Device for extracorporeal treatment of blood and method for calculating a set flow rate in a medical device for extracorporeal treatment of blood

Abstract

CRRT equipment includes a control unit configured to receive a patient prescription including clinical prescribing parameters and to allow input of a specified dialysis dose to be delivered (D). set The settings and indications must be parameters of steady-state acid-base balance in the blood of patients undergoing CRRT blood treatment (nNBL; Cp). HCO3_pat The target value is determined by executing a flow rate setting procedure, which calculates the set value of the relevant fluid flow rate by determining the operating parameters. The relevant fluid flow rate includes the fluid flow rate (Q) through the anticoagulant injection line. cit ), fluid velocity (Q) through the PBP injection line PBP ), fluid flow rate (Q) through the pre-dilution infusion line rep.pre ), fluid flow rate (Q) through the post-dilution infusion pipeline rep.post ), the fluid flow rate (Q) through the post-diluted bicarbonate injection pipeline HCO3 ), fluid flow rate (Q) through the ion balance infusion line ca ), the blood flow velocity through the extracorporeal blood circuit (Q) b ), the fluid flow rate (Q) through the dialysate supply line dial ) and the fluid velocity (Q) through the outflow pipeline. eff One or more of the following, wherein the setpoint for calculating the fluid flow rate is based at least on the specified dialysis dose (D). set The set values ​​and parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp) HCO3_pat The target value.

Description

Technical Field

[0001] This invention relates to a medical device for extracorporeal blood processing. The invention also relates to a method for calculating and setting a flow rate in a medical device for extracorporeal fluid processing.

[0002] More specifically, the present invention applies to continuous renal replacement therapy (CRRT) with or without anticoagulation (e.g., CRRT with or without systemic anticoagulation (e.g., heparin) / with or without local anticoagulation (e.g., citrate)). In particular, the present invention can be advantageously used for administering local citrate anticoagulation (RCA) during continuous renal replacement therapy (CRRT). Background Technology

[0003] The kidneys perform a variety of functions, including removing water, excreting catabolism products (or metabolic waste products such as urea and creatinine), regulating the concentration of electrolytes in the blood (such as sodium, potassium, magnesium, calcium, bicarbonate, phosphate, and chloride), and regulating the body's acid-base balance, specifically by removing weak acids and producing ammonium salts. In individuals who (temporarily or permanently) lose kidney function, the body accumulates metabolically generated water and waste products and exhibits electrolyte excess, often resulting in acidosis, where the plasma pH shifts downward to below 7.35 (blood pH typically varies within a narrow range of 7.35 to 7.45). As mentioned above, to overcome renal insufficiency, traditionally, extracorporeal blood therapy is used, involving circulation through an exchanger with a semipermeable membrane (dialyzer). In this method, the patient's blood circulates on one side of the membrane, while dialysate, containing the blood's major electrolytes, circulates on the other side at concentrations close to those found in the blood of healthy subjects. Furthermore, a pressure difference is created between the two compartments of the dialyzer, defined by a semipermeable membrane, causing a portion of the plasma fluid to pass through the membrane via ultrafiltration and enter the compartment containing dialysate. The blood treatment of metabolic waste and electrolytes performed in the dialyzer is generated by two molecular transport mechanisms across the membrane. On one hand, molecules migrate from a liquid with a higher concentration to a liquid with a lower concentration. This is diffusion transport. On the other hand, certain catabolic products and certain electrolytes are entrained by the plasma fluid, which is filtered through the membrane under the pressure difference created between the two compartments of the exchanger. This is convective transport. Three of the aforementioned renal functions—removal of water, excretion of catabolic products, and regulation of blood electrolyte concentration—are therefore performed in conventional blood treatment devices through a combination of dialysis and hemofiltration (this combination is called hemodialysis). To perform one or more of the above treatments, extracorporeal blood treatment devices may include multiple lines for delivering fluid directly to the patient or to an extracorporeal blood circuit.

[0004] When setting up the machine, the operator typically applies the blood pump flow rate, the individual flow rate for each infusion line, and the flow rates for the dialysis and outflow lines (the latter can actually be calculated based on the set patient fluid removal rate). The flow rate setpoint for each line controls the corresponding pump: in other words, multiple pumps are used, each drawing fluid from or supplying fluid to its corresponding fluid container according to the set flow rate value for that line. Therefore, machine setup is cumbersome because it requires the operator to define and input a relatively large number of flow rates. Furthermore, the independent setting of each flow rate does not provide the operator with intuitive information regarding medically relevant prescribing parameters. Finally, the need to independently set multiple parameters can be a source of error and does not allow for optimization of fluid consumption.

[0005] WO 2013 / 030642 relates to blood processing equipment and methods for setting up medical devices for delivering or collecting fluids, wherein a control unit is configured to calculate setpoints for two or more fluid flow rates based on fluid flow rates and prescribed dose values ​​set by an operator. However, WO 2013 / 030642 does not focus on acid-base balance management and does not specifically address the acid-base balance problem in local anticoagulation in the context of CRRT.

[0006] Regarding the regulation of acid / base balance in the body, the method used to overcome kidney deficiency involves acting on the mechanisms that regulate acid / base balance. This mechanism consists of the blood's buffering system, one of the main components of which involves the combination of carbonic acid, a weak acid, with its alkali metal salt, bicarbonate. This is why, to correct acidosis in patients with renal insufficiency, bicarbonate is administered directly or indirectly via the vascular route during hemodialysis. In the field of kidney treatment, continuous renal replacement therapy (CRRT) has been widely used in critically ill patients with acute kidney injury, and extracorporeal blood anticoagulation is essential for maintaining circuit patency. In recent decades, different anticoagulation strategies have been adopted clinically, with heparin being the most commonly used anticoagulant. While heparin has advantages such as low cost, ease of monitoring, and simple reversal, it may also increase bleeding. In addition, there is the risk of heparin-induced type II thrombocytopenia, which can lead to life-threatening complications. Local citrate anticoagulation (RCA), first introduced into clinical use in the early 1980s, has been recommended as the most suitable form of local circuit anticoagulation in CRRT and has even been safely used in patients with severe hepatic impairment. However, citrate infusion in critically ill patients can affect multiple metabolic systems, potentially leading to metabolic alkalosis, hypocalcemia, and citrate overload / toxicity. These potential interferences can be partially mitigated through careful monitoring, adherence to treatment protocols, and supervision by trained personnel in clinical practice. Despite these critical factors, citrate anticoagulation therapy has become the preferred anticoagulation method for continuous renal replacement therapy (CRRT) because it minimizes the risk of bleeding (local anticoagulation effect) and prolongs the lifespan of the extracorporeal circulation circuit. While RCA has some limitations in terms of compatibility with "high" flow rates, this is not an issue in CRRT, as the efficiency of CRRT is primarily driven by the rate of fluid exchange, and the vast majority of treatments are delivered at flow rates below 200 ml / min. Rapid metabolism of infused citrate is one of the key mechanisms for the success of RCA. Citrate metabolism produces energy, as well as bicarbonate and CO2, while releasing complex calcium. Infusion of large amounts of citrate into patients can lead to significant bicarbonate production, potentially resulting in metabolic alkalosis. Citrate accumulation is consistent with a significant increase in systemic citrate concentration. It can occur in two scenarios: a combination of "normal" citrate load and poor citrate metabolism, and a combination of "normal" citrate metabolism and a large citrate load. The first scenario may lead to metabolic acidosis because the rate of citrate to bicarbonate conversion is low. This application considers and addresses the second scenario, particularly in CRRT treatment within the context of RCA. The consequence of citrate accumulation is the need to increase total calcium concentration to maintain (systemic) ionized calcium within physiological ranges. This can be achieved by increasing the calcium infusion rate. This problem is transient during the initial treatment period, as a safe steady state is reached after systemic citrate concentrations stabilize (6–8 hours).However, discontinuation of treatment may lead to hypercalcemia (because citrate is metabolized, releasing bound calcium). In a clinical setting, citrate accumulation is diagnosed by monitoring the ratio of total calcium to ionized systemic calcium (a ratio >2.5 indicates possible citrate accumulation). Furthermore, once citrate enters the systemic circulation, it is metabolized to bicarbonate in a 1:3 ratio; therefore, 1 mmol (millimole) of citrate produces 3 mmol of bicarbonate. Under high citrate load, large amounts of bicarbonate are produced, and there is a risk of metabolic alkalosis. Therefore, although local anticoagulation can significantly reduce the adverse effects of heparin, RCA requires appropriate monitoring of the patient's blood acid-base balance to avoid the risk of severe alkalosis.

[0007] EP0678301 relates to an artificial kidney for intensive care, particularly suitable for treating patients with temporary kidney failure following accidents or surgery. As explained in prior art documents, the kidneys play a crucial role in maintaining the acid-base balance of the blood, in addition to purifying plasma waste (e.g., urea) and removing excess water. A major problem with EP0678301 is that the final concentration of bicarbonate in the blood rarely corresponds precisely to the desired concentration, as the final concentration depends on the concentration of bicarbonate in the perfusion or dialysate, their respective flow rates, and the flow rate of the patient's blood through the membrane exchanger. EP0678301 describes a blood processing device comprising a dialyzer with two chambers separated by a membrane. A dialysate container (which does not contain any bicarbonate) is connected to a fluid pump via a conduit extending to the second chamber of the dialyzer. Electromagnetic clamps are provided for connecting the container to the dialyzer or blood circuit. A bubble trap is provided in the return line of the blood circuit. The bubble trap is connected to an infusion container containing a bicarbonate solution. According to EP0678301, regardless of the type of treatment delivered to the patient, the flow rate Q of the circulation pump... HCO3 All were controlled to the flow rate Q of the dialysis fluid pump. OUT The function is expressed by the following equation:

[0008] Q HCO3 =Q OUT *[HCO3] DES / [HCO3] SOL

[0009] Or through the following equation:

[0010] Q HCO3 =Cl*[HCO3] DES / [HCO3] SOL

[0011] in:

[0012] Q HCO3 The flow rate of the circulating pump;

[0013] Q OUT The flow rate Q of the dialysate pump OUT ;

[0014] [HCO3] DES It is the expected concentration of bicarbonate in the patient's blood;

[0015] [HCO3] SOL It refers to the concentration of the solution in the container;

[0016] Cl represents the removal of bicarbonate by the dialyzer.

[0017] It is worth noting that this prior art aims to properly regulate the patient's blood acid-base balance by using specific controls for post-infusion of bicarbonate solution based on the clearance / dialysis fluid flow rate, which is only effective in the following dialysis machine configurations: HF with post-dilution and HD(F) with post-dilution. Therefore, the problem of proper acid-base management in configurations involving pre-infusion of citrate (e.g., local anticoagulation systems) and / or pre-infusion of bicarbonate-containing solutions remains unresolved.

[0018] Regarding adaptation to specific patient conditions, protocols may (but have not yet been systematically developed) include guidelines for adjusting citrate infusions or dialysis fluid / displacement rates in cases where patient monitoring data indicate alkalosis or acidosis. When present, these guidelines appear to be primarily empirical. In cases of acidosis, some literature reports on the infusion of bicarbonate “dosages.” Although some published protocols are derived from upstream modeling, none clearly provide parameters representing the expected buffer balance for treatment, regardless of what “original” protocol parameters were used or after further adjustments to patient monitoring data. To date, the prediction and control of acid-base balance during CRRT, particularly with the use of local citrate anticoagulation (RCA), remains a challenge, especially when unproven prescriptions are intended. Summary of the Invention

[0019] In this context, the overall objective of this embodiment is to provide a technical solution that can overcome one or more of the aforementioned disadvantages.

[0020] More specifically, the objective of this embodiment is to provide a CRRT medical device for extracorporeal blood processing and a method configured to provide adjunctive prescriptions, while taking into account appropriate acid-base blood balance, particularly in the case of local anticoagulation. Specifically, the aim of this embodiment is to allow acid balance control / management, wherein the system is also designed to alter the buffer balance of the extracorporeal blood circuit in an easy, safe, and controllable manner.

[0021] One object of the present invention is to provide an apparatus and method that allows for the proper calculation of a set flow rate while taking into account appropriate buffer balance, and is able to minimize the actions required to set up the apparatus.

[0022] Another objective of various aspects of this invention is to define devices and methods that allow operators to set up CRRT blood processing equipment using medically meaningful parameters, which can result in a more user-friendly interface. In particular, an object of this invention is to provide supplementary prescriptions where the prescription includes parameters specifying a target for steady-state acid-base balance, parameters that are particularly important in the case of citrate anticoagulation.

[0023] An auxiliary objective of the present invention is to provide a medical device for fluid processing and a method for calculating a set flow rate in the device, which can help set the flow rate before and during processing and optimize fluid consumption relative to prescription goals and system constraints.

[0024] Another auxiliary objective is a device that can control operating parameters in a safe manner.

[0025] The apparatus according to one or more of the appended apparatus claims substantially achieves at least one of the above objectives. The method according to any one of the appended method claims also substantially achieves one or more of the above objectives.

[0026] The apparatus and methods according to various aspects of the present invention are described below.

[0027] The first independent aspect relates to a continuous renal replacement therapy (CRRT) device, comprising:

[0028] The filtration unit (2) has a main chamber (3) and a secondary chamber (4) separated by a semi-permeable membrane (5);

[0029] An extracorporeal blood circuit (17) has a blood extraction line (6) connected to the inlet of the main chamber (3) and a blood return line (7) connected to the outlet of the main chamber (3). The extracorporeal blood circuit (17) is configured to connect to the patient's cardiovascular system.

[0030] A blood pump (21) is configured to control the flow of blood through the external blood circuit (17);

[0031] The outflowing material pipeline (13) is connected to the outlet of the auxiliary chamber (4);

[0032] One or more additional fluid lines, selected from the group consisting of:

[0033] A pre-dilution infusion line (29) is connected at one end to a blood collection line (6).

[0034] The post-dilution infusion line (63) is connected at one end to the blood return line (7).

[0035] The post-diluted bicarbonate infusion line (23) is connected at one end to the blood return line (7).

[0036] An ion-balanced infusion line (74) is connected at one end to a blood return line (7) or to a patient catheter.

[0037] The dialysate supply line (8) is connected at one end to the inlet of the auxiliary chamber (4).

[0038] The pre-blood pump-PBP infusion line (52) is connected at one end to the blood extraction line in the area where the blood extraction line is located upstream of the blood pump (21) during use.

[0039] An anticoagulant infusion line (51) is connected at one end to a blood extraction line in the area of ​​the blood extraction line, which is located upstream of the blood pump (21) during use.

[0040] The syringe fluid line (22) has one end connected to the blood extraction line.

[0041] Actuators are used to regulate the flow of fluids (24, 25, 26, 31, 53, 54, 65, 75) through fluid lines (23, 8, 13, 29, 52, 51, 63, 74);

[0042] Memory (16) stores one or more mathematical relations; and

[0043] A control unit (12), connected to a memory (16) and an actuator, is configured to execute a flow rate setting program, which includes:

[0044] - Receiving patient prescriptions that include clinical prescribing parameters, the receiving steps include:

[0045] ο Allow input parameters (nNBL; Cp) HCO3_pat The target value of the parameter (nNBL; Cp) HCO3_pat This indicates the need for blood transfusions in patients requiring CRRT to maintain stable acid-base balance in their blood.

[0046] - Use one or more mathematical relationships to determine one or more operating parameters. The determination of operating parameters includes calculating setpoints for one or more fluid flow rates selected from a group including:

[0047] • Fluid flow rate (Q) through the anticoagulant injection line (51) cit ),

[0048] • Fluid flow rate (Q) through the PBP injection line (52) PBP ),

[0049] • Fluid flow rate (Q) through the pre-dilution infusion line (29) rep.pre ),

[0050] • Fluid flow rate (Q) through the post-dilution injection line (63) rep.post ),

[0051] • Fluid flow rate (Q) through the post-diluted bicarbonate injection pipeline (23) HCO3 ),

[0052] • Fluid flow rate (Q) through the ion balance delivery line (74) ca ),

[0053] • Blood flow velocity (Q) through the extracorporeal blood circuit (17) b ),

[0054] • Fluid flow rate (Q) through syringe fluid line (22) syr ),

[0055] • Fluid flow rate (Q) through the dialysate supply line (8) dial ),and

[0056] • The fluid velocity (Q) through the outflow pipeline (13) eff ),

[0057] The calculation of one or more fluid flow rate setpoints is based at least on parameters (nNBL; Cp) that indicate the steady-state acid-base balance in the blood. HCO3_pat The target value is as stated in the text.

[0058] In one aspect of the foregoing, receiving a patient prescription includes allowing the input of a prescribed dialysis dose to be delivered (D). set The setting value of the fluid flow rate is determined, and determining one or more operating parameters includes determining at least two operating parameters, wherein determining the operating parameters includes calculating the setting value of at least two fluid flow rates selected in the group, and calculating the setting value of at least two fluid flow rates is based at least on a specified dialysis dose (D). set The set values ​​and parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp) HCO3_pat The target value is as stated in the text.

[0059] Another independent aspect relates to a method of setting up a continuous renal replacement therapy (CRRT) device, the device comprising:

[0060] The filtration unit (2) has a main chamber (3) and a secondary chamber (4) separated by a semi-permeable membrane (5);

[0061] An extracorporeal blood circuit (17) having a blood extraction line (6) connected to the inlet of the main chamber (3) and a blood return line (7) connected to the outlet of the main chamber (3), the extracorporeal blood circuit (17) being configured to connect to the patient’s cardiovascular system;

[0062] A blood pump (21) is configured to control the flow of blood through an external blood circuit (17);

[0063] The outflowing material pipeline (13) is connected to the outlet of the auxiliary chamber (4);

[0064] One or more additional fluid lines, selected from the group consisting of:

[0065] • A pre-dilution infusion line (29), one end of which is connected to a blood collection line (6).

[0066] • A post-dilution infusion line (63), one end of which is connected to a blood return line (7).

[0067] • A post-dilution bicarbonate infusion line (23) is connected at one end to a blood return line (7).

[0068] • An ion-balanced infusion line (74), one end of which is connected to a blood return line (7) or to a patient catheter.

[0069] • The dialysate supply line (8) is connected at one end to the inlet of the auxiliary chamber (4).

[0070] • The pre-blood pump-PBP infusion line (52), one end of which is connected to the blood extraction line in the area of ​​the blood extraction line, which is located upstream of the blood pump (21) during use.

[0071] • An anticoagulant infusion line (51), one end of which is connected to the blood extraction line in the area of ​​the blood extraction line, which is located upstream of the blood pump (21) during use, and

[0072] • Syringe fluid line (22), one end of which is connected to the blood extraction line,

[0073] Actuators for regulating the flow of fluids (24, 25, 26, 31, 53, 54, 65, 75) through the fluid lines (23, 8, 13, 29, 52, 51, 63, 74);

[0074] Memory (16) stores one or more mathematical relations; and

[0075] The control unit (12) is connected to the memory (16) and the actuator.

[0076] The method includes the following steps that can be performed by the control unit:

[0077] - Receiving patient prescriptions that include clinical prescribing parameters, the receiving steps include:

[0078] ο Allow input of the prescribed dialysis dose to be delivered (D set The set value of )

[0079] ο Allow input parameters (nNBL; Cp) HCO3_pat The target value of the parameter (nNBL; Cp) HCO3_pat This indicates the need for blood transfusions in patients requiring CRRT to maintain stable acid-base balance in their blood.

[0080] - The operating parameters are determined using one or more of the mathematical relationships, the determination of which includes calculating setpoints for at least two fluid flow rates selected from a group including:

[0081] • Fluid flow rate (Q) through the anticoagulant injection line (51) cit ),

[0082] • Fluid flow rate (Q) through the PBP injection line (52) PBP ),

[0083] • Fluid flow rate (Q) through the pre-dilution infusion line (29) rep.pre ),

[0084] • Fluid flow rate (Q) through the post-dilution injection line (63) rep.post ),

[0085] • Fluid flow rate (Q) through the post-diluted bicarbonate injection pipeline (23) HCO3 ),

[0086] • Fluid flow rate (Q) through the ion balance delivery line (74) ca ),

[0087] • Blood flow velocity (Q) through the extracorporeal blood circuit (17) b ),

[0088] • Fluid flow rate (Q) through the dialysate supply line (8) dial ),and

[0089] • The fluid velocity (Q) through the outflow pipeline (13) eff ),

[0090] The setpoints for calculating at least two fluid flow rates are based at least on a specified dialysis dose (D). set The set values ​​and parameters (nNBL; Cp) HCO3_patThe target value of the parameter (nNBL; Cp) HCO3_pat It indicates the steady-state acid-base balance in the blood.

[0091] In another separate aspect, a continuous renal replacement therapy (CRRT) device is provided, comprising:

[0092] The filtration unit (2) has a main chamber (3) and a secondary chamber (4) separated by a semi-permeable membrane (5);

[0093] An extracorporeal blood circuit (17) having a blood extraction line (6) connected to the inlet of the main chamber (3) and a blood return line (7) connected to the outlet of the main chamber (3), the extracorporeal blood circuit (17) being configured to connect to the patient’s cardiovascular system;

[0094] A blood pump (21) is configured to control the flow of blood through an external blood circuit (17);

[0095] The outflowing material pipeline (13) is connected to the outlet of the auxiliary chamber (4);

[0096] One or more additional fluid lines, selected from the group consisting of:

[0097] A pre-dilution infusion line (29) is connected at one end to a blood collection line (6).

[0098] The post-dilution infusion line (63) is connected at one end to the blood return line (7).

[0099] The post-diluted bicarbonate infusion line (23) is connected at one end to the blood return line (7).

[0100] An ion-balanced infusion line (74) is connected at one end to a blood return line (7) or to a patient catheter.

[0101] The dialysate supply line (8) is connected at one end to the inlet of the auxiliary chamber (4).

[0102] The pre-blood pump-PBP infusion line (52) is connected at one end to the blood extraction line in the area where the blood extraction line is located upstream of the blood pump (21) during use.

[0103] An anticoagulant infusion line (51) is connected at one end to a blood extraction line in the area of ​​the blood extraction line, which is located upstream of the blood pump (21) during use.

[0104] The syringe fluid line (22) has one end connected to the blood extraction line.

[0105] Actuators for regulating the flow of fluids (24, 25, 26, 31, 53, 54, 65, 75) through the fluid lines (23, 8, 13, 29, 52, 51, 63, 74);

[0106] Memory (16) stores one or more mathematical relations; and

[0107] A control unit (12), connected to a memory (16) and an actuator, is configured to execute a flow rate setting program, which includes:

[0108] - Receiving patient prescriptions that include clinical prescribing parameters, the receiving steps include:

[0109] ο Allow input of the prescribed dialysis dose to be delivered (D set The set value of )

[0110] ο Allow input parameters (nNBL; Cp) HCO3_pat The target value of the parameter (nNBL; Cp) HCO3_pat This indicates the need for blood transfusions in patients requiring CRRT to maintain stable acid-base balance in their blood.

[0111] - The operating parameters are determined using one or more of the mathematical relationships, the determination of which includes calculating setpoints for at least two fluid flow rates selected from a group including:

[0112] • Fluid flow rate (Q) through the anticoagulant injection line (51) cit ),

[0113] • Fluid flow rate (Q) through the PBP injection line (52) PBP ),

[0114] • Fluid flow rate (Q) through the pre-dilution infusion line (29) rep.pre ),

[0115] • Fluid flow rate (Q) through the post-dilution injection line (63) rep.post ),

[0116] • Fluid flow rate (Q) through the post-diluted bicarbonate injection pipeline (23) HCO3 ),

[0117] • Fluid flow rate (Q) through the ion balance delivery line (74) ca ),

[0118] • Blood flow velocity (Q) through the extracorporeal blood circuit (17) b ),

[0119] • Fluid flow rate (Q) through the dialysate supply line (8)dial ),and

[0120] • The fluid velocity (Q) through the outflow pipeline (13) eff ),

[0121] The calculation of at least two fluid flow rate setpoints is based at least on the specified dialysis dose (D). set The set values ​​and parameters (nNBL; Cp) mentioned above. HCO3_pat The target value of the parameter (nNBL; Cp) HCO3_pat It indicates the steady-state acid-base balance in the blood.

[0122] It is worth noting that, according to the foregoing, each setpoint for calculating at least two fluid flow rates is based at least on a specified dialysis dose (D). set The set values ​​and parameters (nNBL; Cp) HCO3_pat The target value is a parameter indicating the steady-state acid-base balance in the blood. For example, the first fluid flow rate in the list (e.g., the fluid flow rate (Q) through the post-dilution infusion line (63)). rep.post Based on the prescribed dialysis dose (D) set The set values ​​and parameters (nNBL; Cp) HCO3_pat The target value is used to calculate the parameter (nNBL; Cp). HCO3_pat ) indicates the steady-state acid-base balance in the blood, and the second fluid flow rate in the list (e.g., the fluid flow rate (Q) through the dialysate supply line (8) dia Based on the prescribed dialysis dose (D) set The set values ​​and parameters (nNBL; Cp) HCO3_pat The target value is used to calculate the parameter (nNBL; Cp). HCO3_pat It indicates the steady-state acid-base balance in the blood.

[0123] In another separate aspect, a continuous renal replacement therapy (CRRT) device is provided, comprising:

[0124] The filtration unit (2) has a main chamber (3) and a secondary chamber (4) separated by a semi-permeable membrane (5);

[0125] An extracorporeal blood circuit (17) has a blood extraction line (6) connected to the inlet of the main chamber (3) and a blood return line (7) connected to the outlet of the main chamber (3). The extracorporeal blood circuit (17) is configured to connect to the patient's cardiovascular system.

[0126] A blood pump (21) is configured to control the flow of blood through an external blood circuit (17);

[0127] The outflowing material pipeline (13) is connected to the outlet of the auxiliary chamber (4);

[0128] One or more additional fluid lines, selected from the group consisting of:

[0129] A pre-dilution infusion line (29) is connected at one end to a blood collection line (6).

[0130] The post-dilution infusion line (63) is connected at one end to the blood return line (7).

[0131] The post-diluted bicarbonate infusion line (23) is connected at one end to the blood return line (7).

[0132] An ion-balanced infusion line (74) is connected at one end to a blood return line (7) or to a patient catheter.

[0133] The dialysate supply line (8) is connected at one end to the inlet of the auxiliary chamber (4).

[0134] The pre-blood pump-PBP infusion line (52) is connected at one end to the blood extraction line in the area where the blood extraction line is located upstream of the blood pump (21) during use.

[0135] An anticoagulant infusion line (51) is connected at one end to a blood extraction line in the area of ​​the blood extraction line, which is located upstream of the blood pump (21) during use.

[0136] The syringe fluid line (22) has one end connected to the blood extraction line.

[0137] Actuators for regulating the flow of fluids (24, 25, 26, 31, 53, 54, 65, 75) through the fluid lines (23, 8, 13, 29, 52, 51, 63, 74);

[0138] Memory (16) stores one or more mathematical relations; and

[0139] A control unit (12), connected to a memory (16) and an actuator, is configured to execute a flow rate setting program, which includes:

[0140] - Receiving patient prescriptions that include clinical prescribing parameters, the receiving steps include:

[0141] ο Allow input of the prescribed dialysis dose to be delivered (D set The set value of )

[0142] ο Allow input parameters (nNBL; Cp) HCO3_ The target value of the parameter (nNBL; Cp) HCO3_atThis indicates the need for blood transfusions in patients requiring CRRT to maintain stable acid-base balance in their blood.

[0143] - Use the one or more mathematical relationships to determine one or more operating parameters, the determination of which includes calculating setpoints for at least two fluid flow rates selected from a group including:

[0144] • Fluid flow rate (Q) through the anticoagulant injection line (51) cit ),

[0145] • Fluid flow rate (Q) through the PBP injection line (52) PBP ),

[0146] • Fluid flow rate (Q) through the pre-dilution infusion line (29) rep.pre ),

[0147] • Fluid flow rate (Q) through the post-dilution injection line (63) rep.post ),

[0148] • Fluid flow rate (Q) through the post-diluted bicarbonate injection pipeline (23) HCO3 ),

[0149] • Fluid flow rate (Q) through the ion balance delivery line (74) ca ),

[0150] • Blood flow velocity (Q) through the extracorporeal blood circuit (17) b ),

[0151] • Fluid flow rate (Q) through syringe fluid line (22) syr ),

[0152] • Fluid flow rate (Q) through the dialysate supply line (8) dial ),and

[0153] • The fluid velocity (Q) through the outflow pipeline (13) eff ),

[0154] This is at least based on the prescribed dialysis dose (D set The set values ​​and parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp) HCO3_pat ) Calculate the setpoint of any one of the following:

[0155] The fluid flow rate (Q) through the anticoagulant injection line (51) cit ),

[0156] The fluid flow rate (Q) through the PBP injection line (52)PBP ),

[0157] The fluid flow rate (Q) through the pre-dilution infusion line (29) rep.pre ),

[0158] (It should be noted that this flow rate is one of at least two flow rates mentioned in the foregoing aspects), and

[0159] The setpoint for calculating at least one other fluid flow rate is based at least on the specified dialysis dose (D). set The set values ​​and parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp) HCO3_pat The target value is as stated in the text.

[0160] In another aspect of any of the foregoing aspects, the at least another fluid velocity (or one of at least two velocities) is:

[0161] The fluid flow rate (Q) through the dialysate supply line (8) dial );or

[0162] The fluid velocity (Q) through the outflow pipeline (13) eff ),

[0163] Furthermore, the setpoint for calculating the other fluid flow rate is based at least on parameters (nNBL; Cp) that indicate the steady-state acid-base balance in the blood. HCO3_pat The target value, and based on the specified dialysis dose (D) set The set value mentioned above.

[0164] In the second aspect according to any of the foregoing aspects, the anticoagulant infusion line (51) is connected at one end to a blood extraction line in the area of ​​the blood extraction line, which is located upstream of the blood pump (21) during use; and an anticoagulant source (10) is connected at the opposite end of the anticoagulant infusion line (51), wherein receiving a patient prescription also includes allowing the input of a local anticoagulant dose (D) indicating the intensity of local anticoagulation. cit Specifically, this refers to the set value for the citrate dosage.

[0165] In the third aspect according to the foregoing, the local anticoagulant dose (D) cit It has the same units as concentration, and is more detailed as the amount of anticoagulant injected per liter of treated blood (mmol / L blood).

[0166] In the fourth aspect according to the two aspects mentioned above, the control unit (12) is configured to use the citrate flow rate mathematical relationship to make the fluid flow rate (Q) through the anticoagulant delivery line (51) cit The set value of ) and the local anticoagulant dose (D) cit The setpoints are mathematically related, specifically calculated as the local anticoagulant dose (D). cit The fluid velocity (Q) is a function of the set value. cit The setting value of ).

[0167] In the fifth aspect according to any of the three aspects mentioned above, the control unit (12) is configured to use the citrate flow rate mathematical relationship to make the fluid flow rate (Q) through the anticoagulant infusion line (51) cit The set value of ) and blood flow rate (Q) b The concentrations of the anticoagulant (specifically citrate) in the anticoagulant source (10) and / or the anticoagulant source (10) are mathematically correlated, specifically calculated as blood flow rate (Q). b The fluid flow rate (Q) is a function of the concentration of the anticoagulant (specifically citrate) in the anticoagulant source (10) and / or the anticoagulant source (10). cit The setting value of ).

[0168] In the sixth aspect according to any of the four aspects mentioned above, the one or more mathematical relationships include a citrate flow rate mathematical relationship, and the fluid flow rate (Q) through the anticoagulant infusion line (51) is calculated based on the citrate flow rate mathematical relationship stored in the memory (16). cit ):

[0169]

[0170] The meanings of the symbols are given in the glossary.

[0171] In the seventh aspect according to any of the foregoing aspects, the control unit (12) is configured to drive the anticoagulant pump (54) at a calculated fluid flow rate (Q) for the anticoagulant. cit An anticoagulant is infused into the blood extraction tubing.

[0172] In aspect 8 according to either aspect 2 or 3 above, the local anticoagulant dose (D) cit ) is the fluid flow rate (Q) through the anticoagulant injection line (51). cit ).

[0173] In the ninth aspect according to any of the aforementioned seven aspects, calculating the setpoint includes calculating at least three fluid flow rates, and also based at least on the local anticoagulant dose (D). cit The set value of ) is specifically used by using at least one of the one or more mathematical relations.

[0174] In the 10th aspect according to any of the foregoing aspects, the CRRT device includes: an ion-balanced infusion line (74) connected at one end to a blood return line (7) or to a patient catheter; and a source (11) of ion-balanced solution connected at the opposite end of the ion-balanced infusion line (74), wherein receiving a patient prescription further includes allowing input of ion regeneration solution parameters (CaComp; D). ca The set value of ) is specifically the set value of the calcium compensation parameter, which indicates the intensity of the ion balance, specifically the intensity of the calcium ion balance.

[0175] In the 11th aspect according to the foregoing, the ion regeneration solution parameter (CaComp) represents the compensation value or compensation percentage of calcium removed in the filtration unit (2), for example, between 0.05% and 2% or between 5% and 200%.

[0176] In the 12th aspect according to the aforementioned aspect 10, the ion regeneration solution parameters (D) ca ) is a dose expressed as an ion (e.g., calcium) concentration, specifically, the calcium dose is the total calcium concentration in the effluent.

[0177] In the 13th aspect according to any of the three aspects mentioned above, the control unit (12) is configured to use the calcium flow rate mathematical relationship to make the fluid flow rate (Q) through the ion balance infusion line (74) ca The set values ​​of ) and the parameters of the ion regeneration solution (CaComp; D) ca The set values ​​are mathematically related, specifically calculated as parameters of the ion regeneration solution (CaComp; D). ca Fluid velocity (Q) as a function of the setpoint ca The setting value of ).

[0178] In the 14th aspect according to any of the aforementioned four aspects, the control unit (12) is configured to use a calcium flow rate mathematical relationship to make the fluid flow rate (Q) through the ion balance infusion line (74) ca The set value of ) and the outflow velocity (Q) eff In mathematics, this is related to the calculation of the outflow velocity (Q). eff The fluid velocity (Q) is a function of ) ca The setting value of ).

[0179] In the 15th aspect according to any of the aforementioned five aspects, the control unit (12) is configured to use a calcium flow rate mathematical relationship to make the fluid flow rate (Q) through the ion balance infusion line (74) ca The set value of ) and the calcium concentration (C) in the source (11) of the ion equilibrium solution.ca ) and / or the calcium concentration in the auxiliary container (64) connected to the post-dilution infusion line (63). Mathematically correlated with, and / or related to, the calcium concentration in the bicarbonate container (28) connected to the post-dilution bicarbonate infusion line (23). Mathematically, this is related to the calcium concentration (C) in the source (11) of the ion equilibrium solution. ca The calcium concentration is a function of and / or serves as a function of the calcium concentration in the auxiliary container (64) connected to the post-dilution bicarbonate infusion line (63). The function and / or the calcium concentration in the bicarbonate container (28) connected to the post-dilution bicarbonate infusion line (23). The function to calculate the fluid velocity (Q) ca The setting value of ).

[0180] In the 16th aspect according to any of the aforementioned six aspects, the one or more mathematical relationships include a calcium flow rate mathematical relationship, and wherein the fluid flow rate (Q) through the ion balance delivery line (74) is calculated based on the calcium flow rate mathematical relationship stored in the memory (16). ca The setting value is:

[0181]

[0182] The meanings of the symbols are given in the glossary.

[0183] In the 17th aspect according to aspect 12 above, the one or more mathematical relationships include a calcium flow rate mathematical relationship, and wherein the fluid flow rate (Q) through the ion balance delivery line (74) is calculated based on the calcium flow rate mathematical relationship stored in the memory (16). ca The setting value is:

[0184]

[0185] The meanings of the symbols are given in the glossary; if any infusion line is missing, the corresponding flow rate is not present in the mathematical relation, or the corresponding flow rate is set to zero.

[0186] In the 18th aspect according to any of the foregoing aspects, the control unit (12) is configured to drive the ion balance pump (75) to deliver the ion regeneration solution at a calculated fluid flow rate (Q) for the ion regeneration solution. ca Infuse into the blood return line (7) or into the patient (P).

[0187] In the 19th aspect according to any of the preceding nine aspects, calculating the setpoint includes calculating at least three fluid flow rates, and also based at least on ion regeneration solution parameters (CaComp; D).ca The set value is specifically determined by using at least one of the one or more mathematical relations.

[0188] In aspect 20, according to any of the foregoing aspects, receiving a patient prescription also includes allowing the infusion of blood flow rate (Q). b The setpoints are calculated by calculating at least three fluid flow rates, and the calculation of one or more (two or all) of the at least three fluid flow rates is also based at least on the blood flow rate (Q). b The set value is specifically determined by using at least one of one or more mathematical relations.

[0189] In aspect 21, according to any of the foregoing aspects, receiving a patient prescription further includes allowing the patient to input at least the fluid removal rate (Q). PFR The setpoint is calculated by calculating at least three fluid flow rates, and the setpoint is also based at least on the fluid removal rate from the patient (Q). PFR The set value is specifically determined by using at least one of the one or more mathematical relations.

[0190] In aspect 22 according to any of the foregoing aspects, the control unit (12) is configured to use an outflow velocity mathematical relationship to control the fluid velocity (Q) through the outflow body pipeline (13). eff ) and fluid removal rate (Q PFR The setpoints are mathematically related, specifically based on the fluid removal rate (Q). PFR The set value is used to calculate the fluid velocity (Q) through the outflow pipeline (13). eff ).

[0191] In the 23rd aspect according to either of the two aspects mentioned above, the control unit (12) is configured to mathematically correlate, specifically calculate, the fluid velocity (Q) through the outflow body pipeline (13) based on the outflow velocity mathematical relation included in the one or more mathematical relations. eff ):

[0192] Q eff

[0193] =Q PBP +Q cit +Q syr +Q dial +Q rep.pre +Q rep.post +Q HCO3 +Q PFR +Q ca

[0194] The meanings of the symbols are given in the glossary; if any infusion line or dialysate supply line is missing, there is no corresponding flow rate in the mathematical formula, or the corresponding flow rate is set to zero.

[0195] In aspect 24 according to any of the foregoing aspects, the CRRT device includes a fluid source for supplying fluid to one of the one or more of the additional fluid lines, the solution comprising at least one buffer in the form of a bicarbonate or a bicarbonate precursor.

[0196] In aspect 25 of the foregoing, the bicarbonate precursor includes citrate, lactate and / or acetate.

[0197] In aspect 26 according to any of the foregoing aspects, the parameter (nNBL) indicating the steady-state acid-base balance in the blood of a patient undergoing CRRT is a parameter function of the net buffer load (NBL) expected in the patient at steady state, wherein the net buffer load is the sum of: bicarbonate produced from bicarbonate precursor metabolism (e.g., citrate or lactate metabolism), bicarbonate balance in the extracorporeal blood circuit (17), and / or bicarbonate infusion to the patient and / or acid infusion (e.g., citrate infusion) in the extracorporeal blood circuit (17).

[0198] In aspect 27 of the foregoing, net buffer load is the normalized net buffer (nNBL) load expected in the patient's body under steady-state conditions, specifically the net buffer load normalized based on the patient's body weight (BW). More specifically, the parameter (nNBL) indicating the steady-state acid-base balance in the blood of a patient undergoing CRRT is either the net buffer load (NBL) or the normalized net buffer load (nNBL):

[0199]

[0200] In aspect 28 according to any of the foregoing aspects, the parameter (nNBL) indicating the homeostatic acid-base balance in the patient's blood is based on one or more of the following, specifically the following four:

[0201] • An estimate of the amount of bicarbonate produced per unit time from the metabolism of bicarbonate precursors infused to the patient, specifically citrate (J met_cit ) and / or lactate (J met_lact Estimate the quantity of )

[0202] • Bicarbonate balance from CRRT blood processing (J HCO3_bal ), delivered in units of time;

[0203] • Lactate balance from CRRT blood processing (J lact_bal), delivered in units of time;

[0204] • Acid infusion per unit time from citric acid contained in a fluid source (J H+ ).

[0205] In aspect 29 of the foregoing, the parameter (nNBL) indicating homeostatic acid-base balance in the patient's blood is the precursor metabolism of bicarbonate (J). met_cit J lact ), bicarbonate balance (J HCO3_bal ) and acid infusion (J H+ The algebraic sum of estimates of ), specifically, acid infusion (J H+ ) is a negative term that provides a buffer against loss for the patient.

[0206] In aspect 30 of the foregoing, the parameter (nNBL) indicating the homeostatic acid-base balance in a patient's blood is defined as follows:

[0207]

[0208] Alternatively, when lactate balance is also considered, the parameter (nNBL) indicating the steady-state acid-base balance in a patient's blood is defined as follows:

[0209]

[0210] In aspect 31 according to any of the foregoing aspects, the parameter (nNBL; Cp) indicating the homeostatic acid-base balance in the patient's blood. HCO3_pat Based on acid infusion per unit time from citric acid contained in a fluid source (J) H+ ), of which acid infusion (J H+ ) is the concentration of citric acid (C citric_pbp ) and citric acid infusion rate (Q cit The function of ), specifically, acid infusion (J H+ ) equals the concentration of citric acid (C citric_pbp Multiply by the citric acid infusion rate (Q) cit 3 times that of ).

[0211] In aspect 32 according to any of the foregoing aspects, the parameter (nNBL) indicating the steady-state acid-base balance in the blood of a patient undergoing CRRT is assumed to be the patient's plasma bicarbonate concentration (Cp). HCO3_pat The parameter is defined by a constant value of 0, for example, 25mM.

[0212] In aspect 33 according to any of the foregoing aspects, the steady-state bicarbonate concentration parameter (Cp) in the patient's blood is indicated. HCO3_patNet buffer load (J) is estimated based on indicators of the patient's steady-state acid-base balance. buffer_load / BW).

[0213] In another aspect of any of the foregoing aspects, the parameter (Cp) indicating the steady-state bicarbonate concentration in the patient's blood. HCO3_pat The normalized net buffer load (NBL) is defined as a constant value applied to a patient in a steady state, such as NBL = nNBL0·BW = 0.1 mmol / h / kg.

[0214] In aspect 34 according to any of the foregoing aspects, the parameter (Cp) indicating the steady-state bicarbonate concentration in the patient's blood. HCO3_pat The normalized net buffer load (NBL) is defined as a constant value applied to a patient in a steady state, such as nNBL0·BW = 0.1 mmol / h / kg.

[0215] In aspect 35 according to any of the foregoing aspects, one or more mathematical relations include a steady-state bicarbonate indicator mathematical relation, and wherein the steady-state bicarbonate indicator mathematical relation makes the parameter (Cp) indicating the steady-state bicarbonate concentration in the patient's blood... HCO3_pat It is associated with at least two flow rates in the group.

[0216] In the 36th aspect according to any of the foregoing aspects, the one or more mathematical relations include a steady-state bicarbonate indicator mathematical relation, and wherein the steady-state bicarbonate indicator mathematical relation makes the parameter (Cp) indicating the steady-state bicarbonate concentration in the patient's blood... HCO3_pat ) and the fluid flow rate (Q) through the pre-dilution infusion line (29) rep.pre ), the fluid flow rate (Q) through the dialysate supply line (8) dial ), fluid velocity (Q) through the anticoagulant injection line (51) cit ), fluid velocity (Q) through PBP injection line (52) PBP One or more of them are associated, specifically making the parameter (Cp) HCO3_pat ) and the fluid velocity (Q) in the fluid flowing in the corresponding pipeline. rep.pre Q dial Q cit Q PBP Multiply by the corresponding bicarbonate concentration Related.

[0217] In aspect 37 according to any of the foregoing aspects, the one or more mathematical relations include a steady-state bicarbonate indicator mathematical relation, and wherein the steady-state bicarbonate indicator mathematical relation makes the parameter (Cp) indicating the steady-state bicarbonate concentration in the patient's blood... HCO3_pat ) and blood flow velocity (Q) b It is related to blood fluid flow rate (Q) bw The blood flow rate (Q) at the inlet of the filtration unit (2) and / or the filtration unit (2) bw_inlet (related to)

[0218] In aspect 38 according to any of the foregoing aspects, the one or more mathematical relations include a steady-state bicarbonate indicator mathematical relation, and wherein the steady-state bicarbonate indicator mathematical relation makes the parameter (Cp) indicating the steady-state bicarbonate concentration in the patient's blood... HCO3_pat The concentration of bicarbonate in the fluid flowing in the dialysate supply line (8) and / or with bicarbonate removal (K) of filter unit (2) HCO3 (related to)

[0219] In aspect 39 according to any of the foregoing aspects, the one or more mathematical relations include a steady-state bicarbonate indicator mathematical relation, and wherein the steady-state bicarbonate indicator mathematical relation makes the parameter (Cp) indicating the steady-state bicarbonate concentration in the patient's blood... HCO3_pat The concentration of bicarbonate in plasma water (Cpw) at the inlet of the filtration unit HCO3_inlet Related.

[0220] In the 40th aspect according to any of the foregoing aspects, the one or more mathematical relations include a steady-state bicarbonate indicator mathematical relation, and wherein the steady-state bicarbonate indicator mathematical relation makes the parameter (Cp) indicating the steady-state bicarbonate concentration in the patient's blood... HCO3_pat ) and the ultrafiltration flow rate (Q) in the filtration unit (2) fil This is related to, specifically, the ultrafiltration flow rate (Q). fil Multiply by the concentration of bicarbonate in the fluid flowing in the dialysate supply line (8). Related.

[0221] In aspect 41 according to any of the foregoing aspects, the one or more mathematical relations include a steady-state bicarbonate indicator mathematical relation, and wherein the steady-state bicarbonate indicator mathematical relation makes the parameter (Cp) indicating the steady-state bicarbonate concentration in the patient's blood... HCO3_pat ) and removal of bicarbonate from used dialysate flowing in the effluent line (13) (J HCO3_eff (related to)

[0222] In aspect 42 according to any of the foregoing aspects, the one or more mathematical relations include a steady-state bicarbonate indicator mathematical relation, and wherein the steady-state bicarbonate indicator mathematical relation is as follows:

[0223]

[0224]

[0225]

[0226] J buffer_load =nNBL×BW

[0227] The meanings of the symbols are given in the glossary; if any infusion line or dialysate supply line is missing, there is no corresponding flow rate in the mathematical formula, or the corresponding flow rate is set to zero.

[0228] It should be noted that if Cp HCO3_ As a parameter indicating the steady-state acid-base balance in a patient's blood, nNBL must (implicitly) be treated as a constant, i.e., nNBL0; conversely, if nNBL is used as a parameter indicating the steady-state acid-base balance in a patient's blood, then Cp must (implicitly) be treated as a constant. HCO3_pat As a constant, i.e., Cp HCO3_pat 0.

[0229] In aspect 43 according to any of the foregoing aspects, the parameter (nNBL; Cp) indicating the homeostatic acid-base balance in the patient's blood. HCO3_pat The target value affects the fluid flow rate (Q) through the pre-dilution infusion line (29). rep.pre The set value of ) is determined by the fluid flow rate (Q) through the pre-dilution infusion line (29). rep.pre The set value is an operating parameter calculated by the control unit (12). Specifically, this is based on the specified dialysis dose (D). set The set values ​​and parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp) HCO3_pat The target value is calculated from one of at least two flow rates.

[0230] In aspect 44 according to any of the foregoing aspects, the parameter (nNBL; Cp) indicating the homeostatic acid-base balance in the patient's blood. HCO3_pat The target value affects the fluid flow rate (Q) through the post-dilution injection line (63). rep.post The set value of ) is the fluid flow rate (Q) through the post-dilution infusion line (63). rep.post The set value is an operating parameter calculated by the control unit (12). Specifically, this is based on the specified dialysis dose (D). setThe set values ​​and parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp) HCO3_pat The target value is calculated from one of at least two flow rates.

[0231] In aspect 45 according to any of the foregoing aspects, the parameter (nNBL; Cp) indicating the homeostatic acid-base balance in the patient's blood. HCO3_pat The target value affects the fluid flow rate (Q) through the dilute bicarbonate injection pipeline (23). HCO3 The set value of ) is the fluid flow rate (Q) through the post-diluted bicarbonate injection pipeline (23). HCO3 The set value is an operating parameter calculated by the control unit (12). Specifically, this is based on the specified dialysis dose (D). set The set values ​​and parameters indicating the steady-state acid-base balance in the blood (nNBL; CpCp) HCO3_pat The target value is calculated from one of at least two flow rates.

[0232] In aspect 46 according to any of the foregoing aspects, the parameter (nNBL; Cp) indicating the homeostatic acid-base balance in the patient's blood. HCO3_pat The target value affects the fluid flow rate (Q) through the ion balance delivery line (74). ca The set value of ) is determined by the fluid flow rate (Q) of the ion balance delivery line (74). ca The set value is an operating parameter calculated by the control unit (12). Specifically, this is based on the specified dialysis dose (D). set The set values ​​and parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp) HCO3_pat The target value is calculated from one of at least two flow rates.

[0233] In aspect 47 according to any of the foregoing aspects, the parameter (nNBL; Cp) indicating the homeostatic acid-base balance in the patient's blood. HCO3_pat The target value affects the fluid flow rate (Q) through the dialysate supply line (8). dial The set value of ) is determined by the fluid flow rate (Q) through the dialysate supply line (8). dial The set value is an operating parameter calculated by the control unit (12). Specifically, this is based on the specified dialysis dose (D). set The set values ​​and parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp) HCO3_pat The target value is calculated from one of at least two flow rates.

[0234] In aspect 48 according to any of the foregoing aspects, the parameter (nNBL; Cp) indicating the homeostatic acid-base balance in the patient's blood. HCO3_patThe target value affects the fluid velocity (Q) through the anticoagulant injection line (51). cit The set value is specifically the blood flow rate (Q) through the external blood circuit (17). b When the set value of ) is determined as the operating parameter by the control unit (12), the fluid flow rate (Q) through the anticoagulant injection line (51) cit The set value is an operating parameter calculated by the control unit (12). Specifically, this is based on the specified dialysis dose (D). set The set values ​​and parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp) HCO3_pat The target value is calculated from one of at least two flow rates.

[0235] In aspect 49 according to any of the foregoing aspects, the parameter (nNBL; Cp) indicating the homeostatic acid-base balance in the patient's blood. HCO3_pat The target value affects the fluid flow rate (Q) through the PBP injection line (52). PBP The set value of ) is determined by the fluid flow rate (Q) through the PBP injection line (52). PBP The set value is an operating parameter calculated by the control unit (12). Specifically, this is based on the specified dialysis dose (D). set The set values ​​and parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp) HCO3_pat The target value is calculated from one of at least two flow rates.

[0236] In aspect 50 according to any of the foregoing aspects, the parameter (nNBL; Cp) indicating the homeostatic acid-base balance in the patient's blood. HCO3_pat The target value affects the blood flow rate (Q) through the extracorporeal blood circuit (17). b The set value of ) is determined by the blood flow rate (Q) of the external blood circuit (17). b The set value is an operating parameter calculated by the control unit (12). Specifically, this is based on the specified dialysis dose (D). set The set values ​​and parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp) HCO3_pat The target value is calculated from one of at least two flow rates.

[0237] In aspect 51 according to any of the foregoing aspects, the parameter (nNBL; Cp) indicating the homeostatic acid-base balance in the patient's blood. HCO3_pat The target value affects the fluid velocity (Q) through the outflow pipeline (13). eff The set value of ) is the fluid velocity (Q) of the fluid flowing out of the material pipeline (13). effThe set value is an operating parameter calculated by the control unit (12). Specifically, this is based on the specified dialysis dose (D). set The set values ​​and parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp) HCO3_pat The target value is calculated from one of at least two flow rates.

[0238] It is worth noting that, when relevant (i.e., if a line exists and the applied treatment requires the use of a line with a set flow rate other than zero), the parameters indicating the steady-state acid-base balance in the patient's blood (nNBL; Cp) HCO3_pat The target value is used to calculate most, and especially all, of the fluid flow rates indicated above.

[0239] In aspect 52 according to any of the foregoing aspects, at least a plurality of the one or more mathematical relations make the parameter (nNBL; Cp) indicative of the steady-state acid-base balance in the blood of a patient who must undergo CRRT blood treatment. HCO3_pat It is associated with at least two flow rates selected from the group.

[0240] In aspect 53 according to any of the foregoing aspects, the fluid velocity (Q) through the anticoagulant delivery line (51) is calculated. cit The setpoints are based at least on parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp). HCO3_pat The target value, and / or based on the specified dialysis dose (D) set The set value, especially the blood flow rate (Q) through the extracorporeal blood circuit (17). b When the set value of ) is determined by the control unit (12) as an operating parameter, specifically, the control unit (12) uses the mathematical formula to calculate the fluid flow rate (Q) through the anticoagulant infusion line (51). cit The setting value of ).

[0241] In aspect 54, according to any of the foregoing aspects, the fluid velocity (Q) through the PBP injection line (52) is calculated. PBP The setpoints are based at least on parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp). HCO3_pat The target value, and / or based on the specified dialysis dose (D) set The set value, specifically, wherein the control unit (12) uses the mathematical formula to calculate the fluid flow rate (Q) through the PBP infusion line (52). PBP The setting value of ).

[0242] In aspect 55 according to any of the foregoing aspects, the fluid flow rate (Q) through the pre-dilution infusion line (29) is calculated.rep.pre The setpoint is based at least on parameters indicating steady-state acid-base balance in the blood (nNBL; Cp). HCO3_pat The target value, and / or based on the specified dialysis dose (D) set The set value, specifically, wherein the control unit (12) uses the mathematical formula to calculate the fluid flow rate (Q) through the pre-dilution infusion line (29). rep.pre The setting value of ).

[0243] In aspect 56 according to any of the foregoing aspects, the fluid flow rate (Q) through the post-dilution infusion line (63) is calculated. rep.post The setpoints are based at least on parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp). HCO3_pat The target value, and / or based on the specified dialysis dose (D) set The set value, specifically, wherein the control unit (12) uses the mathematical formula to calculate the fluid flow rate (Q) through the post-dilution infusion line (63). rep.post The setting value of ).

[0244] In aspect 57 according to any of the foregoing aspects, the fluid flow rate (Q) through the post-diluted bicarbonate injection pipeline (23) is calculated. HCO3 The setpoints are based at least on parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp). HCO3_pat The target value, and / or based on the specified dialysis dose (D) set The set value, specifically, wherein the control unit (12) uses the mathematical formula to calculate the fluid flow rate (Q) through the post-diluted bicarbonate injection line (23). HCO3 The setting value of ).

[0245] In aspect 58, according to any of the foregoing aspects, the fluid flow rate (Q) through the ion balance delivery line (74) is calculated. ca The setpoint is based at least on parameters indicating steady-state acid-base balance in the blood (nNBL; Cp). HCO3_pat The target value, and / or based on the specified dialysis dose (D) set The set value, specifically, wherein the control unit (12) uses the mathematical formula to calculate the fluid flow rate (Q) through the ion balance delivery line (74). ca The setting value of ).

[0246] In aspect 59 according to any of the foregoing aspects, the blood flow velocity (Q) through the extracorporeal blood circuit (17) is calculated. b The setpoints are based at least on parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp). HCO3_patThe target value, and / or based on the specified dialysis dose (D) set The set value, specifically, wherein the control unit (12) uses the mathematical formula to calculate the fluid flow rate (Q) through the extracorporeal blood circuit (17). b The setting value of ).

[0247] In aspect 60, according to any of the foregoing aspects, the fluid flow rate (Q) through the dialysate supply line (8) is calculated. dial The setpoints are based at least on parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp). HCO3_pat The target value, and / or based on the specified dialysis dose (D) set The set value, specifically, wherein the control unit (12) uses the mathematical formula to calculate the fluid flow rate (Q) through the dialysate supply line (8). dial The setting value of ).

[0248] In aspect 61 according to any of the foregoing aspects, the fluid velocity (Q) through the outflowing material pipeline (13) is calculated. eff The setpoints are based at least on parameters indicating the steady-state acid-base balance in the blood (nNBL; Cp). HCO3_pat The target value, and / or based on the specified dialysis dose (D) set The set value, specifically, wherein the control unit (12) uses the mathematical formula to calculate the fluid velocity (Q) through the outflow material pipeline (13). eff The setting value of ).

[0249] In aspect 62 according to any of the foregoing aspects, wherein said one or more mathematical relations include a net buffer load mathematical relation, the net buffer load mathematical relation making the parameter (nNBL; Cp) indicating the steady-state acid-base balance in the blood... HCO3_pat It is associated with at least one of the following, and in particular all of the following:

[0250] οBicarbonate balance (J HCO3_bal ),

[0251] ο by citrate (J met_cit ) or citrate loading (J cit_load The metabolism of bicarbonate, specifically, the metabolism of citrate load results in the production of 3 moles of bicarbonate per mole of citrate at steady state, i.e., J met_cit =3·J cit_load ,

[0252] οBy lactate (J met_lact ) or lactate balance (J lact_balThe metabolism of lactate produces bicarbonate, specifically, the metabolism of lactate results in the production of 1 mole of bicarbonate per mole of lactate at steady state, i.e., J met_lact =J lact_bal ,

[0253] ο Acid Infusion J H+ ,

[0254] Optionally, the mathematical formula for net buffer load is:

[0255]

[0256] The meanings of the symbols are given in the glossary; if any mass transfer rate is missing, the corresponding mass transfer term is not present in the mathematical relation, or the corresponding value is set to zero.

[0257] In aspect 63 according to any of the foregoing aspects, the one or more mathematical relations include a bicarbonate balance mathematical relation, said bicarbonate balance mathematical relation being based on the bicarbonate balance (J) from CRRT blood processing delivered in amounts per unit time. HCO3_bal Specifically, the bicarbonate balance (J) HCO3_bal ) is the bicarbonate infusion rate (J) from the dialysate supply line (8) and / or infusion line. HCO3_inf ) and the removal of bicarbonate entering the dialysate (J HCO3_dial The difference between them, specifically the mathematical relationship of bicarbonate equilibrium, is:

[0258] J HCO3_bal =J HCO3_inf -J HCO3_eff

[0259] The meanings of the symbols are given in the glossary; if any mass transfer rate is missing, the corresponding mass transfer term is not present in the mathematical relation, or the corresponding value is set to zero.

[0260] In aspect 64 of the foregoing, the bicarbonate infusion rate (J) from the dialysate supply line (8) HCO3_inf ) is the fluid flow rate (Q) through the dialysate supply line (8). dial The concentration of bicarbonate in the dialysate flowing in the dialysate supply line (8) and the dialysate supply line (8) The function, specifically the fluid velocity (Q) dial Multiply by the bicarbonate concentration

[0261] In aspect 65, which is based on either of the two aspects mentioned above, the bicarbonate infusion rate (J) from the infusion pipeline HCO3_inf Q is the fluid velocity per second. rep.pre Qrep.post Q cit Q PBP Q HCO3 Q ca and the corresponding bicarbonate concentration The function, specifically the fluid velocity per second (Q). rep.pre Q rep.post Q cit Q PBP Q HCO3 Q ca Multiply by the corresponding bicarbonate concentration

[0262]

[0263] In aspect 66 according to any of the three aspects mentioned above, the one or more mathematical relationships include a bicarbonate infusion mathematical relationship, and wherein the bicarbonate infusion rate (J) from the dialysate supply line (8) and the infusion line is... HCO3_inf Specifically, based on the mathematical relationship of bicarbonate infusion:

[0264]

[0265] The meanings of the symbols are given in the glossary; if any infusion line or dialysate supply line is missing, there is no corresponding flow rate in the mathematical formula, or the corresponding flow rate is set to zero.

[0266] In aspect 67 according to any of the aforementioned four aspects, the removal of bicarbonate from the effluent used in the dialysis fluid (J) HCO3_eff ) is the fluid flow rate (Q) through the dialysate supply line (8). dial The concentration of bicarbonate in the dialysate flowing in the dialysate supply line (8) and the dialysate supply line (8) The function, specifically the fluid velocity (Q) dial Multiply by the bicarbonate concentration

[0267] In aspect 68 according to any of the aforementioned five aspects, the removal of bicarbonate from the dialysis solvent used in the effluent line (13) (J HCO3_eff ) is the concentration of bicarbonate in the dialysis fluid (C HCO3_dial The function is specifically the bicarbonate plasma water concentration (Cpw) at the filter inlet. HCO3_inlet ) and the concentration of bicarbonate in the dialysis fluid (C HCO3_dial A function of the difference between ).

[0268] In aspect 69 according to any of the aforementioned six aspects, the removal of bicarbonate from the dialysis solvent used in the effluent line (13) (JHCO3_eff ) is the ultrafiltration flow rate (Q) in the filtration unit (2). fil The concentration of bicarbonate in the dialysate flowing in the dialysate supply line (8) and the concentration of bicarbonate in the dialysate. The function, specifically the ultrafiltration flow rate (Q) fil Multiply by the bicarbonate concentration

[0269] In aspect 70, according to any of the aforementioned seven aspects, the removal of bicarbonate from the dialysis solvent used in the effluent line (13) (J HCO3_eff ) is the removal of bicarbonate (K HCO3 The function of ).

[0270] In aspect 71, according to any of the aforementioned eight aspects, the removal of bicarbonate from the dialysis solvent used in the effluent line (13) (J HCO3_eff ) is the fluid velocity (Q) of the fluid flowing out of the material pipeline (13). eff The function of ), specifically, where bicarbonate scavenging (K HCO3 The outflow velocity (Q) is estimated to be equal to the outflow velocity of the material. eff ).

[0271] In aspect 72 according to any of the foregoing aspects, the removal of bicarbonate from the dialysis solvent used in the effluent line (13) (J HCO3_eff ) is the removal of bicarbonate (K HCOO The function of ) and bicarbonate scavenging (K HCO3 ) is a function of one or more flow rates, specifically including the fluid flow rate (Q) through the dialysate supply line (8). dial The ultrafiltration rate (Q) in the filtration unit (2) fil ) and blood flow rate (Qbw) inlet One or more of the following.

[0272] According to aspect 73 of the foregoing, bicarbonate scavenging (K... HCO3 ) is a function of the filter unit (2) used for CRRT treatment, specifically the bicarbonate sieving coefficient (SC). HCO3 ) and / or the surface area of ​​the filter unit and the diffusion mass transfer resistance of bicarbonate (S / RT) HCO3 A function of the ratio of ).

[0273] In aspect 74 according to any of the foregoing aspects, the one or more mathematical relations include the following bicarbonate scavenging mathematical relations:

[0274]

[0275]

[0276]

[0277] The meanings of the symbols are given in the glossary; if any infusion line or dialysate supply line is missing, there is no corresponding flow rate in the mathematical formula, or the corresponding flow rate is set to zero.

[0278] It should be noted that the above equation does not apply to Q. dial =0 or Q fil =0; in this case, Q can be replaced (artificially) with, for example, 1 or 0.1 ml / h. dial and / or Q fil One or two zero values ​​can be used to move values ​​to infinity. Otherwise, specific equations of pure CVVHD or pure CVVH can be used instead.

[0279] In aspect 75 according to any of the foregoing aspects, the one or more mathematical relationships include an ultrafiltration flow rate mathematical relationship, which makes the ultrafiltration flow rate (Q) of the filtration unit (2) such that... fil ) and the fluid removal rate from the patient (Q PFR ) and the infusion rate per second (Q) in the extracorporeal blood circuit (17) PBP Q cit Q rep.pre Q rep.post Q HCO3 Q ca This is related to, specifically, based on:

[0280] Q fil =Q PBP +· cit +· syr +Q rep.pre +Q rep.post +Q HCO3 +Q PFR +Q ca

[0281] The meanings of the symbols are given in the glossary; if any infusion line is missing, the corresponding flow rate is not present in the mathematical relation, or the corresponding flow rate is set to zero.

[0282] In aspect 76 according to any of the foregoing aspects, the one or more mathematical relations include a blood flow velocity mathematical relation, which makes the blood flow velocity (Q) bw ) and blood fluid velocity (Q) b It is associated with hematocrit (Hct) specifically based on:

[0283] Qbw = Qb ·[(1-Hct)·F p +Hct·Frbc]

[0284] The meanings of the symbols are given in the glossary.

[0285] In aspect 77 according to any of the foregoing aspects, the one or more mathematical relationships include a mathematical relationship for the blood-water flow rate at the inlet of the filtration unit, the mathematical relationship for the blood-water flow rate at the inlet of the filtration unit causing the blood-water flow rate Qbw at the inlet of the filtration unit to be... inlet With blood fluid velocity (Q) bw ), fluid velocity (Q) through the anticoagulant injection line (51) cit ), fluid velocity (Q) through PBP injection line (52) PBP ) and the fluid flow rate (Q) through the pre-dilution infusion line (29). rep.pre One or more of the following are associated, specifically, the mathematical relationship of the blood flow velocity at the inlet of the filtration unit is as follows:

[0286] Qbw inlet =Q bw +Q cit +Q PBP +Q rep.pre +Q syr

[0287] =Q b ·[(1-Hct)·Fp+Hct·Frbc]+Q cit +Q PBP +Q rep.pre +Q syr

[0288] The meanings of the symbols are given in the glossary.

[0289] In aspect 78 according to any of the foregoing aspects, the one or more mathematical relations include a bicarbonate removal mathematical relation, specifically, wherein the bicarbonate removal mathematical relation is:

[0290]

[0291] The meanings of the symbols are given in the glossary.

[0292] In aspect 79 according to any of the foregoing aspects, the one or more mathematical relationships include a mathematical relationship for the plasma water concentration at the filter inlet, which represents the bicarbonate plasma water concentration (Cpw) at the filter inlet. HCO3_inlet The correlation is a function of flow rate, which includes the blood-water flow rate (Q). bw), Blood flow rate at the filter inlet (Qbw) inlet ), fluid velocity (Q) through the anticoagulant injection line (51) cit ), fluid velocity (Q) through PBP injection line (52) PBP ) and the fluid flow rate (Q) through the pre-dilution infusion line (29). rep.pre One or more of the following, and / or associated with the bicarbonate concentration in the fluid flowing in the corresponding infusion line. and patient plasma bicarbonate concentration The function.

[0293] In aspect 80 of the foregoing, the mathematical relationship for the plasma water concentration at the filter inlet is:

[0294]

[0295] The meanings of the symbols are given in the glossary; if any infusion line is missing, the corresponding flow rate is not present in the mathematical relation, or the corresponding flow rate is set to zero.

[0296] In aspect 81 according to any of the foregoing aspects, the one or more mathematical relations include a bicarbonate balance mathematical relation, said bicarbonate balance mathematical relation being based on the bicarbonate balance (J) from CRRT blood processing delivered in amounts per unit time. HCO3_bal Specifically, the mathematical equation for the bicarbonate equilibrium is:

[0297]

[0298] The meanings of the symbols are given in the glossary; if any infusion line or dialysate supply line is missing, there is no corresponding flow rate in the mathematical formula, or the corresponding flow rate is set to zero.

[0299] It should be noted that the above equation assumes that there is no bicarbonate in the ion-displaced (Ca) solution.

[0300] In aspect 82, according to any of the foregoing aspects, the net buffer load mathematical relation of aspect 62 and the bicarbonate balance mathematical relation of aspect 81 (or alternatively, aspect 63+66+78) make the parameter indicating the steady-state acid-base balance in the blood (nNBL; Cp) HCO3_pat The control unit (12) uses the net buffer load mathematical relation of aspect 62 and the bicarbonate balance mathematical relation of aspect 81 (or alternatively, aspect 63+66+78) to calculate the setpoints of the at least two fluid flow rates in association with the at least two fluid flow rates selected in the group.

[0301] In aspect 83 of the aforementioned aspects, the mathematical relationships of aspects 75, 76, 77 and 78 are also used by the control unit (12) to calculate the set values ​​of the at least two flow rates.

[0302] In aspect 84 according to any of the foregoing aspects, the one or more mathematical relationships include a citrate load mathematical relationship, said citrate load mathematical relationship being based on the patient's citrate load (J) in amounts per unit time. cit_load Specifically, the citrate loading (J) cit_load ) is the citrate infusion rate (J) through the anticoagulant infusion line (51). cit_PBP ) and the citrate removal rate (J) of the effluent in the effluent line (13) cit_dial The difference between them, specifically, the mathematical relationship of citrate loading is:

[0303] J citrate_load =J cit_PBP -J cit_dial

[0304] The meanings of the symbols are given in the glossary; if any mass transfer rate is missing, the corresponding mass transfer term is not present in the mathematical relation, or the corresponding value is set to zero.

[0305] In aspect 85 of the foregoing, citrate loading (J) cit_load Specifically, the citrate removal rate of the effluent (J) cit_dial ) is the patient's citrate metabolism clearance (K cit_met The function of metabolic clearance, specifically, is based on patient body weight (BW), for example, metabolic clearance is proportional to patient body weight (BW), determined as follows:

[0306]

[0307] Among them, the patient's citrate metabolism clearance (K cit_met ) is measured in [ml / min], and body weight (BW) is measured in [kg].

[0308] In aspect 86, which is based on either of the two aforementioned aspects, the citrate loading (J) cit_load ) is citrate scavenger (K cit The function of ).

[0309] According to aspect 87 of any of the three aspects mentioned above, the citrate loading J cit_load ) is the fluid velocity (Q) of the fluid flowing out of the material pipeline (13). eff The function of ), specifically, where citrate scavenging (K citThe outflow velocity (Q) is estimated to be equal to the outflow velocity of the material. eff ).

[0310] In aspect 88 according to any of the foregoing aspects, citrate loading (J) cit_load ) is a function of citrate clearance, and according to the citrate clearance mathematical relation of the one or more mathematical relations, citrate clearance (K) cit ) is a function of one or more flow rates, specifically including the fluid flow rate (Q) through the dialysate supply line (8). dial The ultrafiltration rate (Q) in the filtration unit (2) fil ) and plasma flow rate (Qpw) at the inlet of the filtration unit inlet One or more of the following.

[0311] According to aspect 89 of the foregoing, citrate loading (J) cit_load ) is a function of the filtration unit (2) used for CRRT treatment, specifically the citrate sieving coefficient (SC). cit ) and / or the surface area of ​​the filter unit and the diffusion mass transfer resistance of citrate (S / RT) cit A function of the ratio of ).

[0312] In aspect 90, according to one of the foregoing aspects, the one or more mathematical relations include the following citrate scavenging mathematical relations:

[0313]

[0314]

[0315]

[0316] The meanings of the symbols are given in the glossary; if any infusion line or dialysate supply line is missing, there is no corresponding flow rate in the mathematical formula, or the corresponding flow rate is set to zero.

[0317] In aspect 91 according to any of the foregoing aspects, the one or more mathematical relations include a plasma flow rate mathematical relation that correlates plasma flow rate (Qp) with blood fluid flow rate (Qb) and hematocrit (Hct), specifically according to:

[0318] Qp = Q b ·(1-Hct)

[0319] The meanings of the symbols are given in the glossary.

[0320] In aspect 92 according to any of the foregoing aspects, the one or more mathematical relations include a plasma flow rate mathematical relation that correlates the plasma flow rate (Qpw) with the blood fluid flow rate (Qb) and the hematocrit (Hct), specifically according to:

[0321] Qpw = Q b ·(1-Hct)·F p

[0322] The meanings of the symbols are given in the glossary.

[0323] In aspect 93 according to any of the foregoing aspects, the one or more mathematical relationships include a mathematical relationship for the plasma flow rate at the inlet of the filtration unit, which makes the plasma flow rate Qpw at the inlet of the filtration unit... inlet With plasma flow rate (Q) pw ), fluid velocity (Q) through the anticoagulant injection line (51) cit ), fluid velocity (Q) through PBP injection line (52) PBP ) and the fluid flow rate (Q) through the pre-dilution infusion line (29). rep.pre One or more of the following are associated, specifically, the mathematical relationship for the blood flow velocity at the inlet of the filtration unit is:

[0324] Qpw inlet =Qpw+Q cit +Q syr +Q PBP +Q rep.pre

[0325] =Q b ·(1-Hct)·Fp+Q cit +Q PBP +Q rep.pre

[0326] The meanings of the symbols are given in the glossary; if any infusion line or dialysate supply line is missing, there is no corresponding flow rate in the mathematical formula, or the corresponding flow rate is set to zero.

[0327] In aspect 94 according to any of the foregoing aspects, the citrate loading J cit_load Optionally, the citrate dosage (D) cit ) and blood flow velocity (Q) b The function of D, that is, according to D cit ·Q b Or the citrate flow rate (Q) in the anticoagulant line (51). cit ) and total citrate concentration (C cit_pbpThe function of ), that is, according to · cit ·C citPBP .

[0328] In aspect 95 according to any of the foregoing aspects, the one or more mathematical relations include a citrate loading mathematical relation, which makes the citrate loading (J) cit_load The citrate dose (D) at the inlet of the filtration unit (2) cit ) and / or blood flow velocity (Q b ) and / or citrate removal (K cit ) and / or plasma flow rate (Q pw_inlet This is related, specifically, the mathematical relationship for citrate loading is:

[0329]

[0330] or:

[0331]

[0332] The meanings of the symbols are given in the glossary.

[0333] In aspect 96 according to any of the foregoing aspects, the net buffer load mathematical relation of aspect 67 and the citrate load mathematical relation of aspect 95 make the parameter (nNBL; Cp) indicating the steady-state acid-base balance in the blood... HCO3_pat Associated with at least two fluid flow rates selected from the group, the control unit (12) uses the net buffer load mathematical relation of aspect 67 and the citrate load mathematical relation of aspect 95 to calculate the set values ​​of the at least two fluid flow rates.

[0334] In aspect 97 of the aforementioned aspects, the mathematical relationships of aspects 85, 90, 91, 92 and 83 are also used by the control unit (12) to calculate the set values ​​of the at least two fluid flow rates.

[0335] In aspect 98 according to any of the foregoing aspects, the control unit (12) is configured to calculate two or more fluid flow rates selected in the group.

[0336] In aspect 99 according to any of the foregoing aspects, the control unit (12) is configured to calculate three or more fluid flow rates selected in the group.

[0337] In the 100th aspect according to any of the foregoing aspects, the control unit (12) is configured to calculate four or more fluid flow rates selected in the group.

[0338] In aspect 101 according to any of the foregoing aspects, the control unit (12) is configured to receive a plurality of, i.e., 'n', clinical prescription parameters and calculate a plurality of, i.e., 'm', fluid flow rates selected from the group, wherein the plurality of fluid flow rates are higher than or equal to the plurality of clinical prescription parameters, i.e., m≥n.

[0339] In aspect 102 according to any of the foregoing aspects, the control unit (12) is configured to receive a plurality of, i.e., 'n', clinical prescription parameters, including the prescribed dialysis dose (D set ) and the parameters (nNBL; Cp) that indicate the homeostatic acid-base balance in the patient's blood. HCO3_pat And one or more of the following:

[0340] ο Local anticoagulant doses such as citrate (D cit Adding parameters such as calcium ion regeneration solution parameters (CaComp; D) ca );

[0341] ο Fluid removal rate from the patient (Q PFR );and

[0342] Blood flow velocity (Q) b );

[0343] The control unit (12) is further configured to calculate a plurality of fluid flow rates selected in the group, namely “m”, wherein the plurality of fluid flow rates are greater than or equal to the number of the clinical prescription parameters, i.e., m≥n.

[0344] In aspect 103, which is based on either of the two aspects mentioned above, if m > n, the control unit (12) provides optional additional treatment configuration parameters, which add additional mathematical relationships for calculating “m” fluid flow rates. Specifically, if m = n + 1, then one additional treatment configuration parameter is optional, and if m = n + 2, then two additional treatment configuration parameters are optional.

[0345] In aspect 104, according to any of the foregoing aspects, the further mathematical relations include one or more of convection-diffusion relations, blood pre-dilution relations, and pre- and post-infusion relations.

[0346] In aspect 105 according to any of the foregoing aspects, the device is configured to perform localized anticoagulation treatment and includes:

[0347] -An anticoagulant infusion line (51), one end of which is connected to the blood extraction line in the area of ​​the blood extraction line, which is located upstream of the blood pump (21) when in use;

[0348] - A source (10) of local anticoagulant, which supplies anticoagulant to the anticoagulant delivery line (51), the source specifically including citrate;

[0349] - An ion-balanced infusion line (74), one end of which is connected to the blood return line (7) or to the patient catheter, and

[0350] - A source (11) of ion balance solution, which supplies ion balance solution to the ion balance delivery line (74), the source specifically including calcium ions;

[0351] The control unit (12) is configured to execute the flow rate setting procedure, which includes:

[0352] - Receiving patient prescriptions, the receiving process also includes:

[0353] ο Allow input of the specified dose of anticoagulant to be delivered (D) cit The set value of )

[0354] - Determine the operating parameters, including using one or more of the mathematical relationships, to calculate the at least two fluid velocities, at least the fluid velocity (Q) through the anticoagulant delivery line (51). cit ) and the fluid flow rate (Q) through the ion balance delivery line (74). ca The setting value of ).

[0355] In aspect 106 of the foregoing, at least based on the prescribed dialysis dose (D) set The set value, especially the blood flow rate (Q) through the extracorporeal blood circuit (17). b When the set value of ) is determined as the operating parameter by the control unit (12), the fluid flow rate (Q) through the anticoagulant injection line (51) is calculated at least. cit ) and / or the fluid flow rate (Q) through the ion balance delivery line (74). ca The setting value of ).

[0356] In aspect 107 of the foregoing, at least based on the parameters (nNBL; Cp) indicating the steady-state acid-base balance in the blood. HCO3_pat The target value, particularly when the blood flow rate (Q) through the extracorporeal blood circuit (17) is... b When the set value of ) is determined as the operating parameter by the control unit (12), the fluid flow rate (Q) through the anticoagulant injection line (51) is calculated at least. cit ) and / or the fluid flow rate (Q) through the ion balance delivery line (74). ca The setting value of ).

[0357] In aspect 108 according to any of the foregoing aspects, one or more of the mathematical relations make the parameter (nNBL; Cp) indicating the homeostatic acid-base balance in the patient's blood... HCO3_pat ) and citrate (J) infused to the patient met_cit This is related to an estimate of the amount of bicarbonate produced per unit time by the metabolism of citrate, specifically, where the metabolism of citrate load produces 3 moles of bicarbonate per mole of citrate at steady state, i.e.:

[0358] J met_cit =3·J cit_load .

[0359] In aspect 109 according to any of the foregoing aspects, the control unit (12) is further configured to control the actuator to regulate the flow of fluid based on the set value and calculated value of the fluid flow rate.

[0360] In aspect 110 according to any of the foregoing aspects, the actuator (24, 25, 26, 31, 53, 54, 65, 75) for regulating fluid flow includes a pump (e.g., a rotary pump and / or a peristaltic pump) and / or a valve.

[0361] In aspect 111 according to any of the foregoing aspects, the one or more mathematical relations make the parameters (nNBL; Cp) indicative of the steady-state acid-base balance in the blood of patients who must undergo CRRT blood treatment. HCO3_pat It is associated with at least two fluid flow rates selected from the group.

[0362] In aspect 112 according to any of the foregoing aspects, the control unit (12) is further configured to transmit the predetermined dose value (D) by means of the predetermined dose value (D). set The target values ​​of the parameters indicating the steady-state acid-base balance in the blood are applied to the mathematical relationship to calculate the set values ​​of at least two fluid flow rates.

[0363] In aspect 113, which is based on either of the two aspects mentioned above, the control unit (12) is further configured to calculate set values ​​for at least two fluid flow rates by applying clinical prescription parameters to the mathematical relation.

[0364] In aspect 114, which is based on any of the three aspects mentioned above, the clinical prescribing parameters also include the patient's fluid removal rate (Q) according to the mathematical relationship. pfr ).

[0365] In aspect 115, which is based on any of the four aspects mentioned above, the clinical prescribing parameters also include the blood flow rate (Q) in the extracorporeal blood circuit (17). b ).

[0366] In aspect 116, which is based on any of the aforementioned five aspects, the clinical prescribing parameters also include specifying the dialysis dose (D). set ) and parameters indicating the homeostatic acid-base balance in a patient's blood (nNBL; Cp HCO3_pat ).

[0367] In aspect 117, which is based on any of the aforementioned six aspects, the clinical prescribing parameters also include the local anticoagulant dose (D). cit ) and / or ion regeneration solution parameters (CaComp; D ca ).

[0368] In aspect 118 according to any of the foregoing aspects, the memory (16) stores a plurality of additional mathematical relationships relating at least two fluid flow rates selected in the group to each other.

[0369] In aspect 119 of the foregoing, the CRRT device includes: - a predetermined number of pre-dilution lines selected from the group consisting of: the pre-dilution infusion line (29), one end of which is connected to the blood extraction line (6); the pre-blood pump-PBP infusion line (52), one end of which is connected to the blood extraction line in the region of the blood extraction line, the blood extraction line being located upstream of the blood pump (21) in use; and the anticoagulant infusion line (51), one end of which is connected to the blood extraction line in the region of the blood extraction line, the blood extraction line being located upstream of the blood pump (21) in use;

[0370] - A predetermined number of post-dilution lines selected from the group consisting of: the post-dilution infusion line (63) connected at one end to the blood return line (7); the post-dilution bicarbonate infusion line (23) connected at one end to the blood return line (7); and the ion balance infusion line (74) connected at one end to the blood return line (7) or to a patient catheter;

[0371] The further mathematical relations stored in the memory include one or more of the following:

[0372] - Convection-diffusion relationship, which determines the total fluid velocity (Q) passing through the preset number of pre-dilution lines and post-dilution lines. rep.pre +Q rep.post +Q pbp +Q HCO3 +Q ca +Q cit ) and the fluid flow rate (Q) through the dialysate supply line (8) dial Related to,

[0373] - Blood pre-dilution relationship, blood (Qb ) or plasma (Q p The flow rate of the blood sample is the same as the total fluid flow rate (Q) infused into the blood collection line through the predetermined number of pre-dilution lines. rep.pre +Q pbp +Q cit Related to,

[0374] - The relationship between the preceding and following stages will determine the total fluid flow rate (Q) through the preset number of pre-dilution pipelines. rep.pre +Q pbp +Q cit ) and the total fluid flow rate (Q) through the preset number of post-dilution pipelines rep.post +Q HCO3 +Q ca (related to)

[0375] In aspect 120 of the foregoing, the convection-diffusion relationship defines the total fluid velocity (Q) through the predetermined number of pre-dilution lines and post-dilution lines. rep.pre +Q rep.post +Q pbp +Q HCO3 +Q ca +Q cit ) and the fluid flow rate (Q) through the dialysate supply line (8) dial The first division between the pre-dilution and post-dilution lines, specifically, the convection-diffusion relationship defines a first percentage division or a first ratio R1, which will affect the total fluid velocity (Q) passing through the predetermined number of pre-dilution and post-dilution lines. rep.pre +Q rep.post +Q pbp +Q HCO3 +Q ca +Q cit ) divided by the fluid flow rate (Q) through the dialysate supply line (8). dial The first percentage division or first ratio R1 obtained is obtained from this.

[0376] In aspect 121, which is based on either of the two aspects mentioned above, the blood predilution relationship defines a second ratio R2, which represents the total fluid flow rate (Q) infused into the blood extraction line (6) through the predetermined number of predilution lines. rep.pre +Q pbp +Q cit ) divided by blood (Q) b ) or plasma (Q p The second ratio R2 is obtained by measuring the flow rate of the flow.

[0377] In aspect 122, based on any of the three aspects mentioned above, the preceding-following relationship defines the total fluid velocity (Q) through the predetermined number of pre-dilution lines. rep.pre +Qpbp +Q cit ) and the total fluid flow rate (Q) through the preset number of post-dilution pipelines rep.post +Q HCO3 +Q ca The third division between the pre- and post-dilution lines, specifically, the pre- and post-dilution relationship defines a third percentage division or a third ratio R3, which will affect the total fluid flow rate (Q) through the predetermined number of pre-dilution lines. rep.pre +Q pbp +Q cit ) divided by the total fluid flow rate (Q) through the preset number of post-dilution pipelines rep.post +Q HCO3 +Q ca This yields the third percentage division or the third ratio R3.

[0378] In aspect 123 according to any one of the three aspects mentioned above, the control unit (12) is further configured to store a preset value or preset range for each of the first, second and third divisions / ratios R1, R2, R3.

[0379] In aspect 124, which is based on any of the four aspects mentioned above, the control unit (12) is further configured to allow the operator to input a set value or set range for each of the first, second, and third divisions / ratios R1, R2, R3.

[0380] In aspect 125 of any of the seven aspects mentioned above, the control unit (12) is further configured to allow a user to select one or more treatment configurations, said treatment configurations including at least one of the additional mathematical relations, and optionally including two or three of the additional mathematical relations, and by means of a prescribed dose (D) input by the operator. set The set values ​​and parameters indicating the steady-state acid-base balance in the patient's blood (nNBL; Cp) HCO3_pat The target value is applied to mathematical relations and additional mathematical relations selected by the user to calculate at least two set values ​​for the fluid flow rate.

[0381] In aspect 126 according to any of the foregoing aspects, the control unit (12) is further configured to allow a user to select one or more treatment configurations, wherein selecting the treatment configuration includes net buffer load (nNBL; NBL) and steady-state patient bicarbonate (Cp) HCO3_pat Between these parameters, select the blood parameters (nNBL; Cp) of patients who must undergo CRRT blood processing. HCO3_pat ).

[0382] In aspect 127 according to any of the foregoing aspects, the control unit (12) is further configured to allow a user to select one or more treatment configurations, wherein selecting the treatment configuration includes selecting a specified dialysis dose (D). set The definition of ).

[0383] In aspect 128 according to any of the foregoing aspects, the control unit (12) is further configured to allow a user to select one or more treatment configurations, wherein selecting the treatment configuration includes selecting blood flow rate as a clinical prescription parameter or as an operational parameter.

[0384] In aspect 129 according to any of the foregoing aspects, the control unit (12) is further configured to allow user input of processing configuration values, including receiving one or more of the following inputs:

[0385] -Patient weight (BW);

[0386] -The patient's hematocrit (Hct);

[0387] - Filter unit parameters, such as filter mass transfer coefficient (K0.A), sieving coefficient (SC), and solute removal (K0.A) based on surface area. sol ), filter unit surface (S), diffusion mass transfer resistance (RT), or any combination thereof;

[0388] - The concentration of substances supplied to one or more containers of the pipelines (29, 63, 23, 74, 8, 52, 51), specifically the concentration of bicarbonate and / or lactate and / or citrate and / or calcium.

[0389] In aspect 130 of the foregoing, the control unit (12) is further configured to calculate setpoints for at least two fluid flow rates by applying the processing configuration value to the mathematical relation.

[0390] In aspect 131, which is based on either of the two aspects mentioned above, the concentration of the substance in one or more containers is determined by the operator of each respective container through a user interface (15) connected to the control unit (12), and / or by the control unit (12) associating an identification code on each respective container with the corresponding substance concentration.

[0391] In aspect 132, which is based on any of the three aspects mentioned above, the filter unit parameters for the filter unit are input by the operator, and / or the filter unit parameters are determined by the control unit (12) by associating the identification code on the filter unit (2) with the filter unit parameters.

[0392] In aspect 133 according to any of the foregoing aspects, the device includes a dialysate supply line (8) connected to the inlet of the sub-chamber, wherein the control unit is configured to be based on at least a portion of the clinical prescription parameters and / or the prescribed dialysis dose value (D). set To calculate the fluid flow rate (Q) in the dialysate supply line (8). dial The set value of ) (not set by the operator), at least a portion of the clinical prescription parameters are specifically set by the operator, and the parameters (nNBL; Cp) indicate steady-state acid-base balance. HCO3_pat The target value.

[0393] In aspect 134 according to any of the foregoing aspects, the device comprises: a pre-dilution infusion line (29) connected at one end to a blood extraction line (6), specifically, a blood pump (21) activated corresponding to a segment of the blood extraction line (6), and the pre-dilution infusion line (29) connected to the blood extraction line (6) downstream of the blood pump (21), wherein the control unit is configured to, based on at least a portion of the clinical prescription parameters, particularly the parameters indicating the steady-state acid-base balance (nNBL; Cp) set by the operator. HCO3_pat The target value and / or the dialysis dose value (D) based on the specified value. set To calculate the fluid velocity (Q) in the pre-dilution injection line (29). rep.pre The setting value is not set by the operator.

[0394] In aspect 135 according to any of the foregoing aspects, the device includes: a post-dilution infusion line (63) connected at one end to a blood return line (7), wherein the control unit is configured to indicate, based on at least a portion of clinically prescribed parameters, particularly the parameters (nNBL; Cp) indicating a steady-state acid-base balance set by the operator. HCO3_pat The target value and / or the dialysis dose value (D) based on the specified value. set To calculate the fluid velocity (Q) in the post-dilution injection pipeline (63). rep.pre The setting value is not set by the operator.

[0395] In aspect 136 according to any of the foregoing aspects, the device comprises: a post-dilution bicarbonate infusion line (23), one end of which is connected to a blood return line (7), wherein the control unit is configured based on at least a portion of clinically prescribed parameters, particularly the parameters (nNBL; Cp) indicating a steady-state acid-base balance set by the operator. HCO3_pat The target value and / or the dialysis dose value (D) based on the specified value. setThe fluid velocity (Q) in the post-diluted bicarbonate injection pipeline (23) is calculated. HCO3 The setting value is not set by the operator.

[0396] In aspect 137 according to any of the foregoing aspects, the device includes an ion-balancing infusion line (74) connected at one end to a blood return line (7) or a patient catheter, wherein the control unit is configured based on at least a portion of clinically prescribed parameters, particularly the parameters (nNBL; Cp) indicating a steady-state acid-base balance set by the operator. HCO3_pat The target value and / or the dialysis dose value (D) based on the specified value. set To calculate the fluid velocity (Q) in the ion balance delivery line (74). ca The setting value is not set by the operator.

[0397] In aspect 138 according to any of the foregoing aspects, the device includes a pre-blood pump-PBP infusion line (52), one end of which is connected to the blood extraction line in the region of the blood extraction line, the blood extraction line being located upstream of the blood pump (21) in use, specifically, the blood pump (21) being activated corresponding to a segment of the blood extraction line (6), wherein the control unit is configured to indicate, based on at least a portion of the clinical prescription parameters, particularly the parameters (nNBL; Cp) indicating a steady-state acid-base balance set by the operator. HCO3_pat The target value and / or the dialysis dose value (D) based on the specified value. set ), to calculate the fluid velocity (Q) in the infusion line (52) of the pre-blood pump. PBP The setting value is not set by the operator.

[0398] In aspect 139 according to any of the foregoing aspects, the device includes an anticoagulant infusion line (51) connected at one end to the blood extraction line in the region of the blood extraction line, the blood extraction line being located upstream of the blood pump (21) in use, specifically the blood pump (21) being activated corresponding to a segment of the blood extraction line (6), wherein the control unit is configured to be based on at least a portion of the clinical prescription parameters, particularly the parameters indicating the steady-state acid-base balance (nNBL; Cp) set by the operator. HCO3_pat The target value and / or the dialysis dose value (D) based on the specified value. set To calculate the fluid flow rate (Q) in the anticoagulant injection line (51). cit The setting value is not set by the operator.

[0399] In aspect 140 according to any of the foregoing aspects, the operating parameters further include the blood flow rate (Q) in the extracorporeal blood circuit (17). b The control unit is configured to indicate, based on at least a portion of clinical prescription parameters, particularly the parameters (nNBL; Cp) of the steady-state acid-base balance set by the operator. HCO3_pat The target value and / or the dialysis dose value (D) based on the specified value. set To calculate the blood flow velocity (Q) in the extracorporeal blood circuit (17). b The setting value is not set by the operator.

[0400] In aspect 141 according to any of the foregoing aspects, the control unit (12) is configured to calculate three or more, particularly four or more, setpoints for the fluid flow rate selected in the group.

[0401] In aspect 142 according to any of the foregoing aspects, the control unit (12) is configured to calculate the patient fluid removal rate (Q) of the patient. PFR The setting value of ).

[0402] In aspect 143 according to any of the foregoing aspects, the specified dialysis dose value (D) set This includes specified values ​​for flow velocity or combinations of flow velocities.

[0403] In aspect 144 according to any of the foregoing aspects, the specified dialysis dose value (D) set This includes a specified value selected from a group, the group comprising:

[0404] - Effluent dose-flow rate (D eff_set ), which is the specified value of the flow velocity through the effluent pipeline (13),

[0405] - Convection dose rate (D conv_set ), which is through all infusion lines (Q rep.pre Q rep.post Q PBP Q cit Q ca Q HCO3 The flow rate and patient fluid removal rate (Q) PFR The specified value of the sum of the ) can optionally include a correction for the specified convective dose flow rate value for pre-dilution.

[0406] -Diffusion dose flow rate (D dial_set ), which is the flow rate (Q) through the dialysis fluid line. dial The specified value,

[0407] -Urea dosage (D) urea_set This is the estimated urea clearance value.

[0408] - Clearance dose (K solute_set ), which is the estimated clearance value for a given solute.

[0409] In aspect 145 according to any of the foregoing aspects, the control unit (12) is configured to, when the infusion line (29; 51; 52) is present and fluid is delivered upstream of the processing unit (2), multiply the dose value by the dilution factor (F). dilution To correct for the selected one of the above-mentioned limited doses, the dilution factor (F) is used to account for the pre-dilution effect. dilution If the value is less than 1, as shown in the following formula:

[0410] Dose corr_xxx =F dilution ×Dose _xxx (where xxx = eff, conv, dial).

[0411] In aspect 146 according to any of the foregoing aspects, the control unit (12) is configured to use input or calculated blood flow (Q) b The blood pump (21) is controlled by the set value of ).

[0412] In aspect 147 according to any of the foregoing aspects, the CRRT device further includes a graphical user interface (15) connected to the control unit (12), the control unit being configured to:

[0413] - A prompt appears on the graphical user interface prompting the user to enter or select the specified dialysis dose (D). set The setting value of ) is marked.

[0414] - Display prompts on the graphical user interface to allow the user to input or select the parameters (nNBL; Cp) that indicate the steady-state acid-base balance in the patient's blood. HCO3_ The target value of ) is marked.

[0415] - Displaying markers on the graphical user interface that allow the user to select one or more additional mathematical expressions, including markers that allow the user to input or select set values ​​for the mathematical expressions, specifically inputting or selecting one or more of the first, second, and third ratios.

[0416] -Detect the choice of further mathematical relations, and

[0417] - Use the additional mathematical formula to calculate the set values ​​for at least two fluid flow rates selected in the group.

[0418] In aspect 148 according to any of the foregoing aspects, the actuator for regulating the flow of fluid through the fluid line includes: a pre-injection pump (31) for regulating the flow through the pre-dilution injection line (29); and / or a post-injection pump (65) for regulating the flow through the post-dilution injection line (63).

[0419] In aspect 149 according to any of the foregoing aspects, the dialysate supply line (8) is connected to the inlet of the sub-chamber (4), and the actuator for regulating the flow of fluid through the fluid line includes at least one dialysate pump (25) for regulating the flow through the dialysate supply line (8).

[0420] In the 150th aspect according to any of the foregoing aspects, the actuator for regulating the flow of fluid through the fluid line includes: a PBP infusion pump (53) for regulating the flow through the pre-blood pump-PBP infusion line (52); and / or an anticoagulant pump (54) for regulating the flow through the anticoagulant infusion line (51).

[0421] In aspect 151 according to any of the foregoing aspects, the actuator for regulating the flow of fluid through the fluid line comprises: a bicarbonate pump (24) for regulating the flow through the post-dilution bicarbonate infusion line (23); and / or an ion balance pump (75) for regulating the flow through the ion balance infusion line (74).

[0422] In aspect 152 according to any of the foregoing aspects, the CRRT apparatus further includes a collection container (62) connected to the end of the outflow fluid line (13) to collect used dialysate.

[0423] In aspect 153 according to any of the foregoing aspects, the CRRT device further includes a replacement container (30) for fresh fluid connected to the end of the pre-dilution infusion line (29), specifically, the container (30) is a bag containing the replacement solution.

[0424] In aspect 154 according to any of the foregoing aspects, the CRRT device further includes a secondary container (64) for fresh fluid connected to the end of the post-infusion line (63), specifically, the container (64) being a bag containing a replacement solution.

[0425] In aspect 155 according to any of the foregoing aspects, the CRRT device further includes a liquid container (14) for fresh fluid connected to the end of the dialysate supply line (8), specifically, the container (14) is a bag containing fresh dialysate.

[0426] In aspect 156 according to any of the foregoing aspects, the CRRT device further includes a PBP container (18) for fresh fluid connected to the end of the pre-blood pump infusion line (52), specifically, the container (18) is a bag containing a replacement solution.

[0427] In aspect 157 according to any of the foregoing aspects, the CRRT device further includes a container (10) for a local anticoagulant, the container (10) being connected to the end of the anticoagulant infusion line (51), specifically, wherein the container (10) is a bag and contains citrate and optionally citric acid.

[0428] In aspect 158 ​​according to any of the foregoing aspects, the CRRT apparatus further includes a bicarbonate container (24) connected to the end of a post-diluted bicarbonate infusion line (23), specifically, the container (24) being a bag containing a bicarbonate solution, optionally a concentrated bicarbonate solution.

[0429] In aspect 159 according to any of the foregoing aspects, the CRRT device further includes an ion balance solution container (11) connected to the end of the ion balance infusion line (74), specifically, the container (11) being a bag or syringe containing a calcium concentrate solution.

[0430] In aspect 160 according to any of the foregoing aspects, the CRRT device further includes one or more scales for weighing one or more of the containers, specifically, the device includes a corresponding scale for each of the containers, the one or more scales being connected to the control unit and sending a corresponding weight signal to the control unit.

[0431] In aspect 161 according to any of the foregoing aspects, the memory (16) stores one or more optimization criteria, and the control unit (12) is configured to calculate a set value of fluid flow rate per second by applying the optimization criteria.

[0432] In aspect 162 of the foregoing, the optimization criteria include a first optimization criterion that specifies that the emptying time of fresh fluid in containers (10; 18; 30; 64; 28; 11; 14) and / or the filling time of collection container (62) are substantially the same as or multiples of the emptying time of one or more other fresh fluid containers.

[0433] In aspect 163, which is based on either of the two aspects mentioned above, the optimization criterion includes a second optimization criterion that specifies that fluid consumption through the fluid pipeline is minimized.

[0434] In aspect 164, which is based on any of the three aspects mentioned above, the optimization criteria include a third optimization criterion that specifies maximizing the lifetime of the filter unit (2).

[0435] In aspect 165, which is based on any of the four aspects mentioned above, the optimization criterion includes a fourth optimization criterion that specifies that the urea clearance or dialysis rate for a given solute is maximized.

[0436] In aspect 166, which is based on any of the five aspects mentioned above, the control unit (12) is configured to allow a user to select one or more of the criteria and to calculate the at least one flow rate using the selected criteria.

[0437] In aspect 167, according to any of the preceding six aspects, the control unit (12) is configured to allow a user to select one or more of the stated criteria and one or more of the stated further mathematical relations, and to use the selected criteria and the selected additional mathematical relations to calculate at least three or more flow rates.

[0438] In aspect 168 according to any of the foregoing aspects, the control unit (12) is configured to determine whether the further mathematical relations of the selection are compatible or conflicting with each other, and then:

[0439] Provided the selected additional mathematical relation is compatible, the flow rate per second is calculated based on the selected additional mathematical relation and clinical prescription parameters.

[0440] If one or more of the selected additional mathematical relations conflict with each other, then one or more of the following sub-steps are executed:

[0441] Notify users,

[0442] • Allows users to assign priorities to each selected additional mathematical expression.

[0443] • Priority ranking is assigned to selected supplementary mathematical expressions, where the priority ranking is predetermined or user-adjustable. Then, once the flow rate has been calculated from the preferred supplementary mathematical expressions, the supplementary mathematical expressions are ignored.

[0444] • Use preset rules to define trade-offs between additional mathematical relations.

[0445] In aspect 169 according to any of the foregoing aspects, the control unit (12) is configured to store in memory (16) the volume or weight of fresh fluid contained in each container (10; 18; 30; 64; 28; 11; 14) and optionally in collection container (62).

[0446] In aspect 170 of the foregoing, the volume or weight of the fluid is detected by a sensor associated with each respective container and connected to the control unit (12).

[0447] In aspect 171 of the foregoing, the volume of the fluid is detected based on a signal associated with a corresponding pump acting on an infusion line fluidly connected to the respective container, such as a signal from a Hall sensor associated with a peristaltic pump or based on the position of a plunger in an injection pump.

[0448] In aspect 172 of the foregoing, the fluid volume is detected based on a signal associated with a corresponding pump of one or more of the following:

[0449] -Ion balance delivery pipeline (74);

[0450] - Syringe fluid line (22);

[0451] -Anticoagulant infusion pipeline (51).

[0452] In the 173rd aspect of the aforementioned aspect 170, the sensor is a weight scale for weighing at least one of the containers.

[0453] In the 174th aspect of the aforementioned aspect 170, the sensor is a droplet counter that determines weight and / or volume based on droplet counting.

[0454] In a 175th aspect according to any of the foregoing aspects, a data carrier is provided that includes instructions, when executed by a control unit of a device according to any of the foregoing aspects, such that the instructions configure the control unit to perform the corresponding steps described in the foregoing aspects. Attached Figure Description

[0455] Aspects of the invention are illustrated in the accompanying drawings, which are provided by way of non-limiting example, wherein:

[0456] Figure 1 A CRRT extracorporeal blood processing device according to aspects of this disclosure is shown;

[0457] Figures 2 to 6 A schematic representation of a blood processing device according to aspects of this disclosure is shown;

[0458] Figure 7 Examples illustrating aspects of the invention Figures 1 to 6 A flowchart for calculating the set flow rate in a type of CRRT extracorporeal blood processing device. Detailed Implementation

[0459] As described above, extracorporeal blood processing (dialysis) can be used for patients with rapidly declining kidney function (referred to as acute renal failure) or slowly deteriorating kidney function (referred to as stage 5 chronic kidney disease (or end-stage renal disease)). In the following description, some embodiments of the extracorporeal blood processing device will first be described as primarily suited or designed for intensive care treatment. Citrate local anticoagulation will then be introduced, followed by the definition of steady-state acid-base balance parameters. Methods for simplifying and / or assisting CRRT prescription based on meaningful clinical parameters will then be described, and these methods can be implemented in any of the described embodiments, as will be apparent from the following description.

[0460] definition

[0461] Unless otherwise defined, all technical and scientific terms used have the same meaning as commonly understood by one of ordinary skill in the art.

[0462] The term "downstream" refers to the position of the first component relative to the second component in a flow path, where the fluid will pass the second component before the first component during normal operation. The first component can be considered "downstream" of the second component, while the second component is "upstream" of the first component. Figure 1 The direction of fluid circulation during normal operation of device 1 is shown (indicated by reference numeral 200).

[0463] "Dialysis fluid" is defined as the treatment fluid introduced into the second chamber of filtration unit 2. Dialysis fluid can be prepared online or pre-packaged in sterile bags. Typically, in CRRT equipment / applications, both dialysis fluid and replacement fluid (and possibly local anticoagulant fluid and / or ion regeneration solution fluid) are packaged in (disposable) bags.

[0464] "Dialysis fluid" or "effluent" is defined as the fluid exiting the second chamber of filtration unit 2. Dialysis fluid or effluent is used dialysis fluid, including uremic toxins removed from the blood, and may include ultrafiltration fluid.

[0465] We define a “local anticoagulant” as a substance that, once mixed with extracorporeal blood, can significantly prevent blood clotting in the extracorporeal blood circuit and can be rapidly metabolized by the patient, thus avoiding systemic anticoagulation.

[0466] We define “net buffer load” during extracorporeal blood processing (such as CRRT) as bicarbonate produced by the metabolism of bicarbonate precursors (e.g., citrate and / or lactate infused to the patient). met_cit J met_lact Bicarbonate balance from extracorporeal blood therapy (J) HCO3_bal(This may be matched with the patient's net loss or net gain) and a combination of acid infusion (e.g., the citrate content from the anticoagulant solution, as relevant). Mathematically, the net buffer load (mmol / h) used below is generally defined as:

[0467] J buffer_load =J met_cit +J HCO3_bal +J met_lact -J H+

[0468] We define “citrate dose” as the amount of citrate injected per liter of treated blood (mmol / L blood); it defines the strength of citrate’s anticoagulant effect.

[0469] We define a patient's "citrate load" as the rate at which citrate returns to the patient (mmol / h).

[0470] J citrate_load =J cit_PBP -J cit_eff

[0471] We define “bicarbonate balance” as the net rate of bicarbonate infusion or loss during extracorporeal blood processing, matched with the difference between the rate of infusion of dialysate and / or replacement fluid and the rate of bicarbonate removal from the dialysate.

[0472] J HCO3_bal =J HCO3_inf -J HCO3_eff

[0473] We define “calcium compensation” (or calcium compensation parameter) as the relative dose of calcium infused in the dialysate to compensate for the estimated calcium loss, expressed as a percentage.

[0474] We define “total calcium concentration” (specifically, total calcium concentration in the effluent) as the total amount of calcium per unit volume of fluid in the effluent, including ionic calcium and bound calcium.

[0475] We define “K0A” as the mass transfer-area coefficient of the filtration unit, where K0 is the clearance at infinite blood and dialysis fluid flow rates, and A is the surface area of ​​the filtration unit. “K0A” is specific to a given solute and therefore varies depending on the specific solute being considered.

[0476] In this application, the term "citrate" refers to a component in the form of a citrate, such as its sodium, magnesium, calcium, or potassium salt. Citric acid (denoted as C6H8O7) is progressively deprotonated, therefore "citrate" includes all different forms of citrate (denoted as C6H5O7). 3- ), hydrogen citrate (represented as C6H6O7) 2-) and dihydrogen citrate (represented as C6H7O) 7- ).

[0477] The term "citrate" or "total citrate" refers to the total amount of citric acid and any of its salts (such as its sodium, magnesium, calcium, or potassium salts). In other words, "total citrate" is the sum of free citrate ions and citrate-containing complexes and ion pairs.

[0478] The term "buffer" refers to bicarbonate or bicarbonate precursors, such as lactate, citrate, or acetate.

[0479] We define the “number of degrees of freedom” as the difference between the number of operational flow rates to be calculated and the number of prescription parameters.

[0480] Vocabulary

[0481] The following terms / parameters are used consistently in the equations provided in the detailed description of the operation of the extracorporeal blood processing device below.

[0482]

[0483]

[0484]

[0485]

[0486]

[0487] It should be noted that the values ​​of the constants mentioned above are exemplary. For example, the patient's plasma bicarbonate concentration may be set at different levels, such as 27 mM, depending on the decision of the medical personnel; the normalized net buffer load may also use different values, such as 0.15 mmol / h / kg. Furthermore, other constants may be estimated with higher (or lower) precision without affecting other parts of this specification.

[0488] Extracorporeal blood processing equipment specifically designed for CRRT treatment

[0489] refer to Figure 1 The number 1 generally refers to extracorporeal blood processing equipment, particularly extracorporeal blood processing equipment used in intensive care treatment. Extracorporeal blood processing equipment 1 is designed to deliver any of the following treatments: hemodialysis, hemofiltration, hemodiafiltration, ultrafiltration, etc. Figure 1The device is specifically designed for continuous renal replacement therapy (CRRT). CRRT systems are configured to provide very specific treatments, designed for patients in an acute state of illness and those who have temporarily lost all kidney function. In this respect, CRRT systems may differ structurally and / or operationally from extracorporeal blood processing systems designed for chronic patient care. Acute patients, compared to chronic patients, typically experience temporary and complete loss of kidney function due to simultaneous severe injury or during surgical recovery. Therefore, acute patients are often extremely weak and cannot tolerate routine dialysis treatment, which can further deteriorate their condition and lead to serious and potentially life-threatening complications. In the described scenario, the CRRT system is designed to treat patients in extremely poor health conditions alone without placing further stress on their bodies, particularly by not allowing important blood parameters related to the patient to deviate from or near ideal values. Therefore, within the scope of this document, the CRRT system itself has one or more of the following characteristics. CRRT involves renal replacement therapy, which means an adjunctive treatment primarily designed to promote continuous fluid removal in patients with diuretic resistance or acute renal failure. Therefore, the CRRT system itself requires continuous net fluid removal from the patient. In other words, CRRT systems require fluid balance control systems, such as weight loss control systems, configured to produce a continuous net weight loss rate (rather than simply controlling parameters to achieve a desired target weight loss, as is often found in chronic patient care). Furthermore, acute patients experience extravascular fluid overload, which cannot be safely removed within a short period (e.g., a few hours in chronic therapy) without potentially serious consequences (e.g., hypovolemic shock, arrhythmias, hypoxemia, inadequate ventilation, etc.). Therefore, the CRRT system itself must include more precise control of system parameters, particularly flow rates, to ensure the required low flow rates for the use of extracorporeal blood and therapeutic fluids (infused in the extracorporeal circuit or diffused through the dialyzer). Additionally, continuous CRRT treatment (e.g., for days or even weeks, with minimal or no interruptions (e.g., downtime for changing bags)) is necessary. Therefore, CRRT treatment settings are based on flow rate settings, rather than settings associated with a specific treatment time (which is unknown because the duration of treatment for acute patients is unknown). Therefore, the operation of a CRRT system cannot be based on some predefined absolute weight loss to be achieved. Instead, it requires continuous adjustment of multiple operating parameters based on carefully controlled fluid balance in the patient’s body. These operating parameters must be controlled and maintained based on a set weight loss rate throughout the entire (and a priori unknown) treatment period.In addition, CRRT involves treatment that replaces kidney function over a relatively long period of time. Therefore, CRRT systems also require at least fresh dialysis fluid exchange in the dialyzer (in order to remove unwanted substances from the blood and add desired substances to the blood by diffusion) and / or fresh infusion fluid in combination with ultrafiltration (in order to remove unwanted substances from the blood and add desired substances to the blood by convection).

[0490] For at least the reasons mentioned above, a CRRT system needs to exhibit specific technical features that enable the system to:

[0491] - Allows setting a weight loss rate.

[0492] - Continuously remove excess water according to the set weight loss rate.

[0493] - Continuous operation at a relatively low flow rate compatible with CRRT; and

[0494] - Equilibrate ion balance by performing appropriate dialysis and / or by continuously delivering alternative fluids at a controlled flow rate.

[0495] Finally, considering the acute condition of patients requiring treatment and the advance notification of emergencies where no treatment is needed, the CRRT machine is acclimated using an integrated disposable kit to prepare the CRRT equipment as quickly as possible. All tubing and filtration units are grouped together and correctly connected in the disposable kit. Furthermore, all fluids are contained in pre-packaged bags (each bag containing, for example, 2, 5, or 10 liters of dialysis or replacement fluid) or pre-packaged syringes (heparin and / or concentrated calcium replacement solution).

[0496] Figure 1 The device 1 has an external blood circuit 17, which draws blood from the patient P, for example, through a needle, catheter, implant port, or other access device (not shown), introduces the blood into the patient's vein or artery, and delivers the blood (e.g., continuously) to a filtration unit 2 via a blood extraction line 6. The filtration unit 2 has a main chamber 3 and a secondary chamber 4 separated by a semi-permeable membrane 5; depending on the different processes, the membrane of the filtration unit can be selected to have different characteristics and performance.

[0497] Blood passes through the main chamber 3 of unit 2 and, via the blood return line 7, is returned to the patient. Figure 1In the example, the connection to the anticoagulant line 51 is provided immediately downstream of the blood collection area on the blood extraction line 6. Specifically, the machine is equipped with a source 10 for a local anticoagulant, such as at least one auxiliary fluid container or bag for supplying the anticoagulant line 51; the fluid flow rate within the line can be controlled by directly introducing the local anticoagulant into the blood and directly connecting it to the blood extraction line 6 using a corresponding actuator for fluid delivery (e.g., a peristaltic pump in the example shown, which includes an anticoagulant pump 54). After defining the direction of fluid (blood) circulation 200 (during normal use of the device) from the blood extraction line 6 toward the filtration unit 2 and from the filtration unit 2 toward the patient P via the blood return line 7, a known blood pressure sensor 48 (which will not be described in further detail) is positioned immediately downstream of the anticoagulant line 51. The blood circuit 17 includes actuators for fluid delivery, i.e., in this particular case, at least for controlling and managing the appropriate blood flow Q in the circuit. b The blood pump 21. The blood pump 21 is also typically used in blood extraction tubing (e.g., as shown in the image). Figure 1 (As shown) or a peristaltic pump acting on the blood return line. The operator can input the blood flow rate Q through the user interface 15. b The control unit 12 is configured to control the blood pump based on a set blood flow rate during processing. It should be noted that, optionally, the blood pump 21 can be automatically controlled without user input / prescription: in this case, the control unit 12 can control the blood pump 21 at a predetermined flow rate or at a flow rate calculated based on other parameters, such as other flow rates and limits set by the medical operator (as will be apparent from the following description). Alternatively, the blood pump can also be controlled based on pressure; if the blood pump 21 is controlled based on a pressure signal detected upstream of the blood pump, a pressure sensor 48 is present in the blood line upstream of the blood pump 21: for example, the control unit 12 can be designed to drive the blood pump in a manner that maintains the pressure detected by the pressure sensor 48 within a predetermined range or below a predetermined threshold.

[0498] Along the direction of blood circulation, a gas exchanger 46 for removing CO2 from the circulating blood can be connected to the blood circuit. The gas exchanger 46 is in fluid communication with the blood circuit 17 to receive extracorporeal blood, allowing CO2 to be removed from the blood and the blood to be returned to the blood circuit at a downstream point. Figure 1 A gas exchanger 46 is shown positioned upstream of the filtration unit 2; however, alternatively, the gas exchanger may be located downstream of the filtration unit along the direction of blood circulation. As described above, in Figure 1 Arrow 200 indicates the direction of blood circulation during normal use of the device, and also represents the blood flow velocity Q during processing. bDirection. Gas exchanger 46 is connected in series with filtration unit 2 and is positioned downstream of injection point 50, where a localized anticoagulant solution is delivered to the extracorporeal blood. Gas exchanger 46 has a blood chamber and a gas chamber separated by a gas (particularly CO2) permeable membrane; the gas exchanger includes a gas inlet and a gas outlet, the gas inlet being connectable to a gas source, such as a medical gas supply system in a hospital, to receive, for example, pressurized air or oxygen, and the gas outlet being in fluid communication with the gas chamber to discharge exhaust gas from which CO2 has been removed from the extracorporeal blood. The blood inlet and blood outlet enable extracorporeal blood circuit 17 to be in fluid communication with the blood chamber of the gas exchanger.

[0499] The blood then passes through another pressure sensor 49, which controls the proper flow within the blood circuit. After passing through the main chamber 3 of the filtration unit 2 (where proper exchange of matter, molecules, and fluids occurs via a semi-permeable membrane), the treated blood enters the blood return line 7, first passing through an air separator 19, commonly referred to as a "bubble trap," which is designed to ensure the detection and removal of air bubbles present in the blood. The treated blood exiting the air separator 19 passes through a bubble sensor 55 before returning to the patient P, which verifies the absence of the hazardous formations that must be reintroduced into the patient's blood circuit. Immediately downstream of the bubble sensor 55 is a safety valve 20 (or venous clamp), which, in the event of an alarm, can prevent blood from flowing to the patient. Specifically, if the bubble sensor 55 detects the presence of an anomaly in the blood flow, the machine will be able to immediately block the passage of blood via the safety valve 20, thereby preventing any consequences for the patient. A corresponding safety valve 27 (or arterial clamp) is present on the blood extraction line to close the patient's vascular access, completely isolating the patient from the extracorporeal blood circuit if necessary. Downstream of safety valve 20, the processed blood is then transported back to the patient P who is receiving treatment. Figure 1 The extracorporeal blood processing device is equipped with a dialysis fluid circuit 32, which also provides at least a dialysis supply line 8 leading to the filtration unit 2 and an effluent (or dialysate) line 13 from the filtration unit. At least one main fluid container defining the dialysate source 14 is designed to supply the supply line 8 of the dialysis fluid circuit 32 (typically, the main fluid container should consist of one or more bags containing suitable dialysate). The supply line 8 includes actuators for delivering fluid, such as at least a dialysis fluid pump 25 (in... Figure 1 In this implementation, a peristaltic pump is used to control the flow rate Q of the dialysate from the bag. dialIt is used to define the direction 200 of the dialysis fluid circulation. In the direction of circulation 200, downstream of the dialysis fluid pump 25, there is a branch 56 that branches the dialysis supply line 8 upwards into an intake branch 57 and an infusion branch 58. Specifically, the infusion branch 58 connects to the blood return line 7 of the blood circuit 17. In other words, through the infusion branch 58, the contents of the main fluid container can be directly infused into the blood line 17. Conversely, the intake branch 57 delivers fluid directly to the filtration unit 2, particularly to the sub-chamber of that unit. The dialysis fluid circuit 32 is also equipped with a selector 59 for determining the percentage of fluid flow within the infusion branch 58 and the intake branch 57. Generally, the selector 59, typically located near branch 56, can be positioned at least between a first operating state and a second operating state. In the first operating state, selector 59 allows fluid to pass through in intake branch 57 and blocks it from passing through in infusion branch 58. In the second operating state, selector 59 allows fluid to pass through in infusion branch 58 and blocks it from passing through intake branch 57. In other words, selector 59 may include a valve element that operates on the dialysis fluid circuit 32 by alternately blocking fluid passage in either branch. Alternatively, a suitable selector may be provided that is capable of a priori determining the amount of fluid that must pass through both branches simultaneously. The percentage of fluid in either branch may also be varied as a function of time and a predetermined treatment method. Dialysate enters the sub-chamber 4 of filtration unit 2 through intake branch 57. Specifically, the main chamber 3 through which blood flows is separated from the sub-chamber 4 through which dialysate flows by a semipermeable membrane 5, thereby ensuring that hazardous substances / molecules and fluids pass properly from blood to dialysate primarily through convection and diffusion processes, and also ensuring the passage of substances / molecules from dialysate to blood by the same principle. The dialysate then enters the outflow line 13 and passes through a suitable effluent pressure sensor 60. An actuator, such as a dialysate pump 26, is provided for conveying the fluid, which controls the flow rate Q in the outflow line 13 within the fluid circuit 32. eff Furthermore, the pump is typically a peristaltic pump. The fluid to be removed then passes through a blood detector 61 and is delivered to a collection container or bag 62. According to... Figure 1 The device's hydraulic circuit includes at least one additional infusion line 63 for supplying fluid to the blood return line 7 of the blood circuit 17. Specifically, the infusion fluid is drawn from at least one auxiliary container 64 and delivered directly to the blood return line 7 of the blood circuit 17 via an actuator (typically an infusion pump 65 (a peristaltic pump in this example)) for conveying the fluid, which controls its flow rate Q. rep(Total replacement flow rate). Specifically, the infusion fluid can be directly introduced into the air separator 19. It can also be inferred that the infusion branch 58 and infusion line 63 of the dialysis fluid circuit 32 are equipped with a common end section 66 that allows fluid to enter the blood circuit 17. This inlet end section 66 is located downstream of the infusion pump 65 relative to the infusion direction and delivers the fluid directly to the air separator 19. Furthermore, refer to... Figure 1 As shown in the figure, infusion line 63 includes at least one pre-infusion branch 67 connected to the blood extraction line 6 of blood circuit 17. More specifically, downstream of infusion pump 65, there is an infusion branch 68 that branches infusion line 63 upwards into pre-infusion branch 67 and post-infusion branch 69, relative to the infusion direction. Specifically, pre-infusion branch 67 delivers fluid from bag 64 to blood extraction line 6 of blood circuit 17, which is located downstream of blood pump 21 and gas exchanger 46, relative to the direction of blood circulation. Conversely, post-infusion branch 69 is directly connected to common end segment 66. Infusion line 63 also includes a selector 70 for determining the percentage of fluid flow to be delivered to post-infusion branch 69 and pre-infusion branch 67. The selector 70, located near branch 68, can switch between at least a first operating condition and at least a second operating condition. In the first operating condition, selector 70 allows fluid to pass through the pre-infusion branch 67 and blocks it from passing through the post-infusion branch 69. In the second operating condition, selector 70 allows fluid to pass through the post-infusion branch 69 and blocks it from passing through the pre-infusion branch 67. Clearly, similar to selector 59 present on the dialysis fluid circuit 32, the other selectors 70 will also be able to determine the percentage of fluid that must pass through each of the two branches and can change it in a timely manner according to the planned treatment. Furthermore, selector 59 and the other selectors 70 generally (though not necessarily) have the same properties. It is noteworthy that the flow rate through the pre-infusion branch / line 67 can be determined by appropriate control of the infusion pump 65 and the other selectors 70; the control unit 12 can receive the pre-infusion ratio PRE (a value between 0 and 1) of the replacement fluid flow and, based on the pre-infusion ratio PRE and the total replacement flow rate Q... rep Determine the pre-infusion flow rate Q rep In particular, Q rep.pre =PRE·Q rep Alternatively, the post-infusion ratio can be used symmetrically, or the ratio between the pre-infusion rate and the post-infusion rate (R3 = Q) can be used. re.pre / Q rep.post ).

[0500] The device is equipped with means 71 for determining at least the weight of the main fluid container 14 and / or the secondary fluid container 64 and / or the local anticoagulant container 10 and / or the collection container 62. Specifically, means 71 includes weight sensors, such as corresponding scales A, B, C, D, and E (e.g., at least one independent sensor for each fluid bag associated with the machine). Specifically, there will be at least four of these scales, each pair independent of each other, and each measuring the corresponding weight of the bag. It should then be noted that a control unit or CPU 12 exists, operating (at least) on the blood circuit 17, particularly on the pressure sensor 48 for reading pressure values, on the blood pump 21, on the gas exchanger 46, on another pressure sensor 49, on the device 55 for detecting the presence of air bubbles, and on the corresponding safety valves 20, 27. Control unit 12 must also control the dialysate circuit 32, and in particular, should input data detected by scales A, B, C, D and (possibly) E, as well as the weight of bag 14, and should act on pump 25, selector 59, pressure sensor 60, and then dialysate pump 26, and should ultimately receive data detected by scale A, whose function is to determine the weight of collection container 62. Control unit 12 should also act on infusion line 63 to check the weight of auxiliary container 64 (checked by scale C), and will be able to control both infusion pump 65 and other selectors 70. Control unit 12 should also act on anticoagulant line 51, detect the weight of anticoagulant fluid container 10 by scale B, and appropriately control anticoagulant pump 54 according to the process to be implemented as detailed and explained below. Obviously, in Figure 1 Device 1 implements a local anticoagulation system to provide anticoagulation limited to the extracorporeal blood circuit 17. The local anticoagulation system is described in detail in the corresponding descriptive paragraph. However, Figure 1 The device may alternatively (or additionally) provide a systemic anticoagulation system, such as an infusion pump 9 for injecting heparin downstream of blood pump 21. In fact, the algorithms of the embodiments of the invention described in the following detailed description are effective in both CRRT treatment configurations with RCA and CRRT treatment configurations with systemic (or no) anticoagulation but without RCA.

[0501] The control unit 12 is also connected to the memory 16 and the user interface 15, such as a graphical user interface, which receives operator input and displays device output. For example, the graphical user interface 15 may include a touch screen, a display screen, and / or hard keys or a combination thereof for inputting user input.

[0502] Local anticoagulation system

[0503] A local anticoagulant system includes a source 10 of a local anticoagulant, such as a container or bag containing at least one substance with an anticoagulant effect. For example, citrate in the form of pure sodium citrate (Na3citrate) or a mixture of sodium citrate and citric acid can be used for blood anticoagulation. Alternatively, pure citric acid can be used as an anticoagulant. Indeed, citrate has a high affinity for calcium when forming a complex, and several steps of the coagulation cascade depend on (ionic) calcium in the blood. In the presence of citrate, a suitable reduction in the concentration of ionic calcium will inactivate the coagulation cascade.

[0504] Normal plasma contains approximately 1.1 to 1.3 mmol / L of ionized calcium, 0.1 to 0.2 mmol / L of complexed calcium, and 0.9 to 1.2 mmol / L of protein-bound calcium. To achieve adequate anticoagulation, general guidelines adjust the amount / dose of citrate to achieve an ionized calcium concentration of 0.20 to 0.35 mmol / L in the extracorporeal blood circuit after citrate infusion. Plasma supplemented with citrate for anticoagulation will contain (on average) approximately 0.3 mmol / L of ionized calcium, 1.8 mmol / L of complexed calcium (primarily Ca3citrate2), and 0.2 mmol / L of protein-bound calcium. During RCA, the anticoagulation intensity can be adjusted by the amount of citrate infused. The ionized calcium concentration in the post-filtration unit is typically used as a key parameter (target value in the range of 0.20–0.35 mmol / L) and is measured using, for example, a blood gas analyzer.

[0505] A local anticoagulation system is arranged to deliver a local anticoagulant at delivery point 50 in the extracorporeal blood circuit 17. Citrate infusion is preferably administered near the access point of the blood extraction line 6 to achieve complete anticoagulation of the extracorporeal blood circuit 17. Typically, delivery point 50 is located upstream of the blood pump 21; however, it is not excluded that delivery point 50 is located downstream of the blood pump in the blood extraction line 6. Optionally or in combination, the citrate delivery point 50 may be the inlet of the filtration unit 2. In the latter configuration, the dialysate contains citrate in an amount sufficient to achieve an ionized calcium level of approximately 0.25–0.35 mmol / L in the blood circuit downstream of the dialyzer. In cases where the dialysate is prepared online as in devices currently used for chronic treatment, citrate can be added to the processing fluid flowing along the supply line 8 using a suitable concentrate bag / container. Optionally, particularly in the case of CRRT devices, the source 14 of the dialysate is a container / bag containing an appropriate concentration or content of citrate.

[0506] Commercial citrate solutions are typically packaged in individual plastic bags (Source 10) and can be categorized into physiological solutions and concentrated solutions. Physiological citrate solutions are solutions with a sodium concentration of approximately 140 mmol / L, such as Baxter PrismoCitrate 10 / 2 (containing 10 mmol / L sodium nitrate and 2 mmol / L citric acid) and Baxter RegioCit 18 / 0 (containing 18 mmol / L sodium nitrate). For example, concentrated citrate solutions include ACD-A (anticoagulated citrate-glucose solution) from Biomet: a mixture of sodium citrate (75 mmol / L), citric acid (38 mmol / L), and glucose; and 4% citrate from Fresenius: citrate 136 mmol / L.

[0507] When citrate is infused into the blood extraction line 6 near the patient's vascular access, the blood pump speed is automatically adjusted to achieve the blood flow rate from the access site set by the operator (blood pump speed = k * (Q)). b +Q cit ), where Q b Q is the desired, set (or calculated) blood flow rate at the pathway site. cit This refers to the citrate infusion rate. The citrate dosage parameter (D) is used to determine the infusion rate. citrate The specified citrate dosage is the amount of citrate in each liter of treated blood (mmol / L blood). It is important to note that the citrate dosage is not matched to the citrate concentration in the diluted blood reaching the filtration unit. The concept is more precisely to provide an amount of citrate proportional to the amount of calcium to be chelated. The citrate pump 54 is configured as follows:

[0508]

[0509] in

[0510] Q cit This refers to the citrate infusion rate;

[0511] Q b The set blood flow rate;

[0512] D cit It is the dosage of citrate; and

[0513] C cit_pbp This is the citrate concentration in the anticoagulant source. This is the mathematical formula for the citrate flow rate, stored in the memory 16 of the control unit 12, and is applied to a given citrate dose D in the anticoagulant source 10. cit With citrate concentration as input, the citrate infusion rate Q is determined. citBlood flow can be an input value (prescription parameter) or a calculated value (operational parameter), determined by the control unit based on system configuration and prescription parameters (see detailed description below).

[0514] The delivery dose of citrate infusion is designed to maintain ionized calcium levels in the downstream blood circuit of the dialyzer at approximately 0.25–0.35 mmol / L. Typically, citrate doses range from 1.5 to 6.0 mmol / L of blood. The most common concentration range is 2 to 4 mmol / L of blood. Globally, a citrate dose of 3.0 mmol / L of blood is followed as a guideline.

[0515] Ionized calcium and citrate complexes are relatively small molecules that readily transfer through filtration unit 2. The loss rate depends primarily on flow rate, small molecule filtration efficiency, and solute concentration. During standard anticoagulation, approximately half of the total calcium is not available for mass transfer (because it is bound to proteins), while during citrate anticoagulation, approximately 90% of the total calcium is available for mass transfer. Therefore, local citrate anticoagulation combined with calcium-free dialysate and / or replacement fluid implies significant dialysate calcium loss. In extracorporeal blood management during RCA, calcium infusion is required to balance the calcium loss from the dialysate. During RCA, calcium infusion is adjusted to maintain the patient's systemic ionized calcium within the normal range (e.g., 1.0–1.2 mmol / L).

[0516] Therefore, the local anticoagulation system of device 1 includes a source 11 of ion-balanced solution, which is re-infused into the bloodstream, either in a return line 7 (particularly near the venous access) or directly into the patient P (infusion into a central catheter is recommended). The ion-balanced solution 11 is contained in a container, such as a syringe, container, or bag; the local anticoagulation system of device 1 includes an ion-replacement infusion line 74 and a corresponding ion-replacement pump 75 to drive an appropriate ion-replacement infusion rate Q. ca The delivery. Figure 1 A line 74 is shown that is directly infused into the blood return line 7, possibly near a venous access. Alternatively, line 74 can be directly infused into patient P. Figure 1 In the example, the infusion pump 9, typically used for heparin delivery, can alternatively be used to deliver the ion-balanced solution directly to the patient or alternatively to a blood return line. The ion-balanced solution contains ionized (concentrated) calcium, and infusion of this solution restores the patient's systemic ionized calcium to normal levels. Notably, the ion-balanced solution may also contain ionized magnesium, and its infusion is performed to restore the patient's systemic ionized magnesium to normal levels, as magnesium removal from the dialysate also increases during RCA. The ion exchange infusion rate Q can be adjusted based on the revealed concentration of ionized calcium in the patient's blood. ca Alternatively, automatic control may be implemented, such as the automatic control described in patent publication US8668825B2 (incorporated herein by reference).

[0517] In one implementation, the flow rate of the ion balance solution is maintained proportionally to the estimated calcium loss rate in the dialysate. For example, it is calculated by the device control unit using the following formula (calcium flow rate mathematical relationship):

[0518]

[0519] Where CaComp is the calcium compensation parameter, Q ca For the ion equilibrium solution flow rate (ml / h), J ca To estimate the calcium loss rate (mmol / h) in the dialysate, C ca Q represents the calcium concentration (mmol / L) of the ion equilibrium solution. rep.post For the post-dilution displacement flow rate (ml / h), C ca_rep.post Q represents the calcium concentration (mmol / L) of the post-diluted replacement solution. HCO3 To ensure the fluid flow rate (ml / h) through the post-diluted bicarbonate injection line 23, C ca_HCO3 This refers to the calcium concentration in the carbonate container. Calcium compensation is a user-controllable setting that can be configured by the operator, typically ranging from 5% to 200%.

[0520] It is important to note that the above equations take into account both the post-displacement solution containing calcium and the bicarbonate infusion, which also contains calcium. If the post-displacement solution contains no calcium (or no displacement solution is used), the second term of the equation (equals zero) should be ignored. If the bicarbonate displacement solution does not contain calcium (or no bicarbonate solution is used), the third term of the equation (equals zero) should be ignored.

[0521] Control unit 12 also uses a calcium flow rate mathematical relationship to determine the ion reconstruction flow rate Q based on the known (input) calcium concentration in various post-infusion solutions. ca Furthermore, it is assumed that no calcium is infused upstream of filtration unit 2 to avoid undesirable coagulation effects (in this respect, the anticoagulant solution does not contain any calcium and the pre-dilution infusion line 67 is absent or the pre-infused replacement solution does not contain calcium). Additionally, ion compensation parameters are also part of the formulation. The post-infusion flow rate, i.e., Q... rep.post and Q HCO3 These are operating parameters, and the control unit 12 determines them based on prescription parameters and equipment configuration. Furthermore, J is estimated. ca For example, as disclosed in the aforementioned US8668825B2 application.

[0522] Alternatively, medical personnel can provide a "calcium dose" based on the calcium concentration (mmol / L) in the effusion. caConsidering the calcium concentration in the ion equilibrium solution, the calcium concentration in the replacement solution, and the estimated calcium concentration in the blood at the outlet of filtration unit 2, the flow rate Q of the ion equilibrium solution is calculated based on the set calcium dose. ca .

[0523] In practice, dialysis fluids (and replacement solutions) are typically calcium-free to prevent the transfer of ionic calcium into the bloodstream. Furthermore, if concentrated citrate solutions (hypertonic) are used, the dialysis and / or replacement fluids may have adapted buffer contents and sodium levels due to citrate metabolism.

[0524] Regarding buffers, because RCA has a complex effect on acid-base balance due to a significant portion of citrate returning to the patient's body (where citrate is metabolized into bicarbonate), the control unit 12 will need to input the desired steady-state acid-base balance target when adjuvanting prescriptions. In fact, the blood returning to the patient contains a significant concentration of citrate-calcium complexes. These complexes are rapidly metabolized in the liver, skeletal muscle, and kidneys, releasing calcium into the bloodstream, thus preventing the development of systemic anticoagulation; citrate metabolism produces bicarbonate (3 moles of HCO3 for 1 mole of citrate). - ).

[0525] In this respect, the dialysate may be buffer-free, for example, bicarbonate-free. Buffer from source / container / bag 64 can be infused into blood return line 7 via suitable buffer supply lines 63, 69, 66 and corresponding buffer pumps 65. Optionally or in combination, to allow for additional acid balance control, device 1 may also be designed to easily and controllably alter the buffer balance of the extracorporeal blood circuit by setting a (low) buffer concentration of the dialysate and / or using source bags 14, 64 with different buffer concentrations (e.g., for bicarbonate, in the range of 15 to 25 mmol / L (and up to 40 mmol / L and / or as low as 0 mmol / L)). As described above, a specially designed bicarbonate solution can be post-infused to achieve additional acid-base balance control (e.g., see...). Figures 4 to 6 ).

[0526] As mentioned above, citrate accumulation in patients can be associated with hypocalcemia, metabolic acidosis (low bicarbonate production due to poor metabolism), or metabolic alkalosis (excessive bicarbonate production following a high citrate load). Since citrate measurement is not typically available in hospitals, the ratio of total calcium to ionized calcium is used as an indicator; a value below 2.5 is considered normal (normal is below 2.0), and a value above 2.5 indicates a low concentration of ionized calcium relative to total calcium, possibly due to the presence of significant systemic citrate levels. However, this monitoring is considered inadequate, particularly in treatments involving risks associated with acid / base imbalances, such as in RCAs with “high” flow rates, like some SCUF treatments. Specific Implementation

[0528] Figure 2 and Figure 3 The embodiments are shown Figure 1 The different configurations of device 1 shown also include those for... Figure 1 The same components described in the embodiments, and these components are identified by the same reference numerals, will not be described in detail again.

[0529] Figure 2 The embodiments refer to CRRT configurations with or without anticoagulation or with systemic anticoagulation. Specifically, in the case of systemic anticoagulation, a heparin container (e.g., syringe 9) is used to inject a dose of the anticoagulant into the extraction line 6 via a heparin line 22, which is typically infused downstream of the blood pump 21. This embodiment includes a pre-blood pump (PBP) line 52 for infusing a replacement solution (citrate-free) contained in the PBP container 18 using a PBP pump 53, wherein the PBP pump 53 generates a pre-blood pump infusion flow rate Q. PBP Furthermore, a post-infusion line is provided for the post-infusion of the replacement solution contained in the sub-container 64. A dialysate source 14 is also included to provide a dialysate flow rate Q to the sub-chamber 4 of the filtration unit 2. dial The effluent flow rate Q is increased by the dialysate pump 26. eff Guided to collection container 62. If we compare Figure 1 and Figure 2 In the embodiments, we note that Figure 2 The embodiment lacks any ion balance infusion line 74 (no local anticoagulation is provided), fluid from liquid source 14 is directed to the dialyzer (selector 59 is configured to prevent any fluid from flowing to the post-infusion), and the replacement fluid from sub-container 64 is exclusively directed in the post-dilution (an additional selector 70 is configured to prevent any fluid from flowing to the forward infusion).

[0530] Figure 3 Implementation examples and Figure 2The implementation differs because it involves a CRRT configuration with local anticoagulation. Heparin syringe 9 is not used. Container 10 is the source of the local anticoagulant (citrate), and anticoagulant pump 54 produces a citrate infusion flow rate Q. cit This includes a corresponding ion balance infusion line 74 and an ion balance pump 75 to infuse calcium from the source 11 of the ion balance solution at a flow rate Q. ca Infuse a concentrated calcium solution.

[0531] Figure 4 The embodiments include the same dialysis fluid circuit as in Embodiments 2 and 3. As already shown in Embodiment 2, Figure 4 The embodiments refer to CRRT configurations with or without anticoagulation or with systemic anticoagulation. Unlike other configurations, a pre-infusion line is included downstream of blood pump 21 for infusing the replacement solution during pre-dilution. The pre-infusion line may be... Figure 1 The infusion line 63, wherein other selectors 70 are configured to direct all displacement fluid from the pre-dilution sub-container 63 through the pre-infusion branch 67. Optionally, a pre-dilution infusion line 29 is provided to deliver the displacement fluid contained in the displacement source 30. The infusion pump 31 generates a pre-infusion displacement flow rate Q. rep.pre In addition, a post-dilution bicarbonate delivery line 23 for concentrating the bicarbonate solution is included. A bicarbonate pump 24 delivers the concentrated bicarbonate solution from the bicarbonate container 28 at a post-delivery flow rate Q. HCO3 Inject concentrated bicarbonate solution.

[0532] Figure 5 The embodiments involve a CRRT configuration with local anticoagulation. Heparin syringe 9 is not used. Container 10 is the source of local anticoagulant (citrate), and anticoagulant pump 54 produces a citrate infusion flow rate Q. cit This includes a corresponding ion balance infusion line 74 and an ion balance pump 75 to infuse calcium from the source 11 of the ion balance solution at a flow rate Q. ca A calcium concentrate solution is infused. Additionally, a post-infusion line 63 is provided for post-infusion of the displacement solution contained in the auxiliary container 64. Furthermore, a post-infusion line 23 for the concentrated bicarbonate solution is included. A bicarbonate pump 24 infuses bicarbonate from the bicarbonate container 28 at a bicarbonate concentrate post-infusion flow rate Q. HCO3 Inject concentrated bicarbonate solution.

[0533] Figure 6 In another embodiment, the device includes all possible infusion lines, namely two separate pre-blood pump infusion lines: an anticoagulant line 51 for citrate infusion (flow rate: Q). cit ); and a PBP infusion line 52 for pre-blood pump replacement fluid infusion (flow rate: Q) PBPA pre-dilution infusion line 29 infuses replacement fluid (flow rate: Q) from a replacement source 30 (e.g., a pre-packaged container) via a corresponding pre-infusion pump 31. rep.pre A post-dilution infusion line 63 is used to infuse the solution from a secondary container 64 containing the replacement solution (flow rate: Q). rep.post ); One post-dilution bicarbonate injection pipeline 23 (flow rate: Q) HCO3 One ion-balanced infusion line 74 is used for infusing calcium concentrate solution (flow rate: Q). ca A dialysis supply line 8 is used to guide fresh dialysis fluid to the filtration unit (flow rate: Q). dial ); and an outflow line 13 for delivering used dialysate to a collection container 62 (flow rate: Q). eff ).exist Figure 6 In this embodiment, the pre-infusion and post-infusion blood pump line 29 and the post-infusion line 63 are shown as separate and independent lines; alternatively, the two lines 29 and 63 can be as follows: Figure 1 In the embodiments described, the fluids are combined as shown, with one individual bag 64 supplying the same displacement fluid to both branches, one branch guiding the fluid in pre-dilution and the other in post-dilution. The corresponding infusion fluid flow rate Q is obtained by appropriately driving the infusion pump 65 and the selector 70. rep.post and Q rep.pre The flow from a single pump 65 is alternately directed via selector 70 to either the pre-infusion or post-infusion over time; control over the time spent in each of the two states allows for control over the splitting of the flow between the pre-infusion and post-infusion. The desired flow rate value is obtained as an average over a certain time period, which must naturally be long enough, i.e., at least several minutes.

[0534] In addition, the two infusion lines 51 and 52 for infusing pre-pump blood fluid can be replaced by a single line for citrate in the case of local anticoagulation, or for PBP replacement fluid in the case of no anticoagulation or with systemic anticoagulation.

[0535] Finally, it should be noted that in the event of any missing pipeline in a particular circuit configuration, the corresponding flow rate can be omitted (or its value set to zero) in any of the following equations / mathematical relationships.

[0536] Flow velocity equation

[0537] The flow rate equations below express the relationship between the flow rates used in the detailed description. These equations are stored in the device's memory 16. When necessary, the control unit 12 uses the following equations to determine operating parameters (as described in the following sections).

[0538] Plasma flow rate is a function of blood flow rate, as shown below:

[0539] Qp = Q b ·(1-Hct)

[0540] (Equation 3)

[0541] The plasma flow rate is a function of the blood flow rate, as shown below:

[0542] Qpw = Qp·F p =Q b ·(1-Hct)·F p

[0543] (Equation 4)

[0544] The plasma flow rate at the filter inlet is:

[0545] Qpw inlet =Qpw+Q cit +Q syr +Q PBP +Q rep.pre

[0546] =Q b ·(1-Hct)·Fp+Q cit +Q PBP +Q rep.pre

[0547] (Equation 5)

[0548] Blood fluid velocity is a function of blood flow velocity, as shown below:

[0549] Qbw = Q b ·[(1-Hct)·F p +Hct·Frbc]

[0550] (Equation 6)

[0551] The blood flow rate at the filter inlet is:

[0552] Qbw inlet =Q bw +Q cit +Q syr +Q PBP +Q rep.pre

[0553] =Q b ·[(1-Hct)·Fp+Hct·Frbc]+Q cit +Q pBP +Q Pep.pre

[0554] (Equation 7)

[0555] The ultrafiltration rate of the filtration unit is:

[0556] Q fil =Q PBP +Q cit +Q syr +Q rep.pre +Q rep.post +Q HCO3 +Q PFR +Q ca

[0557] (Equation 8)

[0558] When using a single infusion line 63 (e.g.) Figure 1 In the case shown), the displacement flow rate (Q) delivered by the infusion pump 65 can be used as a basis. rep The initial displacement velocity of the displacement fluid is calculated by multiplying the displacement fluid velocity by the previous displacement fluid flow coefficient (PRE).

[0559] Q rep.pre =PRE·Q rep

[0560] Q rep =(Q rep.pre +Q rep.post )

[0561] (Equation 9)

[0562] The outflow velocity is:

[0563] Q eff =Q PBP +Q cit +Q syr +Q dial +Q rep.pre +Q rep.post +Q HCO3 +Q PFR +Q ca =Q dial +Q fil

[0564] (Equation 10)

[0565] Clinical prescription parameters

[0566] Clinical prescribing parameters are parameters that CRRT devices require from healthcare professionals when initiating or updating treatment prescriptions for specific patients. The device can request the physician to enter prescribing parameters or provide suggested values ​​for confirmation or updating. Prescribing parameters for confirmation / updating can be read from the patient card or similar support.

[0567] The purpose of the “Assisted Prescription” process is to operate based on prescription parameters that are clinically meaningful; the selected prescription parameters of interest are listed in the table below.

[0568]

[0569] Not all of the above clinical prescribing parameters are necessary / essential, but their relevance depends on the chosen treatment and the healthcare professional's preferences.

[0570] For example, as described below, the blood flow rates listed in the table can be used as prescription parameters (set by medical personnel) or as operating parameters based on customer preferences (set by the system algorithm).

[0571] Citrate dosage and calcium compensation are associated with local anticoagulation, but not with the absence of anticoagulation or with systemic anticoagulation.

[0572] The patient fluid removal rate can be used as a prescription input, or alternatively, it can be calculated by the control unit.

[0573] Generally, CRRT dosage is a "run" dosage, which must be derived from a clinical target adjusted for system downtime (20 to 25 ml / kg / h according to the KDIGO guidelines); this results in a recommended run dosage in the range of 25–30 ml / kg / h. CRRT dosage will be explained further in the next paragraph.

[0574] As described above, citrate dosage controls anticoagulant strength; it should be adjusted to reduce the concentration of ionized calcium in the extracorporeal blood circuit to the range of 0.2–0.35 mM. Simultaneously, calcium compensation controls the balance level of calcium loss relative to the calculated default loss rate; as a percentage alternative, calcium balance can be defined as the calcium concentration in the effluent (calcium dose D). ca ).

[0575] The target for homeostasis is defined as either the homeostasis of the patient's bicarbonate concentration (requiring an assumption about nNBL) or the normalized net buffer load (requiring an assumption about bicarbonate concentration). The second option is generally preferred. Under homeostasis, nNBL is expected to balance the rate at which the patient's metabolism produces protons (H+). The target for homeostasis will be discussed further in the following paragraphs.

[0576] Patient fluid removal prescriptions are derived directly from patient fluid balance analysis, taking into account all patients' fluid inputs and outputs, as well as the necessary corrections for patient fluid status. It is clear that setting a patient fluid removal rate may be preferred; however, setting another fluid flow rate can allow for the determination of the resulting patient fluid removal rate (e.g., setting the effluent flow rate and using Equation 10 with knowledge of the infusion and dialysis flow rates).

[0577] Aside from some technical considerations regarding the patient's vascular access, no strong clinical context is expected for blood flow rate. If a medical prescription is selected as the prescription parameter, it can provide the desired setpoint or simply define the lower and / or upper limits of the blood flow rate setting range.

[0578] CRRT Dosage Definition

[0579] In this instruction manual, CRRT dose primarily refers to flow rate or flow rate combination (expressed in ml / h). However, it is important to note that another definition of CRRT treatment dose is expressed in ml / kg / h, which is the normalized flow rate (or flow rate combination) to the patient's body weight (BW). Especially for infants, the CRRT dose mentioned in the literature also refers to the treatment dose normalized to the patient's body surface area (BSA).

[0580] Dosage (aside from "normalization" based on patient size) can most commonly be defined as a combination of flow rates, as shown in the following example:

[0581] - Effervescent dose (D eff ):Q eff As a perfect, typical (and simple) example of field practice,

[0582] - Convection dose (D conv ): The sum of all infusion rates to the blood circuit or patient, plus the patient's fluid removal rate.

[0583] -Diffusion dose (D dial ): Dialysis flow rate Q dial ,

[0584] - All of the above dosages are pre-dilution corrected for blood (or plasma) upstream of the filter.

[0585] -Urea dosage (D) urea Estimated urea removal:

[0586] -Clearing dose (D sol ): Any dose calculated based on the estimated clearance of a given solute (=> an expression function for all flow settings and dialyzer / filter related parameters).

[0587] CRRT dialysis dosage formula

[0588] All the following dose expressions are not normalized to patient body size (body weight (BW) or patient surface area (PA); the normalized dose (NDose) can be expressed directly as:

[0589] NDose = Dose / BW; or

[0590] NDose = dose / BSA × 1.73 (normalized to 1.73 mg) 2 (Surface area, patient-body surface area; see pediatric literature)

[0591] For example, one of the following values ​​can be used as a dosage:

[0592] • Outflow dose (D eff ): The flow velocity through the outflow pipe, i.e., D eff =Q eff ;

[0593] • Convection dose (D conv ): The sum of the flow rate through one or more infusion lines directly connected to the patient or connected to the blood circuit and the patient's fluid removal rate, i.e.

[0594] D conv =Q PBP +Q cit +Q syr +Q rep.pre +Q rep.post +Q PFR +Q ca +Q HCO3 ,or

[0595] D conv =Q fil

[0596] Of course, if one or more pipelines are missing, the corresponding flow rate item may not appear in the definition or may be set to 0.

[0597] • Diffusion dose (D) dial ): The fluid velocity supplied to the secondary chamber of the filtration unit, i.e., D dial =Q dial .

[0598] ·Urea dosage (D urea Estimated urea clearance (K) urea It should be noted that, under CRRT conditions, the first approximate expression assumes that the urea removal from the filter is related to the outflow rate Q. eff Broadly the same; in another alternative, the estimate of urea removal is higher than Q. eff More accurate, especially when operating at high flow rates or with small filters (pediatric conditions), can be provided by the following equation:

[0599] a) For pure diffusion mode (where no replacement fluid is infused and the patient fluid removal rate is zero or substantially zero) and countercurrent configuration (the fluid in the chamber of filtration unit 2 is in countercurrent):

[0600]

[0601] If Z≠1

[0602] If Z = 1

[0603] (Equation 11)

[0604] Where: S (effective filter surface area) depends on the hemodialysis unit used (i.e., filtration unit 2); RT is the total mass transfer resistance, which depends on the hemodialysis unit used (membrane characteristics, filter design) and the target solute, which is urea in this example; it should be noted that S / RT is also the mass transfer performance of the filtration unit, i.e., K0.A (ml / min), Qbw inlet It is the blood flow rate at the inlet of filter unit 2.

[0605] b) If the dialysis fluid flow rate Q is present at the same time dial And with one or more fluid infusions, then:

[0606]

[0607]

[0608]

[0609] Where: S (effective filter surface area) depends on the hemodialysis machine used; RT is the total mass transfer resistance, which depends on the hemodialysis machine used (membrane characteristics, filter design) and the target solute, which is urea in this example; Q fil It is the ultrafiltration rate of the CRRT filter; Qbw inlet This refers to the blood flow rate at the inlet of filtration unit 2. SC urea It is the sieving coefficient of urea (depending on the selected filtration unit).

[0610] • Removal dose: An estimated removal rate for a given solute; for some solutes, the first approximation assumes that the solute removal rate from the filter is related to the effluent flow rate Q. eff Broadly the same; alternatively, solute removal can be estimated as a function of all flow settings and dialyzer / filter-related parameters; alternatively, appropriate sensors can be placed to measure conductivity or concentration, thereby allowing the calculation of the actual removal of a given solute (e.g., sodium), for example using one of the methods described in EP patent number 0547025 or EP patent number 0658352 or EP patent number 00920887 (incorporated herein by reference). In another alternative, the equations in paragraphs a) and b) above, as described for urea removal, can be used with adapted RT(K0.A) and SC. xxx Use them together to consider a specific solute "xxx".

[0611] In the following description, reference will be made to the above-mentioned dose definitions related to doses not normalized to patient weight (BW) or patient surface area (BSA). Of course, the same principles and formulas described below can be normalized to body weight or patient surface area by dividing the dose value by body weight (BW) or surface area (BSA). Examples at the end of the description include normalized CRRT doses and patient weights.

[0612] Furthermore, when fluid displacement lines (such as lines 51 and 67 in the attached diagram) are present upstream of the processing unit, the doses defined above can be corrected to account for pre-dilution effects. Each dose defined above can be adjusted by multiplying the dose value by a dilution factor F. dilution To correct:

[0613] Dose corr_xxx =F dilution ·D xxx (where xxx = eff, conv, dial, etc.);

[0614] Dilution factor F dilution It can be defined according to one of the following equations:

[0615] Blood dilution factor:

[0616]

[0617] Plasma dilution factor:

[0618]

[0619] Plasma dilution factor:

[0620]

[0621] Blood dilution factor:

[0622]

[0623] In the above equation, Q cit and / or Q PBP and / or Q rep.pre and / or Q syr If a term does not exist or is negligible, the corresponding term can be canceled (or set to 0). Throughout the application, a term can be ignored whenever it is negligible (this typically applies to syringe flow rates, but is not limited to this), i.e., its value can be treated as 0 or the term can be deleted.

[0624] In fact, the effluent dose that has been corrected for the pre-dilution effect will be: Dose corr_eff =F dilution ×D eff .

[0625] F should be selected based on solute distribution and its ability to pass through the erythrocyte membrane. dilution Coefficients (e.g., creatinine, which diffuses slowly through red blood cells, => plasma dilution coefficient).

[0626] For example, if we assume the urea dose (D) urea Since the urea flow rate is roughly the same as the outflow rate, and urea is distributed throughout the whole blood and can be rapidly transferred across the red blood cell membrane, the correction factor to be considered during predilution should be for whole blood. Therefore:

[0627]

[0628] With Q eff In comparison, more complex equations can provide urea removal (K) urea A more accurate estimate of (as shown in Equations 11 and 12 above), especially when operating at high flow rates or with small filters (pediatric conditions).

[0629] Buffer load definition

[0630] Net buffer load during in vitro therapy (J buffer_load ) is defined as a combination of the following items (one or more):

[0631] • Metabolism of citrate infused to the patient (J met_cit ) and / or the metabolism of lactate infused to the patient (J met_lact This produces bicarbonate (more generally, from the metabolism of all bicarbonate precursors).

[0632] • Bicarbonate balance from extracorporeal blood therapy (J HCO3_bal This may be matched with the patient's net loss or net gain.

[0633] • Acid infusion, from, for example, the citric acid content of anticoagulant solutions (J H+ ), in the relevant time.

[0634] From a mathematical perspective, the general definition of net buffer load is:

[0635]

[0636] Conventionally, the net buffering load is positive when extracorporeal blood therapy provides a buffer / net increase in bicarbonate for the patient; and negative when there is a buffer loss.

[0637] From a physiological perspective, extracorporeal blood therapy promises to provide patients with a net buffer gain to balance proton metabolism (protein metabolism). However, in scenarios where patients begin treatment with (severe) metabolic alkalosis, a net buffer loss may be necessary.

[0638] The buffer balance parameter is modeled from one or more of the following:

[0639] • The rate of citrate infusion to the patient (citrate load),

[0640] • The balance between bicarbonate and other buffers (e.g., lactate).

[0641] • Hypothesis regarding citrate metabolism (1 mole of citrate is metabolized into 3 moles of bicarbonate),

[0642] • Assumptions regarding systemic concentrations of citrate, bicarbonate, and other buffers in patients (which may be fixed values ​​or calculated from other sub-models).

[0643] The set buffer balance target does not match the current buffer balance of CRRT running treatment (which will require knowing the specific situation of the patient's current citrate and bicarbonate levels), but rather matches the expected (normalized) net buffer load when the patient's bicarbonate will stabilize at a steady state of, for example, 25 mM.

[0644] Acid-base steady state is established slowly, and measurable changes usually appear after 24 hours; considering that the acid-base state is reaching steady state under CRRT, two days seems to be a reasonable minimum.

[0645] In the buffer balance analysis framework introduced in this article, acid-base equilibrium steady state is reached when the following conditions are met:

[0646] - The patient's systemic citrate concentration had stabilized in all body sites, therefore the citrate load and bicarbonate production remained constant.

[0647] -Because the net buffer load balances the metabolic proton production rate G H+ Therefore, the patient's bicarbonate concentration has stabilized in all parts of the body.

[0648] Citrate Loading

[0649] Citrate load is defined as the net infusion rate of citrate to the patient, and its relationship with the citrate infusion rate from the pre-blood pump anticoagulant circuit (J). cit_PBP ) and the removal of citrate from the dialysate (J cit_dial The difference between these values ​​matches the difference between citrate infusion in the blood circuit and citrate loss through the dialyzer / dialysis fluid.

[0650] From a mathematical perspective, the following equation aims to calculate the amount of citrate returned to the patient (citrate load), which is related to the acid-base balance prescription during RCA.

[0651] The definition of citrate load in patients is:

[0652] J citrate_load =J cit_PBP -J cit_dial

[0653] (Equation 18)

[0654] According to the citrate dose (D cit The definition of citrate infusion can be expressed in two ways.

[0655] From a mathematical perspective, the citrate infusion rate is defined as follows:

[0656] J cit_PBP =Q cit ·C cit_PBP =D cit ·Q b

[0657] (Equation 19)

[0658] In this method, citric acid and citrate are considered in the same form.

[0659] The removal rate of citrate into the dialysate is determined by the removal of citrate-calcium complex by the filter (K). cit The definition of citrate and the expression of citrate concentration at the filter inlet (plasma water).

[0660] From a mathematical perspective, the removal of citrate from effluent is defined as follows:

[0661] J cit_dial =K cit ·Cpw cit_inlet

[0662] (Equation 20)

[0663] Citrate loading (major variant)

[0664] The assumptions underlying the modeling of citrate mass transfer in the extracorporeal blood circuit include the following: citrate is distributed in plasma (rather than in erythrocytes), CRRT filter citrate clearance is calculated based on the citrate concentration in plasma water used for mass transfer calculations, patient citrate metabolism and non-zero steady-state citrate concentration in the blood pathway are taken into account, and patient citrate clearance is proportional to body weight.

[0665] The plasma flow rate at the filter inlet is defined as follows:

[0666]

[0667] Here (and below), it is assumed that there are no pre-blood pump infusion lines other than the (citrate) anticoagulant line 51, and that heparin is not used / injected because RCA is provided (i.e., PBP replacement fluid and syringe flow rate are not considered (these items are enclosed in parentheses for the sake of explanation)).

[0668] In CRRT with non-zero dialysis fluid and filtration flow rate, the equation for citrate removal is calculated (etc.).

[0669] Equation 21) is as follows:

[0670]

[0671]

[0672]

[0673] It should be noted that the citrate mass transfer parameters used to calculate the above removal rates are known and constant values, depending on the selected dialyzer.

[0674] For example, the following table reports some values ​​for the Baxter Prismaflex suite that have been used:

[0675] Prismaflex Kit <![CDATA[S / RT cit ml / h]]> <![CDATA[SC cit ]]> M100 7500 1.0

[0676] A simpler equation with lower precision can be used. For example, K can be assumed. cit Equal to outflow velocity Q eff .

[0677] The plasma water citrate concentration (Cpw) at the filter inlet can be defined with or without considering an increase in the patient's citrate concentration. cit_inlet ).

[0678] A simple, rough estimate would assume that the patient's citrate concentration is negligible throughout the treatment process (see next paragraph), however, a more accurate approach requires estimating the patient's citrate metabolic clearance (K). cit_met To estimate the patient's systemic citrate concentration (Cp) cit_pat The increase in citrate concentration in the bloodstream is (see below). In fact, during RCA treatment, the concentration of citrate in the bloodstream will never be zero due to the accumulation of some citrate in the patient's body. This accumulation should be accounted for to avoid a bias of approximately 10% (if ignored). This requires understanding the citrate metabolism rate (Kc) in the patient's liver and muscles. cit_metThis metabolic rate can vary widely and deviate significantly from the final estimate. However, it may be relevant to consider the "minimum" accumulation that would occur in patients with "normal" citrate metabolism. In this regard, a typical metabolic clearance of approximately 700 ml / min (from the literature) is assumed for calculating patient citrate concentrations at steady state. Although not described in the literature, it is assumed that patient citrate clearance is proportional to body weight.

[0679] The expression for the systemic citrate concentration in a patient under steady state is as follows:

[0680]

[0681] Based on the above, the estimated citrate metabolic clearance (ml / min) of the patient is:

[0682]

[0683] The expression for the citrate plasma water concentration at the filter inlet is as follows:

[0684]

[0685] The combination of Equations 18, 20, 22 and 24 above allows the elimination of the citrate concentration parameter and expresses the patient's citrate load as a function of flow rate and clearance.

[0686]

[0687] The mathematical relationship of the above citrate load is used in the context of this application to correlate the buffer load parameter (which depends on the citrate load) with the citrate dose, blood flow, metabolic clearance and citrate clearance (depending on their respective flow rates) and the plasma flow rate and plasma water flow rate at the inlet of the filtration unit.

[0688] Citrate loading (simplified variant)

[0689] Based on the major variants described above, systemic citrate concentrations (Cp) in patients following citrate anticoagulation are considered and estimated using Equations 22 and 23. cit_pat The increase of ) . This choice yields Equation 25 for citrate loading as reported above.

[0690] A simpler alternative to this formula is to ignore the change in the patient's systemic citrate concentration, treating it as a constant, for example, zero. Therefore, according to this alternative, equations 22 and 23 are not used. This assumes the patient's systemic citrate concentration is zero (Cp... cit_pat When =0), equations 24 and 25 are transformed into the following equations 24' and 25':

[0691] Jcit_PBP =Qpw inlet ×Cpw cit_inlet

[0692] (Equation 24')

[0693]

[0694] Bicarbonate balance in extracorporeal blood circuits

[0695] Bicarbonate balance is defined as the net infusion or loss rate of bicarbonate during extracorporeal blood processing; it is correlated with the infusion rate of dialysis and / or all replacement fluids (J). HCO3_inf ) and the removal rate of bicarbonate entering the effluent (J HCO3_effl The differences between them match.

[0696] The equilibrium rate of bicarbonate is defined as follows:

[0697] J HCO3_bal =J HCO3_inf -J HCO3_eff

[0698] (Equation 26)

[0699] The assumptions used to model bicarbonate mass transfer in an in vitro blood circuit include the following: bicarbonate is distributed in both plasma and erythrocytes, and the bicarbonate concentration Cp at the blood pathway is... HCO3_pat 0 is fixed (e.g., equal to 25 mM); of course, different (fixed) values ​​can be used for bicarbonate concentrations in the blood pathway.

[0700] Other assumptions include: the citrate solution contains no bicarbonate, and there are no other pre-blood pump infusions containing bicarbonate (in the opposite case, the bicarbonate content / concentration will be considered in the bicarbonate balance, i.e.) and / or The removal of bicarbonate in the CRRT filtration unit is the same as that of urea removal, and the removal of bicarbonate in the dialysate is calculated based on an equation similar to that of citrate, taking into account the concentration of bicarbonate in the plasma water used for mass transfer calculations.

[0701] The calculation of bicarbonate infusion rate is based on knowledge of the fluid composition (i.e., the known bicarbonate concentration).

[0702]

[0703] If bicarbonate is present in calcium-replacement infusion line 74 (which is unlikely due to the potential risk of precipitation), then add a term to Equation 27. Fluid composition (i.e., bicarbonate concentration and / or replacement fluid prescription) can be entered by the physician (as requested by the dialysis device) or read by, for example, a reader of the dialysis device, such as by associating the product name with its bicarbonate content / concentration.

[0704] The equations for bicarbonate removal from dialysate are very similar to those for citrate removal; however, they differ in that bicarbonate is present in the dialysate, the mass transfer parameter (KOA) values ​​are different, and a fixed value of systemic bicarbonate in the patient is considered. Clearly, if citrate is present in the dialysate, the corresponding citrate load / balance can be accounted for in the corresponding citrate equation, in the same manner as described below for bicarbonate.

[0705] The definition of bicarbonate removal in dialysate is as follows:

[0706]

[0707] Unlike citrate, bicarbonate readily transfers between erythrocytes and plasma; therefore, whole blood is considered in the calculations for mass transfer to the dialysate. Furthermore, based on the molecular weights of bicarbonate and urea (61 g / mole vs. 60 g / mole), the diffusion mass transfer coefficient of the CRRT filter is the same as that of urea. The sieving coefficient is taken as 1.

[0708] Consider the constant physiological value of bicarbonate in the blood pathway.

[0709] The blood flow rate at the filter inlet is defined as follows:

[0710] Qbw inlet =Q bw +Q cit +Q syr +Q PBP +Q rep.pre

[0711] =Q b ·[(1-Hct)·Fp+Hct·Frbc]+Q cit +Q syr +Q PBp +Q rep.pre

[0712] (Equation 7)

[0713] In CRRT with non-zero dialysis fluid and filtration rate, the equation for calculating bicarbonate clearance is similar to that for citrate; however, due to the reasons mentioned above, the mass transfer coefficients SC and K0A differ, and the flow rate considered in the blood loop is the total blood flow rate (Qbw), not the plasma flow rate (Qpw). In reality, bicarbonate is distributed in both plasma and erythrocytes, based on the assumption of unimpeded transfer; therefore, the total blood flow rate is considered when assessing clearance. The equation for calculating citrate clearance in CRRT with non-zero dialysis fluid and filtration rate (Equation 29) is as follows:

[0714]

[0715]

[0716]

[0717] It should be noted that the bicarbonate mass transfer parameters used to calculate the above removal rates are known and are constant values ​​depending on the selected dialyzer.

[0718] For example, the following table reports some values ​​for the Baxter Prismaflex suite that have been used:

[0719] Prismaflex Kit <![CDATA[S / RT bic ml / h]]> <![CDATA[SC bic ]]> M100 17000 1.0

[0720] In addition to the complexity of the above equation (Equation 29), a reasonable approximation of bicarbonate removal in most cases is given by the following equation, which simplifies the estimation of filter bicarbonate removal:

[0721] K HCO3 =Q eff

[0722] (Equation 30)

[0723] The plasma concentration at the filter inlet is obtained from the following set of equations 31, namely:

[0724]

[0725]

[0726] From the above equation, the expression for the concentration of bicarbonate in plasma water at the filter inlet is:

[0727]

[0728] Lactate balance in extracorporeal blood circuits (optional)

[0729] Lactate balance is defined as the net infusion or loss rate of lactate during extracorporeal blood processing; it is related to the infusion rate from dialysate and / or replacement fluid (J).lact_inf ) and lactate removal rate (J) entering the dialysate lact_dial The differences between them match.

[0730] Lactate can be used as an alternative buffer to bicarbonate, offering the advantage of a more stable solution. Lactate-based dialysates are well-known in dialysis; for example, they are used in the home dialysis version of the NxStage System One device. Additionally, lactate is also present in a certain amount of bicarbonate solution as lactate to control pH and solution stability. This is the case with the Baxter Hemosol / PrismaSol CRRT solution range (containing 3 mM lactate). Similar to citrate, lactate is rapidly metabolized to bicarbonate upon infusion into the patient, with a conversion rate of 1 mole per mole. Assuming a steady-state plasma lactate concentration of approximately 1.5 mM in the patient, lactate can be modeled in much the same way as bicarbonate.

[0731] Lactate clearance can be assumed to be the same as urea clearance, although the molecular weight of lactate is approximately twice that of urea (112 g / mole vs. 60 g / mole). However, in CRRT environments where flow rate is the primary limiting factor, clearance estimation error is minimized. Of course, more precise estimates can also be used, such as by using the ability of KOA to depend on the solute molecular weight (meaning that KOA_lactate can be derived from the known KOA of urea, creatinine, vitamin B12, and inulin).

[0732] The assumptions underlying lactate mass transfer modeling in the extracorporeal blood circuit include: lactate is distributed in plasma and erythrocytes, and lactate clearance in the CRRT filtration unit is the same as urea clearance. Furthermore, it is assumed that the steady-state plasma lactate concentration at the blood circuit is fixed at 1.5 mM; obviously, different fixed values ​​can be assumed and used. Lactate mass balance in the extracorporeal blood circuit is calculated using an equation similar to that for bicarbonate, taking into account the metabolism of lactate load, with 1 mole of lactate corresponding to 1 mole of bicarbonate.

[0733] The mass transfer equation for lactate is as follows. The lactate equilibrium ratio is defined as follows:

[0734] J lact_bal =J lact_inf -J lact_eff

[0735] (Equation 33)

[0736] The calculation of the lactate infusion rate is based on knowledge of the fluid composition (i.e., the known lactate concentration); it is assumed here that no bicarbonate concentrate is infused / that lactate is not present in the bicarbonate concentrate (otherwise, these terms Q would need to be considered). HCO3 ·Clact.HCO3 The same applies to pre-blood pump infusion.

[0737]

[0738] Fluid composition (i.e., lactate concentration and / or replacement fluid prescription) can be entered by the physician or read by a reader, for example, a dialysis device.

[0739] The definition of lactate removal in dialysate is as follows:

[0740] J lact_eff =Q dial ·C lact_dial +K lact ·(Cpw lact_inlet -C lact_dial )+Q fil ·C lact_dial

[0741] (Equation 35)

[0742] Lactate readily transfers between red blood cells and plasma; therefore, whole blood is considered for use in the mass transfer calculations to the dialysate. Furthermore, the bicarbonate diffusion mass transfer coefficient of the CRRT filter is taken as the same as that of urea. The sieving coefficient is taken as 1.

[0743] Lactate clearance (K lact ) is considered equal to bicarbonate removal (K HCO3 Therefore, the control unit uses the same equation and performs calculations in the same way as before. The expression for the lactate plasma water concentration at the filter inlet is:

[0744]

[0745] Patient buffer net load

[0746] The patient's net buffer load is defined as being related to the patient's citrate infusion rate (i.e., citrate load) and bicarbonate production. To achieve this, assumptions about citrate metabolism include the following: the metabolism of citrate load results in the production of 3 moles of bicarbonate per mole of citrate, and the net buffer load (NBL) may decrease due to the rate of acid infusion (e.g., citric acid). The rate of bicarbonate production during citrate metabolism (steady-state) is expressed as follows:

[0747] J met_cit =3·J cit_load

[0748] (Equation 37)

[0749] The expression involving the acid infusion rate is as follows:

[0750] J H+=3·J citric_acid =3·Q cit ·C cit_PBP

[0751] (Equation 38)

[0752] Combining equations 17, 37, and 38, we obtain the expression for the net buffer load as a function of citrate loading and bicarbonate balance:

[0753] J buffer_load =3·J cit_load +J HCO3_bal -3·J citric_acid

[0754] (Equation 39)

[0755] It should be noted that J is given in Equation 25 (or the simplified Equation 25'). citrate_load The expression), and J HCO3_bal The complete expression is derived from equations 26, 27, 28, 29 (or simplified equation 30) and 32. J citric_acid This is derived from equation 38.

[0756] From a therapeutic perspective, the net buffer load should be positive to offset the protons (H+) produced by metabolism. + Generation rate G H+ Literature reports typical G H+ The value is approximately 1 mmol / day / kg, or 0.04 mmol / h / kg. However, the protons produced by metabolism are strongly dependent on protein catabolism.

[0757] If lactate is considered (optional), the net buffer load, as a function of citrate load, lactate balance, and bicarbonate balance, is expressed as follows:

[0758] J buffer_load =3·J cit_load +J HCO3_bal +J lact_bal -3·J citric_acid

[0759] (Equation 40)

[0760] In this case, besides the one mentioned for J citrate_load J HCO3_bal and J citric_acid In addition to the equation, it is also necessary to use J lact_bal The equations, namely equations 33, 34, 35, and 29 (if lactate clearance K is considered to be K), are... lact Equivalent to the removal of K by bicarbonate HCO3 -(or the corresponding equation for lactate clearance, or simplified K) lact =Q eff ) and Equation 36.

[0761] Steady-state acid-base balance prescription

[0762] The equipment control unit is configured to receive a steady-state acid-base balance target, i.e., the steady-state acid-base balance prescription setpoint prior to the start of processing. This additional prescription value affects various flow rates to be determined by the control unit 12. In practice, the definition of the steady-state acid-base balance target depends on almost all operating parameters and other prescription parameters (as well as system configuration).

[0763] As mentioned above, the steady-state acid-base balance formulation can be specified as follows:

[0764] A) Steady-state patient bicarbonate concentration (requires an assumption about nNBL, i.e., nNBL0), or

[0765] B) Normalized net buffer load or nNBL (requires an assumption regarding bicarbonate concentration, i.e., (Cp) HCO3_pat 0)).

[0766] Under steady-state conditions, nNBL is expected to balance the rate of proton (H+) generation produced by the patient's metabolism.

[0767] nNBL

[0768] The control unit 12 of the device for extracorporeal blood processing allows the operator to input parameters (J buffer_load / BW), this parameter indicates the steady-state acid-base (or buffer) balance in the blood of patients who must undergo CRRT blood processing. This parameter defines quantitative information about the intensity of treatment in response to an increase or decrease in net patient buffer (bicarbonate). This parameter has high specific significance in complex cases of citrate anticoagulation, but it is also relevant to any extracorporeal dialysis treatment (systemic anticoagulation or non-anticoagulation operation). More specifically, control unit 12 receives the net buffer load at device setup (i.e., before CRRT processing begins).

[0769] The normalized net buffer load (nNBL) is defined as follows:

[0770]

[0771] nNBL was chosen as an indicative parameter of steady-state acid-base balance level and expressed as the buffer volume infused per unit time and per patient kg (mmol / h / kg).

[0772] In this regard, it is important to note that, using the equation mentioned earlier, J... buffer_load It is associated with several other flow rates. In fact, J buffer_loadTherefore, NBL or nNBL is defined based on equations 17, 26, 27, 28 (or 26', a combination of equations 26, 27, and 28), 29 (or 30), 32, and 38; in the presence of lactate, it is further defined based on equations 29 (or 30), 33, 34, 35, and 36. All these equations are functions of one or more other flow rates configured for the CRRT device. Thus, imposing setpoints on the steady-state acid-base balance formulation creates constraints among various fluid flow rates, thereby affecting the operating flow rate of the device. By solving the aforementioned equations, the device control unit 12 can derive the corresponding flow rate for the operating parameters matched to the formulation (as will be apparent from the detailed description below).

[0773] It is noteworthy that a review of published clinical data on CRRT using RCA at steady state showed that the nNBL parameter correlated well with both bicarbonate and alkali excess in steady-state patients. Therefore, once the normalized net buffer load (nNBL) is assumed to be the "default" value, the buffer balance parameter can be expressed as steady-state bicarbonate concentration instead of using the (normalized) net buffer load defined above; see further paragraphs on this topic.

[0774] In the previously described embodiment, when the patient reaches the assumed bicarbonate level, nNBL matches the buffer balance value (e.g., 25 mM) => nNBL 25 If nNBL 25 Matching the proton production rate (G), a steady state is reached, and the patient will stabilize at the assumed HCO3 level (25 mM). Alternatively, if nNBL... 25 If the rate of bicarbonate production is greater than the proton production rate, the patient's bicarbonate levels will increase to C. eq For example, nNBL Ceq Matches the (current) proton production rate. If nNBL 25 Below G H+ If this is the case, the patient's bicarbonate levels will stabilize at a value below the assumed level.

[0775] Although the parameter indicating the steady-state acid-base (or buffer) balance in a patient's blood has been described as being normalized based on the patient's weight, it can also be normalized based on the patient's body surface or another patient-related variable. Of course, even if this is not considered the optimal approach, the control unit 12 can receive the net buffer load (mmol / h) without any normalization.

[0776] Variant-Cp with steady-state HCO3 indicator HCO3_pat

[0777] Patient bicarbonate concentration (Cp) HCO3_patThis can also serve as an indicative parameter of steady-state acid-base balance, provided that a (desired / target) nNBL level has been selected. In this case, the previous equations can be rearranged to express the patient's steady-state bicarbonate concentration as a function of a predefined nNBL level (e.g., nNBL0 = 0.1 mmol / h / kg). The citrate equations (i.e., equations 18-25, 24', and 25') remain unchanged.

[0778] The difference is that the bicarbonate equation requires some rearrangement. More specifically, the expression for bicarbonate in a steady-state patient (a rearrangement of Equation 31) is as follows:

[0779]

[0780] The expression for the concentration of plasma bicarbonate at the filter inlet (rearranged Equation 28) becomes:

[0781]

[0782] Combining equations 42 and 43 provides the following expression for steady-state patient bicarbonate:

[0783]

[0784] The expression for the loss of bicarbonate in the effluent (based on Equations 17 and 26):

[0785]

[0786] Select / set nNBL0 and J buffer_load The relationship between them is as follows:

[0787] J buffer_load =nLBL0×BW

[0788] (Equation 45)

[0789] Therefore, equation 44 can be expressed as follows:

[0790] J HCO3_eff =J HCO3_inf +J met_cit -J H+ -nNBL0×BW

[0791] (Equation 44')

[0792] According to equation 45, J buffer_load According to equation 38, J H+ According to equations 37 and 25 or 25', J met_cit And J according to Equation 27 HCO3_infThe input is given to equation 44; then the latter is combined with equation 43 such that all terms of the combined expression are known. Finally, Cpw is introduced into equation 42. HCO3_inlet This allows us to derive an expression for the variable that defines the steady-state value of the patient's bicarbonate, a parameter to be set by the healthcare professional, which affects almost all fluid flow rates to be set.

[0793] It is evident that the solution provides an alternative parameter for the normalized buffer load parameter, namely the steady-state patient bicarbonate concentration (which again indicates the steady-state acid-base balance in the blood of patients who must undergo CRRT blood treatment), allowing medical personnel to set appropriate values ​​and allowing the control unit 12 to maintain appropriate acid-base balance during CRRT treatment.

[0794] Treatment configuration parameters

[0795] Treatment configuration parameters are user settings that can be configured within the system to tailor the CRRT mode based on local protocols and / or certain client preferences. While treatment configuration parameters can be set at any time as needed, these user settings are typically set once at a particular client and then applied to all patients receiving the treatment.

[0796]

[0797] Other default treatment configuration parameters may stem from system technical limitations and / or manufacturer choices. These constraints are embedded in the system and cannot be selected by the user. Examples of these parameters are the flow operating range of a fluid loop (e.g., calcium infusion in an RCA), or the imposed relationship between a specific flow rate and safety or technical considerations (e.g., the relationship between maximum PBP or citrate flow rate and blood flow rate).

[0798] Process configuration parameters

[0799] The processing configuration parameters are variables specific to the patient being treated and the composition of the prescription fluid (which is also part of the medical prescription).

[0800]

[0801] It is worth noting that hematocrit can also be measured directly by the device and monitored online.

[0802] Several default processing configuration parameters may come from the filter type, such as flow operating range and / or mass transfer coefficient. These are not user-selectable but are provided by the manufacturer. Of course, it is possible to manually enter the relevant parameter values ​​instead of providing the filter type to the device (by reading the filter unit code with a reader or by entering / selecting the filter unit used on the user interface). As will become apparent from the following description, in the simplest method of estimating the removal of small solutes to be the same as the effluent flow rate, filter identification is not required. This method becomes inaccurate when dialysate and blood flows become similar, such as in pediatric applications or high-volume CRRT.

[0803] Operating parameters

[0804] The operating parameters are CRRT monitoring processing parameters calculated by the assisted prescription algorithm (shown below here), as a function of the following parameters:

[0805] -Prescription parameters

[0806] -Treatment configuration parameters

[0807] - Handle configuration parameters.

[0808] All operating parameters are flow rates. The list of operating parameters depends on the anticoagulation method and the performance and configuration of the CRRT system.

[0809] In some embodiments, calcium infusion during RCA may not be directly controlled by the CRRT system, and the infusion may be performed by a separate infusion pump. In this case, the calculated prescribed value should be input into an external ion balance infusion pump 75, and the control unit 12 may not need to verify or ensure compliance with the auxiliary prescription. This also applies to anticoagulant infusion during systemic anticoagulation (typically syringe-dose infusion).

[0810] CRRT systems can have a variable number of pumps that can be used for fluid infusion at different locations along the extracorporeal blood circuit. See also Figures 2 to 6 Examples of different numbers of infusion lines and / or pumps.

[0811] The table below lists the operating parameters (related to the respective pumps) that will be considered in the examples. While this list mentions a maximum of seven pumps (including blood pumps), systems with more pumps and infusion lines can also be considered.

[0812] The table shows the PBP and citrate flow rates, but in alternative configurations, they are typically delivered by the same pump. The PBP flow rate is specific to treatments that do not use citrate for anticoagulation. It is important to note that... Figure 6 The embodiments provide two different pre-blood pump infusion lines, namely an anticoagulant (citrate) infusion line 51 and a separate PBP infusion line 52.

[0813]

[0814]

[0815] Adjunctive prescriptions for not using / using systemic anticoagulation

[0816] In the case of systemic anticoagulation, a concentrated anticoagulant solution is infused into the extracorporeal blood circuit. While this prescription is clinically important, heparin infusion is not particularly relevant in terms of CRRT prescription and flow rate calculations because the (heparin) infusion flow rate is very low, typically less than 5 ml / h, matching approximately 0.1% of all fluid infusion rates, and therefore does not significantly affect the CRRT dose, and the anticoagulant used does not interfere with acid-base balance. Due to these characteristics, the anticoagulant prescription during systemic anticoagulation during RRT can be considered completely independent of the RRT prescription itself and will not be addressed in the next section, which can therefore address all prescriptions with or without systemic anticoagulation simultaneously.

[0817] When systemic anticoagulation is not used or is used, a CRRT prescription can be constructed according to the following equation:

[0818] 1. CRRT dosage,

[0819] 2. Steady-state acid-base balance target,

[0820] 3. Patient fluid removal rate (PFR)

[0821] 4. Optionally, blood flow rate.

[0822] If systemic anticoagulation is required, an anticoagulation prescription can also be listed; however, it will not measurably interfere with any other prescription parameters and can be resolved independently.

[0823] In a system with three fluid infusion pumps and one outflow pump, four fluid flow rates are defined based on the three first prescription parameters described above. Therefore, one degree of freedom exists that allows an additional setting from the treatment configuration to be considered in the definition of the operating flow rate parameters. If an additional infusion pump is added, two degrees of freedom become available, and two further settings can be selected to allow the control unit to propose a corresponding flow rate matching the prescription and settings. With one less infusion pump, the three first prescriptions are sufficient to define the fluid flow rates of the treatment configuration.

[0824] Qualitative dependence of operating parameters

[0825] The next table provides indications for the interdependence between operational and prescribing parameters in the absence of anticoagulation or in the presence of systemic anticoagulation; it is worth noting that this dependence depends on the definition / selection of the CRRT dose.

[0826]

[0827] X1: The contribution of flow rate to CRRT dose depends on the given definition (see previous paragraph). Most relevant definitions use all flow rates (regardless of whether it refers only to Q). eff Or it refers to an estimated clearance).

[0828] X2: The contribution of blood flow velocity to CRRT dose also depends on the chosen dose definition. Blood flow is relevant as long as the pre-dilution effect is taken into account (this is not the case when the outflow velocity is simply referred to as the CRRT dose).

[0829] X3: Based on the fluid composition associated with each infusion solution, all infusion or dialysis fluids contribute to acid-base balance. Blood flow rate affects the pre-dilution and concentration of the buffered solute at the CRRT filter inlet.

[0830] X4: The patient’s fluid removal rate prescription is directly controlled by the definition of the outflow rate and all other infusion rates of the dialysis system (including anticoagulant flow rate, if relevant).

[0831] X5: When blood flow is defined as a prescription parameter, one degree of freedom is lost in the definition of the operating flow rate, meaning fewer constraints from treatment configuration parameters can be used. The number of degrees of freedom is defined as the difference between the number of operating flow rates to be calculated and the number of prescription parameters.

[0832] Control unit and auxiliary prescription algorithm

[0833] Control unit 12 is connected to various sensors, actuators for regulating flow rates through the pipelines (in the above example, these actuators include pumps and switching valves operating on the pipelines), and a user interface. Control unit 12 may include a digital processor (CPU) and necessary memory (or multiple memories), such as memory 16, analog circuitry, or a combination thereof. In the methods described herein, it is indicated that the control unit is "configured" or "programmed" to perform certain steps: this can be achieved in practice by any means that allows the control unit to be configured or programmed. For example, in the case where the control unit includes one or more CPUs, a program may be stored in a suitable memory containing instructions that, when executed by the control unit, cause the control unit to perform the steps described herein. Alternatively, if the control unit is analog, the circuitry of the control unit may be designed to include circuitry configured, in use, to perform the steps disclosed herein. The steps in various aspects of the method are generally performed by the control unit unless otherwise stated.

[0834] exist Figures 1 to 6 In the example, control unit 12 is configured to execute the flow rate setting procedure as described below. From Figure 2In the initial embodiment, five pumps are to be set up, which together define (or generate) five flow rates; the flow rates should be received by medical personnel or calculated by control unit 12.

[0835] The flow rate setting procedure includes an initial setting (or acceptance or maintenance) of the treatment configuration. In practice, the control unit 12 is configured to allow the user to select one or more treatment configurations. Available treatment configurations are exemplarily disclosed in the preceding paragraph of this specification. The CRRT dialysis dose will be selected from the described (or additional) possibilities. For example, the CRRT dose can be selected as the effluent dose D. eff Alternatively, you can choose urea dosage D. urea Or any different dose type. Select an acid-base balance parameter, such as between (normalized) net buffer load (n) NBL or the patient's systemic bicarbonate plasma concentration. Blood flow rate can be determined as a prescribed parameter or an operational parameter. Finally, depending on the number of degrees of freedom (i.e., depending on the number of flow rates set by control unit 12 minus the prescribed parameters), it is possible not to select any of the convection-diffusion relationship, blood pre-diffusion relationship, and before-and-after relationship, or to select one, two, or more of the convection-diffusion relationship, blood pre-diffusion relationship, and before-and-after relationship as additional constraints (see [link to relevant documentation]). Figure 7 Step 100 in the middle.

[0836] After setting up / receiving treatment, the necessary processing configurations will be provided. See also Figure 7 Step 101. In particular, patient-specific values ​​and device-specific or solution-specific values ​​must be provided. Typically, the patient's weight (BW) is required (or equivalent data for CRRT dose-surface BSA, depending on parameter normalization). This is required if any patient prescription is normalized based on patient weight according to the examples at the end of this disclosure. Hematocrit (Hct) is required depending on the device configuration. If the device-specific calculation of operating parameters and mathematical relationships requires it, the concentrations of certain solutes contained in the relevant bag should also be provided. In particular, the concentrations and specific locations of all solutes that contribute to acid-base balance are required. For example, the concentrations of all bicarbonate solutions, as well as citrate and calcium in various bags, are typically required; lactate and other bicarbonate precursors such as acetate are also necessary. Finally, filtration unit data for one or more solutes, such as KO.A., may be requested. As already noted, data can be entered manually or obtained automatically, for example, via a reader. For example, the device memory may include data associated with product codes (e.g., solution bag codes or filtration unit codes). Of course, the device input system (graphical user interface) can prompt for only the necessary values / parameters to be entered, or alternatively, request all data, and then the control unit 12 will use only the necessary data.

[0837] After the above steps, the device is ready to receive prescription parameters, the values ​​of which are entered by the operator (see [link]). Figure 7 (Step 102 in the previous step). Once obtained, the control unit 12 uses one or more of the aforementioned mathematical relationships, along with the input processing configuration data and prescription parameters, to determine the operating parameters consisting of various requested flow rates. In this regard, the control unit 12 uses a set of mathematical relationships that correlate the processing configuration data, prescription parameters, and operating parameters as a set of equations, which, once solved, provide all relevant flow rates to be suggested or set. At the end of step 103, the control unit 12 stores the calculated operating parameters in memory 16 and provides the calculated values ​​to the user interface for display to the user. Generally, the control unit 12 waits for the acceptance of the suggested values ​​before driving the corresponding actuator (pump) and achieving the calculated flow rate in the corresponding pipeline. In another embodiment, once the flow rate is available, the control unit 12 automatically sets the pump to achieve the flow rate in the corresponding pipeline.

[0838] In cases of conflicting applied conditions—that is, when the flow rate system has no solution given the treatment and processing configuration, applied and existing constraints, and prescription parameters—an alert is issued to the user. It is possible that the user is provided with one or more solutions for suggested operating flow rates approaching the applied conditions via the user interface. For example, additional mathematical relationships (convection-diffusion relationships, blood pre-dilution relationships, and pre- and post-dilution relationships) are given lower priority than other primary mathematical relationships that associate the input prescription parameters. A hierarchy can also be imposed on the said convection-diffusion relationships, blood pre-dilution relationships, and pre- and post-dilution relationships. Alternatively, if blood flow rate is selected as the prescription parameter, blood flow is moved to the operating parameter, and its value is calculated rather than received. In other words, the control unit 12 can be configured to manage conflicting situations with different intervention protocols. Optionally, more than one set of solutions for operating flow rates is provided to the user.

[0839] Go to Figure 2 For example, only the PBP infusion tubing and post-dilution infusion tubing are used for replacement fluid. Five flow rates need to be set, namely the blood flow rate Q. b Dialysis fluid flow rate Q dial PBP flow rate Q PBP Post-dilution flow rate Q rep.post and outflow logistics speed Q eff As described above, once a treatment configuration is received, a processing configuration must be provided. If the effluent dose is selected from the available dose types (meaning that pre-dilution of blood does not affect the CRRT dialysis dose), and the assumption is made that the removal of small solutes by the filtration unit is sufficiently equal to the effluent flow rate, then filter data is not required. Body weight, hematocrit, and bicarbonate concentration must be entered into memory via the user interface. The control unit then waits to receive the specified dose value D. set Patient fluid removal rate Qpfr Specified values, target steady-state acid-base balance parameters, and blood flow velocity Q b Settings (see) Figure 7 Step 102 in the middle.

[0840] The memory 16 associated with or connected to the control unit 12 stores multiple mathematical formulas that determine the fluid flow rate Q. PBP Q rep.post Q eff Q b Q PFR and Q dial Related. Because there are four prescription parameters and five flow rates to set, an additional constraint can be selected. In this regard, additional mathematical relationships are stored in the memory, which can be as follows:

[0841] - Convection-diffusion relationship, which is the total fluid velocity through the infusion line plus the patient fluid removal rate Q PBP +Q rep.post +Q PFR With the dialysis fluid line Q dial The fluid velocity is related; the convection-diffusion relationship can actually be defined by a first ratio R1 = (Q PBP+ Q rep.post+ Q PFR ) / (Q dial ),

[0842] - Blood predilution relationship, which determines the flow rate Q of blood or plasma. b Or Q p The fluid flow rate Q infused into the blood extraction line via the pre-dilution infusion line 52 is compared with the fluid flow rate Q. PBP Related; the blood predilution relationship can be defined as a second ratio R² = Q. b / (Q PBP ) or R2 = Q p / (Q PBP );

[0843] - The relationship between the preceding and following stages: the fluid flow rate Q through the pre-dilution infusion line. PBP The fluid flow rate Q after passing through the dilution infusion pipeline rep.post Related; the preceding and following relationship can actually be defined as a third ratio R3 = (Q PBP ) / (Q rep.post ).

[0844] The control unit 12 allows the user, for example, to select one of the relationships via the user interface 12, and then the user can select the dose D input by the operator. set The set values, the target values ​​for steady-state acid-base balance, and the set blood flow rate Q. band fluid removal rate Q pfr The setpoints are applied to the previously discussed mathematical relationships to calculate all flow velocities Q. PBP Q rep.post Q eff and Q dial The set value, this mathematical relationship, associates the steady-state acid-base balance parameter with various flow rates and the additional mathematical relationships identified and selected by the user (as well as the fluid balance equation that needs to be satisfied in order to maintain fluid balance according to the prescription: Q). PBP +Q rep.post +Q dial +Q pfr =Q eff (FBE - Fluid Equilibrium Equation).

[0845] If the use of a syringe pump to inject auxiliary fluids, such as heparin, into the blood extraction line is also present or considered, the above equation can be modified accordingly to account for syringe flow rate.

[0846] It should be noted that the preset values ​​of each of the first, second, and third ratios R1, R2, and R3 can be pre-stored in the memory, or the control unit can allow the operator to input the set value or set range of each of the first, second, and third ratios R1, R2, and R3, for example, via the user interface 12.

[0847] In one choice, Figure 1 The device's memory 16 can (further) store multiple optimization criteria, which the control unit 12 can use to calculate alternative or combined with the aforementioned ratios R1, R2, R3 related operating flow rate settings.

[0848] For example, the optimization criteria stored in memory 16 may include a first optimization criterion specifying that the emptying time of at least one of the containers for fresh fluid 14, 64, 10, 11 and / or the filling time of waste container 62 are substantially the same as, multiples of, or proportional to the emptying time of one or more other containers for fresh fluid. A second optimization criterion stored in memory 16 may specify minimizing fluid consumption through the fluid lines. A third optimization criterion stored in memory 16 may specify maximizing the lifetime of filter unit 2. A fourth optimization criterion stored in memory 16 may specify maximizing the urea removal or dialysis rate for a given solute.

[0849] In practice, if the optimization criteria are stored in the memory 16, the control unit 12 can be configured to allow the user, for example via the user interface 12, to select the criteria he / she wishes to meet (step 100), and can also be configured to calculate the setpoint of the relevant operating flow rate based on the previously discussed mathematical relationship relating the steady-state acid-base balance parameters to various flow rates and the selected optimization criteria, as well as based on the fluid balance equation (FBE) mentioned above.

[0850] If the selected mathematical relation (and the ultimately selected criterion) are compatible, the set flow rate is calculated based on the selected mathematical relation (and the ultimately selected optimization criterion). On the other hand, in the event of a conflict between the selected mathematical relation (and / or the selected criterion), the control unit 12 can be configured to perform one or more of the following sub-steps:

[0851] - Notify the user; the user then has the right to re-enter a compatible option;

[0852] - Assign priorities to mathematical expressions (and / or selected criteria); the priority ordering is predetermined or user-adjustable: in either case, the control unit is configured to ignore the criteria or mathematical expressions once the flow rate has been calculated from the preferred criteria / mathematical expressions;

[0853] - Use preset rules to define trade-offs between conflicting mathematical relations and / or standards.

[0854] According to one variant, the control unit can use a flow rate setting program to initially calculate flow rate setpoints through various pipelines, and during a first interval of control processing, use said calculated setpoints to control the actuator for adjustment. Then, after a certain time interval or upon detecting user input, the control unit can specifically recalculate the flow rate setpoints through the various pipelines based on one or more different prescription values ​​and / or different selected (or modified) additional mathematical relationships, and apply the newly calculated setpoints during a second time interval following the first time interval. For example, the flow rate setting program can allow setting the flow rate to achieve a certain delivery dosage. On the other hand, if at some point the user desires the privilege of synchronous bag emptying, he can choose to apply a first optimization criterion, allowing the control unit to recalculate the flow rate setpoints, thereby allowing for as synchronous as possible emptying of the fluid bag.

[0855] Figure 3 Different configurations of a CRRT device using a localized anticoagulation scheme are shown. In this second example, six flow rates need to be set, i.e., Q... cit Q rep.post Q eff Q b Q ca and Q dialHowever, local anticoagulation requires citrate dosage and calcium compensation parameters as prescribed parameters for the patient. Therefore, the control unit 12 of the CRRT device requires the medical staff to input the CRRT dialysis dose, acid-base balance parameters, patient fluid removal rate, citrate dosage, and calcium compensation parameters. If blood flow rate is selected as the prescribed parameter, there are no further degrees of freedom. Therefore, once the required information is entered by the physician, no other mathematical equations can be selected. The control unit 12 calculates the operating parameters using a set of equations relating relevant mathematical relationships. Of course, the relevant mathematical relationships used by the control unit 12 will vary depending on the different system configurations (i.e., post-infusion of additional calcium) and the different contents of the used bags (e.g., citrate in bag 10). Figure 2 The examples are different (as will be apparent from the detailed examples reported below). The system of equations defines some constraints, primarily due to citrate infusion and the need to maintain the applied acid-base parameters, which may result in a system of equations with no solution for the flow rate. Again, in this case, one or more of the methods defined above can be employed. Again, detailed examples illustrate this situation.

[0856] Figure 4 The configuration provides an HDF configuration, which uses a pre-dilution line and a bicarbonate post-dilution line. Specifically, the post-dilution line infuses a displacement solution with a high bicarbonate concentration. This configuration allows for more flexible adjustment of the acid-base balance. Also in this configuration, the control unit 12 utilizes relevant mathematical relationships based on the CRRT device design, the determined prescription parameter types / properties, processing configuration parameters, applied values ​​of prescription parameters, and corresponding relevant mathematical relationships.

[0857] Figure 5 Another embodiment of the CRRT device: an HDF configuration with localized anticoagulation, which includes a post-dilution replacement solution and a post-dilution bicarbonate solution in addition to the calcium reinfusion line. There are a total of seven flow rates to be set, typically with six prescribed parameters: blood flow rate, acid-base balance target, CRRT dialysis dose, citrate dose, and calcium reinfusion parameter values. Therefore, the user can again select from convection / diffusion splitting, pre-dilution ratio, and pre- and post-infusion ratio. Figure 5 The configuration requires the control unit 12 to use several mathematical relationships to properly account for the interactions of various fluids, especially in terms of acid-base balance.

[0858] Example

[0859] This section provides some examples to better explain how CRRT devices work.

[0860] In the context of CRRT without anticoagulation or with systemic anticoagulation, the possibility of adjusting steady-state acid-base balance appears to be limited when using fluids with similar bicarbonate content. Some possibilities exist when using a fluid with low bicarbonate content (e.g., below 25 mM) and a fluid with high bicarbonate content (e.g., above 40 mM) simultaneously.

[0861] refer to Figure 2 The device shown is equipped with four fluid pumps (dialysis fluid pump 25, effluent pump 26, PBP infusion pump 53 and post-dilution infusion pump 65), thus enabling it to perform HDF treatment.

[0862]

[0863] The following examples S1-S5 (S represents systemic anticoagulation or no anticoagulation) are based on the above circuit configuration and Figure 2 .

[0864] Example S1

[0865] The effluent dose is chosen as the CRRT dose, so blood predilution does not affect the dose, and the equation is easier to solve. In this simplified approach, filter clearance for small solutes (such as bicarbonate) is also equal to the effluent flow rate; therefore, information about filter type / performance is not required.

[0866] In addition, steady-state bicarbonate is selected as the acid-base balance prescription parameter (when steady-state bicarbonate is selected, the device control unit assumes nNBL0 equals 0.1 mmol / h / kg); blood flow rate is also selected in the prescription parameters (reducing the degrees of freedom in configuration). Five pumps are available, and four prescription values ​​are input. Therefore, the system has one degree of freedom and one treatment configuration constraint, which can be further selected to obtain the calculation of all operating flow rate parameters.

[0867] In the treatment configuration, any of the following can be selected: convection / diffusion split, pre-dilution ratio, and pre- / post-infusion ratio. Predefined (modifiable) values ​​for these relationships are also included in memory and presented to the user.

[0868] In addition, the necessary processing configuration values ​​are also input by the operator or obtained by the control unit 12.

[0869]

[0870] Assume the user enters the following prescription through user interface 12:

[0871] -Patient: BW (body weight) = 75kg

[0872] -Hct(%)=32

[0873] -CRRT dose D eff = 28 ml / kg / h, where the dosage is the "effluent dose" per kg.

[0874] - Target value for steady-state bicarbonate: Cp HCO3_pat =25mmol / l

[0875] -Patient fluid removal rate: Q PFR =120ml / h

[0876] -Blood flow rate: Q b =200ml / min

[0877]

[0878] Several additional constraints exist stored in memory 16, particularly regarding minimum / maximum flow rates; for example, dialysate flow rate (Q). dial ): 0 to 6000 ml / h, displacement flow rate (Q) rep.post ): 0 to 4000 ml / h.

[0879] Operator selection (or pre-configuration):

[0880] - Diffusion / convection split: 50-50, i.e., ratio: R1 = 1.0

[0881] Control unit 12 then calculates the operating parameters, namely the various flow rates as follows:

[0882]

[0883] Specifically:

[0884] The outflow rate is determined based on the CRRT dialysis dose and body weight as follows: Q eff =28×75=2100ml / h,

[0885] -Q dial Q PBP Q rep.post and Q eff Defined by the following system of equations, and explicitly stated:

[0886] R1 = Q dial / (Q rep.post +Q PBP ) = 1.0

[0887] Q dial +Q PBP +Q rep.post +Q PFR =Q eff =2100

[0888] Using the two equations above, Q can be calculated directly. dial And set it to 990ml / h; further Q PBP +Q rep.post That's 990 ml / h.

[0889] Then, Q PBP They are arbitrarily selected as the remaining unknown parameters for calculation in the next step.

[0890] Q fil According to Equation 8, it is calculated to be related to the PBP flow rate, post-dilution flow rate, and patient fluid removal rate:

[0891] Q fil =Q PBP +Q rep.post +Q PFR =990 + 120 = 1110 ml / h

[0892] Then, the patient's steady-state bicarbonate concentration is defined using the following mathematical relationships (i.e., Equations 42 and 43). (Assume K) HCO3 equals Q eff –See Equation 30), which involves various velocities that produce further fluid velocity constraints (in the equations below, terms involving missing fluid lines have been removed from the general formulas provided in Equations 42 and 43):

[0893]

[0894]

[0895] All terms in the two equations above can be calculated or expressed as Q. PBP The function is shown below.

[0896] Use equations 6 and 7 to determine Q. bw and Q bw_inlet :

[0897] Qbw = Q b ·[(1-Hct)·F p +Hct·Frbc]=200·[(1-0.32)·0.95+0.32·0.85]·60

[0898] =11016ml / h

[0899] Qbw inlet =Q bw +Q PBP =11016+Q PBP

[0900] J is determined based on Equation 44.HCO3_eff :

[0901]

[0902] J is determined based on Equation 45. buffer_load (Assume nNBL0 = 0.1):

[0903] J buffer_load =nNBL0×BW=7.5mmol / h

[0904] J is determined based on Equation 27. HCO3_inf Reference J HCO3_inf The unit is mmol / h, Q PBP The unit is ml / h:

[0905]

[0906]

[0907] Using the above expression for the bicarbonate rate, the following expression for the plasma bicarbonate concentration at the filter inlet can be derived:

[0908]

[0909] The expression for steady-state patient plasma bicarbonate therefore becomes:

[0910]

[0911]

[0912]

[0913] A single solution to the above equation is positive and matches the expected PBP flow rate:

[0914]

[0915] The displacement velocity can be easily derived as follows:

[0916] Q rep.post =990-Q PBP =768ml / h

[0917] The flow rate value is finally rounded off.

[0918] Example S2

[0919] Similar to the previous example S1, the effluent dose is selected as the CRRT dose (blood pre-dilution does not affect the dose), and the filter clearance of small solutes (such as bicarbonate) is also considered equal to the effluent flow rate.

[0920] Conversely, the normalized net buffer load nNBL is selected as the acid-base balance prescription (when nNBL, the equipment control unit assumes Cp). HCO3_pat 0 equals 25mm); blood flow rate is also selected in the prescription parameters (reducing the degree of freedom in configuration). As in the previous example, five pumps are available, and four prescription values ​​are entered. Therefore, the system has one degree of freedom, and the treatment configuration constraints can be further selected to obtain the calculation of all operating flow rate parameters.

[0921] In the treatment configuration, any of the following can be selected: convection / diffusion split, pre-dilution ratio, and pre- / post-infusion ratio. Predefined (modifiable) values ​​for these relationships are also included in memory and presented to the user.

[0922] In addition, the necessary processing configuration values ​​are also input by the operator or obtained by the control unit 12. The changed values ​​are identified by different background shadows.

[0923]

[0924] It should be noted that the acid-base balance formulation has been switched to nNBL, and solutions with both low and high bicarbonate concentrations are used to provide some possibility for adjusting the acid-base balance.

[0925] Assume the user enters the following prescription through user interface 12:

[0926] -Patient: BW (body weight) = 75kg

[0927] -Hct(%)=32

[0928] -CRRT dose D eff = 28 ml / kg / h, where the dosage is the "effluent dose" per kg.

[0929] - Normalized net buffer load target value nNBL: nNBL = 0.15 mmol / h / kg

[0930] -Patient fluid removal rate: Q PFR =120ml / h

[0931] -Blood flow rate: Q b =200ml / min

[0932]

[0933]

[0934] This time, the operator chose:

[0935] - The pre-infusion / post-infusion ratio is 33%-67%, i.e., the ratio R² = 0.5.

[0936] Control unit 12 then calculates the operating parameters, namely the various flow rates as follows:

[0937]

[0938] Specifically:

[0939] The outflow velocity is determined as follows: Q eff =28 x 75 = 2100 ml / h

[0940] -Q dial Q PBP Q rep.post and Q eff By defining the system of equations as explicitly stated below:

[0941] R2 = Q PBP / Q rep.post =0.5

[0942] Q dial +Q PBP +Q rep.post +Q PFR =Q eff =2100

[0943] Then, the normalized net buffer balance (nNBL) is defined based on the following mathematical relationships, namely Equations 41, 26, 27, and 28, which involve various velocities that generate further fluid velocity constraints (terms related to missing fluid pipelines have been removed from the relevant equations):

[0944]

[0945]

[0946] Based on the assumption, K HCO3 Approximate to the outflow velocity (see Equation 30):

[0947]

[0948] Q fil Calculate according to Equation 8:

[0949] Q fil =Q PBP +Q rep.post +Q PFR

[0950] Based on Equation 32, it is assumed that the patient's plasma bicarbonate concentration is specified as 25 mM:

[0951]

[0952] Use equations 6 and 7 to determine Q. bw and Q bw_inlet :

[0953] Qbw = [Q b ·(1-Hct)·F p +Hct·Frbc]

[0954] Qbw inlet =Q bw +Q PBP =Q b ·[(1-Hct)·Fp+Hct·Frbc]+Q PBP

[0955] Make Q dial =600ml / h, Q rep.post =920ml / h, Q PBP =460ml / h

[0956] Example S3

[0957] Similar to Example S2 above, the effluent dose is selected as the CRRT dose, the filter clearance of small solutes (such as bicarbonate) is considered equal to the effluent flow rate, and the normalized net buffer load nNBL is also selected as the acid-base balance formulation (when nNBL, the device control unit assumes Cp). HCO3_pat (Equal to 25mM).

[0958] Conversely, blood flow rate is removed from the prescription parameters (increasing the degree of freedom in configuration). Now, five pumps are available, and three prescription values ​​are input. Therefore, the system has two degrees of freedom, and two more treatment configuration constraints can be selected to obtain the calculation of all operating flow rate parameters.

[0959] In the treatment configuration, any of the following can be selected: convection / diffusion split, pre-dilution ratio, and pre- / post-infusion ratio. Predefined (modifiable) values ​​for these relationships are also included in memory and presented to the user.

[0960] In addition, the necessary processing configuration values ​​are also input by the operator or obtained by the control unit 12. The changed values ​​are identified by different background shadows.

[0961]

[0962]

[0963] It should be noted that the acid-base balance formulation has been switched to nNBL, and solutions with both low and high bicarbonate concentrations are used to provide some possibility for adjusting the acid-base balance.

[0964] Assume the user enters the following prescription through user interface 12:

[0965] -Patient: BW (body weight) = 75kg

[0966] -Hct(%)=32

[0967] -CRRT dose D eff = 28 ml / kg / h, where the dosage is the "effluent dose" per kg.

[0968] - Normalized net buffer load target value nNBL: nNBL = 0.15 mmol / h / kg

[0969] -Patient fluid removal rate: Q PFR =120ml / h

[0970]

[0971] Operator selection:

[0972] - Diffusion / convection split: 50-50, i.e., ratio: R1 = 1.0

[0973] - The pre-infusion / post-infusion ratio is 33-67, i.e., the ratio R² = 0.5.

[0974] Due to Q b The operating parameters to be calculated are therefore additional mathematical relations for convection-diffusion, which are added to the preceding equations / mathematical relations used for example S2.

[0975] Control unit 12 then attempts to calculate the operating parameters, namely the various flow rates. The additional degrees of freedom provided by the blood flow settings left for the control unit to calculate allow for the selection of additional equations for the specified pre / post infusion ratio. The other equations used are the same as those used in the previous example S2; however, in the present case, the set of equations has no solution under the specified settings.

[0976]

[0977] *Q b Assuming 100 ml / min is the minimum acceptable value

[0978] In examples S1 and S2, operational parameters that perfectly match all prescription parameters and CRRT flow configuration constraints can be found. In example S3, utilizing an additional degree of freedom (blood flow), it is impossible to simultaneously satisfy all prescription parameters of both CRRT flow configuration constraints; in this case, the system should select one of the two flow configuration constraints (possibly from a predefined priority order) to provide an operational flow rate that satisfies all prescription parameters, except for the second constraint.

[0979] In the same example S3, multiple solutions exist once only one of the two treatment flow configuration constraints is considered. The system can report the solution closest to the "abandoned" flow constraint (in example S3, Q). b A set of parameters equal to 100 ml / min, where the convection-diffusion fraction is 66%–34% instead of 67%–33%, or several options are provided to the operator. In this example, in addition to the closest solution, a larger blood flow rate (Q) is also recommended. b =200ml / min) operation parameters.

[0980] ***

[0981] The following examples S4 and S5 include the same system configurations considered in the preceding series of examples; furthermore, examples S4 and S5 are identical to examples S1 and S2, except for the definition of the CRRT dose selection; in examples S4 and S5 below, the CRRT dose refers to urea clearance, thus taking into account the effects of pre-dilution.

[0982] In this case, more complex equations are used to estimate the removal of urea (CRRT dose - see Equation 12) and bicarbonate (acid-base balance analysis); the mass transfer performance (K0.A) of the filter must be known.

[0983] Example S4

[0984] This example is the same as example S1, but the definition for the selected CRRT dose is different.

[0985]

[0986]

[0987]

[0988] Using the above prescription data and selected constraints, the control unit can suggest the following operating flow rate parameters to the user:

[0989]

[0990] Example S5

[0991] This example is the same as example S2, but the definition for the selected CRRT dose is different.

[0992]

[0993]

[0994]

[0995] Using the above prescription data and selected constraints, the control unit can suggest the following operating flow rate parameters to the user:

[0996]

[0997] The K0.A parameter is related to the type of CRRT filter in use and specifies the diffusion mass transfer properties of bicarbonate or urea, which are assumed to be the same in these examples; this assumption relies on similar molecular weights for both substances (60 g / mole for urea, HCO3-). - (61g / mole).

[0998] As expected with the dilution effect before CRRT dose integration, the calculated effluent flow rates in Examples S4 and S5 were higher than those in Examples S1 and S2.

[0999] Adjunctive prescriptions using citrate anticoagulation

[1000] In the case of citrate anticoagulation, as described above, the citrate solution is infused into the access line of the extracorporeal circuit, particularly adjacent to the patient's vascular access, upstream of the blood pump. Simultaneously, a calcium solution for restoring the ion content of the blood is infused directly into the patient or into the return line of the circuit to balance the loss of calcium (and possibly other ions) in the effluent.

[1001] The flow rates of the two infusions are related to the anticoagulant prescription (titering citrate to achieve a certain level of ionic calcium in the extracorporeal blood circuit) and the CRRT dosage prescription (for calcium loss) as well as the corresponding concentrations of citrate and calcium solutions.

[1002] Even in the case of “concentrated” solutions (such as 110–140 mM citrate and >500 mM calcium), the combined flow rate of citrate and calcium infusion has a measurable effect on CRRT dosage (in the range of 5–10%).

[1003] In addition, some of the infused citrate will return to the patient's body and be metabolized, leading to the release of calcium and the production of bicarbonate, which in turn affects the acid-base balance.

[1004] Therefore, unlike systemic anticoagulation, citrate anticoagulation formulations have complex interactions with CRRT dosage and acid-base balance management. These interactions lead to a significant increase in complexity in CRRT formulations using citrate anticoagulation.

[1005] prescription

[1006] When using citrate anticoagulation, CRRT patient prescriptions can be constructed based on the following clinical prescribing parameters, which are of clear significance to healthcare professionals performing CRRT:

[1007] 1. CRRT dosage,

[1008] 2. Steady-state acid-base balance target,

[1009] 3. Anticoagulant (citrate) dosage,

[1010] 4. Ion (calcium) balance,

[1011] 5. Patient fluid removal rate (PFR),

[1012] 6. Selectable blood flow rate.

[1013] In a system with four fluid pumps (dialysis + infusion pump) and one effluent pump, five fluid flow rates are defined according to the five first prescription parameters mentioned above. Therefore, there are no remaining degrees of freedom, nor are there options to consider additional settings for the treatment configuration (unless blood flow is defined as an operating parameter).

[1014] Qualitative dependence of operating parameters

[1015] The table below lists the interdependencies between operating parameters and prescription parameters; importantly, this dependence can be conditional upon the definition of the CRRT dose administered.

[1016]

[1017]

[1018] X1: The contribution of flow rate to CRRT dose depends on the given definition (see previous paragraph). Most relevant definitions use all flow rates (regardless of whether they refer only to Q). eff Or it refers to an estimated clearance).

[1019] X2: The contribution of blood flow rate to CRRT dose depends on the chosen dose definition. In the case of RCA, where citrate infusion is proportional to blood flow, the blood flow rate will interfere with almost all practical CRRT dose expressions.

[1020] X3: Depending on the relevant fluid composition, all fluid infusions or dialysates contribute to acid-base balance. The effect of blood flow rate is more significant than with or without systemic anticoagulation, as it defines the amount of citrate returned to the patient (and the associated bicarbonate production), in addition to the predilution effect. When associated with very low infusion rates (<20 ml / h), the contribution of calcium infusion is negligible.

[1021] X4: The patient fluid removal rate prescription is directly controlled by defining the outflow rate and comparing it to all other infusion rates in the dialysis system (including anticoagulant rates, if relevant).

[1022] X5rca: When blood flow is defined as a prescription parameter, the definition of the operating flow rate loses one degree of freedom, meaning fewer constraints can be used from treatment configuration parameters. In most current CRRT systems with RCA, there are no degrees of freedom when blood flow is selected as a prescription parameter and acid-base balance is intended to be specified.

[1023] X6: The citrate infusion rate in the RCA is typically specified via a citrate dose factor, proportional to blood flow. The resulting flow rate is usually administered via a pre-blood pump and matched to the PBP flow rate for systemic anticoagulation.

[1024] X7: Calcium infusion is defined based on estimated effluent losses. These losses depend on the removal rate of the citrate-calcium complex, and therefore on all operating flow rates and the mass transfer characteristics of the filter. The basic system can assume calcium losses proportional to the effluent flow rate.

[1025] Example

[1026] While simplified expressions could be considered, the complexity of the interactions between the citrate complex and bicarbonate in the mass transfer of CRRT filters justifies the use of more accurate filter clearance estimates, which requires knowledge of the mass transfer characteristics of the filters in use. In this case, all examples will include these parameters.

[1027] The example will illustrate the use of “concentrated” or “diluted” citrate solutions, as is commonly used in clinical practice.

[1028] In all the following examples, it is assumed that the calcium concentration in the citrate and dialysate solutions is zero. In some examples, the presence of calcium in the post-infusion fluid will be considered.

[1029] All flow rates are rounded to the next tens digit, unless they are less than 100 ml / h.

[1030] The system configuration used in the following examples is equivalent to that considered in Examples S1 through S5, but with the addition of a pump for calcium infusion. Of course, the pre-blood pump infusion line infuses citrate instead of the replacement solution used in the preceding Examples S1 through S5. Although the pre-blood pump infusion line can physically be used in the preceding examples (see...) Figure 1 The same reference figures are used, but the symbol "cit" is used to identify the corresponding flow rate and container concentration of citrate, and different reference figures are used (see [reference figure]). Figure 3 and Figure 2 The RCA system includes five fluid pumps and one blood pump.

[1031] The following table lists the CRRT system definitions for examples C1 to C6.

[1032]

[1033] The next examples, C1 through C5, are based on the loop configurations described above. Figure 3 .

[1034] Example of effluent dose as CRRT dose

[1035] In the first series of examples, the CRRT dose refers to the effluent rate without pre-dilution correction.

[1036] In the consecutive examples in this section, the parameters that are changed are identified by colored cells.

[1037] Example C1

[1038] The first reference example was constructed using normalized net buffer load as the acid-base balance prescription and diluted citrate solution and blood flow rate as clinical prescription parameters.

[1039] The treatment configuration is set according to the table below. Request and enter the processing configuration data based on the second table in the report below.

[1040]

[1041]

[1042] As shown, the following clinical prescription parameters are entered by medical staff:

[1043]

[1044] Since the prescription parameters provide 6 constraints, there are no degrees of freedom available to further configure additional treatment settings.

[1045] With the above equipment setup, the control unit determines the following operating flow rate (indicator Q). b However, it is a prescription parameter that has been set to 130 ml / min.

[1046]

[1047] Specifically, the outflow rate Q is determined based on the CRRT dose and the patient's weight. eff :

[1048] Q eff =30·85=2550ml / h

[1049] Anticoagulant flow rate Q cit The relationship between citrate flow rate and blood flow rate is established through the mathematical formula (Equation 1):

[1050]

[1051] Due to the applied blood flow rate Q b and citrate dosage D cit Since the citrate concentration is known, Q can be immediately derived from the above equation. cit .

[1052] The calcium flow rate is derived from the mathematical relationship of calcium flow rate (Equation 2); missing flow rate sums equal to zero or negligible terms have been removed from the general formula describing the flow rate.

[1053]

[1054] As shown in the previous example, the outflow velocity should take into account fluid balance (see Equation 10):

[1055] Q eff =Q cit +Q dial +Q rep.post +Q PFR +Q ca

[1056] The last, but more complex, constraint is based on the normalized net buffer load parameter target nNBL, as it interacts with all flow rates and is affected by the buffer balance of bicarbonate and bicarbonate precursors (i.e., citrate).

[1057] The mathematical relationship for net buffer load relates this parameter to citrate load and bicarbonate balance (Equations 40 and 41):

[1058] J buffer_load =3·J cit_load +J HCO3_bal

[1059]

[1060] Citrate load was determined based on a mathematical relationship of citrate load (Equation 25), which takes into account citrate metabolic clearance:

[1061]

[1062] Citrate scavenging K cit According to equation 21, (where SC) we obtain... cit =1):

[1063]

[1064]

[1065]

[1066] The plasma flow rate Qpw at the inlet of the filtration unit inlet From equation 5, we can derive:

[1067] Qpw inlet =Q b ·(1-Hct)·Fp+Q cit

[1068] Plasma flow rate Q pw The result can be obtained from equation 4:

[1069] Qpw = Q b ·(1-Hct)·F p

[1070] The ultrafiltration flow rate through filtration unit 2 is (Equation 8):

[1071] Q fil =Q cit +Q rep.post +Q PFR +Q ca

[1072] The metabolic clearance of citrate was estimated using Equation 22:

[1073]

[1074] Conversely, the second term of the net buffer load, namely the bicarbonate balance J, is... HCO3_bal From, for example, equation 26', we can derive:

[1075]

[1076] Bicarbonate removal can be more accurately estimated using the mathematical relationship of bicarbonate removal (Equation 29); SC HCO3 =1:

[1077]

[1078]

[1079]

[1080] Blood flow rate Qbw at the inlet of the filtration unit inlet From equation 7, we can derive:

[1081] Qbw inlet =Q b ·[(1-Hct)·Fp+Hct·Frbc]+Q cit

[1082] The blood flow velocity is derived from equation 6:

[1083] Qbw = Qb ·[(1-Hct)·F p +Hct·Frbc]

[1084] Finally, the required plasma water bicarbonate concentration Cpw at the filter inlet. HCO3_inlet From equation 32, we can derive:

[1085]

[1086] The concentration of bicarbonate in the patient's plasma is fixed at steady state and is assumed to be constant (e.g., 25 mM).

[1087] Using all the above mathematical relationships, control unit 12 determines all operating prescription parameters.

[1088] Example C2

[1089] The second example uses the previous example C1 as a reference and illustrates the further flow rate changes required to alter the citrate dosage prescription, which may require maintaining ionic calcium in the blood circuit at recommended levels (e.g., in the range of 0.25–0.35 mM).

[1090] The treatment configuration is set according to the table below. Request and enter the processing configuration data based on the second table in the report below.

[1091]

[1092]

[1093]

[1094] Since the prescription parameters provide 6 constraints, there are no degrees of freedom available to further configure additional treatment settings.

[1095] With the above equipment setup, the control unit determines the following operating flow rate (indicator Q). b However, this was a pre-set parameter of 130 ml / min. It can be seen that all operating flow rates are significantly affected by changes in citrate dosage, except for the outflow rate.

[1096]

[1097] Example C3

[1098] In the continuation of the previous two examples, example C3 illustrates the further changes required to increase the citrate dosage.

[1099] The treatment configuration is set according to the table below. Request and enter the processing configuration data based on the second table in the report below.

[1100]

[1101]

[1102]

[1103] Since the prescription parameters provide 6 constraints, there are no degrees of freedom available to further configure additional treatment settings.

[1104] With the aforementioned equipment in place, the control unit attempts to determine the operating flow rate (indicated by Q in the second column). b However, this is a prescription parameter that has been set to 130 ml / min. Therefore, there is no solution to the system of equations that matches the prescription.

[1105] All operating flow rates are significantly affected by changes in citrate dosage, but the effluent flow rate is not, and it is impossible to achieve the desired target. The third column provides the Q... b Consider the suggested solution as an operating parameter (which may vary within specified limits).

[1106]

[1107]

[1108] Example C4

[1109] Example C4 is based on the C1 reference, but uses a "concentrated" citrate solution instead of a diluted citrate solution; the calcium solution is also replaced with a lower concentration solution.

[1110] The highlighted changes are those in reference example C1.

[1111] The treatment configuration is set according to the table below. Request and enter the processing configuration data based on the second table in the report below.

[1112]

[1113]

[1114]

[1115] Since the prescription parameters provide 6 constraints, there are no degrees of freedom available to further configure additional treatment settings.

[1116] With the aforementioned equipment in place, the control unit attempts to determine the operating flow rate (indicated by Q in the second column). b However, this is a prescription parameter that has been set to 130 ml / min. Therefore, there is no solution to the system of equations that matches the prescription.

[1117] All operating flow rates are significantly affected by changes in citrate dosage, but the effluent flow rate is not, and it is impossible to achieve the desired target. The third column provides the Q... b Consider the suggested solution as an operating parameter (which may vary within specified limits).

[1118]

[1119] Examples C1 to C4 above illustrate the importance of blood flow rate during citrate anticoagulation for defining adequate acid-base balance when the bicarbonate composition of the fluid is constant.

[1120] Example of using urea clearance dose as CRRT dose

[1121] Similar to the series of examples provided in the context of no anticoagulation or with systemic anticoagulation, the following examples are provided in the context of RCA, where the CRRT dose includes a pre-dilution factor, such as where it refers to the urea clearance dose.

[1122] The same system configuration is used in examples C1 through C4 (see...). Figure 3 The mathematical relationships used are basically the same as those used in Example C1, but the CRRT dialysis dose is determined using Equation 12.

[1123] Example C5

[1124] This example is constructed with reference to Example C1, replacing the effluent CRRT dose with the urea clearance dose (see relevant paragraph). The changes are highlighted in Example C1.

[1125] The treatment configuration is set according to the table below. Request and enter the processing configuration data based on the second table in the report below.

[1126]

[1127]

[1128]

[1129] Since the prescription parameters provide 6 constraints, there are no degrees of freedom available to further configure additional treatment settings.

[1130] With the above equipment setup, the control unit determines the following operating flow rate (indicator Q). b However, it is a prescription parameter that has been set to 130 ml / min.

[1131]

[1132] Example C6

[1133] Here, a similar simulation as that performed between examples C2 and C1 is repeated between C6 and C5.

[1134] The changes between C6 and C5 are highlighted in the next table.

[1135] The treatment configuration is set according to the table below. Request and enter the processing configuration data based on the second table in the report below.

[1136]

[1137]

[1138]

[1139] Since the prescription parameters provide 6 constraints, there are no degrees of freedom available to further configure additional treatment settings.

[1140] With the above equipment setup, the control unit determines the following operating flow rate (indicator Q). b However, it is a prescription parameter that has been set to 130 ml / min.

[1141]

[1142] Examples C5 and C6 illustrate the major effects of blood predilution when using a “diluted” citrate solution and referring to a CRRT dose that integrates the effects of predilution (such as a urea clearance dose). The outflow rate is significantly increased (approximately 400 to 500 ml / h) between Examples C5-C6 and C1-C2.

[1143] These examples also illustrate the key adjustments to the dialysate and post-displacement flow rate required to maintain the desired acid-base balance while increasing the CRRT dose.

[1144] configuration of post-bicarbonate infusion system

[1145] This section provides examples of an adjunctive prescription in a system context, where a concentrated bicarbonate solution is infused after filtration and contributes to the main fraction of all bicarbonate infused via CRRT treatment (via all fluids, including dialysate). Ideally, this main fraction exceeds 50% and may reach 100%; in the latter case, this means that all fluids are bicarbonate-free except for the concentrated bicarbonate infusion.

[1146] The goal of the system configuration is to separate the acid-base balance prescription from the CRRT dose and / or citrate dose prescription as much as possible, thereby providing greater freedom when changing these parameters independently.

[1147] All examples provided in this section were constructed using urea clearance-based CRRT doses, thus taking into account the effects of pre-dilution.

[1148] No examples of anticoagulation or systemic anticoagulation.

[1149] The system configuration used in the following example is comparable to the system configuration considered in Examples S1 to S5 in terms of the number of fluid pumps (n=4) and the presence of a pre-dilution and a post-dilution infusion loop; however, it includes several variations reported in the next table.

[1150] Refer to the CRRT system definitions for examples BS1 to BS2 (BS stands for bicarbonate + systemic anticoagulation or no anticoagulation) in the table below and Figure 4 .

[1151]

[1152] Example BS1

[1153] This example is similar to example S5, but differs in fluid composition and treatment configuration parameters.

[1154] The treatment configuration is set according to the table below. Request and enter the processing configuration data based on the second table in the report below.

[1155]

[1156]

[1157]

[1158] Since one degree of freedom is available, an additional constraint can be selected. In this case, the convection-diffusion split (or ratio) is selected and set to 50%-50% or R1=1.

[1159] Given the above clinical prescription parameters and additional user selections for treatment configuration, control unit 12 determines the following operating parameters (Q b (It is part of the prescription):

[1160]

[1161]

[1162] Example BS2

[1163] This example is similar to the previous one, but the goal is a much higher net buffer load. The changes to BS1 in the previous example are highlighted with background cells.

[1164] The treatment configuration is set according to the table below. Request and enter the processing configuration data based on the second table in the report below.

[1165]

[1166] The clinical prescribing parameters are the same as in the previous example BS1, but nNBL is changed from 0.15 to a significantly higher value of 0.25.

[1167]

[1168]

[1169] The calculation flow rates for the remaining operating parameters are as follows (Q) b (Still part of the prescription):

[1170]

[1171] In systems with only bicarbonate infusion as a post-infusion, treatment parameters such as the pre- / post-infusion ratio are irrelevant or impossible to include because the post-infusion rate is determined by the acid-base balance prescription. In other words, choosing the pre- / post-infusion ratio would cause the control unit to fail to return to the solution of the system of equations. Therefore, choosing the convection / diffusion ratio appears to be the only reasonable option within the additional constraints of treatment.

[1172] The comparison of examples BS1 and BS2 illustrates the strong and direct dependence of acid-base balance on the post-bicarbonate infusion rate in configurations where more than 80% of the total bicarbonate infusion comes from a single source.

[1173] It is worth noting that the “high” nNBL level prescription of Example BS2 cannot be provided in the routine system and bicarbonate fluid configuration of Examples S4-S5 unless a very high CRRT is used to specify the dialysis dose (e.g., about 50 ml / kg / h).

[1174] citrate anticoagulant example

[1175] The concept of bicarbonate infusion is further elaborated in the context of citrate anticoagulation (RCA).

[1176] The selected system configuration is comparable to the example C1-C6 configurations of the infusion pump after the addition of bicarbonate. Therefore, the system comprises six fluid pumps and one blood pump (see [link to system configuration]). Figure 5 (Example).

[1177] The definitions of CRRT systems for examples BC1 to BC3 (BC represents bicarbonate + citrate anticoagulation) are shown in the table below:

[1178]

[1179]

[1180] For the circuit configuration used, please refer to Figure 5 .

[1181] Example BC1

[1182] This example is similar to the previous example C5, but bicarbonate was added in the post-infusion and unbuffered dialysate was used.

[1183] The treatment configuration is set according to the table below. Request and enter the processing configuration data based on the second table in the report below.

[1184]

[1185]

[1186] As shown below, in addition to the prescribed dialysis dose (D) to be delivered set -Urea clearance), normalized net buffer load, patient fluid removal rate (Q) PFR In addition to ) and RCA prescriptions, Q b Still prescription parameters:

[1187]

[1188] Based on six prescription parameters and seven flow rates to be determined, there is one degree of freedom. However, given the system configuration and clinical prescription parameters, the selected convection-diffusion split cannot be achieved.

[1189]

[1190] Control unit 12 provides a solution related to the flow rate of the operating parameters, which best approximates the selected convection-diffusion ratio. In this example, the convection-diffusion ratio is 57%–43% (R1 = 1.33). Alternatively, Q... b The prescription parameters were changed to the operating parameters, and the convection-diffusion ratio was maintained at 50%-50% of the initially set value. The resulting blood flow rate was reduced to 100 ml / min.

[1191] Example BC2

[1192] Example BC2 is similar to BC1, except that the citrate solution is changed to a higher concentration. Changes from BC1 are highlighted.

[1193] The treatment configuration is set according to the table below. Request and enter the processing configuration data based on the second table in the report below.

[1194]

[1195]

[1196] Regarding example BC1, the clinical prescribing parameters remain unchanged:

[1197]

[1198] As the concentration of the citrate anticoagulant bag changes (increases), the control unit 12 finds a solution for operating the flow rate without changing the set blood flow rate and / or altering the convection / diffusion split:

[1199]

[1200]

[1201] Example BC3

[1202] BC3 illustrates the change in flow rate when the citrate dosage prescription given in example BC2 is changed.

[1203] The changes in BC2 are highlighted.

[1204] The treatment configuration is set according to the table below. Request and enter the processing configuration data based on the second table in the report below.

[1205]

[1206]

[1207] As shown below, the citrate dosage increased from 3.1 mmol / L to 3.5 mmol / L:

[1208]

[1209] The calculation parameters are as follows (blood flow rate is a prescription parameter):

[1210]

[1211] The addition of bicarbonate to the infusion pump adds a degree of freedom and allows for consideration of a treatment configuration constraint in example BC1 (compared to C5). However, using a “diluted” citrate solution results in significant convective flow and makes it difficult to obtain an HDF formulation with equal convective and diffusion flow rates.

[1212] Example BC2 documented the benefits of a more concentrated citrate solution when used in CRRT treatment configurations with a significant dialysis / diffusion contribution, further reducing the flow rate of the citrate solution (which facilitates convective fluid exchange).

[1213] Example BC3 shows that changes in citrate dosage (for the purpose of adjusting anticoagulant strength) can be easily balanced by adjusting the post-bicarbonate infusion rate to maintain the same acid-base balance target.

[1214] Compatibility with other system features

[1215] There is a high level of interaction between auxiliary prescription features and optional features and advanced CRRT systems.

[1216] Blood flow rate management: In configurations where the system is equipped with a module that automatically optimizes blood pump speed as a function of vascular access performance, the system should operate using blood flow parameters defined as operational parameters rather than prescription parameters. However, a maximum blood flow rate value should be provided as an operator-configurable constraint. In these cases, the control unit should automatically recalculate various flow settings each time blood flow rate is adjusted via the "Blood Pump Management" module.

[1217] TMP Monitoring / Convection: In systems equipped with modules that automatically optimize convection flow rates as a function of TMP (or other pressure parameters), the auxiliary prescription system (i.e., the control unit) should automatically recalculate various flow rate settings each time the convection flow rate is adjusted.

[1218] Dosage control: The adjuvant prescription module calculates flow rate settings, while the dose control system monitors the "instantaneous" CRRT dose requirements during treatment to achieve the total CRRT dose clinical target over several days of treatment. The addition of acid-base balance prescription parameters enhances the adjuvant prescription, making the dose control system safe and practical for citrate anticoagulation therapy.

[1219] Mathematical Relationship

[1220] Hereinafter, the main mathematical relationships used by control unit 12 to associate patient prescription parameters, treatment configuration parameters, and operating parameters are reported. These mathematical relationships have been described in detail in the preceding sections of this application. Upon receiving the necessary and / or selected patient prescription parameters and treatment configuration parameters, control unit 12 is configured to use the relevant mathematical equations to calculate the set flow rate of the fluid in the pipeline for the operating parameters.

[1221] The control unit 12 can then output a set and calculated flow rate for user acceptance, and upon acceptance, drive various actuators (pumps) to achieve the set and calculated flow rate in the relevant pipeline. Alternatively, the control unit 12 can automatically set the actuators to achieve the set and calculated flow rate.

[1222] Equation 1 - Mathematical Relationship of Citrate Flow Rate

[1223]

[1224] Equation 2 - Mathematical Relationship of Calcium Flow Rate

[1225]

[1226] Equation 3 - Mathematical Relationship of Plasma Flow Rate

[1227] Qp = Q b ·(1-Hct)

[1228] Equation 4 - Mathematical Relationship of Plasma Flow Rate

[1229] Qpw = Qp·F p =Q b ·(1-Hct)·F p

[1230] Equation 5 - Mathematical Relationship of Plasma Flow Rate at the Inlet of the Filtration Unit

[1231] Qpw inlet =Qpw+Q cit +Q syr +Q PBP +Q rep.pre

[1232] =Q b ·(1-Hct)·Fp+Q cit +Q syr +Q PBP +Q rep.pre

[1233] Equation 6 - Mathematical Relationship of Blood Flow Velocity

[1234] Qbw = Q b ·[(1-Hct)·F p +Hct·Frbc]

[1235] Equation 7 - Mathematical Relationship of Blood Flow Velocity at the Inlet of the Filtration Unit

[1236] Qbw inlet =Q bw +Q cit +Q syr +Q PBP +Q rep.pre

[1237] =Q b ·[(1-Hct)·Fp+Hct·Frbc]+Q cit +Q syr +Q PBP +Q rep.pre

[1238] Equation 8 - Mathematical Relationship of Ultrafiltration Flow Rate

[1239] Q fil =Q PBP +Q cit +Q syr +Q rep.pre +Q rep.post +Q HCO3+Q PFR +Q ca

[1240] Equation 9 - Front and Back Division

[1241] Q rep.pre =PRE·Q rep

[1242] Q rep ×(Q rep.pre +Q rep.post )

[1243] Equation 10 - Mathematical Relationship of Outflow Velocity

[1244] Q eff =Q PBP +Q cit +Q syr +Q dial +Q rep.pre +Q rep.post +Q HCO3 +Q PFR +Q ca

[1245] Equation 11 - Urea removal (pure diffusion mode)

[1246]

[1247]

[1248] If Z≠1

[1249]

[1250] If Z = 1, Equation 12 - Urea Removal (Diffusion and / or Convection Mode)

[1251]

[1252]

[1253]

[1254] Equation 13 / 14 / 15 / 15' - Dilution factor

[1255]

[1256]

[1257]

[1258]

[1259] Equation 16 - Urea dosage (correction for pre-dilution)

[1260]

[1261] Equation 17 - Mathematical Relationship of Net Buffer Load

[1262]

[1263] Equations 18 / 19 / 20 - Mathematical Relationship of Citrate Load

[1264] J citrate_load =J cit_PBP -J cit_dial

[1265] J cit_PBP =Q cit ·C cit_PBP =D cit ·Q b

[1266] J cit_dial =K cit ·Cpw cit_inlet

[1267] Equation 21 / 22 / 23 / 24 / 24' - Mathematical relationship between citrate clearance and inlet concentration

[1268]

[1269]

[1270]

[1271]

[1272]

[1273]

[1274] J cit_PBP =Qpw inlet =Cpw cit_inlet

[1275] Equation 25 / 25' - Citrate Loading Mathematical Relationship

[1276]

[1277]

[1278] Equation 26 / 26' - Mathematical Relationship of Bicarbonate Equilibrium

[1279] JHCO3_bal =J HCO3_inf -J HCO3_eff

[1280]

[1281] Equation 27 - Mathematical Relationship of Bicarbonate Infusion

[1282]

[1283] Equation 28 - Mathematical Relationship for Bicarbonate Removal

[1284]

[1285] Equation 29 / 30 - Mathematical Relationship for Bicarbonate Removal

[1286]

[1287]

[1288]

[1289] K HCO3 =Qeff

[1290] Equation 31 - Blood plasma water bicarbonate concentration equation

[1291]

[1292]

[1293] Equation 32 - Mathematical relationship between plasma water bicarbonate concentration at the filter inlet

[1294]

[1295] Equations 33 / 34 / 35 / 36 - Mathematical relationships of lactate

[1296] J lact_bal =J lact_inf -J lact_eff

[1297]

[1298] J lact_eff =Q dial ·C lact_dial +K lact ·(Cpw lact_inlet -C lact_dial )+Q fil ·C lact_dial

[1299]

[1300] Equation 37 - Patient citrate metabolism clearance

[1301] J met_cit =3·J cit_load

[1302] Equation 38 - Acidic Infusion Equation

[1303] J H+ =3·J citric_acid =3·Q cit ·C cit_PBP

[1304] Equations 39 / 40 / 41 - Mathematical Relationship of Net Buffer Load

[1305] J buffer_load =3·J cit_load +J HCO3_bal -3·J citric_acid

[1306] J buffer_load =3·J cit_load +J HCo3_bal +J lact_bal -3·J citric_acid

[1307]

[1308] Equations 42 / 43 / 44 / 45 / 42' / 44' - Mathematical Relationship of Steady-State Acid-Base Balance Indicator

[1309]

[1310]

[1311]

[1312] J buffer_load =nNBL×BW

[1313]

[1314] J HCO3_eff =J HCO3_inf +J met_cit -J H+ -nNBL0×BW (Equation 44')

Claims

1. A continuous renal replacement therapy (CRRT) device configured for local anticoagulation, and comprising: The filtration unit (2) has a main chamber (3) and a secondary chamber (4) separated by a semi-permeable membrane (5); An extracorporeal blood circuit (17) having a blood extraction line (6) connected to the inlet of the main chamber (3) and a blood return line (7) connected to the outlet of the main chamber (3), the extracorporeal blood circuit (17) being configured to connect to the patient’s cardiovascular system; A blood pump (21) is configured to control the flow of blood through the external blood circuit (17); The outflow material pipeline (13) is connected to the outlet of the sub-chamber (4); An anticoagulant infusion line (51) has one end connected to the blood extraction line in the region thereof, the blood extraction line being located upstream of the blood pump (21) during use. A local anticoagulant source (10) supplies anticoagulant to the anticoagulant delivery line (51); One or more additional fluid lines, selected from the group consisting of: A pre-dilution infusion line (29) is connected at one end to the blood extraction line (6). The post-dilution infusion line (63) is connected at one end to the blood return line (7). A post-diluted bicarbonate infusion line (23) is connected at one end to the blood return line (7). An ion-balanced infusion line (74), one end of which is connected to the blood return line (7) or to a patient catheter, A dialysate supply line (8) is connected at one end to the inlet of the sub-chamber (4). A pre-blood pump PBP infusion line (52), one end of which is connected to the blood extraction line in the area of ​​the blood extraction line, which is located upstream of the blood pump (21) during use, and A syringe fluid line (22), one end of which is connected to the blood extraction line. Actuators for regulating the flow of fluids (24, 25, 26, 31, 53, 54, 65, 75) through the post-dilution bicarbonate infusion line (23), the dialysate supply line (8), the outflow fluid line (13), the pre-dilution infusion line (29), the pre-blood pump PBP infusion line (52), the anticoagulant infusion line (51), the post-dilution infusion line (63), and the ion balance infusion line (74); Memory (16) stores one or more mathematical expressions; as well as Control unit (12), connected to the memory (16) and the actuator, is configured to execute a flow rate setting procedure, the flow rate setting procedure including: - Receiving a patient prescription that includes clinical prescription parameters, and receiving the patient prescription further includes: o Allows input of the set value for the specified dialysis dose to be delivered. The system allows inputting target values ​​for parameters that indicate the homeostatic acid-base balance in the blood of patients who must undergo CRRT blood treatment. o Allows input of the set value for the specified dose of anticoagulant to be delivered. - Use the one or more mathematical relationships to determine one or more operating parameters, the determination of which includes calculating setpoints for three or more fluid flow rates selected from a group including: The fluid flow rate through the anticoagulant delivery line (51), The fluid flow rate through the PBP infusion line (52), The fluid flow rate through the pre-dilution infusion line (29), The fluid flow rate through the post-dilution infusion line (63), The fluid flow rate through the post-diluted bicarbonate injection line (23), The fluid flow rate through the ion balance delivery line (74), The blood flow rate through the extracorporeal blood circuit (17), The fluid flow rate through the syringe fluid line (22), The fluid flow rate through the dialysate supply line (8), and The fluid velocity through the outflow pipeline (13), Each setpoint for calculating three or more fluid flow rates is based on at least: The set value of the specified dialysis dose. The target value of the parameter indicating the steady-state acid-base balance in the blood, and The specified value for the prescribed anticoagulant dosage.

2. The CRRT device according to claim 1, wherein, With the set value of the blood flow rate through the extracorporeal blood circuit (17) determined by the control unit (12) as an operating parameter, the target value of the parameter indicating the steady-state acid-base balance in the patient's blood affects the set value of the fluid flow rate through the anticoagulant infusion line (51). The set value of the fluid flow rate through the anticoagulant infusion line (51) is an operating parameter calculated by the control unit (12).

3. The CRRT device according to claim 1, wherein, Calculating the set values ​​for the three or more fluid flow rates includes determining the operating parameters, including calculating the set values ​​for the fluid flow rates through the anticoagulant infusion line (51), wherein the specified anticoagulant dose is a citrate dose indicating local anticoagulant strength.

4. The CRRT device according to claim 1, wherein, The specified anticoagulant dose has the same unit as concentration, and the specified anticoagulant dose is the amount of anticoagulant injected per liter of treated blood.

5. The CRRT apparatus according to any one of the preceding claims, wherein, The control unit (12) is configured to calculate, using a citrate flow rate mathematical relationship, the set value of the fluid flow rate through the anticoagulant delivery line (51) as a function of one or more of the following: The specified set value for the anticoagulant dosage, The set value of the fluid flow rate through the anticoagulant infusion line (51) is related to the blood fluid flow rate; and The concentration of anticoagulant in anticoagulant source (10).

6. The CRRT apparatus according to any one of claims 1 to 4, wherein, The one or more mathematical relationships include a citrate flow rate mathematical relationship, and the fluid flow rate through the anticoagulant infusion line (51) is calculated based on the citrate flow rate mathematical relationship stored in the memory (16): Q cit The fluid flow rate Q through the anticoagulant injection pipeline b It is the blood fluid velocity, D cit It is the set value for the prescribed anticoagulant dosage. It is the total citrate concentration in the citrate anticoagulant solution.

7. The CRRT apparatus according to any one of claims 1 to 4, wherein, The control unit (12) is configured to control the anticoagulant pump (54) to infuse the anticoagulant into the blood extraction line at a calculated fluid flow rate through the anticoagulant infusion line.

8. The CRRT apparatus according to any one of claims 1 to 4, comprising: The ion balance infusion line (74) has one end connected to the blood return line (7) or to a patient catheter; A source (11) for the ion balance solution is connected to the opposite end of the ion balance infusion line (74), wherein receiving a patient prescription also includes allowing input of set values ​​for ion regeneration solution parameters, which indicate the strength of the ion balance. The calculation of three or more fluid flow rate settings includes the calculation of four or more fluid flow rate settings, and the determination of operating parameters includes the calculation of fluid flow rate settings at least through the ion balance delivery line (74).

9. The CRRT apparatus according to claim 8, wherein the parameters of the ion regeneration solution are one of the following: - The compensation value or percentage of calcium removed in the filtration unit (2); or - Calcium dosage in terms of ion concentration, wherein the calcium dosage is the calcium concentration in the effluent.

10. The CRRT apparatus according to claim 8, wherein, The control unit (12) is configured to calculate, using a calcium flow rate mathematical relationship, the set value of the fluid flow rate through the ion balance delivery line (74) as a function of one or more of the following: The set values ​​for the parameters of the ion regeneration solution; Outflow logistics speed; The calcium concentration in the source (11) of the ion equilibrium solution; The calcium concentration in the auxiliary container (64) connected to the post-dilution infusion line (63); The calcium concentration in the bicarbonate container (28) connected to the post-dilution bicarbonate infusion line (23).

11. The CRRT apparatus of claim 8, wherein the one or more mathematical relationships include a calcium flow rate mathematical relationship, and wherein a set value for the fluid flow rate through the ion balance delivery line (74) is calculated based on the calcium flow rate mathematical relationship stored in the memory (16), the mathematical relationship being: or in It is the calcium concentration in the source of the ion equilibrium solution. The calcium concentration in the auxiliary container (64) connected to the post-dilution infusion line (63) is... The calcium concentration in the bicarbonate container (28) connected to the post-dilution bicarbonate infusion line (23), CaComp is the calcium compensation parameter, and Q is the calcium concentration in the bicarbonate container (28). ca The fluid flow rate is through the ion balance infusion line (74). It is the mass transfer rate of calcium solute, Q rep.post The fluid flow rate Q is obtained through the post-dilution infusion line (63). HCO3 The fluid flow rate D is through the post-diluted bicarbonate injection line (23). ca Q is the calcium dosage or concentration in the outflow material pipeline (13). eff The fluid velocity is through the outflow pipeline (13). If any infusion line is missing, the corresponding flow rate is not present in the mathematical formula, or the corresponding flow rate is set to zero.

12. The CRRT apparatus according to any one of claims 1 to 4, wherein, The set value for calculating the fluid flow rate through the ion balance infusion line (74) is based at least on the target value of the parameter indicating the steady-state acid-base balance in the blood and / or the set value of the prescribed dialysis dose, wherein the control unit (12) uses the mathematical formula to calculate the set value for the fluid flow rate through the ion balance infusion line (74).

13. The CRRT apparatus according to any one of claims 1 to 4, wherein, The control unit (12) is configured to control the ion balance pump (75) to infuse the ion regeneration solution into the blood return line (7) or into the patient at a fluid flow rate calculated for the ion regeneration solution.

14. The CRRT apparatus according to any one of claims 1 to 4, wherein, The one or more mathematical relationships include relating the parameter indicating the homeostatic acid-base balance in the blood to at least one of the following: bicarbonate balance o Bicarbonate or citrate load produced by the metabolism of citrate, wherein the metabolism of citrate load results in the production of 3 moles of bicarbonate per mole of citrate at steady state. The metabolism of lactate results in a balance between bicarbonate and lactate, where the metabolism of lactate leads to the production of 1 mole of bicarbonate per mole of lactate at steady state. o acid infusion .

15. The CRRT apparatus according to any one of claims 1 to 4, wherein the mathematical relationship of the net buffer load is: in It is the net buffer load. It is bicarbonate produced by the metabolism of citrate. It is a bicarbonate equilibrium. It is bicarbonate produced by lactate metabolism. It is acid infusion. If any mass transfer rate is missing, the corresponding mass transfer term is either absent in the mathematical relation or its value is set to zero.

16. The CRRT apparatus according to any one of claims 1 to 4, wherein, The one or more mathematical relationships include a mathematical relationship for citrate load, which is based on the amount of citrate load on the patient per unit time, wherein the citrate load is the difference between the citrate infusion rate of the anticoagulant infusion line (51) and the citrate removal rate of the effluent in the effluent fluid line (13).

17. The CRRT apparatus according to claim 16, wherein, The mathematical relationship for the citrate loading is: in It is the citrate loading, The citrate infusion rate is achieved through the anticoagulant infusion line (51). It is the citrate removal rate of the effluent in the effluent material pipeline (13). If any mass transfer rate is missing, the corresponding mass transfer term is either absent in the mathematical relation or its value is set to zero.

18. The CRRT apparatus of claim 16, wherein the citrate removal rate of the effluent is a function of one or more of the following: The patient's citrate metabolism clearance is directly proportional to the patient's body weight. The fluid velocity through the outflow material line (13), wherein the citrate removal estimate is equal to the outflow material velocity, Citrate removal, and according to the citrate removal mathematical relation in one or more of the mathematical relations, citrate removal is a function of one or more of the fluid flow rate of the dialysate supply line (8), the ultrafiltration rate in the filtration unit (2), and the plasma water flow rate at the inlet of the filtration unit.

19. The CRRT device of claim 18, wherein the patient's citrate metabolic clearance is determined as follows: in The patient's citrate metabolic clearance is measured in ml / min, and BW is the patient's body weight measured in kg.

20. The CRRT apparatus according to any one of claims 1 to 4, wherein the one or more mathematical relationships include the following citrate removal mathematical relationship: in It is citrate removal, Q is the plasma flow rate at the inlet of the filtration unit. dial The fluid flow rate, S / RT, is obtained through the dialysate supply line (8). cit It is the ratio of the surface area of ​​the citrate filtration unit (2) to the diffusion mass transfer resistance. Q is the sieving coefficient of the citrate filtration unit (2). fil It is the ultrafiltration rate in the filtration unit (2). If any infusion line or dialysate supply line is missing, there is no corresponding flow rate in the mathematical formula, or the corresponding flow rate is set to zero.

21. The CRRT device according to any one of claims 1 to 4, wherein the citrate load is a function of the citrate dose and the blood flow rate, based on ,in This is the set value for the prescribed anticoagulant dosage. The blood fluid flow rate, or citrate load, is a function of the citrate flow rate and total citrate concentration in the anticoagulant infusion line (51), based on ,in The fluid flow rate is through the anticoagulant delivery line (51), and It is the total citrate concentration.

22. The CRRT apparatus according to any one of claims 1 to 4, wherein, The one or more mathematical relationships include a mathematical relationship for citrate load, which associates the citrate load with one or more of the following: citrate dose, blood flow rate, citrate clearance, and plasma flow rate at the inlet of the filtration unit (2).

23. The CRRT apparatus of claim 22, wherein the mathematical relationship for the citrate loading is: or: in It is citrate loading, D cit It is the set value of the prescribed anticoagulant dosage, Q. b It is the blood flow rate. It is citrate removal, It is the plasma flow rate at the inlet of the filtration unit (2). It is the clearance of citrate metabolized by the patient, Q p It refers to the plasma flow rate.

24. The CRRT apparatus according to any one of claims 1 to 4, wherein, Based on the set value of the prescribed dialysis dose, and with the set value of the blood flow rate through the extracorporeal blood circuit (17) determined by the control unit (12) as an operating parameter, the set value of the fluid flow rate through at least the anticoagulant infusion line (51) and / or the fluid flow rate through the ion balance infusion line (74) is calculated.

25. The CRRT apparatus according to any one of claims 1 to 4, wherein, Based at least on the target value of the parameter indicating the steady-state acid-base balance in the blood, when the set value of the blood fluid flow rate through the extracorporeal blood circuit (17) is determined by the control unit (12) as an operating parameter, the set value of the fluid flow rate through the anticoagulant infusion line (51) and / or the set value of the fluid flow rate through the ion balance infusion line (74) is calculated.

26. The CRRT apparatus according to any one of claims 1 to 4, wherein, The parameter indicating the steady-state acid-base balance in the blood of a patient undergoing CRRT is a parameter function of the net buffer load expected in the patient under steady-state conditions, wherein the net buffer load is the sum of: bicarbonate generation from bicarbonate precursor metabolism, bicarbonate balance in the extracorporeal blood circuit (17), bicarbonate infusion to the patient, and acid infusion in the extracorporeal blood circuit (17).

27. The CRRT apparatus according to any one of claims 1 to 4, wherein, The parameter indicating the steady-state bicarbonate concentration in a patient's blood is defined as a constant value applied to a patient in a steady-state state with a normalized net buffer load.

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