Combination in vitro and drug delivery system and method

Abstract

An extracorporeal and drug delivery system includes: (i) a renal failure treatment machine operable with a blood filter in fluid communication with an arterial line and a venous line, the machine including: (a) an effluent pump for pumping effluent from the blood filter at an effluent flow rate; and at least one of: (b) a dialysis fluid pump for pumping dialysis fluid to the blood filter at a dialysis fluid flow rate; (c) a pre-dilution pump for pumping replacement fluid into the arterial line at a pre-dilution flow rate; or (d) a post-dilution pump for pumping replacement fluid into the venous line at a post-dilution flow rate; (ii) an infusion pump operable to deliver an intravenous ("IV") drug to a patient at an IV drug flow rate; and (iii) a coordination logic implementer configured to adjust the IV drug flow rate based on an amount of the IV drug removed via the effluent flow rate.

Description

[0001] Priority Statement

[0002] This application claims priority and benefit to U.S. Provisional Application No. 62 / 946,205, filed December 10, 2019, entitled “Combined Extracorporeal and Drug Delivery System and Method,” which is incorporated herein by reference in its entirety. Background Technology

[0003] Acute kidney injury (“AKI”) is more common than most people realize and is underrecognized in hospitalized patients, particularly in some countries. It is reported that 20% of hospitalized patients worldwide suffer from AKI. A significant number of intensive care unit (“ICU”) patients have AKI, with 15% to 25% of these patients receiving some form of renal replacement therapy (“RRT”). Approximately 27% of pediatric and young adult ICU patients develop AKI within the first week of admission.

[0004] The main factors leading to AKI include septic shock (approximately 47% of cases), major surgery (approximately 34% of cases), cardiogenic shock (approximately 27% of cases), hypovolemia (approximately 25% of cases), drug-induced (approximately 19% of cases), hepatorenal syndrome (approximately 6% of cases), and obstructive urinary tract disease (approximately 3% of cases).

[0005] RRT for AKI patients includes intermittent hemodialysis (“IHD”) and continuous renal replacement therapy (“CRRT”). For example, IHD may treat a patient for three to four hours every other day. In contrast, CRRT uses a much slower flow rate of blood and treatment fluids to continuously treat the patient. Some studies have shown that CRRT is superior to IHD for managing AKI. For example, patients receiving CRRT may have lower fluid accumulation after several days of hospitalization compared to those receiving IHD. Furthermore, CRRT may be superior to IHD in terms of the frequency of patients eventually developing chronic kidney disease (“CKD”), i.e., patients receiving CRRT are less likely to develop CKD compared to those receiving IHD.

[0006] CRRT is performed using a CRRT machine. CRRT machines perform different types of CRRT treatments, such as slow continuous ultrafiltration (“SCUF”) for fluid removal only, continuous venous-venous hemodialysis (“CVVHD”), continuous venous-venous hemodiafiltration (“CVVHDF”), and continuous venous-venous hemofiltration (“CVVH”). CRRT machines can also perform other types of treatments, such as therapeutic plasma exchange (“TPE”), which typically involves plasma filtration and has multiple indications, such as for autoimmune diseases, hemoperfusion involving adsorption devices, MARS treatment for liver support, and extracorporeal CO2 removal (“ECCO2R”), such as for lung support using an oxygenator. CRRT machines also allow different types of anticoagulation modalities, such as systemic anticoagulation (e.g., heparin) and local citrate anticoagulation (“RCA”).

[0007] Hospitalized patients with AKI often require multiple medications to manage other conditions, administered at precise intervals and concentrations to ensure proper recovery. Therefore, these patients are simultaneously connected to either a CRRT or IHD machine. Both machines remove blood from the patient's body, passing it through filters to remove solutes, thus disrupting the concentrations or pharmacokinetics of other treatments, medications, or solutions applied to the patient during the same hospitalization.

[0008] To compensate for the impact of basic extracorporeal therapy, physicians must manually calculate changes when adding or altering a treatment, which can lead to under- or over-delivery of medication and pose risks to the patient. Therefore, an improved overall protocol for managing hospitalized patients with AKI is needed. Summary of the Invention

[0009] This disclosure presents a combined extracorporeal and drug delivery system and method, which provides a coordination logic actuator that coordinates the operation of a CRRT machine or IHD machine (such as a chronic hemodialysis machine) with one or more infusion pumps that simultaneously deliver drugs to the same patient. Synchronization may include: (i) electronically and / or digitally connecting to all infusion and extracorporeal devices used to treat the patient; (ii) recording treatment settings, including blood flow rate, treatment fluid flow rate, fluid removal rate, drug type, and drug dosage; (iii) providing decision support to the prescribing physician regarding the drugs to be applied and the target dosage, following generally accepted literature guidance and taking into account patient characteristics, disease type, and status; (iv) calculating actual dose dispensing to achieve the desired dose dispensing and adjusting as needed to maintain the desired dosage over time; (v) transmitting flow rate or adjustment information to the operator for approval, or sending such information to connected infusion and extracorporeal devices for automatic adjustment to administer drugs and / or treatment fluids to the patient; and (vi) optionally synchronizing with associated hospital IT systems such as electronic medical record databases, medical monitoring, telemedicine, or operating platforms to report treatment data and other data, such as treatment outcomes, the type and dosage of drugs delivered, and nurse notes such as the patient's subjective feelings, the presence of sepsis, or infection status. For example, decision support for target dosing can include indications of the risk and probability of the patient's future condition, such as changes in blood pressure, fluid overload, and / or cardiac problems. In this way, synchronized operation can provide value beyond coordinating renal failure with infusion pump operation.

[0010] Intravenous (“IV”) medications administered during CRRT or IHD treatment may include any type of antibiotic, such as vancomycin, gentamicin, cefepime, piperacillin, tazobactam, ceftazidime, avibactam, cefazolin, aztreonam, nafcillin, and oxacillin. Other medications include meropenem, cefepime, and fluconazole. According to this disclosure, dose distribution is challenged by renal failure treatment and therefore benefits from other medications synchronized with the renal failure flow rate, including any type of fluid resuscitation medication, systemic anticoagulants such as heparin or citrate, vasopressors, electrolytes, trace elements, nutritional supplements, anticonvulsants, antifungals, antitumor drugs, neuromuscular blocking agents, analgesics, and / or immunosuppressants. This system and method are contemplated to administer any medication that can be combined with CRRT or IHD treatment.

[0011] The coordination logic implementer of this disclosure is expected to operate with existing CRRT machines, IHD machines, and infusion pumps (including, but not limited to, high-volume infusion pumps (“LVP”), syringe pumps, bladder pumps, drip pumps, and any other type of IV drug pump). Therefore, in one embodiment, the coordination logic implementer is located external to each of these machines, for example, placed on, connected to, or positioned adjacent to the CRRT or IHD machine. In a preferred embodiment, the coordination logic implementer communicates electronically and / or data with the CRRT or IHD machine, for example, via a wired or wireless connection. In an alternative embodiment, the coordination logic implementer may be provided as part of the overall control unit of the CRRT or IHD machine and thus located therein.

[0012] In various embodiments, the coordination logic implementer may or may not communicate electronically and / or data with one or more infusion pumps, depending on the communication capabilities of the pumps. The coordination logic implementer may be able to communicate wired or wirelessly with all infusion pumps, some infusion pumps, or none at all. If the infusion pumps are connected to the coordination logic implementer, they can be controlled automatically or by operator confirmation and setting. If the infusion pumps are not connected to the coordination logic implementer, they can be manually controlled after operator confirmation and setting, with the operator viewing the proposal on the display screen of the coordination logic implementer, CRRT, or IHD machine.

[0013] The coordination logic implementer coordinates the operation of the CRRT or IHD machine and infusion pump in several ways. One way is to make the system take into account the flow rate of IV drugs in prescription fluid removal or ultrafiltration calculations. The goal of CRRT or IHD treatment may be to remove fluid from the patient so that patients with AKI do not receive fluid over time. IV drugs can significantly increase the total amount of fluid delivered to the patient. The IV delivery volume is taken into account when determining the instantaneous effluent rate removed by the CRRT or IHD machine. The coordination logic implementer also knows when to deliver IV drugs, allowing it to command a higher effluent rate during drug delivery and a lower effluent rate when drug delivery stops. The coordination logic implementer repeats this analysis for each IV drug delivered during CRRT or IHD treatment and combines the results when two or more drug deliveries overlap.

[0014] Another way the coordination logic actuator coordinates the operation of the CRRT or IHD machine and infusion pumps is to adjust the administration rate of one or more infusion pumps to compensate for a portion of the medication planned for the patient, rather than removing it from the extracorporeal circuit as effluent via CRRT or IHD treatment. In one embodiment, the percentage of medication in the removed effluent is estimated. One or more assumptions can be used for estimation, such as the effluent being completely homogeneous and the patient's blood volume being estimated based on the patient's weight. In an alternative embodiment, the patient's blood volume can be determined prior to treatment and entered into the coordination logic actuator, for example, via a user interface associated with the coordination logic actuator, or via a user interface associated with the CRRT or IHD machine, which then transmits the blood volume to the coordination logic actuator wired or wirelessly.

[0015] If the estimated percentage of medication is, for example, one percent, the coordination logic actuator may increase the flow rate associated with the prescribed medication by one percent, or propose a flow rate setpoint to the operator that is one percent higher than the flow rate associated with the prescribed dose. If implemented automatically or if accepted by the operator, the increased IV medication flow rate may be taken into account in the effluent flow rate adjustments discussed above, or it may be ignored if it has a negligible effect. Increasing the IV medication flow rate in this way compensates for the amount of IV medication removed via effluent removal from a CRRT or IHD machine.

[0016] When determining whether to adjust the IV drug flow rate, the coordinating logic actuator may consider whether the CRRT or IHD machine is actually operating. For example, if the IV drug is delivered before or after a CRRT or IHD treatment, the coordinating logic actuator will not adjust the IV drug flow rate based on the flow rate associated with the prescribed dose. If the CRRT or IHD machine stops during treatment for any reason, such as due to an alarm, alert, supply bag change, etc., the coordinating logic actuator is notified of the stop and may react in several alternative ways, such as (i) automatically reducing or suggesting a reduction in the IV drug flow rate to the flow rate associated with the prescribed dose while the stop continues, (ii) maintaining the IV drug flow rate at an increased flow rate during the stop but counting the additional flow rate as part of the administered dose, thereby reducing the total drug delivery time to meet the prescribed dose, or (iii) completely shutting off the IV drug flow rate, for example, if the drug is intended to accompany a CRRT or IHD treatment, such as if the drug is an anticoagulant, phosphate supplement, etc.

[0017] As a means of adjusting the IV pump flow rate so that the actual IV dose received by the patient, despite IV drug loss due to effluent removal for renal failure treatment, meets the patient's prescribed dose, this system and method can also be envisioned to adjust the IV drug concentration. For example, the actual concentration of one or more IV drugs can be increased from the prescribed concentration so that, taking into account the amount of drug lost through effluent removal, the actual amount of drug absorbed by the patient meets the patient's expected amount of prescribed drug absorption.

[0018] The system and method are designed to compensate for (e.g., reduce) the increase in IV drug flow rate or concentration caused by blood filter clotting over time, which could reduce the amount of IV drug removed at a set effluent removal flow rate. The amount of clotting can be estimated by an increase in pressure (e.g., an increase in effluent line pressure), which is correlated empirically with different reductions in IV drug removal in a lookup table. The system of this disclosure receives an increased pressure signal during treatment, invokes a lookup table, and adjusts (e.g., reduces) the percentage increase in IV drug flow rate and / or concentration accordingly.

[0019] Alternatively, the IV fluid flow rate or concentration can be adjusted based on the dilution caused by the displacement fluid flow and / or dialysis fluid flow, rather than the effluent fluid flow rate. Here, the adjustment can be based on the relationship between the IV fluid, displacement fluid flow, and / or dialysis fluid flow rates.

[0020] In another aspect of the systems and methods disclosed herein, the chemical composition of IV fluids, replacement fluids, and / or dialysis fluids is analyzed, and overlapping chemicals or components are compared to permissible levels to determine whether the chemical composition of the IV fluid should be adjusted, or whether the dosage of combined chemicals or components is acceptable. For example, if it is determined that an IV drug composition needs modification, the system outputs a revised formulation for approval and subsequent dispensing in a hospital pharmacy.

[0021] At the end of CRRT or IHD treatment and drug delivery, or at any appropriate time during the entire CRRT or IHD treatment and drug delivery process, it is envisioned that any or all relevant treatment data be sent to the hospital's Electronic Medical Record (“EMR”) database, which stores patient-related documents. For this purpose, it is envisioned that a coordination logic implementer communicates with the hospital server or other computer storage devices used for the EMR database, data warehouse, or data lake via wired or wireless communication.

[0022] In a typical hospital or emergency room setting, there may be only one CRRT or IHD machine and one or more associated infusion pumps. In this case, there would be a dedicated coordination logic implementer to arrange these machines, acting as a hub for the branch medical machines. In more clinical settings, such as when using hemodialysis machines for IHD, where IV drug delivery can still be performed, it is envisioned to provide a dedicated coordination logic implementer for two or more CRRT or IHD machines and associated infusion pumps. Here, the coordination logic implementer could be (i) also a hub for all branch medical machines (including the CRRT or IHD machine), or (ii) a higher-level hub for each of the branch CRRT or IHD machines in its cluster, where the CRRT or IHD machine is, in turn, a lower-level hub for its associated branch infusion pumps. The latter arrangement may be preferred when short-range wireless communication is available.

[0023] According to the disclosure herein, without limiting the scope of the invention in any way, in a first aspect of this disclosure, this aspect may be combined with any other aspect or part thereof listed herein, an extracorporeal and drug delivery system comprising: (i) a renal failure treatment machine capable of operating in conjunction with a blood filter, the blood filter being in fluid communication with an arterial line and a venous line, the arterial line being for removing blood from a patient to the blood filter, the venous line being for returning blood from the filter to the patient, the renal failure treatment machine comprising: (a) an effluent pump, the effluent pump being positioned and arranged to pump effluent from the blood filter at an effluent flow rate; and (b) a permeation The dialysis fluid pump is positioned and arranged to pump dialysis fluid to the blood filter at a dialysis fluid flow rate, the pre-dilution pump is positioned and arranged to pump replacement fluid to the arterial line at a pre-dilution flow rate, and the post-dilution pump is positioned and arranged to pump replacement fluid to the venous line at a post-dilution flow rate; (ii) an infusion pump operable to deliver intravenous (“IV”) drugs to the patient at an IV drug flow rate; and (iii) a coordination logic implementer configured to determine the adjustment of the IV drug flow rate based on the amount of IV drug removed via the effluent flow rate.

[0024] In a second aspect of this disclosure, which may be combined with any other aspect or part thereof listed herein, the renal failure treatment machine is a continuous renal replacement machine, and the renal failure treatment machine includes the effluent pump and includes at least two of the dialysis fluid pump, the pre-dilution pump, or the post-dilution pump.

[0025] In a third aspect of this disclosure, which may be combined with any other aspect or part thereof listed herein, the renal failure treatment machine is a hemodialysis machine and includes the effluent pump and the dialysis fluid pump.

[0026] In a fourth aspect of this disclosure, the fourth aspect may be combined with any other aspect or part thereof listed herein, and the coordination logic implementer may be disposed separately from the renal failure treatment device and the infusion pump, wherein the coordination logic implementer is wired or wirelessly connected to at least the renal failure treatment device.

[0027] In a fifth aspect of this disclosure, which may be combined with the fourth aspect, or with any other aspect or part thereof listed herein, the system is configured such that the total patient fluid input is transmitted to or determined by the coordination logic implementer to enable the coordination logic implementer to determine the adjustment of the IV drug flow rate based on the amount of IV drug removed via the effluent flow rate.

[0028] In a sixth aspect of this disclosure, which may be combined with any other aspect or part thereof listed herein, the system is configured to perform at least one of (i) or (ii): (i) automatically implementing regulation of the IV drug flow rate at the infusion pump; (ii) displaying the regulation for implementation at one or more of the renal failure treatment machine, the infusion pump, or the coordination logic actuator.

[0029] In the seventh aspect of this disclosure, which may be combined with any other aspect or part thereof listed herein, the coordination logic implementer is integrated into the renal failure treatment machine.

[0030] In the eighth aspect of this disclosure, which may be combined with any other aspect or part thereof listed herein, wherein the infusion pump is a first infusion pump, the IV drug is a first IV drug, the IV drug flow rate is a first IV drug flow rate, the extracorporeal and drug delivery system includes a second infusion pump operable to deliver a second IV drug to the patient at a second IV drug flow rate, and wherein the coordination logic implementer is configured to determine the adjustment of the second IV drug flow rate based on the amount of the second IV drug removed via the effluent flow rate.

[0031] In the ninth aspect of this disclosure, which may be combined with any other aspect or part thereof listed herein, the system is configured such that the outflow rate can take into account the adjustment of the IV drug flow rate and at least one of the dialysis fluid flow rate, the pre-dilution flow rate, or the post-dilution flow rate.

[0032] In the tenth aspect of this disclosure, which may be combined with any other aspect or part thereof listed herein, the system is configured such that the outflow rate takes into account the prescription patient fluid loss rate.

[0033] In the eleventh aspect of this disclosure, which may be combined with any other aspect or part thereof listed herein, the amount of the IV drug removed via the effluent flow rate includes a percentage of the IV drug in the effluent flow rate.

[0034] In a twelfth aspect of this disclosure, which may be combined with any other aspect or part thereof listed herein, the coordination logic implementer is configured to determine the adjustment of the IV drug flow rate based on the amount of IV drug removed via the effluent flow rate and based on an estimate of the patient's blood volume.

[0035] In the thirteenth aspect of this disclosure, which may be combined with any other aspect or part thereof listed herein, the coordination logic implementer is further configured to take into account blood filter patency or coagulation when determining the adjustment of the IV drug flow rate.

[0036] In the fourteenth aspect of this disclosure, which may be combined with the thirteenth aspect, or with any other aspect or part thereof listed herein, the system is configured such that: when an amount of the IV drug is removed via the effluent flow rate, the adjustment causes the IV drug flow rate to meet the prescribed IV drug flow rate.

[0037] In the fifteenth aspect of this disclosure, which may be combined with any other aspect or part thereof listed herein, the renal failure treatment device is a first renal failure treatment device, the infusion pump is a first infusion pump, the extracorporeal and drug delivery system includes a second renal failure treatment device associated with a second infusion pump, and wherein the coordination logic implementer is configured to determine the adjustment of the IV drug flow rate for the second infusion pump.

[0038] In the sixteenth aspect of this disclosure, which may be combined with any other aspect or part thereof listed herein, the coordination logic implementer is alternatively or additionally configured to determine the adjustment of the concentration of the IV drug based on the amount of the IV drug removed via the effluent flow rate.

[0039] In the seventeenth aspect of this disclosure, which may be combined with the sixteenth aspect, or with any other aspect or part thereof listed herein, the system is configured to display the adjustment of the concentration for implementation at one or more of the renal failure treatment machine, the infusion pump, or the coordinating logic implementer.

[0040] In the eighteenth aspect of this disclosure, which may be combined with the sixteenth aspect, or with any other aspect or part thereof listed herein, the system is configured such that: when an amount of the IV drug is removed via the effluent flow rate, the concentration is adjusted such that the dose of IV drug received by the patient meets the prescribed IV drug dose.

[0041] In the nineteenth aspect of this disclosure, which may be combined with the sixteenth aspect, or with any other aspect or part thereof listed herein, the infusion pump is a first infusion pump, the IV drug is a first IV drug, the extracorporeal and drug delivery system includes a second infusion pump operable to deliver a second IV drug to the patient, and wherein the coordination logic implementer is configured to determine the adjustment of the concentration of the second IV drug based on the amount of the second IV drug removed via the effluent flow rate.

[0042] In the twentieth aspect of this disclosure, which may be combined with any other aspect or part thereof listed herein, the coordination logic implementer is alternatively or additionally configured to determine the adjustment of the flow rate and / or concentration of the IV drug based on the amount of dilution of the IV drug caused by at least one of the dialysis fluid flow rate, the pre-dilution flow rate, or the post-dilution flow rate.

[0043] In the twenty-first aspect of this disclosure, which may be combined with the twentieth aspect, or with any other aspect or part thereof listed herein, the dilution amount is based on the relationship between at least one of the dialysis fluid flow rate, the pre-dilution flow rate, or the post-dilution flow rate and the flow rate of the IV drug.

[0044] In the twenty-second aspect of this disclosure, which may be combined with any other aspect or part thereof listed herein, the coordination logic implementer is alternatively or additionally configured to determine whether a component of the IV drug is present in at least one of the dialysis fluid, pre-dilution replacement fluid, or post-dilution replacement fluid, and if present, to determine whether the IV drug should be reformulated.

[0045] In the twenty-third aspect of this disclosure, the twenty-third aspect may be combined with the twenty-second aspect, or with any other aspect or part thereof listed herein, wherein the formulation adjustment includes reducing or eliminating the ingredient in or from the IV drug.

[0046] In the twenty-fourth aspect of this disclosure, with Figures 1 to 4 Any of the structures, functions, and alternatives associated with any graph in the diagram can be related to... Figures 1 to 4 Any combination of structures, functions, and alternatives associated with any other graph.

[0047] In view of this disclosure and the foregoing aspects, the advantage of this disclosure is that it provides a combined in vitro and drug delivery system and method that can reduce the workload of doctors, nurses and caregivers.

[0048] Another advantage of this disclosure is that it provides a combined in vitro and drug delivery system and method that can improve the accuracy of fluid removal.

[0049] Another advantage of this disclosure is that it provides a combination of in vitro and drug delivery systems and methods that can improve the accuracy of drug dosing delivery.

[0050] Another advantage of this disclosure is that it provides a combined in vitro drug delivery system and method that can be implemented using existing equipment.

[0051] Another advantage of this disclosure is that it provides a combination of in vitro and drug delivery systems and methods that can modify IV drug flow rates and / or concentrations.

[0052] Another advantage of this disclosure is that it provides a combination of in vitro and drug delivery systems and methods that modify IV drug flow rates or concentrations based on the removal or dilution of effluent (e.g., due to displacement and / or dialysis fluid flow rates).

[0053] Another advantage of this disclosure is that it provides a combined in vitro and drug delivery system and method that takes into account overlapping chemicals or components in IV drugs and replacement fluids and / or dialysis fluids to see whether the amount of overlapping fluid in the IV drug is permissible, should be reduced, or should be eliminated.

[0054] Additional features and advantages of the disclosed apparatus, systems, and methods are described in the following detailed description and accompanying drawings, and will become apparent therefrom. The features and advantages described herein are not exhaustive, and in particular, many additional features and advantages will be apparent to those skilled in the art in light of the drawings and description. Furthermore, any particular embodiment may not necessarily possess all the advantages listed herein. It should also be noted that the language used in this specification has been chosen primarily for readability and instructional purposes, and not to limit the scope of the subject matter of the invention. Attached Figure Description

[0055] Figure 1 This is a perspective view of one embodiment of the combined in vitro and drug delivery system disclosed herein.

[0056] Figure 2 This is a schematic diagram of one embodiment of the combined in vitro and drug delivery system disclosed herein.

[0057] Figure 3 This is a schematic flowchart illustrating example dose correction adjustments that can be performed according to the combined in vitro and drug delivery system of this disclosure.

[0058] Figure 4 This is a schematic diagram of one embodiment of the combined in vitro and drug delivery system disclosed herein. Detailed Implementation

[0059] Now refer to the attached diagram, especially Figure 1 An embodiment of the combined extracorporeal and drug delivery system 10 of this disclosure is illustrated. System 10 includes a renal failure treatment machine 20, such as a continuous renal replacement therapy (“CRRT”) machine or an intermittent hemodialysis (“IHD”) machine, and an intravenous (“IV”) drug infusion pump 70, 80, and / or 90. The renal failure treatment machine 20 can perform, for example, types of renal treatment, such as arteriovenous hemofiltration, continuous arteriovenous hemodialysis, continuous arteriovenous hemodiafiltration, continuous venous hemodiafiltration, continuous venous hemodiafiltration, slow continuous ultrafiltration, hemoperfusion, therapeutic plasma exchange, cytopheresis, continuous ultrafiltration in conjunction with periodic intermittent hemodialysis, fluid overload treatment, congestive heart failure, drug overdose, poisoning, immune disorders, sepsis, acid imbalance, and any combination thereof.

[0060] The illustrated renal failure treatment machine 20 includes a housing 22 supported by a rolling frame 24, allowing the machine to be moved or oriented to a location convenient for operation in a ward or intensive care unit (“ICU”). The illustrated renal failure treatment machine 20 includes scales 26a to 26n, which enable the determination of the weight and thus volume and flow rate of one or more fluids (e.g., dialysis fluid, replacement fluid, or effluent). For example, in one embodiment, scale 26a may be used to monitor the flow of fresh dialysis fluid, while scale 26b may be used to monitor the flow of effluent. The illustrated renal failure treatment machine 20 also includes external devices 28 supported by the housing 22, which may include, for example, pumps, pressure sensors, air detectors, blood leak detectors, valves such as tubing clamp valves, which will be discussed in more detail.

[0061] All sensor outputs from scales 26a to 26n and instrument 28 are sent to control unit 30, which controls all electrically actuated devices 28 of the renal failure treatment machine 20. The control unit 30 in the illustrated embodiment includes one or more processors 32 and one or more memories 34, a video card, a sound card, a wireless transceiver, or a wired interface 36, etc. Control unit 30 communicates with coordination logic implementer 100 via wired or wireless communication. For example, any wired communication discussed herein may be via Ethernet or fiber optic connection. Any wireless communication discussed herein may be via Bluetooth. TM WiFi TM , Z- It may be performed using any of the following protocols: Wireless Universal Serial Bus (“USB”), Radio Frequency (“RF”), Ultrasonic, Optical, Microwave, or Infrared, or via any other suitable wireless communication technology.

[0062] The renal failure treatment machine 20 in the illustrated embodiment also includes a graphical user interface (“GUI”) 40, which enables the operator to input data and commands into and / or receive information from the control unit 30. The GUI 40 includes a video monitor, which can also operate in conjunction with a touchscreen overlay placed on the video monitor for inputting commands into the control unit 30. The GUI 40 may also include one or more electromechanical input devices, such as membrane switches or other buttons. The control unit 30 may also include an audio controller for playing sound files, such as alarm or alert sounds, on one or more speakers of the renal failure treatment machine 20. Although the GUI 40 is shown attached to the housing 22, the GUI 40 can also be detached from the control unit 30 and communicate wirelessly with the control unit 30 via any of the protocols described above.

[0063] The coordination logic implementer 100 in the illustrated embodiment includes its own control unit 110. The control unit 110 in the illustrated embodiment includes one or more processors 112 and one or more memories 114, a video card, a sound card, and a wireless transceiver or wired interface 116 for communicating with the control unit 30 of the renal failure treatment machine 20, and, if enabled, with the control units of the IV drug infusion pumps 70, 80, and / or 90.

[0064] The coordination logic implementer 100 in the illustrated embodiment also includes a graphical user interface (“GUI”) 120, which enables an operator to input data and commands into and / or receive information from the control unit 110. The GUI 120 includes a video monitor, which can also operate in conjunction with a touchscreen overlay placed on the video monitor for inputting commands to the control unit 110. The GUI 120 may also include one or more electromechanical input devices, such as membrane switches or other buttons. The control unit 110 may also include an audio controller for playing sound files, such as alarm or alert sounds, on one or more speakers of the coordination logic implementer 100.

[0065] Although the shown coordination logic implementer 100 is located near the renal failure treatment machine 20, it may alternatively be located on or connected to the renal failure treatment machine 20. In another alternative embodiment, the coordination logic implementer 100 is integrated within the renal failure treatment machine 20, such that the control unit 110 and its software and programming are integrated into the control unit 30. However, providing a coordination logic implementer 100 separate from the renal failure treatment machine 20 allows it to operate with existing renal failure treatment machines, perhaps through software upgrades. It is envisioned that the coordination logic implementer 100 be implemented as a standalone device, part of any medical fluid machine, and / or third-party hardware, and / or abstracted somewhere (e.g., in EMR, edge computing, cloud services, etc.) in software.

[0066] IV drug infusion pumps 70, 80, and / or 90 each include control units 72, 82, and 92. Control units 72, 82, and 92 may also each include one or more processors, one or more memories, a video card, a sound card, and a wireless transceiver or wired interface for communicating with control unit 110 of the coordination logic implementer 100. IV drug infusion pumps 70, 80, and / or 90 also each include one or more pump actuators 74, 84, and 94 under the control of control units 72, 82, and 92, such as peristaltic, platen, or other types of tubing or syringe pump actuators. IV drug infusion pumps 70, 80, and / or 90 also each include one or more graphical user interfaces (“GUIs”) 76, 86, and 96. Each GUI 76, 86, and 96 may include a video monitor, which may also operate in conjunction with a touchscreen overlay placed on the video monitor for inputting commands to control units 72, 82, and 92, respectively. Each GUI 76, 86 and 96 may also include one or more electromechanical input devices, such as membrane switches or other buttons.

[0067] In one embodiment, the renal failure treatment machine 20 and the external infusion pumps 70, 80, and 90 each include addresses that, from the perspective of the coordination logic implementer 100, distinguish the machine and the pumps from each other. These addresses specify the pumps and infusion pumps 70, 80, and 90 of the renal failure treatment machine 20 associated with a specific patient undergoing AKI or other renal failure treatment. If multiple treatments occur simultaneously and are very close to each other, such as in adjacent ICUs or treatment centers, these addresses prevent erroneous communication between multiple renal failure treatment machines 20 and their associated infusion pumps 70, 80, and 90. Wireless communication carries a greater risk of erroneous communication.

[0068] The aforementioned addresses enable information to be transferred back and forth between the coordination logic implementer 100, the renal failure treatment machine 20, and the infusion pumps 70, 80, and 90. For example, current treatment data can be sent from one or both of the renal failure treatment machine 20 and the infusion pumps 70, 80, and 90 to the coordination logic implementer 100. The coordination logic implementer 100 can send one or more defined operating parameters to one or more of the renal failure treatment machine 20 and the infusion pumps 70, 80, or 90 for (i) automatic input and actuation by the corresponding control unit 30, 72, 82, or 92, and / or (ii) display at the corresponding GUI 40, 76, 86, or 96 for approval or acceptance. In another alternative embodiment, the coordination logic implementer 100 can display one or more defined operations at its GUI 120 as an alternative or supplement to those displayed on GUI 40, 76, 86, or 96.

[0069] System 10 and the associated method envision the following situations: (i) communication exists between the coordination logic implementer 100 and the renal failure treatment machine 20, and system 10 is authorized to automatically input and actuate one or more operating parameters sent from the coordination logic implementer 100 to the renal failure treatment machine 20; (ii) communication exists between the coordination logic implementer 100 and infusion pumps 70, 80, or 90, and system 10 is authorized to automatically input and actuate one or more operating parameters sent from the coordination logic implementer 100 to infusion pumps 70, 80, or 90; (iii) communication exists between the coordination logic implementer 100 and the renal failure treatment machine 20, but system 10 is not authorized to automatically input and actuate one or more operating parameters sent from the coordination logic implementer 100 to the renal failure treatment machine 20, such that said one or more parameters are displayed as suggested parameters in the GUI. (iv) There is communication between the coordinating logic actuator 100 and the infusion pumps 70, 80, or 90, but the system 10 is not authorized to automatically input and actuate one or more operating parameters sent from the coordinating logic actuator 100 to the infusion pumps 70, 80, or 90, such that the one or more parameters are displayed as suggested parameters at one or more GUIs 120, 76, 86, or 96 for operator reference; and (v) there is no communication between the coordinating logic actuator 100 and the infusion pumps 70, 80, or 90, such that one or more parameters determined by the coordinating logic actuator 100 are displayed as suggested IV drug parameters at one or more GUIs 120 or (of the machine 20) 40 for operator reference. In the latter case (v), the prescribed dose or the flow rate corresponding to the prescribed drug dose is initially manually entered into the coordinating logic actuator 100 via GUI 120 or manually entered into the renal failure treatment machine 20 via GUI 40.

[0070] Figure 1 The system 10 further illustrates that the coordination logic implementer 100 is configured to communicate with the hospital's electronic medical record (“EMR”) database 150, for example, via wired or wireless communication. In one embodiment, at the end of a CRRT or IHD procedure and associated medication delivery, any or all relevant procedure data is sent from the coordination logic implementer 100 to the EMR database 150, which stores patient-related documents. Other procedure information, such as delivered medications, alarms, alerts, and notes entered by caregivers or operators during the procedure, such as date and time stamps, may also be sent from the coordination logic implementer 100 to the EMR database 150.

[0071] For reference Figure 2 System 10 schematically illustrates an embodiment of different types of fluid inputs that may affect the determination of the total outflow velocity. Figure 2 System 10 in the middle includes, for example, combining Figure 1 The described renal failure treatment machine 20, the coordinating logic implementer 100, and the infusion pumps 70, 80, and 90. Figure 2 It also shows the combination Figure 1 The fresh dialysis fluid scale 26a and effluent scale 26b are described, along with auxiliary scales, namely, upstream pre-dilution scale 26c, downstream pre-dilution scale 26d, and post-dilution scale 26e. (See also...) Figure 2 As shown, the coordination logic implementer 100 communicates with the EMR database 150.

[0072] Weighing scales 26a to 26e are used to weigh the fluids in dialysis fluid container 52a, effluent container 52b, upstream pre-dilution container 52c, downstream pre-dilution container 52d, and post-dilution container 52e, respectively. Containers 52a to 52c form part of a disposable kit 50, which is attached to the housing 22 of the renal failure treatment machine 20. Figure 1 The disposable kit 50 in the illustrated embodiment also includes an arterial line 54 for removing blood from patient P, a venous line 56 for returning blood to patient P, and an instillation device 58 placed in the venous line 56 to remove any air from the blood before returning it to patient P. A blood filter or dialyzer 60 separates the arterial line 54 from the venous line 56. The blood filter or dialyzer 60 includes a blood compartment 60a and a dialysate compartment 60b, which are separated by a semipermeable membrane 62. The arterial line 54 leads to the blood compartment 60a, while the venous line 56 extends from the blood compartment 60a. Similarly, a fresh dialysate line 64 extends from the dialysate container 52a to the dialysate compartment 60b, while an effluent line 66 extends from the dialysate compartment 60b to the effluent container 52b.

[0073] Figure 2The disposable kit 50 in the embodiment also includes an upstream pre-dilution line 68c, a downstream pre-dilution line 68d, and a post-dilution line 68e. The upstream pre-dilution line 68c extends from the upstream pre-dilution container 52c to the arterial line 54, the downstream pre-dilution line 68d extends from the downstream pre-dilution container 52d to the arterial line 54, and the post-dilution line 68e extends from the post-dilution container 52e to the venous line 56.

[0074] Figure 1 This section summarizes the pumps, sensors, valves, etc., associated with the housing 22 of the renal failure treatment machine 20, which serves as an external device 28. These external devices... Figure 2 The diagram, shown in more detail, includes a fresh dialysis fluid pump 42b operating with a fresh dialysis fluid line 64, an effluent pump 42b operating with an effluent line 66, an upstream pre-dilution pump 42c operating with an upstream pre-dilution line 68c, a downstream pre-dilution pump 42d operating with a downstream pre-dilution line 68d, and a post-dilution pump 42e operating with a post-dilution line 68e. Additionally, a blood pump 44 is provided that pumps blood from patient P along an arterial line 54, through a blood filter 60, and back to patient P via a venous line 56. Multiple valves, such as a venous valve 46, are provided. A level detector 48 is also provided to detect the level of fluid in the infusion set 58.

[0075] All pumps, valves, detectors, scales, sensors, etc., are under the control of control unit 30, or send output signals to control unit 30, such as... Figure 2 As shown by the dashed line. Figure 2 An embodiment of CRRT for the renal failure treatment machine 20 is shown. IHD or hemodialysis embodiments for the renal failure treatment machine 20 appear very similar, but may alternatively (i) have online dialysis fluid generation and domestic drainage facilities instead of containers 26a and 26b, (ii) use different types of pumps and valve adjustments (e.g., peristalsis and clamping as shown for CRRT, or pneumatic and / or electromechanical for IHD), (iii) use volume or flow rate determination instead of CRRT weight detection for fluid control and balancing, and (iv) not deliver treatment fluid to blood lines 54 or 56. Therefore, CRRT demonstrates a scenario where the number of different types of fluids that can be input into the effluent equation shown below is significant, thus also supporting the IHD embodiment. However, it should be understood that the CRRT of system 10 does not necessarily use a replacement fluid, or may have one or both of pre-dilution and / or post-dilution replacement fluids. Furthermore, CRRT may or may not have a dialysis fluid flow. The CRRT of system 10 can have any combination of these fluid flows.

[0076] Figure 2 The diagram shows the flow rates associated with different pumping sources, including the Q of blood flow.BLOOD Q of fresh dialysis fluid flow DIAL Q of outflow logistics EFF Q before the blood pump PBP (e.g., heparin anticoagulants), Q of pre-dilution replacement fluid flow REP1 Q of the post-dilution displacement fluid flow REP2 Q of the drug flow from the infusion pump 70 D70 Q of the drug flow rate of the infusion pump 80 D80 Q of the drug flow from the infusion pump 90 D90 Besides Q, which is used for blood flow BLOOD In addition, system 10 determines the outflow logistics Q EFF When considering Q DIAL Q PBP Q REP1 Q REP2 Q D70 Q D80 and Q D90 Each of them. In one embodiment, Q DIAL Q PBP Q REP1 and Q REP2 Fluid loss or ultrafiltration removal rate Q by physicians and prescribed patients UF Let's write the prescription together. The Q of the medication. D70 Q D80 and Q D90 It can be the flow rate corresponding to the dosage prescribed by the doctor, or it can be adjusted according to the prescription flow rate, as discussed in detail below.

[0077] Figure 2 The overall fluid balance equations for system 10 are as follows:

[0078] Q UF =Q EFF -[Q DIAL +Q PBP +Q REP1 +Q REP2 +Q D70 +Q D80 +Q D90 ]

[0079] In one example, Q UF =200ml / hr, Q DIAL =1000ml / hr, Q PBP =600ml / hr, Q REP1 =800ml / hr, Q REP2= 800 ml / hr. The drug flow rate is initially determined based on the dosage prescribed by the doctor. The dosage can be delivered over several hours in the form of mg / (kg patient weight), i.e., a known patient weight gives g / hr, and a known drug density produces ml / hr. Assume Q in this example... D70 60ml / hr, Q D80 100ml / hr, Q D90 If the flow rate is 80 ml / hr, then the above equation is as follows:

[0080] 200 = Q EFF -[1000+600+800+800+60+100+80]

[0081] 200 = Q EFF -[3440 (Total patient fluid intake)]

[0082] Q EFF =3640ml / hr

[0083] It is noteworthy that in the above calculations, the total drug component (60+100+80) of 240 ml / hr represents seven percent of the total patient fluid input of 3440 ml / hr, which is relatively significant and produces a similar percentage increase in outflow accuracy. In one embodiment, the above calculations are performed at a coordinating logic implementer 100, which is capable of obtaining all input information from all prescription information issued by the physician, which is (i) electronically obtained from the renal failure treatment machine 20 and / or infusion pumps 70, 80 and 90, (ii) manually entered at the GUI 120, or (iii) some combination thereof.

[0084] Given effluent Q EFF =3640 ml / hr, based on the prescribed doses of three drugs for infusion pumps 70, 80, and 90, system 10 now compensates for the outflow of fluid Q. EFFThe removed medication portion. The coordinating logic implementer 100 receives the patient P's weight at the start of treatment and uses a conversion algorithm to calculate the patient's corresponding blood volume. Assuming patient P weighs 80 kg, an estimator (https: / / reference.medscape.com / calculator / estimated-blood-volume) estimates patient P's blood volume to be 6000 ml. It is known that 3440 ml will be added in the next hour, resulting in a total cumulative volume of 9440 ml. The volume percentage of each medication in the next hour is (i) 60 / 9440 or 0.63% for medications in infusion pump 70, (ii) 100 / 9440 or 1.1% for medications in infusion pump 80, and 80 / 9440 or 0.84% ​​for medications in infusion pump 90.

[0085] The coordinating logic implementer 100 then increases the actual flow rate of each infusion pump 70, 80, and 90 so that the patient receives the prescribed dose of medication within one hour. In this example, the flow rate of pump 70 will increase from 60 ml / hr to 60.38 ml / hr (an increase of 0.63%). The flow rate of pump 80 will increase from 100 ml / hr to 101 ml / hr (an increase of 1.1%). The flow rate of pump 90 will increase from 80 ml / hr to 80.67 ml / hr (an increase of 0.84%). Assuming the flow rate adjustment is relatively small, as here, it is not necessary to perform the outflow flow Q again. EFF The calculation. However, for larger drug flow rate adjustments, it is conceivable that system 10 determines Q in the manner described above. EFF Adjustments should be considered. However, from a pharmacological perspective, adjusting the drug flow rate is important because the patient is currently receiving the prescribed dose of medication.

[0086] When determining whether to adjust the IV drug flow rate, the coordination logic actuator 100 may consider whether the CRRT or IHD machine 20 is actually operating. For example, if the IV drug is delivered before or after CRRT or IHD treatment, the coordination logic actuator 100 will not adjust or recommend adjusting the IV drug flow rate based on the flow rate associated with the prescription dose. If the CRRT or IHD machine 20 stops during treatment for any reason, such as due to an alarm, alert, supply bag change, etc., the machine 20 transmits the stop (e.g., wired or wirelessly) to the coordination logic actuator 100, which can be programmed to react in any of a variety of alternative ways, such as (i) while the stop continues, causing at least one infusion pump 70, 80, 90 to automatically reduce or recommend reducing its IV drug flow rate at at least one infusion pump 70, 80, 90 as described herein, (ii) maintaining at least one IV drug flow rate at an increased flow rate during the stop, but counting the additional flow rate as part of the administered dose and transmitting it to at least one infusion pump 70, 80, 90 or its operator, thereby reducing the total drug delivery time to meet the prescribed dose, or (iii) completely shutting down one or more infusion pumps 70, 80, 90, for example, if the drug is intended to accompany CRRT or IHD treatment, such as if the drug is an anticoagulant, phosphorus supplement, etc.

[0087] In one embodiment, all enabled communication is bidirectional, enabling the coordination logic implementer 100 to know when one or more infusion pumps 70, 80, 90 are operating during operation of the renal failure treatment machine 20. In one embodiment, the logic implementer 100 periodically (e.g., every second, every few seconds, or less than one second) polls the control units 72, 82, 92 of each of the infusion pumps 70, 80, 90 to see if they are currently in pumping mode. The control units 72, 82, 92 appropriately respond to the control unit 110 of the coordination logic implementer 100, and the coordination logic implementer 100 reacts accordingly. In the above-described determination of Q... EFF In the example, during the operation of the renal failure treatment machine 20 and knowing Q D70 60ml / hr, Q D80 100ml / hr and Q D90 At a rate of 80 ml / hr, the logic actuator 100 will (i) automatically increase / decrease or suggest increasing / decrease Q at 60 ml / hr when the infusion pump 70 starts / stops pumping. EFF (ii) When the infusion pump starts / stops at 80°C, automatically increase / decrease or suggest increasing / decrease Q at 100 ml / hr. EFF (iii) Automatically increase / decrease or suggest increase / decrease Q at 80 ml / hr when the infusion pump starts / stops at 80. EFF .

[0088] The extent to which starting or stopping any of the infusion pumps 70, 80, or 90 significantly affects the total patient fluid input (3440 ml / hr in the example above) is such that the coordination logic actuator 100 is configured to adjust or suggest adjusting the flow rate of any other currently operating infusion pump 70, 80, or 90 upward or downward. In this way, the system 10 is configured to regulate the operation of any of the other infusion pumps 70, 80, or 90 based on their current state (e.g., pumping relative to not pumping).

[0089] The above examples involve adjusting the IV drug flow rate to compensate for a portion of the prescribed medication that is removed from the patient's body as an effluent from the treatment of renal failure, rather than being absorbed by the patient and used for the patient's disposal. According to this disclosure, another way to compensate for effluent removal is to adjust the concentration of the IV drugs so that the amount of medication actually absorbed by the patient matches the prescribed amount. In the examples above, (i) the amount or percentage of IV drug lost by infusion pump 70 in one hour is 0.63%, (ii) the amount lost by infusion pump 80 in one hour is 1.1%, and (iii) the amount lost by infusion pump 90 in one hour is 0.84%. Therefore, it is conceivable that the coordinating logic implementer 100 could suggest to physicians, technicians, machine operators, etc., that the concentration of the IV drugs be increased according to the percentage lost, so that the patient receives the prescribed amount of each IV drug despite some medication loss due to effluent removal from the treatment of renal failure. In one example, if (i) the concentration of IV drug in infusion pump 70 is 20% by volume, its concentration increases by 0.63% to 20.13% by volume; (ii) the concentration of IV drug in infusion pump 80 is 10% by volume, its concentration increases by 1.1% to 10.11% by volume; and (iii) the concentration of IV drug in infusion pump 90 is 12% by volume, its concentration increases by 0.84% ​​to 12.1% by volume.

[0090] The above example assumes that the prescription flow rate is not adjusted, i.e., using the adjusted concentration, Q D70 Maintain at 60ml / hr, Q D80 Maintain at 100ml / hr, Q D90 Maintain at 80 ml / hr. In another alternative embodiment, the coordinating logic implementer 100 of system 10 is envisioned to provide a combination of regulated flow rate and regulated concentration, such that the prescribed dosage is met even if some of the IV drug is removed via the effluent stream.

[0091] Many hospitals have advanced dispensing systems or units capable of achieving highly accurate concentrations, such as those specified above. For example, concentration adjustment relative to the flow rate may be advantageous when the prescription flow rate is at the maximum permissible flow rate of the drug and / or infusion pumps 70, 80, 90. Concentration adjustment may require the coordinating logic actuator 100 to suggest a concentration change to physicians or caregivers, rather than automatically adjusting the concentration, so that physicians or caregivers can order IV drugs with adjusted concentrations from the hospital pharmacy. As with any suggestions from the coordinating logic actuator 100 discussed herein, such suggestions may be provided audibly, visually, or audiovisually at any one or more of the GUI 40 of the renal failure treatment machine 20, the GUI 120 of the coordinating logic actuator 100, and / or the GUIs 76, 86, and 96 associated with the infusion pumps 70, 80, 90.

[0092] Figure 3 Method 210 summarizes the aforementioned adjustments (automatic or recommended) determined by the coordination logic implementer 100 of system 10. In one embodiment, the method is implemented at the control unit 110 of the coordination logic implementer 100. Method 210 begins at ellipse 212. At block 214, control unit 110 sets the IV drug pump flow rate (e.g., Q...) D70 Q D80 and Q D90 Add to outflow velocity (Q) EFF In the overall equation, and as shown above, the outflow velocity (Q) is calculated. EFF ).

[0093] At box 216, control unit 110(i) uses the calculated effluent flow rate and patient blood volume to determine the IV drug flow rate (Q) for each IV drug flow rate as described above. D70 Q D80 Q D90 (ii) The percentage adjustment of IV drug concentrations for infusion pumps 70, 80, and 90, as described above. As discussed herein, adjustments may be performed automatically or suggested to caregivers.

[0094] At rhombus 218, control unit 110 determines the IV drug flow rate (Q). D70 Q D80 Q D90 Does the percentage adjustment (if any) significantly affect the outflow rate (Q) at box 214 when performed together? EFF ) calculation. "Significantly" can be achieved by adjusting the IV drug flow rate (Q... D70 Q D80 Q D90 The joint adjustment of the outflow velocity (Q) is used as the current calculated outflow velocity. EFFThe percentage adjustment is determined by comparing it to a threshold percentage (e.g., 0.5%). If the percentage adjustment meets or exceeds the threshold percentage, the effect is considered "significant" according to diamond box 218. In the example above, Q EFF The flow rate was determined to be 3640 ml / hr, with (i) the flow rate of pump 70 adjusted from 60 ml / hr to 60.38 ml / hr, (ii) the flow rate of pump 80 adjusted from 100 ml / hr to 101 ml / hr, and the flow rate of pump 90 adjusted from 80 ml / hr to 80.67 ml / hr. The total or common adjustment of the IV pumps was 2.05 ml / hr (0.38 ml / hr + 1.00 ml / hr + 0.67 ml / hr), which was taken as the Q of the currently calculated 3640 ml / hr. EFF The percentage is 0.06%, which is far below the example threshold percentage (e.g., 0.5%).

[0095] If the percentage adjustment of the IV drug flow rate significantly affects the effluent flow rate (Q) determined at rhombus 218 EFF If the calculation of ) is completed, then method 210 returns to box 214 to update the outflow velocity (Q). EFF The flow rate adjustment of the IV pump is then updated at box 216. The cycle between diamond 218 and boxes 214 and 216 continues until the percentage adjustment of the IV drug flow rate no longer significantly affects the effluent flow rate (Q) determined at diamond 218. EFF The calculation of ) is then performed, at which point method 210 proceeds to box 220. At box 220, control unit 110 causes the adjustment determined at box 216 to be automatically implemented, or suggests the adjustment to the caregiver in any of the manner described herein. At diamond box 222, method 210 ends.

[0096] Dashed box 217 illustrates options for method 210, where the patency or lifespan of the blood filter 60 (e.g., dialyzer or hemofilter) is taken into account. In CRRT and IHD, it is known that the dialyzer or hemofilter 60 slowly coagulates over time, which can reduce the rate of drug removal, even though the flow rate is set to a constant at the renal failure treatment machine 20. The amount of coagulation can be estimated by sensing the pressure in one or more of the effluent line 66, the arterial line 54, and / or the venous line 56. For example, if the pressure in the effluent line 66 increases during treatment, it can be considered as being caused by coagulation from the blood filter 60. The pressure increase can be empirically correlated with, for example, a percentage decrease in drug removal. In one embodiment, this correlation is stored as a lookup table in the control unit 110 of the coordination logic implementer 100. Here, when the coordinating logic actuator 100 receives an increased pressure signal from a pressure sensor operating with the effluent line 66 during the treatment process, the coordinating logic actuator 100 finds the corresponding percentage reduction in drug removal from a lookup table and accordingly reduces the percentage adjustment of IV drug flow rate and / or IV drug concentration as determined in block 216.

[0097] Method 210 adjusts the IV drug flow rate based on the fact that a patient undergoing treatment for renal failure may be receiving fluid removal in the form of ultrafiltration as the effluent. This fluid removal is presumed to also remove a portion of one or more IV drugs that would otherwise have been used to treat the patient. Method 210 emphasizes two ways to adjust the removal of IV drugs due to effluent removal. However, it should be understood that this disclosure is contemplated without regard to the effluent flow rate (Q). EFF Other methods of compensating for IV drug removal or dilution.

[0098] In an alternative approach, the IV drug flow rate Q D70 Q D80 and Q D90 The adjustment (and / or concentration) of the drug (or, as suggested, by the coordinated logic actuator 100) is changed to be based on the Q of the drug being used in the pre-dilution displacement fluid flow. REP1 and Q for post-dilution displacement fluid flow REP2 The amount of dilution. Here, the IV drug flow rate Q... D70 Q D80 and Q D90 This can be increased, for example, by a percentage equal to the drug flow rate divided by the total displacement fluid flow rate plus the drug flow rate. For example, using the same example flow rate data as above, where Q... REP1 800ml / hr, Q REP2 800ml / hr, Q D70 60ml / hr, Q D80 It is 100ml / hr, and QD90 If the flow rate is 80 ml / hr, then (i)Q D70 Increase by 60ml / hr / (800ml / hr + 800ml / hr + 60ml / hr) or 3.6%, (ii)Q D80 Increase by 100ml / hr / (800ml / hr+800ml / hr+100ml / hr) or 5.9%, while (iii)Q D90 Increase by 80 ml / hr / (800 ml / hr + 800 ml / hr + 80 ml / hr) or 4.8%. Therefore, to compensate for the fact that the three IV drugs are diluted by the pre-dilution and post-dilution replacement fluid streams during treatment, Q D70 The flow rate was increased from 60 ml / hr to 62.2 ml / hr (an increase of 3.6%). Q D80 The flow rate was increased from 100 ml / hr to 106 ml / hr (an increase of 5.9%). Q D90 The flow rate was increased from 80 ml / hr to 83.8 ml / hr (an increase of 4.8%). It should be understood that, in addition to the example compensation just described, those skilled in the art can determine other ways to compensate for IV drug dilution caused by the displacement fluid flow, and IV drug concentrations can be adjusted alternatively or additionally due to the IV drug dilution just described.

[0099] As is well known, pre-dilution replacement fluid and post-dilution replacement fluid are used for hemofiltration (“HF”) and hemodiafiltration (“HDF”) procedures in CRRT or IHD. In HF, there is no dialysis fluid flow Q. DIAL HD and HDF use dialysis fluid flow Q DIAL Theoretically, the dialysis fluid flow does not add to the patient's total blood volume because the dialysis fluid flow travels along the outer side of the dialyzer membrane, whose tiny hollow fiber pores prevent the dialysis fluid from entering the blood side of the membrane. In this case, the dialysis fluid flow rate Q DIAL It will not dilute the IV drug flow rate. However, for high-flux dialyzers, it is likely (if not expected) that a certain percentage of dialysate will migrate into the extracorporeal circuit, thus entering the patient's bloodstream. If the amount of migration becomes significant enough, for example in the case of chronic HD, where the dialysate flow rate is specified in ml / min instead of the example Q of 1000 ml / hr discussed above, this could be problematic. DIAL In such cases, IV drug dilution may occur due to the dialysate flow. This dilution can be compensated for in the same manner (flow rate and / or concentration) used for pre-dilution and post-dilution replacement fluids as described above.

[0100] When compensating for IV drug flow dilution caused by dialysis fluid flow, the coordinating logic actuator 100 estimates the amount or rate of dialysis fluid migrating from the dialysis fluid compartment of the dialyzer to the blood compartment of the dialyzer. This estimate (Q...) EST The following factors may be considered and therefore vary due to any one or more of the following factors: the amount of dialyzer membrane flux or opening, blood flow rate, dialysate flow rate, the relationship between blood flow rate and dialysate flow rate, blood flow pressure through the dialyzer, dialysate flow pressure through the dialyzer, and / or the relationship between blood flow pressure through the dialyzer and dialysate flow pressure (e.g., transmembrane pressure). Once the coordinating logic implementer 100 establishes Q... EST Then the IV drug flow rate Q D70 Q D80 and Q D90 It can be increased (or it is suggested to increase via the coordination logic implementer), for example, by increasing the drug flow rate by Q. EST Add the percentage of drug flow rate. As with any recommendations from the Coordinating Logic Implementer 100 discussed here, the IV drug flow rate recommendations here may be provided audibly, visually, or audiovisually at any one or more of the GUI 40 of the renal failure treatment machine 20, the GUI 120 of the Coordinating Logic Implementer 100, and / or the GUIs 76, 86, and 96 of the associated infusion pumps 70, 80, and 90.

[0101] In another alternative aspect of this disclosure, the chemical formulation of the IV drug is modified due to chemical overlap, for example, with the formulations of pre-dilution replacement fluids, post-dilution replacement fluids, and / or dialysis fluids. As discussed above, many hospitals have advanced formulation systems or units capable of achieving highly accurate concentrations. Therefore, the chemical composition of the IV drug can be adjusted to avoid duplication of specific chemicals with those of the renal therapy replacement fluid or dialysis fluid. For example, both the renal therapy replacement fluid and the IV drug fluid may contain phosphates. Here, system 10 is configured to examine the dosages of the two phosphates to see if they can coexist or if modification of the phosphate composition of the IV drug is necessary.

[0102] If a patient is provided with renal replacement fluid and IV medication fluid during the same hospital treatment (directly and simultaneously or close enough that phosphates or other overlapping components from both sources are present in the patient's body at the same time), it is expected and conceivable that the coordinating logic implementer 100 of system 10 is configured to (i) understand the chemical composition of the renal replacement fluid and IV medication, (ii) identify and combine the doses or flow rates of overlapping components or chemicals in the renal replacement fluid and IV medication, (iii) determine whether the combined dose or flow rate exceeds the maximum dose or flow rate of each overlapping component or chemical, or determine whether the dose or flow rate of a component or chemical should not exceed the dose or flow rate of the IV medication prescription at all, and (iv) notify the clinician, physician, or other users of system 10 and / or the hospital pharmacy if the amount of a component or chemical in the renal replacement fluid should be reduced or eliminated, thereby modifying the IV medication. As with any recommendations from the Coordinating Logic Implementer 100 discussed herein, recommendations for IV drug components may be provided, in an auditory, visual, or audiovisual manner, at any one or more of the GUIs of the renal failure treatment machine 20, the Coordinating Logic Implementer 100, and / or the associated infusion pumps 70, 80, 90, and GUIs 76, 86, and 96.

[0103] In one example, suppose patient P's prescribed phosphate dose is X mg / (kg (patient weight) * hr), and fluid is exchanged from the kidney (Q). REP1 Add Q REP2The phosphate dose received by patient P is X / 3, and the actual phosphate dose received by patient P should not exceed the prescribed dose. Here, the control unit 110 of the coordinating logic implementer 100 is programmed to (i) accept and know the prescribed dose of phosphate for patient P (X mg / kg (patient weight) * hr), (ii) accept and know that the actual dose of phosphate will not exceed the prescribed dose, (iii) accept and know the patient's weight (e.g., measured prior to treatment and delivered directly, wired, or wirelessly to the coordinating logic implementer 100), and thus be able to determine X, (iv) accept and know the chemical composition of replacement fluid 1 and / or replacement fluid 2 (whichever or both are used), (v) accept and know the prescribed flow rate of replacement fluid 1 and / or replacement fluid 2, (vi) calculate the dose of replacement fluid 1 and / or replacement fluid 2 knowing the chemical composition of the replacement fluid and the patient P's weight, (vii) compensate (or eliminate) the amount of phosphate in the IV drug to achieve the prescribed dose, given the known replacement fluid dose, and (viii) communicate the updated chemical formulation of the IV drug with the compensated amount of phosphate component in any manner discussed herein. In the example above, the components of the IV drug are derived from having X The phosphate dose of mg / (kg (patient weight)*hr) is changed to 2X / 3mg / (kg (patient weight)*hr) phosphate dose, so that when delivered in combination with replacement fluid 1 and / or replacement fluid 2 having a phosphate dose of X / 3mg / (kg (patient weight)*hr), the delivered phosphate dose is the prescription dose of X mg / (kg (patient weight)*hr).

[0104] The control unit 110 of the coordinating logic actuator 100 may alternatively be programmed to allow patient P to receive an additional X / 3 mg / (kg (patient weight)*hr) dose of phosphate from replacement fluid 1 and / or replacement fluid 2. Alternatively, the control unit 110 of the coordinating logic actuator 100 may determine that the phosphate dose from replacement fluid 1 and / or replacement fluid 2 exceeds the prescribed dose of the IV drug, in which case the control unit 110 of the coordinating logic actuator 100 generates an alarm or alert to any of the destinations discussed herein in any of these ways. Assuming that a specific and quantifiable dialysis fluid migrates into the extracorporeal circuit as discussed above, the teachings on the use of replacement fluids described above also apply to dialysis fluids. It should be understood that, for example, if the replacement fluid is prepared online at or near the renal failure treatment machine 20, the composition of replacement fluid 1 and / or replacement fluid 2 may be modified alternatively or as a supplement to the modification of the IV drug composition. However, typically, replacement fluids are pre-prepared, bagged, and sterilized. The preceding paragraphs apply to any overlapping chemicals or components and are by no means limited to phosphates.

[0105] For reference Figure 4One embodiment of system 10 illustrates a single coordinating logic implementer 100 that operates a cluster of multiple renal failure treatment machines 20 and their associated infusion pumps 70, 80, and 90 in the manner described above. In one embodiment, the logic implementer 100 is the hub for all branch renal failure treatment machines 20 and all branch infusion pumps 70, 80, and 90, which is Figure 1 and Figure 2 The situation. Figure 4 Alternative embodiments are shown. Here, the coordination logic implementer 100 is shown as a higher-level hub for each of the branch CRRT or IHD machines 20 in its cluster, wherein the CRRT or IHD machine 20 is, in turn, a lower-level hub for their associated branch infusion pumps 70, 80, 90. Figure 4 As shown, the coordination logic implementer 100 communicates with the EMR database 150. When short-range wireless communication is provided, Figure 4 The arrangement may be preferred. Here, for example, (i) treatment parameters or status are transmitted from infusion pumps 70, 80, 90 to the coordinating logic implementer 100 via the corresponding renal failure treatment machine 20, and (ii) operating parameters (automatic or suggested) are determined at the coordinating logic implementer 100 and transmitted from the coordinating logic implementer 100 to the infusion pumps 70, 80, 90 via the renal failure treatment machine 20.

[0106] The term “and / or” as used in this specification (including the claims) is an inclusive or exclusive conjunction. Therefore, the term “and / or” either indicates the presence of two or more things in a set, or indicates a choice that can be made from a set of alternatives.

[0107] Many features and advantages of this disclosure are apparent from the written description, and therefore the appended claims are intended to cover all such features and advantages. Furthermore, since many variations and modifications will readily occur to those skilled in the art, this disclosure is not limited to the exact construction and operation shown and described. Therefore, the described embodiments should be considered illustrative rather than restrictive, and this disclosure should not be limited to the details given herein, but rather should be defined by the full scope of the appended claims and their equivalents, whether now or in the future foreseeable or unforeseeable.

Claims

1. An extracorporeal drug delivery system, comprising: A kidney failure treatment machine, capable of operating in conjunction with a blood filter, the blood filter being in fluid communication with arterial and venous tubing, the arterial tubing being used to remove blood from the patient to the blood filter, and the venous tubing being used to return blood from the blood filter to the patient, the kidney failure treatment machine comprising: An effluent pump, positioned and arranged to pump effluent from the blood filter at an effluent flow rate; and At least one of a dialysis fluid pump, a pre-dilution pump, or a post-dilution pump. The dialysis fluid pump is positioned and arranged to pump dialysis fluid to the blood filter at a dialysis fluid flow rate. The pre-dilution pump is positioned and arranged to pump the displacement fluid into the arterial line at a pre-dilution flow rate. The post-dilution pump is positioned and arranged such that the post-dilution flow rate will pump the displacement fluid into the venous line; An infusion pump, operable to deliver intravenous medication to the patient at an intravenous drug flow rate; and A coordination logic implementer, wherein the coordination logic implementer is configured to: The effluent flow rate is determined using a fluid balance equation that correlates the effluent flow rate with the sum between the ultrafiltration removal rate and the total patient fluid inflow rate, which includes at least one of the dialysis fluid flow rate, the pre-dilution flow rate, or the post-dilution flow rate. Use patient weight to estimate blood volume; The adjustment of the intravenous drug flow rate is determined based on the estimated blood volume of the patient and the amount of intravenous drug removed using the effluent flow rate. The percentage adjustment is determined by dividing the adjustment of the intravenous drug flow rate by the determined outflow rate. When the adjustment percentage is greater than a threshold, the effluent flow rate and the resulting adjustment to the intravenous drug flow rate are iteratively determined until the adjustment percentage is less than the threshold. When the adjustment percentage is less than the threshold, the adjustment of at least the intravenous drug flow rate is performed at the infusion pump.

2. The extracorporeal and drug delivery system of claim 1, wherein the renal failure treatment machine is a continuous renal replacement machine, and the renal failure treatment machine includes the effluent pump and includes at least two of the dialysis fluid pump, the pre-dilution pump, or the post-dilution pump.

3. The extracorporeal and drug delivery system according to claim 1, wherein the renal failure treatment machine is a hemodialysis machine and includes the effluent pump and the dialysis fluid pump.

4. The extracorporeal and drug delivery system of claim 1, wherein the coordination logic implementer is disposed separately from the renal failure treatment machine and the infusion pump, and wherein the coordination logic implementer is wired or wirelessly connected to at least the renal failure treatment machine.

5. The extracorporeal and drug delivery system of claim 4, wherein the extracorporeal and drug delivery system is configured such that the total patient fluid infusion rate is transmitted to or determined by the coordination logic implementer to enable the coordination logic implementer to determine the adjustment of the intravenous drug flow rate.

6. The extracorporeal and drug delivery system of claim 1, wherein the extracorporeal and drug delivery system is configured to display the adjustment of the intravenous drug flow rate at one or more of the renal failure treatment device, the infusion pump, or the coordination logic actuator before the adjustment of the intravenous drug flow rate is implemented.

7. The extracorporeal and drug delivery system of claim 1, wherein the coordination logic actuator is integrated into the renal failure treatment device.

8. The extracorporeal and drug delivery system of claim 1, wherein the infusion pump is a first infusion pump, the intravenous drug is a first intravenous drug, the intravenous drug flow rate is a first intravenous drug flow rate, the extracorporeal and drug delivery system includes a second infusion pump operable to deliver a second intravenous drug to the patient at a second intravenous drug flow rate, and wherein the coordination logic implementer is configured to determine the adjustment of the second intravenous drug flow rate based on the amount of the second intravenous drug removed via the outflow flow rate.

9. The extracorporeal and drug delivery system of claim 1, wherein the extracorporeal and drug delivery system is configured such that the determination of the outflow rate additionally takes into account the regulation of the intravenous drug flow rate.

10. The extracorporeal and drug delivery system of claim 1, wherein the extracorporeal and drug delivery system is configured such that the determination of the outflow rate additionally takes into account the prescription patient fluid loss rate.

11. The extracorporeal and drug delivery system of claim 1, wherein the amount of intravenous drug removed via the outflow rate includes a percentage of the intravenous drug in the outflow rate.

12. The in vitro and drug delivery system of claim 1, wherein the threshold is 0.5%.

13. The extracorporeal and drug delivery system of claim 1, wherein the coordination logic implementer is further configured to take into account blood filter patency or coagulation when determining the adjustment of the intravenous drug flow rate.

14. The extracorporeal and drug delivery system of claim 13, wherein the extracorporeal and drug delivery system is configured such that: when an amount of the intravenous drug is removed via the outflow rate, the adjustment of the intravenous drug flow rate causes the intravenous drug flow rate to meet the prescribed intravenous drug flow rate.

15. The extracorporeal and drug delivery system of claim 1, wherein the renal failure treatment device is a first renal failure treatment device, the infusion pump is a first infusion pump, the extracorporeal and drug delivery system includes a second renal failure treatment device associated with a second infusion pump, and wherein the coordination logic implementer is configured to determine the regulation of a second intravenous drug flow rate to the second infusion pump.

16. An extracorporeal drug delivery system, comprising: A kidney failure treatment machine, capable of operating in conjunction with a blood filter, the blood filter being in fluid communication with arterial and venous tubing, the arterial tubing being used to remove blood from the patient to the blood filter, and the venous tubing being used to return blood from the blood filter to the patient, the kidney failure treatment machine comprising: An effluent pump, positioned and arranged to pump effluent from the blood filter at an effluent flow rate; and At least one of a dialysis fluid pump, a pre-dilution pump, or a post-dilution pump. The dialysis fluid pump is positioned and arranged to pump dialysis fluid to the blood filter at a dialysis fluid flow rate. The pre-dilution pump is positioned and arranged to pump the displacement fluid into the arterial line at a pre-dilution flow rate. The post-dilution pump is positioned and arranged such that the post-dilution flow rate will pump the displacement fluid into the venous line; An infusion pump, operable to deliver intravenous medication to the patient; and A coordination logic implementer, wherein the coordination logic implementer is configured to: The effluent flow rate is determined using a fluid balance equation that correlates the effluent flow rate with the sum between the ultrafiltration removal rate and the total patient fluid inflow rate, which includes at least one of the dialysis fluid flow rate, the pre-dilution flow rate, or the post-dilution flow rate. Use patient weight to estimate blood volume; The concentration adjustment of the intravenous drug is determined based on the estimated blood volume of the patient and the amount of intravenous drug removed using the outflow rate. The adjustment value is determined by comparing the adjustment of the intravenous drug concentration with the determined outflow rate. When the adjustment value is greater than the threshold, the effluent flow rate and the resulting adjustment to the intravenous drug concentration are iteratively determined until the adjustment value is less than the threshold. When the adjustment value is less than the threshold, the outflow rate is at least updated at the outflow pump.

17. The extracorporeal and drug delivery system of claim 16, wherein the extracorporeal and drug delivery system is configured to display, at one or more of the renal failure treatment device, the infusion pump, or the coordination logic actuator, the adjustment of the concentration of the intravenous drug for implementation.

18. The extracorporeal and drug delivery system of claim 16, wherein the extracorporeal and drug delivery system is configured such that: when an amount of the intravenous drug is removed via the outflow rate, the adjustment of the concentration of the intravenous drug results in the intravenous drug dose received by the patient meeting the prescribed intravenous drug dose.

19. The extracorporeal and drug delivery system of claim 16, wherein the infusion pump is a first infusion pump, the intravenous drug is a first intravenous drug, the extracorporeal and drug delivery system includes a second infusion pump operable to deliver a second intravenous drug to the patient, and wherein the coordination logic implementer is configured to determine the adjustment of the concentration of the second intravenous drug based on the amount of the second intravenous drug removed via the outflow rate.

20. An extracorporeal drug delivery system, comprising: A renal failure treatment machine, the renal failure treatment machine being operable in conjunction with a high-flux dialyzer, the high-flux dialyzer being in fluid communication with arterial and venous tubing, the arterial tubing being used to remove blood from the patient into the high-flux dialyzer, and the venous tubing being used to return blood from the high-flux dialyzer to the patient, the renal failure treatment machine comprising: An effluent pump, positioned and arranged to pump effluent from the high-flux dialyzer at an effluent flow rate; and At least one of a dialysis fluid pump, a pre-dilution pump, or a post-dilution pump. The dialysis fluid pump is positioned and arranged to pump dialysis fluid to the high-flux dialyzer at a dialysis fluid flow rate. The pre-dilution pump is positioned and arranged to pump the displacement fluid into the arterial line at a pre-dilution flow rate. The post-dilution pump is positioned and arranged such that the post-dilution flow rate will pump the displacement fluid into the venous line; An infusion pump, operable to deliver intravenous medication to the patient; and A coordination logic implementer, wherein the coordination logic implementer is configured to: The adjustment of the intravenous drug flow rate and / or concentration is determined based on the amount of dilution of the intravenous drug caused by at least one of the dialysis fluid flow rate, the pre-dilution flow rate, or the post-dilution flow rate. The adjustment of the intravenous drug flow rate and / or concentration will be compared with an adjustment threshold. When the adjustment is greater than the adjustment threshold, the adjustment of the intravenous drug flow rate and / or concentration is iteratively determined until the adjustment is less than the adjustment threshold, and When the adjustment is less than the adjustment threshold, the adjustment of at least the flow rate and / or concentration of the intravenous drug is performed at the infusion pump.

21. The extracorporeal and drug delivery system of claim 20, wherein the dilution is based on the relationship between the intravenous drug flow rate, the dialysis fluid flow rate, the pre-dilution flow rate, and the post-dilution flow rate.

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