve the measurement of a property in the extracorporeal blood circuit. Examples of such methods can be found in US 5,685,989, US 5,595,182, US 5,453,576, US 5,510,716, US 5,510,717, US 5,312,550, etc.

Such methods have the disadvantage that they can not detect when the flow of access to such a degree has decreased.

»J? - Í XÍ. ? ÁAzXyAz, yAy zX. - zA * $! ..- and. £ £ * aZZ that recirculation is a risk, and only when recirculation prevails. Furthermore, it is a disadvantage that the injection of a substance is necessary.

A noninvasive technique that allows the formation of an image of the flow through AV grafts is color Doppler ultrasound. However, this technique requires expensive equipment.

The measurement of the access flow rate requires the inversion of the flows in the extracorporeal circuit. A valve for such reversal is shown in US 5605630 and US 5894011. However, these valve constructions comprise dead ends in which the blood will remain immobile for a long period of time and coagulate, which is a disadvantage.

BRIEF DESCRIPTION OF THE INVENTION An object of the present invention is to provide a method and a device for measuring the speed of the access flow without interfering with the blood and without injecting a substance into the blood.

Another object of the invention is to provide a method and a device for measuring the access flow rate without measuring the blood in the extracorporeal blood circuit or in the access or in the blood vessel. In accordance with the invention, it is required to reverse the flow of blood through the access. Therefore, a further object of the invention is to provide a valve for the reversal of blood flow. Still another additional object of the invention is to provide a method for determining when the blood flow velocity is too small for the risk of recirculation to prevail. These objectives are achieved with a method and apparatus for estimating the fluid flow velocity (Qa) in a fluid flow access, comprising the removal of a first fluid flow from said fluid in one position. of removal to an external flow circuit comprising a dialyzer having a semi-permeable membrane, said first fluid flow passing along said membrane on one of its sides and emitting a dialysis fluid on the other side thereof, and returning said first fluid flow of said external flow circuit to said access and in a return position downstream of said removal position, measuring a first variable which is essentially proportional to the concentration (Cd norm) of a substance in said dialysis fluid emitted from the dialyzer, reversing the removal position with the return position and measuring a second variable which is essentially proportional to the concentration (Cd rev) of said substance in said dialysis fluid in the inverted position; and calculating the fluid flow velocity (Qa) in said flow access from said measured concentrations.

Preferably, the calculation of the fluid flow velocity in said access flow takes place by calculating the relation between the first and the second variable and using the formula: Cd norm / Cd rev = 1 + K / Qa, where Cd norm and Cd rev are values proportional to the concentrations of said substance in the dialysis fluid in the normal and inverted positions, respectively, and K is the dialyzer clearance and Qa is the access flow rate.

The access of the blood flow can be in a mammal to obtain access to a blood vessel, such as a hemodialysis access in the nature of an arterial-venous shunt or fistula. In the latter case, debugging l .Í - .: ÍA, < k.¿r -lr.-t - ?? Xx, £. * »*. jy1 * r Xxíllx i. . i zm-t tx A- J-, ^ .yXy- Ai? S «»? «» .. awA, AtyxUy. of the K dialyzer is replaced by the effective depuration of the Keff dialyzer obtained taking into account a cardiopulmonary recirculation and in the normal position.

Preferably the substance is selected from the group consisting of: urea, creatinine, vitamin B12, beta-two-microglobulin and glucose, or it may be an ion selected from the group of: Na +, Cl ", K +, Mg ++, Ca ++, HC03", acetate ion, or any of its combinations as measured by conductivity; and wherein said concentration is measured as the concentration difference between the outlet and the dialyzer entrance, whenever applicable.

It is possible to measure the actual concentration of the substance. However, since only the ratio between the concentrations in the normal and inverted positions is needed, respectively, it is possible to measure a value which is proportional to the concentration of said substance, whereby said value is used in place of said concentration. Said property may be the concentration of the blood of said substance in the external circuit, before or after the dialyzer. Alternatively, the relative global body efficiency (Kwn / V) can be used, as explained in more detail below. í.ixl: i.? lzt ... A-XÍlz-.

The effective Keff depuration can be obtained by the equation Keff = Qd * Cd / Cs, where Qd is the flow of dialysis fluid emitted from the dialyzer, Cd is the concentration of said substance in said dialysis fluid and Cs is the concentration of said dialysis fluid. substance in venous systemic blood.

A method of measuring the concentration (Cs) of said substance in the venous systemic blood comprises the steps of: stopping the flow of blood in the external flow circuit for a sufficient period of time to allow the cardiopulmonary circulation to equalize; initiating blood flow in the external flow circuit at a slow rate to fill the arterial line with fresh blood before measurement; and measuring the equal concentration of said substance in the dialysis fluid at a low flow rate of the dialysate or in the isolated ultrafiltration. It is advantageous to make the measurement of the effective depuration at the beginning of the treatment.

The concentration (Cs) of said substance in the venous systemic blood can be estimated by: the calculation of the total body mass of urea (Murea) in the body of the patient, estimating or measuring the volume of distribution (V) of urea in the body of the patient; and estimating the concentration (Cs) of said substance in the blood by dividing the entire body mass of urea with the volume of distribution. In this way, the average concentration of urea in the whole body is obtained. However, the average concentration in the whole body is slightly higher than the concentration of urea in the systemic blood, except at the beginning of the treatment. Therefore, this calculation should preferably be done or extrapolated at the beginning of the treatment.

It is possible to discriminate between the condition when access or recirculation by fistula has been developed or not. A method for that purpose could be: changing the speed of blood flow (Qb); monitoring the concentration of said substance in the dialysate emitted from the dialyzer; and detecting a possible fistular recirculation in the normal position correlating a change in said concentration to said change in the velocity of the blood flow.

Preferably, the blood flow rate is decreased and a corresponding decrease in the urea concentration is monitored, and said absence of such decrease being an indication of fistular recirculation.

BRIEF DESCRIPTION OF THE DRAWINGS.

Further objectives, advantages and features of the invention appear from the following detailed description of the invention with reference to specific embodiments of the invention shown in the drawings, in which: Figure 1 is a partially schematic view of a forearm of a patient provided with an AV fistula.

Figure 2 is a schematic diagram of an extracorporeal dialysis circuit.

Figure 3 is a schematic diagram of the blood flow circuit in a patient and in the connected extracorporeal blood circuit.

Figure 4 is a schematic diagram similar to Figure 3, but with the extracorporeal circuit in an alternate inverted position.

Figure 5 is a schematic diagram of a blood flow circuit including a bypass valve.

Figure 6 is a diagram of the urea concentration of the dialysis fluid against time, including a portion with inverted access flow according to the invention.

Figure 7 is a schematic diagram similar to the diagram of Figure 5 which comprises an alternative valve arrangement.

Figure 8 is a schematic diagram similar to the diagram of Figure 7 showing the valve arrangement in an inactive position.

Figure 9 is a schematic diagram similar to the diagram of Figure 7 showing the valve arrangement in an inverted position.

Figure 10 is a schematic diagram similar to Figure 5 with the pump in an alternative position.

Figure 11 is a diagram showing the calculations with a relative total body efficiency.

Figure 12 is a cross-sectional view of the shell of a valve to be used in the diagrams I ?. íá .k? zi- k¿, éi-z z. -, J? .ix, schematics of Figures 5 and 7 to 10.

Figure 13 is a bottom view of a valve member to be inserted into the housing of the valve of Figure 12.

Figure 14 is a schematic plan view of the valve casing of Figure 12.

DETAILED DESCRIPTION OF THE INVENTION For purposes of the present disclosure, an access site is a site in which a fluid in a tube can be accessed and removed from and / or returned to the tube. The tube can be a blood vessel of a mammal, or any other tube in which a fluid flows. The access flow rate is the flow velocity of the fluid in the tube or blood vessel immediately upstream of the access site or removal position.

Figure 1 shows a forearm 1 of a human patient. The forearm 1 comprises an artery 2, in this case the radial artery, and a vein 3, in this case the cephalic vein. The openings are surgically created in artery 2 and in vein 3 and the openings are connected to form a fistula 4, in which the arterial blood flow makes a cross circuit with the vein. Due to the fistula, the flow of blood through the artery and vein increases and the vein forms and thickens the area downstream of the connection openings. When the fistula has matured after a few months, the vein is thicker and can be repeatedly punctured. Normally, a thick vein is called a fistula. 10 An arterial needle 5 is placed in the fistula, in the enlarged vein near the connected openings, and a venous needle 6 is placed downstream of the arterial needle, usually at least five centimeters downstream of the arterial needle. that point.

The needles 5 and 6 are connected to a tubular system 7, shown in Figure 2, forming an extracorporeal circuit comprising a pump 8, such as a dialysis circuit. 20 The blood pump propels blood from the blood vessel, through the arterial needle, the extracorporeal circuit, the venous needle and back into the blood vessel.

The extracorporeal blood circuit 7 shown in Figure 2 additionally comprises a clamp valve -yyy-yy ^ St ^? Mim i ^^^^^^^^^^, arterial 9 and a venous clamp valve 10 to isolate the patient from the extracorporeal circuit their error would occur.

Downstream of the pump 8 is a dialyzer 11, comprising a blood compartment 12 and a dialysis fluid compartment 13 separated by a semipermeable membrane 14. Below the dialyzer there is a drip chamber 15 which separates the air of blood.

Blood passes from the arterial needle by passing the arterial clamp valve 9 to the blood pump 8. The blood pump sends the blood through the dialyzer 11 and further via the drip chamber 15 and passes the venous clamp valve 10 back to the patient via the venous needle. The drip chamber may comprise an air detector, adapted to activate an alarm if the blood emitted from the drip chamber comprises air or air bubbles. The blood circuit may additionally comprise components, such as pressure sensors, etc.

The dialysis fluid compartment 14 of the dialyzer 11 is provided with dialysis fluid via a first pump 16, which obtains dialysis fluid from a source of pure water, normally RO water, and one or more ion concentrates, the dosing pumps 17 and 18 are shown for the dosing of such concentrates. The preparation of the dialysis fluid is conventional and is not described in more detail here.

An exchange of substances between the blood and the dialysis fluid takes place in the dialyzer through the semipermeable membrane. The urea passes markedly from the blood, through the semipermeable membrane and the dialysis fluid present on the other side of the membrane. The exchange can take place by diffusion under the influence of a concentration gradient, called hemodialysis, and / or by convection due to the flow of blood fluid to the dialysis fluid, called ultrafiltration, which is an important characteristic of hemodiafiltration or hemofiltration .

From the dialysis fluid compartment 14 of the dialyzer a fluid called dialysate is emitted, which is directed by a second pump 19 via a urea monitor 20 to be drained. The urea monitor continuously measures the urea concentration in the dialysate emitted from the dialyzer, to provide a dialyzed urea concentration curve during a dialysis treatment. Such a urea concentration curve can be used for various purposes, such as obtaining a mass of total body urea, as described in WO 9855166, and to obtain a prediction of the total dose of body dialysis Kt / V as also described in said request. The contents of WO 9855166 is incorporated in the present specification as a reference.

As described above, the present invention provides a method of noninvasive measurement of the access flow in the fistula immediately before the arterial needle, using the urea monitor and the dialysis circuit as shown in Figure 2.

By measuring the concentration of the dialysis urea during normal dialysis and subsequently reversing the positions of the needles and measuring the concentration of dialysis urea with the needles in the inverted position, it is possible to calculate the blood flow at the access of the dialysis urea. blood, without the addition of any substance in the blood or in the dialysis fluid.

Figure 3 shows a simplified schematic diagram of the blood vessel circuit of a patient and a portion of the dialysis circuit according to Figure 2. The blood circuit of the patient comprises the heart, wherein the right chamber of the heart is symbolized by an upper pump 21 and the left chamber of the heart is symbolized by a lower pump 22. Lungs 23 are located between the upper and lower pumps. From the outlet of the pump of the left chamber 22 of the heart, the blood flow is divided into a first branch 24 going to the access 25, usually in the left forearm of the patient, and a second branch 26 going to the rest of the body, such as organs, other limbs, head, etc., symbolized by a block 27. The blood that comes back from the body from the organs, etc., that is, from block 27, is combined with the blood that comes back from the access and enters the pump of the right chamber 21.

The flow velocity of the cardiac output is defined as Qco and the access flow rate is defined as Qa, which means that Qco-Qa enters block 27. Venous blood returning from block 27 before being mixed with blood from the Access, venous systemic blood, has a urea concentration of Cs. The blood left by the left chamber pump 22 has a urea concentration of Cf equal to that which passes access 25 as well as to block 27.

For the measurement of the access flow rate, it is necessary to reverse the flow through the arterial needles a ... ^^ .. ¿feaAa ^ ^ A ^ faith; and venous. One way to achieve this is to manually invert the needles.

Alternatively, Figure 5 shows a valve 28 performing the same operation. The arterial needle 5 is connected to an arterial inflow line 29 of the valve and the venous needle 6 is connected to a venous inlet line 30 of the valve. The blood pump is connected to a first outlet line 31 of the valve and the blood returning from the dialyzer 11 is connected to the second outlet line 32 of the valve.

The valve comprises a valve casing and a pivotable valve member 33, which can pivot from a normal position shown in the drawing to a reverse position pivoted 90 ° relative to the normal position.

In the normal position shown in Figure 5, the arterial needle 5 is connected to the blood pump 8 and the venous needle 6 is connected to the dialyzer outlet, via the drip chamber, see Figure 2. In the inverted position , the arterial needle 5 is connected to the dialyzer outlet and the venous needle 6 is connected to the blood pump 8, as required. áJkA, 3é ??? Aís¡í¿k.? - A -JLU fc. , ... "z. ^ -X.Í.ZX. ^ .i «. - l, An alternative design of the valve arrangement is shown in Figures 7, 8 and 9. In the embodiment of Figure 7, the arterial line 29 is connected to an enlarged opening 29a and the venous outlet line 30 is connected to the enlarged opening 30a, the openings in the valve housing 28a being arranged diametrically opposite one another. Two enlarged openings 31a and 32a are arranged in the housing of the valve 28a opposed diametrically to one another and displaced 90 ° relative to the enlarged openings 29a and 30a. The pivotable member of the valve 33a is normally disposed as shown in Figure 7 and forms a partition that divides the valve chamber into two semicircular portions. The valve member has a width, which is smaller than the peripheral dimension of the enlarged openings. The valve member can pivot 90 ° to a reverse position, shown in Figure 9, in which blood flows through the arterial and venous needles as required.

During its movement from the inverted to the normal position, the valve member 33a passes through an inactive position shown in Figure 8, in which all the four enlarged openings are interconnected, because the width of the valve member is smaller ÍÁ? .A.¿ílyi? Á and? ¡^ Mixi? AX..i: .., .-. .....ai. . .- ,,,.,.,. ,,-..-., " "to .- . i. - .- iz. . . . ...... ...... you ..... than the peripheral dimension of the openings, enlarged. With this inactive position, damage to the blood cells can be prevented. Such damage can be caused by high cutting forces which can occur if the inlet line 31 to the blood pump or the outlet line 32 of the dialyzer is completely occluded. By means of the inactive position, another advantage is obtained, that the blood needles are not exposed to the rapid change of the flows, which in some instances may even result in the dislodging of the needles. When the valve member moves from the normal position to the inactive position, the flow through the needles changes from the normal flow of, for example, 250 ml / min to an essentially zero flow. The valve member can be placed in the inactive position for a few seconds. Then, the valve member is moved to the reverse position, and the flow through the needle changes from an essentially zero flow to -250 ml / min. In this way, a smoother change between the normal and inverted flows can be obtained.

The notation is made that the positions of the openings and the valve member can be different such that the pivoting movement can be less than or greater than 90 °. In addition, the openings do not need to be arranged diametrically in order to achieve the desired operation. _üt i. -t ..., -irJ - * ---- ~ .a ?? .. * A Additionally, the dimensions of the enlarged openings in relation to the pipes and lines are not to scale, but the diameter of the enlarged openings It is rather of the same dimension as the inner diameter of the tube, as it appears more clearly below.

The notation is made that the valve is constructed to have as few dead end portions as possible, in which blood can be stopped and coagulated. From the drawing, it is seen that no portion of the valve has a dead end construction at any position on the valve body.

In addition, another schematic diagram incorporating a valve is shown in Figure 10. Figure 10 differs from Figure 5 only in the placement of the pump 8a, which the mode according to Figure 10 is placed between the arterial needle 5. and the valve 28. In this way, the pressure through the valve body 33 is smaller compared to the mode according to Figure 5. The operation is somewhat different. The blood pump stops, and the valve is placed in the reverse position. Finally, the pump starts and pumps the blood in the opposite direction reversing the rotational direction of the pump. titJtmji.A. A t * ¿? ± -A¿ á kt * t.a., ..

In order to verify that no air has been introduced into the interior of the patient in any position of the valve, it may be advantageous to add an air detector 34 and 35 immediately before each of the arterial and venous needles, or at least before the arterial needle. Air detectors trigger an alarm if they measure air bubbles in the blood going back to the blood vessels. Normally the air detector in the drip chamber is sufficient for this purpose.

The detailed construction of a valve intended to be used in the present invention is presented in Figures 12, 13 and 14. The valve comprises a valve casing 36 comprising two input connectors and two output connectors. All four connectors open inside the cylindrical chamber 41 of the valve, the four openings being offset 90 ° in relation to one another.

As shown in Figure 14, the valve comprises a blood inlet connector 37 connected to the arterial needle 5 and a blood outlet connector 38 connected to the venous needle 6. The connector portions are arranged as male Luer connectors for 'connect with hose ends with a female Luer connector.

In addition, the valve comprises an output connector of the circuit 39 connected to the blood pump 8 and a connector to the circuit 40 connected to the dialyzer outlet. The connector portions 39 and 40 are arranged as female Luer connectors to couple with male Luer connectors of the circuit.

As shown in Figure 12, the cylindrical chamber 41 of the valve is closed at the bottom. From the top, a valve member 42 can be inserted into the cylindrical chamber of the valve. The valve member 42 comprises a valvular partition 43 as seen from Figure 13.

The valve member also comprises an operating wing 44 by which the valve member can pivot 90 ° between a normal position, in which the valvular partition 43 is positioned as shown by dotted lines in Figure 14, and a reverse position. The pivoting movement is limited by a shoulder 45 of the valve member 42, which cooperates with a slot 46 in the valve shell. The shoulder 45 is provided with a projection 46a which cooperates with two recesses 47 and 48 in the normal position and the inverse position, respectively to maintain the valve member in each position. The slot 46 may be provided with three recesses (not shown in the drawing) in order to define said inactive position. A recess of this type is located between the two recesses 47 and 48.

The valve member and housing are provided with appropriate seals to ensure safe operation. The operation of the valve is evident from the above description.

By studying the theoretical concentrations of dialyzed urea resulting from a certain clearance of the K-dialyzer, a certain access blood flow Qa and a certain concentration of urea of the blood Cs in the venous systemic blood returning from the body, it has been found that the Keff's effective urea clearance of the dialyzer, taking into account cardiopulmonary recirculation, is necessary for the calculation of the access flow. Effective debugging can be measured, for example as described in EP 658 352, the content of which is incorporated herein by reference.

Alternatively, effective debugging can be calculated from simultaneous measurements of urea concentrations of venous systemic blood Cs and dialyzed Cd, as by means of blood samples.

The concentration of systemic blood urea Cs can be measured by the so-called stopped-flow slow technique, where the blood flow stops for a couple of minutes to allow the cardiopulmonary recirculation to equalize. Subsequently, the pump operates slowly to fill the arterial line with fresh blood before taking the blood sample. The concentration of urea in the blood sample obtained in this way is equal to the concentration of urea Cs in the systemic venous blood returning from the body to the heart.

Alternatively to taking the blood sample the dialysis fluid flow on the other side of the membrane is stopped and the slowly flowing blood is allowed to equalize with the dialysate on the other side of the membrane, where the concentration of Dialysate urea is measured to obtain the urea concentration of the venous systemic blood Cs.

A further method for obtaining an effective depuration is described in WO 9929355. In accordance with the invention described in WO 9929355, the blood concentration ....... ai,. ?.?, j £ y, ~ í .. "- ', zi -zk < ,; a, aa.

Systemic Cs is measured before or at the start of treatment, for example by the stopped flow technique - slow flow with the blood sample or the equalization as described above. After obtaining valid values of Cd dialyzed urea concentration from a urea monitor connected to the dialyzer output line, the initial concentration of dialyzed urea Cd? N? C at the start of the treatment is extrapolated by means of the curve obtained from dialyzed urea.

An additional method for obtaining the systemic blood urea concentration Cs is the calculation of the mass of Mwh urea in the whole body and the extrapolation of the urea mass at the beginning of the treatment. By dividing the total urea mass of the Mwh body with the volume of distribution V, the concentration of systemic blood urea Cs is obtained at the beginning of the treatment.

Dividing the concentration of dialyzed urea Cd with the urea concentration of systemic blood Cs and multiplying with the dialyzed flow rate. Qd, you get Keff effective debugging. It is advantageous to measure the effective Keff clearance at the start of treatment.

In addition, in the method of the invention, the flows of ? tz? .a - t && amp; & i.? x -i blood in the arterial and venous needles are reversed. The concentrations of urea dialyzed in both cases with the normal position of the needles and with the inverted position of the needles can be calculated as follows, with reference to Figures 3 and 4.

The concentration of urea in the blood Cs in the venous blood returning from the body is assumed not to change when the lines are reversed, and the clearance of the K-dialyzer is also assumed to be unchanged. For simplicity it is assumed that the ultrafiltration is zero, but it is also possible to handle a UF different from zero.

The following notations are used Qco - Cardiac output Qa - Access flow Qb - Blood flow in the extracorporeal circuit Qd - Dialysate flow K - Keff dialyzer depuration - Effective debugging of the dialyzer Cs - Blood urea concentration in venous systemic blood returning from the body Ca - Concentration of urea in the blood in the access Cb - Concentration of urea in the blood in the entrance of the dialyzer Cd - Urea concentration in the dialysate The definition of debugging is: K = (urea removed) / Cb = Qd * Cd / Cb (1) Consider first the case in which Qa > Qb and the needles are in the normal position. In this case Cb = Ca.

Removal of blood should equal the appearance in the dialysate, which is why K * Ca = Qd * Cd (2) A mass balance for urea at point V, see Figure 3, when the venous blood is mixed back with the blood from the access given: Ca * Qco = Cs * (Qco - Qa) + Ca * (Qa - K) (3) Therefore, a relationship between Ca and Cs is obtained.

Combining the equations 2 and 3 we obtain: Cd = (K / Cd * Cs / [1 + K / (Qco - Qa)] (4) The definition of Keff effective debugging implies that Cs should be used in the denominator instead of Cb as is normally used in the dialyzer clearance, which means that Keff = K * (Cb / Cs) = K / [1 + K / Qco - Qa)] (5) If we turn now to the case with inverted lines, see Figure 4, we still have that what has been removed from the blood must enter the dialysate, so that in this case K * Cb = Qd * Cd (6) The flow in the fistula between the needles will be Qa + Qb and we can calculate the blood urea concentration at the entrance of the dialyzer from a mass balance of urea at the point P where the blood of the dialyzer enters the access again Cb * (Qb - K) + Ca * Qa = Cb * (Qb + Qa) (7) We also have the mass balance at point Q in «Agfcj? MiHilto, y- - .. iyyX xíÍÁÁ? X? & where the return venous blood meets the dialyzed blood in the access return flow: Ca * Qco = Cs * (Qco - Qa) + Cb * Qa (8) By eliminating Ca and Cb we obtain Cd = (K / Cd) * Cs / [1 + (Qco / Qa) * K / (Qco - Qa)] (9) Given that Cs, K and Qd do not change in both cases, it is possible to obtain the ratio of urea concentrations in the dialysate: Cd norm / Cd rev = 1 + (K / Qa) / [1 + K / (Qco-Qa)] = = 1 + Keff / Qa (10) In practice, the two urea concentrations of the dialysate are probably best supported by a curve fitting for the urea curves of the dialysate before and after the line change, with an extrapolation at the time of the change from the respective side, see Figure 6, showing the concentration of Cd urea in the dialysate during a normal hemodialysis treatment.

Over a period of time of approximately 10 ií i í .l, yÁ.-tixtx¡Í ... a¿Mt - ^ .-. t - »^ i ^, a¿afe¿i? iMAaMíifcfc» .J __-_- ^? f «'-« «IMlwtJ., ^?» Te. , -. • --.- ¿, ..- > fc.A?, ¿faith.-. minutes, marked with a ring in Figure 6, the arterial and venous needles are inverted. After an initial period of time to allow the urea monitor to measure accurately, the urea concentration with inverted lines is approximately 0.8 times the original urea concentration, which means that Cdnorm / Cdrev = 1.25. Therefore, if Keff is 200 ml / min, when measured with the needles in the normal or estimated position as described above, the access flow is 800 ml / min.

Effective depuration can also be obtained as a coarse estimation from blood and dialyzer flows and dialyzer characteristics, for example, from the dialyzer data sheet.

In the present specification, three different depurations are used, namely dialyzer debugging, effective debugging, and total body cleansing. If the clearance of the dialyzer is 250 ml / min for a certain blood flow rate and dialysate flow rate, the effective clearance is usually 5 to 10% lower, such as 230 ml / min. The total purification of the body is still 5 to 15% lower, such as 200 ml / min. The purification of the dialyzer is the purification as measured directly in the dialyzer. The effective debugging is the . .: zx -, - tÍM. More clearance that also takes into account cardiopulmonary recirculation. Finally, the total depuration of the body is the effective depuration that also takes into account other membranes in the body that restrict the flow of urea from any part of the body to the dialysate. The concept of total body purification is described in WO 9855166, the content of which is incorporated herein by reference.

The effective depuration used in the formula can also be obtained from a measurement according to the method described in EP 658 352 mentioned above, with the needles in the normal position. This will give a measurement of the effective plasma water, which subsequently has to become the total purification of the blood. The method of EP 658 352 essentially comprises that the conductivity of the dialysis fluid upstream of the dialyzer increases, for example, 10% and that it is then returned to the original value. The result on the side of the dialyzer outlet is measured and results in a measurement of the Keff effective debugging of the dialyzer.

Alternatively, effective debugging can be calculated according to the equation Keff = Qd * Cd / Cs.

The concentration of venous systemic urea can be measured at the same time as the urea concentration of the Cd dialysate, Á -l. ^ .- ii¿xt, x x or by means of methods described above.

Another method could be to use the value of the total urea mass of the Murea body obtained by the method according to WO 9855166, mentioned above. Obtaining the volume of distribution of urea V by means of the Watson formula or any other method, the concentration of venous urea could be approximately: Cs = Murea / V (11) In the method of WO 9855166, the total body relative efficiency of the Kwb / V dialysate process is obtained. Note that total body cleansing is used, as indicated by the subscript wb. According to said WO 9855166, the urea concentration is proportional to the total body relative efficiency according to the formula: K "b / V = (Qd.« Cd) / m (12) Therefore, if (Kwb / V) is used instead of Cd in the above equation (10), a similar result is obtained, if it is presumed that m is constant, that is, the measurement must be extrapolated to the same instance of time: (V) norm / (Kwb / V) rev = 1 + Keff / Qa (13) As mentioned in said WO 9855166, it is possible to calculate the total relative body efficiency only from the urea measurement of the dialysate. Since we are only interested in the relationship in the normal and inverted position, we do not need to calculate the "real" K.

Figure 11 shows a graph of the total body relative efficiency K / V (min "1) The period with inverted lines is shown in a circle In all other aspects, the same discussion applies as given above.

The above calculations assume that the velocity of extracorporeal blood flow Qb does not exceed the rate of access flow Qa. If this is the case there will be recirculation of access and the flow in the access will be reversed when the needles are in the normal position. The calculation of the urea concentration in the dialysate does not change for the needles in the inverted position, but must be modified for the needles in the normal position. The calculations corresponding to those above show that the previous relationship between the urea concentrations of the dialysate for the positions of the normal and * T rtffc tá 3. »ÍAJüé A ¡i á. .. Ja-a .. - «... .-. ij, .... a »-AHM.i l.ti inverted will be: Cd norm / Cd rev = 1 + Keff / Qb (14) where Keff is the effective depuration with the effect of the recirculation included, that is to say with the needles in the normal position.

The only difference is that the calculation will now give the extracorporeal blood flow Qb instead of the access flow. This blood flow is known, so in practice this means that when the result is an access flow rate Qa close to the flow velocity of the blood Qb, recirculation should be suspected, and this always means that the Access has to improve.

Keff / Qb is a number less than one, usually, for example, 0.6 - 0.9. Keff / Qa should be considered minor, for example 0.1 - 0.4. Therefore, when Cd norm / Cd rev approaches or is less than a predetermined number, such as 1.2 or 1.5, additional calculations should be made to determine if access recirculation is present.

A simple procedure is to decrease the flow somewhat lai »¿¿Üz ij. I miss t) ... i. i of blood Qb. If the concentration of dialysate subsequently decreases, this means that there is no access or fistula recirculation at least at the lowest blood flow.

The above calculations can also be made for the case in which ultrafiltration is present. However, it is a simple measure to reduce ultrafiltration to zero during the measurement interval. In addition, the error induced by ultrafiltration is small and can be neglected.

The measurements should be made during a time interval, which is considerably longer than 30 seconds in such a way that cardiopulmonary recirculation has been developed. The measurement time for obtaining valid results can be 5 minutes with the needles inverted, while the measurements with the needles in the correct position can be made in 5 minutes or continuously during the treatment.

The method is also applicable to treatment methods comprising infusion of a dialysis solution into the blood before or after the dialyzer, called hemofiltration and hemodiafiltration. The result is the same as the one given above.

If the access is a venous catheter, there is no cardiopulmonary recirculation and the calculations are simplified. The result is the same, except that the effective Keff depuration is replaced by the clearance of the K dialyzer, since the concentration of venous systemic urea Cs becomes the same as the concentration of inlet urea of the dial iZad Cb.

It should be noted that all flow velocities, purifications and urea concentrations in the calculations are related to the whole blood. Approximately 93% of plasma is water, depending on the concentration of protein, -about 72% of erythrocytes is water. Depending on the hematocrit value, the volume of water in the blood is 10-13% less than the volume of all blood, see for example the Dialysis Manual, Second Edition, by John T. Daugirdas and Todd. S Ing, 1994, page 18.

The effective urea clearance obtained according to EP 658 352 is related to the water of the blood, and should therefore be increased by 10-13% before being used in the present formulas. Blood urea concentration values obtained from a laboratory are generally related to plasma, and therefore should be decreased «Fe ^^^ g« l? & £ &?, * and ixÁ-. X. A & ^^ approximately 7% in order to relate the totality of the blood.

Alternatively, all urea concentrations, flow rates and purifications can be used as in relation to the water of the blood. The effective depuration is then used without change, but the calculated access flow will be related to the water of the blood, and it has to be increased from 10 - 13% to relate the whole blood.

The invention has been described above with reference to its use in the human body and using urea as a marker for the measurement of access flow. However, according to the invention, any other substance present in the blood can be used and can be measured on the dialysate side of the dialyzer, such as creatinine, vitamin B12, beta-two-microglobulin, NaCl, or any combination of ions. . Another alternative is to measure the conductivity.

It is also possible to measure a property proportional to the concentration, since what is involved is the speed in the equations. Therefore, the urea concentration can be measured by measuring the differences in conductivity ,, - --- "• • &.j« ii, J after the urea-containing fluid passes through a urease column, and such a difference in conductivity can be used directly instead of the concentration values in The equations.

Other indirect methods of measuring any of the concentrations of substances mentioned above can be used as well as how the measurements are made on the dialysate side of the dialyzer. Another alternative is to measure blood urea concentrations by any known method, either before or after the dialyser, since these concentrations are proportional to the concentrations in the formulas.

The invention has been described above with reference to the use in the human body. However, the invention can be used in any tubular system where a fluid passes and a portion of it is removed by dialysis, such as in the production of beer or wine.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention. *. & - £ * & * - zXiß j- £ -. -.- t .... & t? I >

Claims (28)

CLAIMS Having described the invention as above, the content of the following claims is claimed as property.

1. A method for estimating the fluid flow velocity (Qa) in a fluid flow access, characterized in that it comprises: the removal of a first fluid flow from said access in a removal position to an external flow circuit which comprises a dialyzer having a semi-permeable membrane, said first fluid flow passing along said membrane on one of its sides and a dialysis fluid being emitted from the other of its sides, and said first fluid flow returning from said external flow circuit to said access and in a return position downstream of said removal position; measuring a first variable which is essentially proportional to the concentration (Cd norm) of a substance in said dialysis fluid emitted from the dialyzer; reversing the removal position with the return position and measuring a second variable which is essentially proportional to the concentration (Cd rev) of @ & L? fa &X.é, AX.z -.z ~~ and -Xí &! »Ufe- ^. Sfe. zzX. & zZX, A. , X ^ z z and z-. "&Jfe. | -. Dicha said substance in said dialysis fluid in the inverted position; and calculating the fluid flow velocity (Qa) in said flow access from said measured concentrations.

2. The method according to claim 1, characterized in that the calculation of the fluid flow velocity in said access flow takes place by means of the formula: Cd norm / Cd rev = 1 + K / Qa wherein Cd norm and Cd rev are values proportional to the concentrations of said substance in the dialysis fluid in the normal and inverted positions, respectively, and K is the clearance of the dialyzer and Qa is the access flow rate.

3. The method according to claim 2, characterized in that said access flow is an access of blood flow in a mammal to obtain access to a blood vessel.

The method according to claim 3, characterized in that said access flow is a hemodialysis access in the nature of an arterial-venous shunt or fistula, and wherein the clearance of the K-dialyzer is replaced by the effective dialyzer clearance Keff obtained taking into account a cardiopulmonary recirculation and in the normal position.

5. The method according to any of the preceding claims, characterized in that said substance is selected from the group consisting of: urea, creatinine, vitamin B12, beta-two-microglobulin and glucose.

The method according to any of the preceding claims, characterized in that said substance is an ion selected from the group of: Na +, Cl ", K +, Mg ++, Ca + V HC03", acetate ion, or any of its combinations measured by conductivity; and said concentration is measured as the concentration difference between the outlet and the dialyzer inlet.

The method according to claim 5 or 6, characterized in that the measurement step is performed by measuring a property which is proportional to the concentration of said substance, whereby said property is used in place of said concentration.

The method according to claim 7, characterized in that said property is any of: the concentration of the blood of said substance in the external circuit; and the relative global body efficiency (KWh / V).

9. The method according to any of claims 3 to 8, characterized in that said Keff is obtained by the equation Keff = Qd * Cd / Cs where Qd is the flow of dialysis fluid emitted from the dialyzer, Cd is the concentration of said substance in said dialysis fluid and Cs is the concentration of said substance in the venous systemic blood.

The method according to claim 9, characterized in that the concentration (Cs) of said substance in the venous systemic blood is measured by: stopping the flow of blood in the external flow circuit for a period of time sufficient to allow that cardiopulmonary circulation equals; the initiation of blood flow in the external flow circuit at a slow rate to fill the arterial line with fresh blood before measurement; the measurement of the equal concentration of said substance in the dialysis fluid at a low flow rate of the dialysate or in the isolated ultrafiltration.

The method according to claim 9, characterized in that the concentration (Cs) of said substance in the venous systemic blood can be estimated by: the calculation of the total body mass of urea (Murea) in the patient's body, estimating or measuring the volume of distribution (V) of urea in the patient's body; the estimation of the concentration (Cs) of said substance in the blood dividing all the body mass of urea with the volume of distribution.

The method according to any of the preceding claims, characterized in that it additionally comprises: the change of the blood flow velocity (Qb); the monitoring of the concentration of said substance in the dialysate emitted from the dialyzer; the detection of a possible fistular recirculation in the normal position correlating a change in said concentration to said change in the velocity of blood flow.

13. The method according to claim 12, characterized in that the blood flow rate is decreased and a corresponding decrease in the urea concentration is monitored, and the absence of such decrease being an indication of fistular recirculation.

14. An apparatus for estimating the fluid flow velocity (Qa) in a flow access of the fluid, characterized in that it comprises: removal means for the removal of a first fluid flow from said access in a removal position to an external flow circuit comprising a dialyzer having a semipermeable membrane, said first fluid flow passing along said membrane on one of its sides and a dialysis fluid being emitted from the other side thereof; return means for returning said first fluid flow from said external flow circuit to said access and in a return position downstream of said removal position; measurement means for the measurement of a first variable which is essentially proportional to the concentration (Cd norm) of a substance in said dialysis fluid emitted from the dialyzer; investment means to invert the removal position with the return position for the measurement of a second variable which is essentially proportional to the 20 concentration (Cd rev) of said substance in said dialysis fluid in the inverted position; and calculating means for calculating the fluid flow velocity (Qa) in said flow access from said measured concentrations.

15. The apparatus according to claim 14, characterized in that the calculation of the fluid flow velocity in said access flow takes place by means of the formula: Cd norm / Cd rev = 1 + K / Qa wherein Cd norm and Cd rev are values proportional to the concentrations of said substance in the dialysis fluid in the normal and inverted positions, respectively, and K is the clearance of the dialyzer and Qa is the access flow rate.

16. The apparatus according to claim 14 or 15, characterized in that said access flow is an access of blood flow in a mammal for obtaining access to a blood vessel.

The apparatus according to claim 16, characterized in that said access flow is a hemodialysis access in the nature of an arterial-venous shunt or fistula, and wherein the clearance of the K dialyzer is replaced by the effective purification of the dialyzer Keff obtained taking into account a cardiopulmonary recirculation.

18. The apparatus according to any of claims 14 to 17, characterized in that said i.i iia, it, J substance is selected from the group consisting of: urea, creatinine, vitamin B12, beta-two-microglobulin and glucose.

19. The apparatus according to any of claims 14 to 18, characterized in that said substance is an ion selected from the group of: Na +, Cl ", K +, Mg ++, Ca ++, HC03", acetate ion, or any of their combinations measured by conductivity; and said concentration is measured as the concentration difference between the outlet and the dialyzer inlet.

20. The apparatus according to claim 18 or 19, characterized in that the measuring means is adapted to measure a property which is proportional to the concentration of said substance, whereby said property is used in place of said concentration.

The apparatus according to claim 20, characterized in that said property is any of: the concentration of the blood of said substance in the external circuit; and the relative global body efficiency (Kwh / V).

22. The apparatus according to any of claims 17 to 21, characterized in that said Keff is obtained by the equation Keff = Qd * Cd / Cs where Qd is the flow of dialysis fluid emitted from the dialyzer, Cd is the concentration of said substance in said dialysis fluid and Cs is the concentration of said substance in the venous systemic blood.

23. The apparatus according to claim 22, characterized in that it additionally comprises means for measuring the concentration (Cs) of said substance in the systemic venous blood including: means for stopping the flow of blood in the external flow circuit during a sufficient period of time to allow the cardiopulmonary circulation to equalize and stop the flow of the dialysis fluid; means for initiating blood flow in the external flow circuit at a slow rate to fill the arterial line with fresh blood before measurement; means for measuring the equal concentration of said substance in the dialysis fluid at a low flow rate of the dialysate or in the isolated ultrafiltration.

24. The apparatus according to claim 22, characterized in that it additionally comprises means for estimating the concentration (Cs) of said substance in the venous systemic blood, including: means for calculating the total body mass of urea (Murea) in the patient's body, means for estimating or measuring the volume of distribution (V) of urea in the patient's body; means for estimating the concentration (Cs) of said substance in the blood by the formula dividing all the body mass of urea with the volume of distribution.

25. The apparatus according to any of claims 14 to 24, characterized in that it additionally comprises: means for changing the blood flow velocity (Qb); means for monitoring the concentration of said substance in the dialysate emitted from the dialyzer; means for the detection of a possible fistular recirculation in the normal position correlating a change in said concentration to said change in the velocity of blood flow.

26. The apparatus according to claim 25, characterized in that it comprises means for decreasing the blood flow rate and means for monitoring a corresponding decrease in the urea concentration, and the absence of such decrease being an indication of fistular recirculation. ^? B. .Í- ^ rfl »jl-¿.--- .. Mia¿ ^ ¿- > ., -. "..,.: - ^^

27. The apparatus according to any of claims 14 to 25, characterized in that said reversal means comprise: a means which is a valve disposed between the reversing means and the dialyzer and between the return means and the dialyzer to reverse the direction of the flow of blood through the removal means and the return means, said means being a valve comprising two inlet and two outlet openings and a member that is a valve, said member being a valve arranged to take a position inactive in which all four inlet and outlet openings are interconnected.

28. The apparatus according to claim 27, characterized in that it additionally comprises an air detector arranged between the means which is a valve and at least one of the needles, the arterial needle and the venous needle.