Determination of intraperitoneal volume during peritoneal dialysis

Abstract

A system for peritoneal dialysis operates according to a measurement method to supply a first fluid (F1) to the peritoneal cavity PC, leaving an intraperitoneal volume of fluid in the PC, extracting a first volume (V1) of fluid from the PC and measuring a first value of a concentration-related parameter of the fluid thus extracted. The system then operates to supply a second volume (V2) of a second fluid (F2) to form a mixture with the intraperitoneal volume of fluid in the PC, extracting a third volume (V3) of the mixture from the PC and measuring a third value of the parameter of the mixture thus extracted. The second fluid (F2) has a second value of the parameter and is compositionally different from the first fluid (F1). The use of such a second fluid (F2) allows the intraperitoneal volume to be determined with high accuracy based on the second volume (V2) and the first, second and third values.

Description

[Technical field]

[0001] The present disclosure relates generally to peritoneal dialysis, and more particularly to techniques for determining or estimating the volume of fluid in the peritoneal cavity during peritoneal dialysis. [Background technology]

[0002] Dialysis therapy may be required to treat individuals suffering from acute or chronic kidney failure. One category of dialysis therapy is peritoneal dialysis (PD). In PD, a therapy fluid ("dialysate") is infused into a person's peritoneal cavity, also known as the peritoneal cavity. This cavity is lined with a highly vascular peritoneal membrane ("peritoneum"). Substances are removed from the patient's blood primarily by diffusion across the peritoneal membrane into the therapy fluid. Excess fluid (water) is also removed by osmosis induced by the therapy fluid, which is hypertonic.

[0003] In automated peritoneal dialysis (APD), the dialysis treatment is controlled by a machine known as a "cycler." The machine is connected in fluid communication with the peritoneal cavity and operates to control the flow of fresh dialysate to and spent dialysate from the peritoneal cavity. Common complications in APD are so-called overfilling and underfilling. Overfilling refers to the inadvertent presence of an excess of fluid volume in the peritoneal cavity. Conversely, underfilling refers to the delivery of an unexpectedly small fluid volume into the peritoneal cavity. Overfilling can cause severe pain to the patient and can even be fatal, as noted by Peter Blanke in his article "Drain pain, overfill, and how they are connected," Peritoneal Dialysis International, Vol. 34, pp. 342-344 (2014). Underfilling can lead to a decrease in the efficiency of PD treatment and can also cause pain when the machine drains to completely empty the peritoneal cavity of fluid.

[0004] The risk of underfilling and overfilling can be mitigated if the actual amount of fluid in the peritoneal cavity is known at one or more points during PD treatment. The actual amount of fluid is commonly called the "intraceretinal volume", IPV for short. Furthermore, knowledge of the IPV when spent dialysate is drained from the peritoneal cavity, known as the "residual volume", can also be used to predict the effectiveness of PD treatment and help clinicians (re)configure the machine for PD treatment.

[0005] EP 2 623 139 A1 proposes a procedure to estimate the residual volume in the peritoneal cavity during normal PD treatment. In the proposed procedure, at the end of the dwell phase, the spent dialysate in the peritoneal cavity is drained, leaving an unknown residual volume in the peritoneal cavity, and the conductivity of the spent dialysate is measured. Then, the conductivity of the unused dialysate is measured and a volume of unused dialysate is infused into the peritoneal cavity. Then, a small volume of fluid is extracted from the peritoneal cavity and its conductivity is measured. By using a dilution formula, the residual volume is calculated based on the infused volume of unused dialysate and the measured conductivity. Although a simple procedure, the calculated residual volume seems to have a low accuracy. Based on the numerical example given in EP 2 623 139 A1, the actual residual volume of 667 ml is estimated with an error of ±98 ml, given as the standard deviation. If the actual residual volume is instead 100 ml, the resulting error is ±66 ml. If the PD machine is set based on such an insufficiently estimated residual volume, the result may be suboptimal PD therapy and the patient may still experience overfilling or underfilling. Summary of the Invention

[0006] It is an object to at least partially overcome one or more of the limitations of the prior art.

[0007] One object is to provide a technique that allows for estimating intraperitoneal volume with improved accuracy during peritoneal dialysis.

[0008] One or more of these objects, as well as further objects that may become apparent from the following description, are achieved at least in part by a system for peritoneal dialysis, a computer-implemented method, and a computer-readable medium, embodiments of which are defined by the dependent claims.

[0009] A first aspect is a system for peritoneal dialysis. The system comprises a fluid supplying device operable to convey fluid to and from the peritoneal cavity, a sensor device operable to measure a concentration-related parameter, and a control device connected to the fluid supplying device and the sensor device. The system is configured to operate the fluid supplying device to supply a first fluid to the peritoneal cavity, and to operate the fluid supplying device to extract a first amount of fluid from the peritoneal cavity leaving an intraperitoneal amount of fluid in the peritoneal cavity after supplying the first fluid, and to obtain from the sensor device a first value of the concentration-related parameter of the fluid thus extracted. The system is further configured to operate the fluid supplying device to supply a second amount of a second fluid to the peritoneal cavity. The second fluid has a second value of the concentration-related parameter and forms a mixture with the intraperitoneal amount of fluid in the peritoneal cavity, where the first fluid and the second fluid differ in composition. The system is further configured to operate the fluid supply device to extract a third amount of the mixture from the peritoneal cavity, obtain from the sensor device a third value of a concentration-related parameter of the mixture so extracted, and determine an intraperitoneal volume based on the second amount and the first, second and third values.

[0010] In some embodiments, the system operates to achieve a difference between the second value and the first value that exceeds a threshold set to achieve a predetermined accuracy of the intraperitoneal volume determined based on the second amount and the first, second and third values.

[0011] In some embodiments, the threshold value is set to correspond to a second value that is approximately 20%-75% greater than the first value or approximately 20%-75% less than the first value.

[0012] In some embodiments, the fluid supply is operable to generate the second fluid on demand, and the control device is configured to operate the fluid supply to generate the second fluid based on the first value to achieve a difference between the second value and the first value.

[0013] In some embodiments, the first fluid is a treatment fluid used in peritoneal dialysis therapy and the second fluid is a test fluid dedicated for use in determining intraperitoneal volume.

[0014] In some embodiments, the second fluid and the first fluid differ in concentration of at least one solute that affects the concentration-related parameter.

[0015] In some embodiments, the solute in the second fluid is the same as the solute in the first fluid.

[0016] In some embodiments, the second fluid has a different concentration of at least sodium compared to the first fluid.

[0017] In some embodiments, the second fluid has a different concentration of an osmotic agent compared to the first fluid.

[0018] In some embodiments, the second fluid has an osmolarity to minimize solvent transfer across the peritoneal membrane within the peritoneal cavity.

[0019] In some embodiments, the second fluid has an osmolality of 250-350 mOsm / l.

[0020] In some embodiments, the second value is less than the first value.

[0021] In some embodiments, the controller is configured to execute a sequence of fluid exchange cycles each including a fill phase, a dwell phase, and a drain phase, the sequence of fluid exchange cycles including a fluid exchange cycle in which the fluid supply device operates to supply a first fluid to the peritoneal cavity in the fill phase and extract a first amount of fluid in the drain phase, and successive fluid exchange cycles in which the fluid supply device operates to supply a second amount of a second fluid to the peritoneal cavity in the fill phase and extract a third amount of the mixture during the drain phase, and the controller is configured to obtain a first value during the drain phase of the first cycle and a third value during the drain phase of the second cycle.

[0022] In some embodiments, the controller is configured to operate the fluid delivery device such that the first amount is between 25% and 95% of an estimated total amount of fluid present in the peritoneal cavity.

[0023] In some embodiments, the controller is configured to operate the fluid supply such that the second amount is between 25% and 100% of the first amount.

[0024] In some embodiments, the control device is configured to determine the intraperitoneal volume by use of a dilution formula given by IPV1=V2·(C3-C2) / (C1-C3), where V2 is the second volume, C1 is the first value, C2 is the second value, and C3 is the third value.

[0025] In some embodiments, the controller is configured to determine an intraperitoneal volume during extraction of the third volume, and terminate extraction of the third volume based on the determined intraperitoneal volume and the second volume.

[0026] In some embodiments, the controller is configured to terminate the extraction of the third amount so as to achieve a predetermined difference between the third amount and the sum of the determined intraperitoneal amount and the second amount.

[0027] A second aspect is a computer-implemented method of operating a system for peritoneal dialysis. The method operates the system to deliver a first fluid to the peritoneal cavity, extract a first amount of fluid from the peritoneal cavity leaving an intraperitoneal amount of fluid in the peritoneal cavity after delivering the first fluid, and measure a first value of a concentration-related parameter of the fluid thus extracted. The method further operates the system to deliver a second amount of a second fluid to the peritoneal cavity. The second fluid has a second value of the concentration-related parameter and forms a mixture with the intraperitoneal amount of fluid in the peritoneal cavity, where the first and second fluids differ in composition. The method further operates the system to extract a third amount of the mixture from the peritoneal cavity, measure a third value of the concentration-related parameter of the mixture thus extracted, and determine the intraperitoneal amount based on the second amount and the first, second and third values.

[0028] A third aspect is a computer-readable medium comprising computer instructions that, when executed by one or more processors, cause the one or more processors to perform the method of the second aspect.

[0029] The measurement technique defined by the aforementioned embodiment provides the technical advantage of allowing a significant improvement in the accuracy of the estimated intraperitoneal volume by virtue of the second fluid having a different composition from the first fluid. The ability to measure intraperitoneal volume requires a difference in a concentration-related parameter (e.g., conductivity) between the second fluid and the fluid to which it is added in the peritoneal cavity, i.e., between the second value and the first value. If the same fluid is used as both the first and second fluid, as proposed in the prior art, this difference is essentially fixed since it is mainly caused by the dilution of the first fluid by the ultrafiltrate while the first fluid is present in the peritoneal cavity in the dwell phase. By using a second fluid that is different in composition from the first fluid, this difference is controllable and can be set to achieve the desired accuracy. The technique of the aforementioned embodiment also allows the intraperitoneal volume to be measured at any time before, during or after PD therapy, not just after the completion of the dwell phase as in the prior art.

[0030] Further objects, aspects, embodiments and technical effects, as well as features and advantages, will become apparent from the following detailed description, the appended claims, and the drawings. It is noted that any embodiment of the first aspect found herein may be adapted and implemented as an embodiment of the second and third aspects. [Brief description of the drawings]

[0031] [Figure 1] FIG. 1 illustrates an exemplary system for automated peritoneal dialysis (APD). [Diagram 2] FIG. 2 is an exemplary plot of intraperitoneal volume versus time during a sequence of fluid exchange cycles in APD therapy. [Diagram 3] FIG. 3 is a flow chart of an exemplary method for determining the intraperitoneal volume of fluid in the peritoneal cavity. [Figure 4] FIG. 4 illustrates the filling of the peritoneal cavity during the method of FIG. [Diagram 5] FIG. 5 is a graph of the estimation error of intraperitoneal volume as a function of the ratio of the first and second concentration related values ​​of fluid present in the peritoneal cavity during the method of FIG. [Figure 6] , [Figure 7] 6-7 illustrate a system for an APD that can be configured to perform the method of FIG. [Figure 8] FIG. 8 is a block diagram of an exemplary control device. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0032] Embodiments will now be described more fully hereinafter with reference to the accompanying drawings, in which some, but not all, embodiments are shown. Indeed, the subject matter of this disclosure may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein, but rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements.

[0033] It will also be understood that, where possible, any of the advantages, features, functions, devices, and / or operational aspects of any of the embodiments described and / or contemplated herein may be included in any of the other embodiments described and / or contemplated herein, and / or vice versa. Additionally, where possible, any term expressed in the singular herein is meant to include the plural and / or vice versa, unless expressly stated otherwise. As used herein, "at least one" means "one or more," and these phrases are intended to be interchangeable. Thus, the terms "a" and / or "an" are intended to mean "at least one" or "one or more," although the phrases "one or more" or "at least one" are also used herein. As used herein, unless the context otherwise requires to express the word or necessary implication, the word "comprise" or variations such as "comprises" or "comprising" are used in an inclusive sense, i.e., to specify the presence of stated features but not to exclude the presence or addition of further features in various embodiments.

[0034] As used herein, the terms "multiple," "plural," and "plurality" are intended to mean the provision of two or more elements. The term "and / or" includes any and all combinations of one or more of the associated listed elements.

[0035] Furthermore, although terms such as first, second, etc. may be used herein to describe various elements, it should be understood that these elements should not be limited by these terms. These terms are used only to distinguish one element from another element. For example, a first element can be a second element, and similarly, a second element can be a first element, without departing from the scope of the present disclosure.

[0036] Well-known functions or configurations may not be described in detail for brevity and / or clarity.Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0037] Like numbers refer to like elements throughout.

[0038] The present disclosure relates to a technique for estimating the volume of fluid in a patient's peritoneal cavity during peritoneal dialysis (PD). Hereinafter, this is referred to as "intraceretine volume", IPV. The peritoneal cavity is located in the patient's abdomen and is lined by a peritoneum composed of parietal and visceral peritoneum. PD uses the peritoneum to exchange fluid and dissolved substances between the therapeutic fluid present in the peritoneal cavity and the patient's blood. PD can be used to remove excess fluid, correct electrolyte problems, and remove toxins. In PD, therapeutic fluid ("PD fluid") is first introduced into the peritoneal cavity and then removed according to a predetermined cycle schedule. PD fluid typically includes electrolytes and osmotic agents. Osmotic agents are substances dissolved in water that can drive the net movement of water by osmosis across the peritoneal membrane due to the concentration difference of the osmotic agent on each side of the membrane. Osmotic agents can include, for example, one or more of glucose (also known as dextrose), L-carnitine, glycerol, icodextrin, fructose, sorbitol, mannitol, or xylitol.

[0039] FIG. 1 shows a schematic of an automated PD system 10 configured to perform a PD therapy on a patient P. The PD system 10 is also configured to estimate an intraperitoneal volume IPV according to the techniques described below. The PD system 10 comprises a controller 11 configured to control the operation of the system 10 and to calculate the IPV. A fluid supply, FSA, 12 is operable to provide a PD fluid for use in the PD therapy, as well as a dedicated test fluid for use in determining the IPV (below). The PD system 10 further comprises a sensor device 13 configured to measure a concentration-related parameter of a fluid, such as a PD fluid or a test fluid. For simplicity, the concentration-related parameter is denoted below as CRP. The CRP represents a relative or absolute amount of one or more substances in a fluid. For example, the CRP may be given by one or more values ​​of conductivity, resistivity or concentration. In the example of concentration, the CRP may represent an osmotic agent, such as sodium and / or glucose. The sensor device 13 may comprise two or more physical sensor units. For example, separate sensor units may be provided for measuring the CRP of the PD fluid and the test fluid, respectively. Alternatively or additionally, different types of sensor units may be provided for measuring different CRPs.

[0040] The PD system 10 of FIG. 1 further comprises a user interface, UI, 14, configured to enable user interaction with the system 10. The user may be a patient P or a caregiver. The term "user interface" is intended to include any and all devices capable of performing guided human-machine interaction. The UI 14 may be configured to present operational data, e.g., current settings of the system, progress of PD therapy, current IPV, user instructions, alerts and warnings. The UI 14 may further be operable to enable a user to input data, e.g., settings or instructions, into the system 10. The UI 14 may comprise a combination of a presentation device and data entry hardware. The presentation device may include a display and / or a loudspeaker. The data entry hardware may include one or more of a keyboard, a keypad, a computer mouse, control buttons, a touch panel, a microphone and voice control capabilities, a camera and gesture control capabilities, and the like. In one implementation, the UI 14 is or comprises a touch-sensitive display, also known as a touch screen.

[0041] 1, the PD system 10 further comprises a fluid connection device 15 coupled to the peritoneal cavity, PC, of ​​the patient P. The fluid connection device 15 may be a tube or the like connected to an implanted catheter (not shown) in fluid communication with the PC. As indicated by the double-headed arrows, the PD system 10 is operable to deliver fluid into and out of the PC via the fluid connection device 15.

[0042] The PD system 10 may be configured for any type of automated PD (APD) therapy, including, but not limited to, continuous cyclic PD (CCPD), intermittent PD (IPD), tidal PD (TPD), or continuous flow PD (CFPD). CCPD is also known as conventional APD. A typical cycling scheme for CCPD consists of 3 to 5 exchanges of PD fluid at night. During the day, a certain amount of PD fluid may or may not remain in the PC. IPD consists of frequent cycles, 3 times a week, for 8 to 10 hours per session. In IPD, the PC is typically drained and "dried up" between sessions. TPD consists of an initial infusion of PD fluid followed by variable dwell and partial drainage of PD fluid, leaving a residual volume in the PC until final drainage. CFPD is a continuous therapy that involves filling the PC with a desired volume of PD fluid, where the inflow and outflow of PD fluid are balanced.

[0043] FIG. 2 is a graph of IPV as a function of time during an exemplary APD session, which includes three consecutive exchange cycles C1-C3, with the PC being drained at the end of the session. At the beginning of the session, the patient has a residual volume VR in the PC. Each exchange cycle comprises a fill phase F, a dwell phase DW, and a drain phase D, as shown for the first exchange cycle C1. In the first exchange cycle C1, an amount VF of PD fluid is infused into the PC. During phases F, DW, and D, fluid is transported through the peritoneum in a process known as ultrafiltration (UF). Depending on the osmotic pressure gradient, both positive and negative UF are possible. During an exchange cycle, as shown in FIG. 2, the accumulated effect of UF is usually an increase in fluid volume. For illustration purposes, the effect of UF is shown only for the dwell phase DW in FIG. 2. During the drain phase, the spent PD fluid is extracted from the PC, leaving a residual volume. This residual volume may differ from the initial residual volume and may also differ between cycles C1-C3.

[0044] It should be understood that the graph of Figure 2 is conceptual and given under the assumption that the fill volume, drain volume, duration, etc. are identical between exchange cycles. In practice, this need not necessarily be the case.

[0045] In PD, UF is usually quantified as the difference between drain volume and infusion volume. The drain volume can vary significantly between cycles, and the calculation of UF by drain volume can be averaged over several daily or weekly cycles. A good estimate of UF and knowledge of the patient's weight are important factors to achieve an adequate dialysis treatment. However, the IPV at any given time is unknown. The IPV can be indirectly estimated using computer simulations if the residual volume (VR), infusion volume (VF) and peritoneal properties are known. As can be seen from Figure 2, the IPV changes over time. By knowing the IPV, it is possible to optimize the PD therapy. For example, it is possible to avoid overfilling the PC in the filling phase F or the dwell phase DW. Overfilling is dangerous for the patient and should be avoided. The risk of overfilling can be exacerbated in some modalities of APD, such as TPD. By knowing the IPV, it is also possible to adjust the residual volume, if necessary. For example, if the IPV is known, the drain phase D can be controlled to leave a smaller fluid volume in the PC after the drain phase D. This reduction in residual volume allows the infusion volume VF to be increased in the following filling phase F (see FIG. 2). The increase in VF leads to an increase in the amount of fresh PD fluid in the PC during the dwell phase DW and may also provide a larger contact surface between the PD fluid in the PC and the peritoneum, resulting in improved therapeutic efficiency. Furthermore, the information of IPV can be used to determine optimal dwell times, determine membrane properties, and perform exchange of different solutes. Furthermore, the information of IPV can be useful to detect catheter displacement or malfunction. The information of IPV can also be used in the draining phase D to reduce the risk of so-called drain pain.

[0046] Traditionally, for IPD patents, PV is not usually measured. Measurement of IPV is only done when it is desired to accurately monitor UF and IPV, for example during clinical trials. Such measurements are performed when PD fluids containing polymeric volume markers are used, which make it possible to track changes in intraperitoneal fluid volume by monitoring the dilution of the volume marker. Examples of such volume markers include radioisotope-labeled dextran (14C), radioactive albumin 2 or hemoglobin. These procedures are very complicated to perform in the patient's home or in the clinic in conjunction with the usual PD therapy.

[0047] Therefore, there is a need for a simple yet accurate technique for determining IPV during PD therapy. This technique is described in detail below with reference to Figure 3 and involves the use of a dedicated test fluid in addition to the PD fluid.

[0048] In accordance with the present disclosure, the IPV is determined by measuring the concentration-related parameter (CRP) of the fluid in the peritoneal cavity before and after injecting a known amount of test fluid into the cavity. If the CRP is also known for the test fluid, the IPV may be calculated by use of a "dilution formula." In its simplest form, the dilution formula is:

number

[0049] Figure 3 is a flow chart of an exemplary measurement method 300 for determining IPV. Figure 3 is presented with further reference to Figure 4, which illustrates the filling status of the peritoneal cavity PC at different stages during the method 300. The method 300 may be performed by the system 10 of Figure 1. In the following description, it is assumed that the volume of fluid infused into and extracted from the PC is measured, for example, by a flow meter, a volumetric pump, weight, etc.

[0050] In step 301A, a first fluid is delivered to the peritoneal cavity PC. This is shown in stage I of FIG. 4, where the first fluid is designated as F1. The first fluid F1 may be a PD fluid with a composition for use in normal PD. As indicated by the dotted line, the subsequent step 301B is optional. Step 301B corresponds to a dwell phase (see DW in FIG. 2), where the first fluid F1 resides in the PC and exchanges solutes and / or water through the peritoneum. The dwell phase is carried out between stages I and II of FIG. 4, and may result in an increase in the amount of fluid in the PC by ultrafiltration (UF). During the dwell phase, the composition of the first fluid F1 changes. The fluid in the PC at the end of the dwell phase is designated "modified first fluid" and designated as F1' in FIG. 4. In step 302, a first volume (V1) of fluid is extracted from the PC, leaving an unknown first intraperitoneal volume IPV1 in the PC. If step 301B is omitted, F1 is extracted in step 302. If step 301B is included, F1' is extracted in step 302, as shown in stage III of FIG. 4. In step 303, the CRP of the extracted fluid is measured by use of the sensor device 13 (FIG. 1) to obtain a CRP value C1. Step 303 may be performed at one or more times during step 302. In step 304, a second amount (V2) of a dedicated test fluid ("second fluid") is provided to form a mixture with the first intraperitoneal amount IPV1 in the PC. The provision of the test fluid, designated as F2, is shown in stage IV of FIG. 4, and the resulting mixture is shown in stage V and designated as F3. The test fluid F2 is different from the first fluid (PD fluid) F1. In particular, the test fluid and the PD fluid are of different composition and have different values ​​of CRP. The CRP value of the test fluid, referred to herein as C2, may be a predetermined value or may be measured by use of sensor device 13 (FIG. 1). For example, if the test fluid is produced on demand, its CRP value may be verified by use of sensor device 13 before the test fluid is delivered to the PC. Using a dedicated test fluid makes it possible to control the accuracy of IPV1 calculated in step 307 (below) by appropriately selecting C2 with respect to C1.

[0051] Mixing of F1' and F2 into F3 may be achieved by waiting a predefined period of time. Alternatively or additionally, mixing may be facilitated by suitable design of the implanted catheter and / or by agitation of the fluids in the PC, for example by the patient moving, for example rolling from side to side. In step 305, assuming that mixture F3 has been formed, a third quantity (V3) is extracted from the PC. The third quantity may be given by a predefined value or may be dynamically determined (see step 308 below). Extraction of V3 is shown in stages VI-VII of FIG. 4. In step 306, the CRP of the extracted fluid (mixture F3) is measured by use of the sensor device 13, resulting in a CRP value C3. Step 306 may be performed at one or more points during step 305. In step 307, IPV1 is determined based on C2, C1, C2 and C3, for example by calculation using the dilution formula defined above.

[0052] Optionally, as indicated by the dotted line, the method 300 may further include step 308 of terminating the extraction of fluid from the PC, which is started in step 305, based on IPV1 and V2. If ultrafiltration is ignored, the amount of mixture F3 in the PC at the start of step 305 is equal to the sum of IPV1 (stage III) and V2 (stage IV). Thus, the total amount of fluid at the start of step 305 is known. In some embodiments, step 308 terminates the extraction to achieve a predetermined difference between V3 and the sum of IPV1 and V2 ("termination condition"). The predetermined difference defines the remaining amount of fluid in the PC at the end. For example, as shown in stage VII of FIG. 4, V3 may be adjusted to effectively drain the fluid of the PC. The ability to control the remaining amount of fluid in the PC at the completion of step 305 provides the advantage of being able to maximize the amount of PD fluid infused into the PC in the subsequent filling phase, as shown in stage VIII of FIG. 4. This increases the efficiency of PD therapy.

[0053] If it is detected during the extraction started in step 305 that the desired amount of fluid cannot be withdrawn from the PC to trigger the termination step 308, the method 300 may include the step of instructing the user (patient or caregiver) to change the patient's position, thereby changing the position of the fluid within the PC. For example, the patient may be instructed to sit up from a lying position. If this does not help, the extraction of the fluid may be terminated.

[0054] It has been found that the sensor data acquired from the sensor device 13 in step 306 can be analyzed to determine the degree of mixing between F2 and F1' in the PC during the extraction of the fluid started in step 305. In particular, the time profile of the CRP value measured by the sensor device 13 during the extraction represents the degree of mixing, at least as long as the influence of the UF is small. If the degree of mixing is incomplete when the extraction is started, the CRP value is expected to stabilize at a value representing complete mixing as the extraction of the fluid continues. Correspondingly, it is possible to determine when C3 given by the sensor data is sufficiently accurate. To improve accuracy, C3 can be calculated in step 306 as an average of at least a part of the time profile of the CRP value, for example the part after the detected stabilization of the CRP value. It is also noted that C1 and C2, if measured, can be determined by averaging the measured time profile of the CRP value.

[0055] It is also conceivable that step 306 is repeatedly performed for each current portion of the time profile to generate a time sequence of C3 values ​​based on sensor data from the sensor device 13, and step 307 is also repeatedly performed to determine a corresponding time sequence of IPV1 values. By analogy with the C3 values, the IPV1 values ​​are likely to become more accurate over time as mixing in the PC improves while the fluid is being extracted. Step 308 can repeatedly update the termination condition based on such IPV1 values ​​generated by step 307.

[0056] As indicated by the dotted line, the method 300 can also include an optional step 309 of estimating the IPV at a selected time point other than the end of step 302 (stage III). By tracking the amount of fluid infused into and extracted from the PC, and optionally by estimating ultrafiltration, the IPV can be estimated at any time point based on the calculated value IPV1. Thereby, it is possible to quantitatively monitor the IPV over time, for example for one or more exchange cycles, to plot a graph similar to that of FIG.

[0057] As mentioned above, the method 300 may include a dwell phase (step 301B). Thereby, the method 300 may be performed during a normal PD therapy, for example, after any of the dwell phases shown in FIG. 2. It is also conceivable to repeatedly perform the method 300 to calculate IPV1 after more than one dwell phase, for example, after every n dwell phases (for example, n=1, 2 or 3). Such repeated execution of the method 300 may further improve the accuracy of IPV1. For example, the repeated execution may reduce the effect of measurement uncertainty of the CRP values ​​C1 and C3, as well as the effect of inappropriate mixing of F1′ and F2 on the accuracy of the CRP value C3.

[0058] It should also be noted that step 302 does not have to be performed after the completion of a normal dwell phase during PD treatment. For example, step 302 may be initiated after partial completion of a dwell phase, or the dwell phase may be omitted entirely. Indeed, method 300 may be performed at any time before, during, or after PD therapy. Furthermore, method 300 is not limited to the PD therapy shown in FIG. 2, but may be performed in conjunction with any modality of PD therapy, including, but not limited to, CCPD, IPD, TPD, and CFPD. Once IPV1 is calculated, the IPV may be tracked during subsequent PD treatment (see step 309).

[0059] The results of the method 300 of FIG. 3 can be compared with the prior art described in the Background section, which uses only PD fluid and relies on dilution of the PD fluid by ultrafiltration during the dwell phase. With respect to the dilution formula defined above, the prior art is limited in terms of the maximum achievable difference between C1 and C2, where C1 is the CRP of the used PD fluid and C2 is the CRP of the unused PD fluid. This limits the minimum achievable error of the calculated remaining volume by the prior art. In the only numerical example given in EP 2 623 139, using the measured conductivity values, the ratio C1 / C2 is 0.96, which means that C1 is only 4% smaller than C2. As mentioned in the Background section, this leads to an error of ±98 ml in the estimation of the remaining volume when the remaining volume is 667 ml.

[0060] In general, the use of a dedicated test fluid offers much greater flexibility in setting the difference between C1 and C2 to achieve better accuracy of the calculated value IPV1.

[0061] For comparison, the magnitude of the error in the calculated IPV1 is simulated and the results are shown in FIG. 5. Before discussing FIG. 5, we briefly present the assumptions behind the simulation. We assume that the PD fluid and the test fluid consist of NaCl, KCl, CaCl2, MgCl2, glucose and water. We assume that the fluid volume in the PC at the start of step 302 is 2 liters and the volume of fluid extracted in step 302 (V1) is 1 liter. Thus, IPV1 is nominally assumed to be 1 liter. The volume of test fluid (V2) injected in step 304 is assumed to be 0.5 liters. Furthermore, the fluid extracted in step 302 is assumed to have a NaCl concentration of 110 mmol / l. This concentration is chosen to result in a conductivity (C1) that matches the conductivity of the actual PD fluid after the dwell phase. The concentrations of NaCl and glucose in the test fluid are adjusted to achieve a given conductivity C2 and an osmolality of 300 mOsm / l (see further below). Referring now to FIG. 5, the vertical axis represents the error of IPV1 given as a standard deviation, and the horizontal axis represents the ratio C2 / C1 for C2 / C1<1. The magnitude of the error has been calculated for each ratio by Monte Carlo simulation. This simulation was therefore repeated for different values ​​of C2 to obtain an estimate of the error of IPV1 calculated as a function of the ratio C2 / C1. As shown, the error increases rapidly with increasing ratio C2 / C1. In one example, it may be desirable to limit the error resulting from a ratio C2 / C1 of about 0.8 to ±20 ml, as shown by the dotted line in FIG. 5. It is also noted that a lower limit for C2 / C1 may be given by considering the potential impact on the patient's health, for example, by having too low a concentration of one or more electrolytes and / or by having too high a concentration of glucose. In FIG. 5, such a lower limit is shown for a ratio C2 / C1 of about 0.25. Thus, the operating region ΔR of C2 / C1 is about 0.25-0.8, which corresponds to C2 being about 20%-75% smaller than C1, as shown in Figure 5. Note that corresponding results can be achieved by setting C2 larger than C1, i.e., C2 / C1>1.Simulations show that the curves in Figure 5 are effectively mirrored for C2 / C1 = 1. Thus, the operating range of C2 / C1 is about 1.2-1.75, which corresponds to a C2 that is about 20%-75% larger than C1. One advantage of setting C2 smaller than C1 is that the test fluid is less costly in terms of raw materials. Although the simulations have been performed for specific test fluids and specific fluid volumes, the results are believed to be generally applicable.

[0062] Based on the above discussion, it is understood that the method 300 can be implemented with a suitable composition of the test fluid to achieve a difference between C2 and C1 that exceeds a threshold value set to achieve a predetermined accuracy of IPV1 determined by step 307. The difference may be given as a relative or absolute value. The predetermined accuracy in terms of standard deviation may be, for example, ±50 ml, ±40 ml, ±30 ml or ±20 ml. As mentioned above, based on FIG. 5, to achieve a predetermined accuracy of at least ±20 ml, the threshold value may be set to correspond to C2 / C1=0.8 or less. This can be compared to C1 / C2=0.96 achieved by the prior art according to the numerical example of EP 2 623 139 A1.

[0063] Returning to stage IV of Figure 4, it may be desirable to limit the period during which test fluid F2 is present in the PC, thereby limiting solute and / or water exchange across the peritoneum that may be driven by the test fluid. However, a certain amount of time may be required to ensure sufficient mixing between the modified first fluid F1' and test fluid F2 in the PC from stage IV to stage V of Figure 4. If necessary, the dilution formula may be altered to compensate for solute and / or water exchange caused by the test fluid.

[0064] Returning to step 304 of FIG. 3, the test fluid can either be pre-manufactured (step 304A) or generated on demand (step 304B). If pre-manufactured, the test fluid can be a so-called ready-made fluid that can be delivered to the point of care in a pre-filled bag. It is conceivable that the test fluid is available in different compositions, each with a different C2, and step 304A is configured to select one of the available compositions based on the C1 provided by step 303 to achieve a suitable difference between C1 and C2. If generated on demand, the test fluid can be given any selected value of C2. Again, the selected value of C2 can be set taking into account C1 to achieve a difference between C1 and C2 that results in an acceptable accuracy of IPV1. On-demand generation can include mixing one or more concentrates with water and / or mixing one or more ready-made fluids.

[0065] Alternatively, a test fluid is provided that is taken independently of C1, as measured in step 303, but has a C2 that is sufficiently different from C1 for all realistic values ​​of C1.

[0066] In some embodiments, the test fluid may have different compositions for different patients, for example, based on the transport properties of the patient's peritoneal membrane. Such transport properties may be determined by a conventional peritoneal equilibrium test (PET). For example, as known in the art, the peritoneum may be classified into one of several transport types depending on its transport properties. Method 300 may be implemented to use different test fluids for different transport types. Alternatively or additionally, method 300 may use different test fluids for different modalities of PD therapy. Different test fluids need not only differ in C2, but may also differ by osmolality (below).

[0067] As mentioned above, the test fluid (second fluid) differs in composition from the PD fluid (first fluid). In some embodiments, this is implemented as a difference in concentration of at least one solute that may be present in both the PD fluid and the test fluid and that affects the CRP. In some embodiments, the at least one solute includes sodium (Na). Such an embodiment may be relevant when the CRP is the conductivity (or equivalently the resistivity) since sodium has a profound effect on the conductivity. Alternatively or additionally, the at least one solute may include an osmotic agent, for example glucose. Such an embodiment may be relevant when the CRP is the concentration of the osmotic agent. For example, concentration sensors for glucose are commercially available at low cost. Alternatively or additionally, the at least one solute may include at least one of magnesium, calcium or lactate.

[0068] In some embodiments, the solutes in the test fluid F2 are the same as the solutes in the PD fluid F1. Such embodiments may be particularly advantageous when the test fluid is generated on demand. For example, the test fluid may be generated as a diluted version of the PD fluid by diluting a pre-manufactured PD fluid with purified water or by mixing one or more concentrates with water. Thus, in the latter example, the same concentrates may be used to generate both the PD fluid and the test fluid.

[0069] In some embodiments, the test fluid F2 is produced on demand by mixing two or more concentrates with water, and the value of C2 of the test fluid is adjusted by changing the amount of at least one of the concentrates. When the PD fluid F1 is produced on demand by mixing at least one concentrate with water, it is conceivable that both the PD fluid and the test fluid are produced by the use of at least one common concentrate.

[0070] In some embodiments, the test fluid F2 is generated on demand by mixing two or more concentrates with water, only one of which contains an osmotic agent, so that the osmolality of the test fluid can be adjusted without being significantly affected by the conductivity.

[0071] In some embodiments, the test fluid F2 has an osmolality to minimize the transfer of solvent through the peritoneal membrane in the PC. As used herein, the term "osmolality" is synonymous with osmolality and is a measure of solute concentration defined as the number of osmoles (Osm) of solute per unit volume of solution. An osmole is the number of moles of solute that contribute to the osmotic pressure of a solution. At a simpler level, osmolality can be seen as the sum of all components in a solution that can drive osmosis. To minimize or effectively eliminate the transfer of solutes through the peritoneal membrane between the fluid and blood in the PC, the fluid should have an osmolality similar to that of plasma, typically in the range of 250-350 mOsm / l, for example, in the range of 280-320 mOsm / l. The osmolality of the test fluid F2 may be set to minimize solute transfer to the test fluid F2 itself or to the mixture F3 produced when the test fluid F2 is mixed with the modified first fluid F1' (see stages IV and V of FIG. 4). Note that the spent PD fluid has typically consumed its ability to drive osmosis across the peritoneal membrane, thus preventing the transfer of solvents through the peritoneal membrane. Thus, when the modified first fluid F1' is produced by a dwell phase and thus corresponds to a spent PD fluid, the transfer of solids can be minimized or effectively eliminated by setting the osmolality of the test fluid F2 similar to that of plasma.

[0072] One reason for setting the osmolality of test fluid F2 is to reduce ultrafiltration through the peritoneal membrane, as ultrafiltration can compromise the accuracy of the calculated IPV1. This is in stark contrast to the prior art, where PD fluid is injected to mix with the used PD fluid inside the PC, as PD fluids are by definition designed to facilitate fluid transfer across the peritoneal membrane.

[0073] Returning to the method 300 of FIG. 3, the first volume V1 and the second volume V2 may be set to improve accuracy, shorten the duration of the method 300, or reduce the risk to the patient. If step 302 is performed after a dwell phase and the PC is filled with used PD fluid (see stage II of FIG. 4), the first volume V1 needs to be large enough to make space for the injection of the second volume V2 of the test fluid F2 into the PC. If V1 is small, V2 also needs to be small. Thereby, C1 of the corrected first fluid F1' may be similar to C3 of the obtained mixture F3, making the decision in step 307 very sensitive to measurement errors in C1 and C3. Furthermore, if C1 is measured by pumping the extracted fluid through a sensor, V1 may need to be large enough to provide a reliable measurement. If V1 is too large and leaves only a small amount of residual fluid IPV1 in the PC, the impact of the measurement error may still be significant. The second volume V2 must be large enough to provide a sufficient difference between C1 and C3. At the same time, a larger V2 increases the duration of the method 300 since V2 must both be pumped into and pumped out of the PC. A larger V2 also increases the time the patient is exposed to the test fluid.

[0074] In some embodiments, V1 is about 25%-95%, or about 70%-90%, of the total amount of fluid present in the PC when step 302 is initiated, and V2 is about 25%-100%, or perhaps about 40%-60%, of V1. As described above with reference to method 300 of FIG. 3, the dwell phase of step 301B may be a normal dwell phase of an ongoing PD therapy. The extraction of fluid in step 302 may also be performed as part of an ongoing PD therapy, specifically as part of a normal drain phase after a normal dwell phase. The normal drain phase may be interrupted at any selected time point, at which point a test fluid is delivered according to step 304. The normal drain phase is then resumed upon completion of steps 305-306 and optionally step 307. The selected time point may be adjusted such that a desired first amount (V1) is extracted from the PC. It is also contemplated that step 304 is performed when the normal drain phase is completed, assuming that a sufficient amount of fluid remains in the PC at this point.

[0075] In some embodiments, the APD system is configured to provide a first fluid as a treatment fluid in a first fluid exchange cycle and a second fluid as a treatment fluid in a consecutive second fluid exchange cycle. In such an APD system, the method 300 of FIG. 3 may be performed without further modification of the PD session. Steps 301A, 301B, 302 may correspond to the fill phase, the dwell phase, and the drain phase, respectively, of the first cycle. Step 303 may be performed during the drain phase of the first cycle. Steps 304, 305 may correspond to the fill phase and the drain phase, respectively, of the second cycle, and step 306 may be performed during the drain phase of the second cycle. Thus, by appropriately timing the measurement of the CRP value during the normal phase of such a PD session, the IPV1 may be determined according to step 307.

[0076] Although the method 300 may be implemented on any type of PD system, it will be described with reference to the examples provided in Figures 6-7. Figure 6 illustrates a fluid system 10' that may be part of the PD system 10 of Figure 1, and Figure 7 illustrates generally an apparatus for control of the PD system 10 of Figure 1. It should be emphasized that Figures 6-7 are provided only as non-limiting examples, and that many variations are possible without departing from the principles of the techniques described herein.

[0077] The fluid system 10' of FIG. 6 includes a water preparation device WPD 16 configured to supply purified water to the fluid supply FSA 12. The WPD 16 includes an inlet tube 4A having a terminal connector 4' for connection to a tap water source (not shown). The tap water source may be a permanent outlet (tap, faucet, tap, etc.) or a tank, and is refilled with tap water manually or automatically as needed. The purification unit 4 is configured to receive and process the tap water to be purified. As used herein, "purification" refers to the process of substantially removing undesirable chemicals, biological contaminants, suspended solids, and gases from water for the purpose of providing water having an acceptable purity for use in PD fluids. Purification may or may not involve sterilization. A number of purification technologies are readily available for use in the purification unit 4. The purified water is supplied to the FSA 12 on fluid line 2C ("water line"). In the illustrated example, the WPD 16 is further connected to receive outlet fluid from the FSA 12 on fluid line 2E ("outlet line"). Depending on the operational phase and implementation of the fluid system 10', the outlet fluid may be any of the fluids mentioned above, such as the first fluid (PD fluid) F1, the modified first fluid F1', the test fluid F2, or the mixture F3. The WPD 16 comprises an outlet tube 4B for directing the outlet fluid to a drain 8 as shown, or to a container. The WPD 16 is provided with a sensor device 13 for measuring the CRP of the outlet fluid.

[0078] In the illustrated example, the FSA 12 is configured to generate PD fluids and test fluids by mixing one or more concentrates with purified water. In FIG. 6, the FSA 12 comprises two containers 1A, 1B for holding the respective concentrates. Here, it is assumed that the respective concentrates are liquids, but it is equally possible to use concentrates in the form of powders that are dissolved in purified water by the FSA 12. The containers 1A, 1B are connected to a valve device 3 by respective fluid lines 2A, 2B. The valve device 3 is operable to selectively establish fluid communication between different fluid lines in the FSA 12 based on one or more control signals from the controller 11 (FIG. 1). The valve device 3 may comprise any number and type of controllable valves. The valve device 3 is also fluidly connected to a water line 2C and an outlet line 2E. The valve device 3 is further fluidly connected to a supply line 2D and a supply line 2F, as well as a fluid connection device 15 that extends to a terminal connector 15' for connection to the implanted catheter described above. The supply line 2D comprises a mixing section 5 and a flow meter 7A. The mixing section 5 is configured to ensure mixing of the concentrate with the purified water and may also be configured to perform further conditioning of the produced fluid, for example temperature regulation and degassing. The supply line 2F connects to the outlet line 2E at a branch point, and a flow meter 7B is arranged in the outlet line 2E between the branch point and the WPD 16. The FSA 12 further comprises a pumping device 6 configured to control the flow of the fluid through the FSA 12, for example when producing and supplying the fluid to the PC and when extracting the fluid from the PC. In the illustrated example, the pumping device 6 comprises three pumps 6A, 6B, 6C. The pumps 6A, 6B are arranged in the supply line 2D upstream and downstream of the mixing section 5, and the pump 6C is arranged in the supply line 2F.

[0079] The FSA 12 may be configured to produce the PD fluid and the test fluid either batchwise or in-line. In batch production, the mixing section 5 is configured to produce the PD fluid and the test fluid in batches and store them in a reservoir (not shown), from which the respective fluids are supplied by the pump 6B along the fluid line 2D as needed. The batch production may be performed, for example, by operating the valve device 3 to fluidly connect the fluid lines 2A, 2B, 2C in sequence to the fluid line 2D, and by operating the pump 6A to meter the purified water and the concentrate into the mixing section 5 according to a proportional scheme for the PD fluid and the test fluid, respectively. In in-line production, the mixing section 5 is configured to produce the PD fluid and the test fluid on demand and without intermediate storage. In-line production may be performed similarly to the batch production, except that the concentrate and the purified water are metered simultaneously into the mixing section 5 to form the PD fluid or the test fluid. Those skilled in the art will appreciate that additional devices may be required in the FSA 12 to ensure proper distribution of the concentrate and the purified water. Furthermore, for in-line generation, pump 6B may be omitted since the flow of PD fluid or test fluid may be driven through mixing section 5 by pump 6A.

[0080] The fluidic system 10' of FIG. 6 is selectively operable in a first supply phase in which PD fluid is pumped through the fluidic connection device 15 into the PC, and a second supply phase in which test fluid is pumped through the fluidic connection device 15 into the PC. The fluidic system 10' of FIG. 6 is further selectively operable in an extraction phase in which fluid is pumped from the PC through the connection device 15 to the drain 8. The extraction phase may also include measuring CRP by the sensor device 13. The fluidic system 10' may also be operable in a measurement phase in which test fluid is pumped through the sensor device 13 to the drain 8. Those skilled in the art will appreciate that the flow of fluid through the fluidic system 10' in the different phases is controlled by a control device 11 (FIG. 1) that provides dedicated control signals to the valve device 3 and the pump device 6.

[0081] Referring to FIG. 7, the PD system 10 may be operated by a controller 11 comprising a control unit 11A and a calculation unit 11B. The control unit 11A is configured to control the operation of a fluid system 10′, here represented by an FSA 12. The control unit 11A is configured to generate dedicated control signals CS for components in the FSA 12, such as the valve device 3 and the pump device 6 (FIG. 6). As shown, the control unit 11A may generate the CS based on a setting SS and feedback data FD. The setting SS may be retrieved from an internal memory of the FD system 10 and / or may be input by a user via the UI 14 (FIG. 1). The feedback data FD is implementation specific and will not be described in detail herein. In the specific example of FIG. 6, the feedback data FD may include data generated by the flow meters 7A, 7B.

[0082] The calculation unit 11B is configured to determine the IPV at one or more time points during PD therapy. As shown, the calculation unit 11B is connected to receive first sensor data S1 from the sensor device 13 and second sensor data S2 from the FSA 12. The first sensor data S1 includes the CRP value, and the second sensor data S2 represents the amount of test fluid (V2) delivered by the FSA 12 to the PC. In the example of FIG. 6, the second sensor data S2 may be generated by the flow meter 7A. In a variant, if the pump 6A (in-line production) or the pump 6B (batch production) is a volumetric pump with a known stroke volume, the second sensor data S2 may indicate the number of pump strokes performed by the pumps 6A, 6B when pumping the test fluid to the PC, thereby enabling a volumetric calculation of the pumped amount of test fluid ("volumetric pumping"). As indicated by the double-ended arrows, the control unit 11A and the calculation unit 11B may exchange data. For example, the computing unit 11B may obtain timing information from the control unit 11A regarding different operation phases of the FD system 10, enabling the computing unit 11B to obtain measurements from the sensor data S1, S2 in a timely manner. As another example, the control unit 11A may request the computing unit 11B to calculate an IPV at a particular time point and adjust its operation based on the calculated IPV.

[0083] The control unit 11A and the computation unit 11B need not be implemented as separate entities as shown, but may instead be combined into a single unit within the control arrangement 11.

[0084] In general, the control device 11 may be implemented by hardware or a combination of software and hardware. In some embodiments, the hardware comprises one or more software-controlled computer resources. For example, as shown in FIG. 8, the control device 11 may comprise one or more processors 111, memory 112, and an interface or circuit 113 for input and output of data. The interface 113 may be configured for wired and / or wireless communication. The memory 112 may include one or more computer-readable storage media, such as a high-speed random access memory, and / or a non-volatile memory, such as one or more magnetic disk storage devices, flash memory devices or other non-volatile solid-state memory devices. The processor 111 may include, for example, one or more of a CPU ("Central Processing Unit"), a DSP ("Digital Signal Processor"), a GPU ("Graphics Processing Unit"), a microprocessor, a microcontroller, an ASIC ("Application Specific Integrated Circuit"), a combination of discrete analog and / or digital components, or some other programmable logic device, such as an FPGA ("Field Programmable Gate Array"). A control program 121 comprising computer instructions may be stored in computer memory 112 and executed by processor 111 to implement logic to perform any of the methods, procedures, functions or steps described herein. The control program 121 may be provided to controller 11 on a computer readable medium 122, which may be a tangible (non-transitory) product (e.g., magnetic medium, optical disk, read-only memory, flash memory, etc.) or a propagated signal.

[0085] The method 300 may be performed by the control device 11 of FIG. 7. Specifically, steps 301A, 301B, 302-306 and 308 may be performed by the control unit 11A, and steps 307 and 309 may be performed by the computing unit 11B. In step 301A, the fluidic system 10' operates in a first supply phase, supplying PD fluid from the mixing section 5 along the fluid line 2D and the fluidic connection device 15' to the PC. The amount of PD fluid injected in step 301A may be monitored by use of a flow meter 7A, volumetric pumping, etc. In optional step 301B, the fluidic system 10' operates to perform a residence phase. In step 302, the fluidic system 10' operates in an extraction phase, discharging a first amount (V1) of fluid from the PC to the drain 8 via the fluidic connection device 15', the supply line 2F and the discharge line 2E. Thereby, the extracted fluid passes through the sensor device 13 which operates to measure C1 (step 303). The amount of extracted fluid in step 302 may be monitored by use of flowmeter 7B, by volumetric pumping, etc. In step 304B, the fluidic system 10' operates in a second supply phase and supplies a second amount (V2) of test fluid from the mixing section 5 along the fluid line 2D and the fluid connection device 15' to the PC. The amount of injected test fluid in step 304B may be monitored by use of flowmeter 7A, by volumetric pumping, etc. Optionally, before step 304B, the fluidic system 10' may operate in a measurement phase and pump the test fluid from the mixing section 5 along the fluid line 2D and the outlet line 2E, while the sensor device operates to measure C2. In step 305, the fluid system 10' operates in an extraction phase and extracts a third amount (V3) of fluid from the PC to the drain 8 via the fluid connection device 15', the supply line 2F and the exhaust line 2E. The extracted fluid thereby passes through the sensor arrangement 13 which operates to measure C3 (step 306). The amount of extracted fluid in step 303 may be monitored by use of a flow meter 7B, by volumetric pumping, etc.In step 307, IPV1 is calculated based on V2, C1, C2 and C3. Once extraction of V3 is completed, either deterministically or dynamically, according to step 308, the fluidic system 10' may be operable to perform a filling phase, as shown in stage VIII of Figure 4, by supplying PD fluid from the mixing section 5 along the fluid line 2D and the fluidic connection device 15' to the PC.

[0086] It should be understood that the fluid system 10' may comprise any number of different concentrates that are mixed to generate the PD fluid and / or test fluid. Other variations for generating the PD fluid and / or test fluid have been described above and will not be repeated. To perform step 304A, the fluid system 10' is reconfigured to supply the test fluid as a pre-made fluid, which may be held in any of the containers 1A, 1B of FIG. 6. In fact, both the PD fluid and the test fluid may be supplied as a pre-made fluid. If the fluid system 10' is configured to use only pre-made fluids, the WPD 16 is omitted.

[0087] The sensor device 13 need not be located within the WPD 16, but may instead be adjacent to a portion of the FSA 12, such as the flow meter 7B. In another example, the sensor device 13 includes sensor units distributed within the FSA 12. For example, the sensor device 13 may include one sensor unit in the fluid line 2D downstream of the mixing section 5 to measure C2, and one sensor unit in the feed line 2F to measure C1 and C3. However, it may be desirable to use one and the same sensor unit within the sensor device 13 to measure C1 and C3, as well as C2, if measured. This may improve accuracy by eliminating systematic errors and / or reduce the need for calibration of separate sensor units.

[0088] While the subject matter of this disclosure has been described in connection with what are presently considered to be the most practical embodiments, it is to be understood that the subject matter of this disclosure is not to be limited to the disclosed embodiments, but on the contrary, is intended to cover various modifications and equivalent arrangements that come within the meaning and equivalents of the appended claims.

[0089] Additionally, although acts are shown in the figures in a particular order, this should not be construed as requiring that such acts be performed in the particular order shown, or in sequential order, or that all of the shown acts be performed, to achieve desirable results.

Claims

1. 1. A system for peritoneal dialysis, the system comprising: a fluid delivery device (12) operable to deliver fluid to and from the peritoneal cavity; a sensor device (13) operable to measure a concentration-related parameter; a control device (11) connected to the fluid supply device (12) and the sensor device (13), operating the fluid supply device (12) to supply a first fluid (F1) to the peritoneal cavity; operating the fluid delivery device (12) to extract a first volume of fluid from the peritoneal cavity after delivering the first fluid (F1), leaving an intraperitoneal volume of fluid within the peritoneal cavity; obtaining a first value (C1) of a concentration-related parameter of the extracted first quantity of fluid from the sensor device (13); operating the fluid supply device (12) to supply a second volume (V2) of a second fluid (F2) to the peritoneal cavity, the second fluid (F2) having a second value (C2) of the concentration-related parameter and forming a mixture (F3) with the intraperitoneal volume of fluid in the peritoneal cavity; operating the fluid supply device (12) to extract a third amount of the mixture (F3) from the peritoneal cavity; obtaining a third value (C3) of the concentration-related parameter of the extracted mixture (F3) from the sensor device (13); a control device (11) configured to determine the intraperitoneal volume based on the second volume (V2) and the first, second and third values ​​(C1, C2, C3); The control device (11) is configured to operate the fluid supply device (12) such that the first fluid and the second fluid (F1, F2) differ in composition.

2. The system of claim 1, which operates to achieve a difference between the second value (C2) and the first value (C1) that exceeds a threshold value set to achieve a predetermined accuracy of the intraperitoneal volume determined based on the second volume (V2) and the first value, the second value, and the third value (C1, C2, C3).

3. 3. The system of claim 2, wherein the threshold is set to correspond to the second value being approximately 20% to 75% greater than the first value (C1) or approximately 20% to 75% less than the first value (C1).

4. 4. The system of claim 2 or 3, wherein the fluid supply device (12) is operable to generate the second fluid (F2) on demand, and the control device (11) is configured to operate the fluid supply device (12) to generate the second fluid (F2) based on the first value (C1) to achieve the difference between the second value (C2) and the first value (C1).

5. 4. The system of claim 1, wherein the first fluid (F1) is a treatment fluid used in peritoneal dialysis therapy and the second fluid (F2) is a dedicated test fluid for use in determining the intraperitoneal volume.

6. 4. The system of claim 1, wherein the second fluid (F2) and the first fluid (F1) differ in the concentration of at least one solute that affects the concentration-related parameter.

7. 4. The system of claim 1, wherein the solutes in the second fluid (F2) are the same as the solutes in the first fluid (F1).

8. 4. The system according to any one of claims 1 to 3, wherein the second fluid (F2) has a different concentration of at least sodium compared to the first fluid (F1).

9. 4. The system according to any one of claims 1 to 3, wherein the second fluid (F2) has a different concentration of an osmotic agent compared to the first fluid (F1).

10. 4. The system of claim 1, wherein the second fluid (F2) has an osmolarity to minimize solvent transfer across the peritoneal membrane in the peritoneal cavity.

11. 4. The system according to claim 1, wherein the second fluid (F2) has an osmolality of 250 to 350 mOsm / l.

12. 4. The system according to claim 1, wherein the second value (C2) is smaller than the first value (C1).

13. 4. The system of claim 1, wherein the control device (11) is configured to execute a sequence of fluid exchange cycles each including a fill phase, a dwell phase, and a drain phase, the sequence of fluid exchange cycles including a fluid exchange cycle in which the fluid supply device (12) operates to supply the first fluid (F1) to the peritoneal cavity in the fill phase and to extract the first amount of fluid in the drain phase, and successive fluid exchange cycles in which the fluid supply device (12) operates to supply the second amount (V2) of the second fluid (F2) to the peritoneal cavity in the fill phase and to extract the third amount of the mixture during the drain phase, and the control device (11) is configured to acquire the first value (C1) during the drain phase of a first cycle and the third value (C3) during the drain phase of a second cycle.

14. 4. The system of claim 1, wherein the control device (11) is configured to operate the fluid supply device (12) so that the first amount (V1) is between 25% and 95% of the estimated total amount of fluid present in the peritoneal cavity.

15. 4. The system according to claim 1, wherein the control device (11) is configured to operate the fluid supply device (12) so that the second quantity (V2) is between 25% and 100% of the first quantity (V1).

16. 4. The system according to claim 1, wherein the control device (11) is configured to determine the intraperitoneal volume by use of a dilution formula given by IPV1=V2·(C3−C2) / (C1−C3), where V2 is the second volume, C1 is the first value, C2 is the second value and C3 is the third value.

17. The system of any one of claims 1 to 3, wherein the control device (11) is configured to determine the intraperitoneal volume during extraction of the third volume and to terminate extraction of the third volume based on the determined intraperitoneal volume and the second volume (V2).

18. The system of claim 17, wherein the control device (11) is configured to terminate the extraction of the third volume so as to achieve a predetermined difference between the third volume and the sum of the determined intraperitoneal volume and the second volume (V2).

19. 1. A computer-implemented method of operating a system for peritoneal dialysis, the method comprising: delivering (301A) a first fluid to the peritoneal cavity; extracting (302) a first volume of fluid from the peritoneal cavity after delivering the first fluid, leaving an intraperitoneal volume of fluid within the peritoneal cavity; obtaining (303) a first value of a concentration-related parameter of the extracted first quantity of fluid; delivering (304) a second volume of a second fluid to the peritoneal cavity, the second fluid having a second value of the concentration-related parameter and forming a mixture with the intraperitoneal volume of fluid within the peritoneal cavity; extracting (305) a third amount of the mixture from the peritoneal cavity; obtaining (306) a third value of the concentration-related parameter of the extracted mixture; operating the system to determine (307) the intraperitoneal volume based on the second volume and the first, second, and third values; The method, wherein the first fluid and the second fluid are different in composition.

20. 20. A computer readable medium comprising program instructions that, when executed by a processor (111) in a system according to any one of claims 1 to 3, cause the processor (111) to perform the method according to claim 19.

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