WO2014008288A1 - Administration d'agent thérapeutique sur la base de valeurs d'analyte de patient stockées - Google Patents

Administration d'agent thérapeutique sur la base de valeurs d'analyte de patient stockées Download PDF

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Publication number
WO2014008288A1
WO2014008288A1 PCT/US2013/049124 US2013049124W WO2014008288A1 WO 2014008288 A1 WO2014008288 A1 WO 2014008288A1 US 2013049124 W US2013049124 W US 2013049124W WO 2014008288 A1 WO2014008288 A1 WO 2014008288A1
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WO
WIPO (PCT)
Prior art keywords
egv
dosage
patient
insulin
processor
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PCT/US2013/049124
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English (en)
Inventor
Yaron Keidar
Michael Higgins
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Edwards Lifesciences Corporation
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Filing date
Publication date
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Publication of WO2014008288A1 publication Critical patent/WO2014008288A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14532—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring glucose, e.g. by tissue impedance measurement
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4836—Diagnosis combined with treatment in closed-loop systems or methods
    • A61B5/4839—Diagnosis combined with treatment in closed-loop systems or methods combined with drug delivery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/74—Details of notification to user or communication with user or patient ; user input means
    • A61B5/742—Details of notification to user or communication with user or patient ; user input means using visual displays
    • A61B5/743—Displaying an image simultaneously with additional graphical information, e.g. symbols, charts, function plots
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
    • A61M5/172—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic
    • A61M5/1723—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body electrical or electronic using feedback of body parameters, e.g. blood-sugar, pressure
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
    • G16H20/10—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
    • G16H20/17—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients delivered via infusion or injection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1486—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using enzyme electrodes, e.g. with immobilised oxidase
    • A61B5/14865—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using enzyme electrodes, e.g. with immobilised oxidase invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2230/00—Measuring parameters of the user
    • A61M2230/005—Parameter used as control input for the apparatus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2230/00—Measuring parameters of the user
    • A61M2230/20—Blood composition characteristics
    • A61M2230/201—Glucose concentration

Definitions

  • Devices for measuring various physiological parameters of a patient have been a standard part of medical care for many years.
  • the vital signs of some patients typically are measured on a substantially continuous basis to enable physicians, nurses, and other healthcare providers to detect sudden changes in a patient's condition.
  • Patient monitors are typically employed to display a variety of physiological patient data to physicians and other healthcare providers. Such patient data facilitates diagnosis of abnormalities or the patient' s current condition.
  • a hospital subject is continuously tested for changes in a blood analyte level, test results are evaluated by a medical professional, and a therapeutic agent is administered based on these test results.
  • test results are evaluated by a medical professional, and a therapeutic agent is administered based on these test results.
  • a therapeutic agent is administered based on these test results.
  • of importance for health care providers with some patients is measurement of the blood glucose levels of the subject, especially in a surgical or intensive care setting. Insulin is frequently delivered in hospitals to medical patients in order to control those patients' blood glucose levels and thereby to avoid hyperglycemia.
  • Embodiments of the invention provide for the use of various algorithms by which a patient analyte such as blood glucose can be measured and a therapeutic agent such as insulin can be delivered to the patent using an automated system.
  • a system can recommend a dosage and a caregiver can readily implement a conventional dosing scheme in response to the recommendation.
  • the system can deliver the therapeutic agent automatically.
  • the system might calculate and deliver a recommended dose, which the caregiver could then accept or modify before instructing or allowing the system to deliver the therapeutic agent.
  • the insulin can be delivered through the use of delivery device such as an electronically controlled insulin pump.
  • a processor-implemented method of facilitating delivery of a therapeutic agent to a patient includes determining and storing a numerical value for a patient analyte and calculating, a dosage of the therapeutic agent based on the stored numerical value. In at least some embodiments, this recommended dosage of the therapeutic again is displayed on a display device. In some embodiments, the processor can then set or cause a delivery device to deliver the therapeutic agent to the patient. In some embodiments, user input triggers the delivery of the agent and in some embodiments the therapeutic agent is delivered automatically in response to the calculating of the dosage of the therapeutic agent by the system.
  • the patient analyte is or includes glucose
  • the numerical value is or includes the estimated glucose value (EGV)
  • the therapeutic agent is or includes insulin.
  • the system as part of calculating the dosage, estimate a confidence in the EGV.
  • the system as part of calculating the dosage, determines a difference between an arterial EGV and a venous EGV.
  • the system stores and maintains historical estimated glucose values and, as part of calculating the dosage, the system determines an EGV rate of change for the patient from the most recent EGV and the historical estimated glucose values.
  • the system determines a difference between a core EGV and a peripheral EGV as part of calculating the dosage, and in some embodiments the system determines a sensor contamination level.
  • Embodiments of the invention can be implemented on a computer system, instruction execution platform, or a workstation with appropriate input and output capabilities.
  • Embodiments of the invention may also be implemented on a patient monitoring and infusion system including a display device, a delivery device and a processor operatively connected to the display device and the delivery device and connected with a memory.
  • the memory may be used to store historical numerical values for the patient analyte as well as non-transitory computer program code which, when executed, causes the processor to carry out all or a portion of the process of an embodiment of the invention.
  • Such a system may also include an input/output (I/O) interface to connect sensors and the like, a network interface, and may include a graphics engine either on-chip with the principal microprocessor or controller, or in a dedicated graphics processor.
  • I/O input/output
  • This hardware along with a sensor interface and any other input and output components form at least some of the means to carry out the various process elements of embodiments of the invention.
  • FIG. 1 is an illustration of a typical operating environment for example embodiments of the present invention.
  • FIG. 2 is an illustration of a typical operating environment for additional example embodiments of the present invention.
  • FIG. 3 is a block diagram of a system according to example embodiments of the invention.
  • FIG. 4 is a flowchart illustrating a process that can be carried out with example embodiments of the invention.
  • FIG. 5 is a flowchart illustrating a process that can be carried out with additional example embodiments of the invention.
  • FIG. 6 is a series of screen shots presented as FIGs. 6A-6N illustrating how a screen display might change over time in example embodiments of the invention.
  • the present invention may be embodied as a method, device, article, system, computer program product, or a combination of the foregoing.
  • Any suitable computer usable or computer readable medium may be utilized for a computer program product including non-transitory computer program code to implement all or part of an embodiment of the invention.
  • the computer usable or computer readable medium may be, for example but not limited to, a tangible electronic, magnetic, optical, electromagnetic, or semiconductor system, apparatus or device. More specific examples (a non-exhaustive list) of the computer readable medium would include the following: a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable
  • the computer usable or computer readable medium may be one or more fixed disk drives or flash drives deployed in instruction execution platforms, such as servers or workstations, forming a "cloud" or network.
  • Computer program code for carrying out operations of the present invention or for assisting in the carrying out of a method according to an example embodiment of the invention may be written in an object oriented, scripted or unscripted programming language such as Java, Perl, Smalltalk, C++ or the like.
  • the computer program code for carrying out operations of the present invention may also be written in conventional procedural programming languages, such as the "C" programming language or similar programming languages.
  • Computer program instructions may be provided to a processor of an instruction execution platform such as a general purpose computer, special purpose computer, server, workstation or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions/acts necessary to carry out an embodiment of the invention.
  • an instruction execution platform such as a general purpose computer, special purpose computer, server, workstation or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions/acts necessary to carry out an embodiment of the invention.
  • a processor used to implement an embodiment of the invention may be a general purpose digital signal processor, such as those commercially available from Texas Instruments, Inc., Analog Devices, Inc., or Freescale Semiconductor, Inc. It may also be a general purpose processor such as those typically provided for either workstation or embedded use by companies such as Advanced Micro Devices, Inc. or Intel Corporation. It could as well be a field programmable gate array (FPGA) as are available from Xilinx, Inc., Altera Corporation, or other vendors. The processor could also be a fully custom gate array or application specific integrated circuit (ASIC). Any combination of such processing elements may also be referred to as a processor, microprocessor, controller, or central processing unit (CPU).
  • CPU central processing unit
  • firmware, software, or microcode can be stored in a non-transitory form on or in a tangible medium that is associated with the processor.
  • a tangible medium may be a memory integrated into the processor, or may be a memory chip that is addressed by the processor to perform various functions.
  • firmware, software or microcode is executable by the processor and when executed, causes the processor to perform its display control and calculation functions.
  • firmware or software could also be stored in or on a tangible medium such as an optical disk or traditional removable or fixed magnetic medium such as a disk drive used to load the firmware or software into a monitoring system according to embodiments of the present invention.
  • analyte as used herein relates to a substance or chemical constituent in a biological sample (e.g., bodily fluids, including, blood, serum, plasma, interstitial fluid, cerebral spinal fluid, lymph fluid, ocular fluid, saliva, oral fluid, urine, excretions, or exudates).
  • a biological sample e.g., bodily fluids, including, blood, serum, plasma, interstitial fluid, cerebral spinal fluid, lymph fluid, ocular fluid, saliva, oral fluid, urine, excretions, or exudates.
  • Analytes can include naturally occurring substances, artificial substances, metabolites, and/or reaction products.
  • the analyte for measurement by the sensor, devices, and methods may include glucose. Any other physiological analyte or metabolite can be substituted or combined with the measurement of glucose.
  • subject as used herein relates to mammals, inclusive of warm-blooded animals (domesticated and non-domesticated animals), and humans.
  • calibration refers to one or more process of determining the relationship between sensor data and a corresponding reference data.
  • a continuous analyte sensor can be initially calibrated, calibration can be updated or recalibrated over time (whether or not if changes in the relationship between the sensor data and reference data occur), for example, due to changes in
  • calibrated values The sensed values produced by a calibrated sensor can be referred to as "calibrated values.”
  • the phrases "operatively connected” and “operably connected” as used herein relate to one or more components linked to one or more other components, such that a function is enabled.
  • the terms can refer to a mechanical connection, an electrical connection, or any connection that allows transmission of signals between the components.
  • one or more electrodes can be used to detect the amount of analyte in a sample and to convert that information into a signal; the signal can then be transmitted to a circuit.
  • the electrode is "operably connected” to the electronic circuitry.
  • the terms include wired and wireless connections, and situations where there is are or may be intervening components.
  • sensor as used herein relates to a device, component, or region of a device capable of detecting and/or quantifying and/or qualifying an analyte in the intravascular and/or subcutaneous space of a subject.
  • sensor system as used herein relates to a device, or combination of devices operating at least in part in a cooperative manner, that is inclusive of the sensor.
  • sensor relates to a device, component, or region of a device capable of detecting and/or quantifying and/or qualifying an analyte in the intravascular and/or subcutaneous space in vivo.
  • FIG. 1 depicts a system that incorporates aspects of some embodiments of the invention.
  • the system 10 is configured to monitor and display blood glucose levels in a hospitalized medical patient.
  • the system is built around a monitor and control unit 12, which comprises programmed electronic circuitry to control the functioning of the system, and a display panel configured to communicate information regarding the system and its functions, as well as the condition of the patient, to a user of the system.
  • the display panel may also serve as a touch screen interface through which a user can enter information and commands for controlling the system's operations.
  • An access point 14 provides access for the system to the patient's body.
  • the access point may provide an entry site for a catheter placed in the vein or another vessel in the vasculature of the patient, access to interstitial fluid located under the patient's skin, or to any other site through which access can be provided to fluids or materials bearing glucose or otherwise providing a reliable indicator of blood glucose levels or corresponding information relevant to the patient.
  • FIG. 1 illustrates a configuration in which an intravascular catheter is disposed inside a vein of the patient, and through which blood can be drawn over an electronic sensor to measure directly glucose levels in the patient' s blood.
  • the sensor in this configuration can be a glucose oxidase sensor configured to produce a current or voltage proportional to the patient's blood glucose level.
  • the system of FIG. 1 further includes a supply of infusion fluid 16 contained inside an infusion bag 32 and in fluid communication with the sensor and the access point 14 through a fluid line 22 between the infusion bag and the access point.
  • a fluid pump 20 controls the flow of fluids back and forth through the fluid line between the access point and the fluid bag. Under control of the pump, blood may be drawn from the patient's vein over the sensor. At other times, infusion fluid may be directed from the bag to flow over and rinse the sensor, or to be infused into the patient.
  • Various other devices can be used in place of the pump, including piezoelectric and impeller-based devices, and any other device that can serve as a fluid controller.
  • the infusion fluid may include normal medical saline solution.
  • the infusion fluid may further include glucose at a known concentration, which may be directed over the sensor from time-to-time in order to calibrate the sensor by reading the resultant current or voltage from the sensor at times when the known-concentration glucose solution in the infusion bag is being directed over and in contact with the sensor.
  • the elements of system 10 are mounted on and supported by a wheeled, movable stand 34, so that the system can be moved as needed with the patient.
  • a signal line 36 provides electrical communication between the sensor near the access point 14 and the monitor and control unit 12. Electrical communication is similarly provided between the monitor and control unit and the fluid pump 20 through a first data and control cable 38.
  • the system 10 of FIG. 1 is an "open-loop" system configured to monitor the patient's blood glucose level, as determined under the control of software and circuitry of the monitor and control unit 12.
  • the visual display and touch-screen control of the monitor and control unit communicate information including the patient' s measured blood glucose level, and other information regarding the system's operations, to a user of the system.
  • the user may input commands to the system through that same visual display and touch-screen control.
  • the system may
  • FIG. 2 depicts an operating environment and a system that incorporates aspects of some embodiments of the invention.
  • analyte information display system 11 is configured to monitor blood glucose levels in a subject.
  • the subject in this case is a hospitalized medical patient.
  • the system is built around a monitor and control unit 13, which comprises programmed processor to control the functioning of the system, and a display device including a visible panel configured to communicate information regarding the system and its functions, as well as the condition of the patient, to a user of the system.
  • the display panel may also serve as a touch screen interface through which a user can enter information and commands for controlling the system's operations.
  • Like reference numbers in the system of FIG. 2 indicate like structures and elements relative to the system of FIG. 1.
  • an access point 14 provides access for the system to the patient's body.
  • the access point may provide an entry site for a catheter placed in the vein or another vessel in the vasculature of the patient, access to interstitial fluid located under the patient's skin, or to any other sight through which access can be provided to fluids or materials bearing glucose or otherwise providing a reliable indicator of blood glucose levels or corresponding information relevant to the subject.
  • FIG. 2 illustrates a configuration in which an intravascular catheter is disposed inside a vein of the patient, and through which blood can be drawn over an electronic sensor to measure directly glucose levels in the patient's blood.
  • the sensor in this configuration again can be a glucose oxidase sensor configured to produce a current or voltage proportional to the patient's blood glucose level.
  • system 11 of FIG. 2 includes a delivery device 18, an insulin supply controller configured to supply insulin in a controlled fashion through an insulin supply line 19 to the fluid line 22 and from there into the body of the patient.
  • system may be used herein to refer to the entire arrangement of electronic elements and connection cables described in either or both of FIG. 1 and FIG. 2.
  • system may also be used to refer only to the monitor and control unit including installed software and/or firmware that together direct and execute the functions described herein.
  • a signal line 36 provides electrical communication between the sensor near the access point 14 and the monitor and control unit 13. Electrical communication is similarly provided between the monitor and control unit and the fluid pump 20 through a first data and control cable 38, and similarly between the monitor and control unit and the delivery device 18 through a second data and control cable 39.
  • the system 11 of Fig. 2 is thus a "closed- loop" system in which the delivery of insulin to the patient is controlled more or less automatically by the system itself, with perhaps little or no intervention by the caregiver user of the system beyond the initial setup, and with perhaps periodic checks to make sure that the system continues to function properly.
  • Intermediate or hybrid systems which combine aspects of open-loop and closed-loop systems, may find use as well.
  • Such systems may, for example, measure the patient's blood glucose level, calculate a recommended or default insulin dosing level or scheme, display that recommendation to the user, and then await the user's input before adjusting or implementing the actual amount and timing of insulin delivery to the patient by addressing the insulin supply controller.
  • Any of these systems described thus far may also be expected to include various alerts, alarms, and similar messages for conveying relevant information clearly to the systems' users.
  • FIG. 3 is an enlarged view, schematically illustrating detail of the monitor and control unit 13 of FIG. 2.
  • the insulin supply portions (other than the controller) of FIG. 2 are omitted.
  • the system includes I/O interface 302, which may in turn include an appropriate connector, and circuitry to monitor signals from the sensor system. This circuitry may include analog-to-digital converters, encoders, decoders, and the like.
  • I/O interface 302 is coupled to a central processing unit (CPU) 304, which controls the operation of the entire system.
  • CPU 304 is further operatively connected to memory 306.
  • Memory 306 stores all of the information needed for the system to operate. Such information may be stored in a temporary fashion, or may be stored more permanently. This memory may include a single, or multiple types of memory. For example, a portion of the memory connected with CPU 304 may be "flash" memory, which stores information semipermanently for use by the system. In either event memory 306 of FIG. 2 in this example embodiment includes computer program code 308 which, when executed by CPU 304, causes the system to carry out the various processes to graphically display information according to example embodiments of the invention. Memory 306 also stores data 310, which in example embodiments includes historical numerical values for the analyte being measured, for example, blood glucose. [0035] Still referring to FIG.
  • monitoring and control unit 13 may also include a network interface 313.
  • This network interface can allow the system to be connected to a wired or wireless network to allow monitoring on a remote display (not shown).
  • the remote display could duplicate, or be used in place of the local display panel.
  • Network interface 313 could also be simply used to trigger an alarm at a nurse's station or on a mobile device.
  • a local display device, 317 is connected with CPU 304 via a graphics engine 324.
  • the local display device may be an LCD panel, plasma panel, or any other type of display component and accompanying circuitry to interface the display device to graphics engine 324.
  • Graphics engine 324 may be on its own chip, or in some embodiments it may be on the same chip as CPU 304.
  • display device 317 may include user input functionality, for example an optical or capacitive touchscreen over the display screen.
  • monitoring control unit 13 may include additional circuitry to process such input.
  • such circuitry may be included in the display device itself, the graphics engine, or the CPU 304.
  • the system shown in FIG. 3 can deliver insulin to a patient based on blood glucose levels measured by the system.
  • the system can programmatically implement a conventional dosing scheme (closed-loop), or programmatically make a recommendation on which a caregiver can act independently (open-loop).
  • a hybrid or "semi-closed loop" system might calculate and deliver a recommended insulin dose, which the caregiver could then accept or modify before the system to delivers the insulin appropriately.
  • the insulin can be delivered through the use of an electronically controlled insulin pump as shown in FIG. 2 as the delivery device. Other delivery devices can be used.
  • blood glucose may be measured once every hour for patients receiving IV insulin, and perhaps once every four hours otherwise.
  • a system of the type described above may draw a small quantity of blood automatically from the patient and measure an estimated glucose value (EGV) as frequently as once every five minutes - 12 times every hour.
  • EUV estimated glucose value
  • Such a system moreover, includes automatic data storage and processing capable of storing historical estimated blood glucose values, and thereafter performing a vast range of calculations, processing, recommendations, and controls based on that historical data, examples of some of which are disclosed herein.
  • Such blood glucose level data may be processed in combination with stored data that reflects insulin delivery, particularly but not necessarily exclusively in closed-loop systems where the delivery of the insulin is directly controlled by the system itself.
  • FIG. 4 is a flowchart illustrating the details of a process for measuring a patient analyte and determining a dosing and/or infusion rate for a therapeutic agent as executed by a system like that shown in FIG. 2 and FIG. 3.
  • FIG. 3 illustrates process 400 as a series of process or sub-process blocks.
  • Block 402 may correspond to the initiation of monitoring of a patient by s witching on or resetting the monitor and control unit.
  • the system obtains readings from the sensor, calculates, and stores numerical values for the patient analyte, for example blood glucose, over time.
  • Block 406 includes the determining and storing of the most recent numerical value based on the most recent sensor reading.
  • the recent numerical value and historical numerical values for the patient analyte are graphically and persistently displayed.
  • the therapeutic dosage of the therapeutic agent is calculated based on at least the latest numerical value for the patient analyte, which is stored in memory.
  • a user may adjust the dosage rate of the therapeutic agent so that the dosage administered by the delivery device is set in response to user input. Otherwise, or if there is no input, the dosage can be set automatically once this system calculates the dosage. If the dosage rate displayed needs to be updated, it is updated at block 418 and the process is continuously repeated.
  • FIG. 5 is a flowchart illustrating sub-process 410 from FIG. 4 in further detail.
  • FIG. 5 shows a number of optional enhancements to the calculation of dosage by the monitor and control unit of the system of FIGs. 2 and 3. These enhancements may all be used together as shown, none may be used, or a subset of these may be used by a system according to example embodiments of the invention.
  • blood glucose is the analyte being monitored by the system
  • an EGV is stored to represent a measured blood glucose value
  • insulin is the therapeutic agent being administered.
  • the sub-process begins.
  • the CPU obtains current and/or historical EGVs as needed from memory.
  • the system estimates a statistical confidence level in the value for the current or possibly some other EGV. For example change in value or statistical average value techniques can be used so that statistical outlying values can be discounted in the calculation of the insulin dosage.
  • Insulin dosing has historically been calculated based on measurements taken at one-hour intervals, any single one of which might be substantially in error. With some embodiments of the invention, measurements are taken 12 times per hour. Confidence can be improved substantially simply by averaging the previous 12 measurements and calculating the new dose based on that calculated average. The insulin dosing algorithm could also be refined by incorporating estimated levels of confidence in the measured data into the determinations of how much insulin to deliver. Outliers can be given relatively little weight in dosing calculations, adjustments could be made in part based on the variance or standard deviations of multiple data points in a data set consisting of a series of measurements, and so forth.
  • a rate of change of EGV is determined and compared to an estimated target value or values 510 if glucose is being measured at more than one place.
  • Systems like those described above take measurements more frequently than is currently the case, and because those systems include means for storing historical data reflecting past measured blood glucose levels (and insulin deliveries), they offer much expanded opportunities for programming.
  • a system according to example embodiments takes into account a difference between a current, measured blood glucose level and a desired, target blood glucose level, in combination with a calculated rate of change in the measured blood glucose level. If blood glucose is nearing an acceptable upper bound, for example, then insulin delivery can be scaled back to avoid overshooting the target and putting the patient's blood glucose below an acceptable hypoglycemic threshold.
  • insulin delivery can be stepped up in an attempt to prompt a faster rate of change.
  • Such determinations can also be used to deliver insulin of different types, or according to different modes of delivery.
  • Measured and calculated rates of change in a patient's blood glucose level can provide bases, for example, for delivering insulin of "fast-acting" or “slow acting" types, alone or in various mixtures - or intravenously (rapid- acting) or subcutaneously (slower-acting), or in appropriate combinations.
  • the availability of near real-time, near continuous blood glucose measurement data allows one to deliver therapies reflective of the changing conditions and needs in the bodies of a variety of individual patients.
  • a difference between an arterial EGV and a venous EGV is calculated so that it can be used to improve calculation of the insulin dosage.
  • the processor in the system determines the difference between a core EGV and a peripheral EGV in the patient's body. Blood glucose is frequently measured in blood in an artery of the patient. Such arterial blood glucose measurements are thought to be useful because they provide a measurement reflective of glucose supply to the body's organs. Arterial glucose concentrations, though, are often higher than those sampled in the same patient at a venous location. This difference may be particularly pronounced, moreover, at times shortly after a patient eats or after nutrition is supplied otherwise to the patient.
  • insulin dosing protocols or algorithms are designed to take such conditions into account by taking into account the difference between arterial and venous EG Vs.
  • dosing protocols based solely on arterial or solely on venous blood glucose measurements can be adjusted to provide insulin in higher or lower quantities, or at higher or lower rates, based on the location of the measurement and the known differences in blood glucose quantities typically seen at alternate sites.
  • Optimal or improved therapies might be devised, moreover, that would utilize arterial and venous measurements in conjunction with one another, including through the use of multiple sensors positioned to measure blood glucose at both an arterial and a venous location.
  • the differences between core and peripheral EGVs can be handled in a similar fashion according to some embodiments of the invention.
  • the human body has the capability to pull blood selectively to its core with a concomitant reduction of blood flow in and supply to the body's periphery. This redirection of blood flow may occur, moreover, particularly when the body is under stress, and thus may be particularly significant in medical patients in hospital settings.
  • blood glucose concentrations measured at peripheral sites may be low in comparison with blood glucose levels in the body's core, with the latter being possibly more relevant to the delivery of optimal therapies for overall glucose control. This difference might delay or interfere with the achievement of optimal or desired blood glucose levels at the body core, when therapies are devised or adjusted based on measurements taken from sites at peripheral vessels.
  • Differences in EGVs based on measurements at varied locations of the body or measured in arterial blood and venous blood can also be based on or include
  • arterial blood can include subcutaneous blood and/or fluids.
  • EGVs taken from interstitial fluids by interstitial fluid sampling can be used with arterial and venous sampling to calculate doses of insulin or other therapeutic agents.
  • the system can determine whether sensor contamination is likely, and also determine the level of sensor contamination in order to use this level in dosing calculations.
  • the process for the current dosing calculation ends, meaning processing returns to FIG. 4.
  • This contamination of the blood samples with the nutritional glucose can lead to artificially high measurements of blood glucose concentration, which can in turn lead to the physician' s believing falsely that the patient is in a persistent state of hyperglycemia.
  • such contamination can be detected or its possibility can otherwise be programmatically accounted for.
  • an adjustment can be made to the dosing, or an alert can be provided to the caregiver.
  • Such measurements or estimates may lead in turn to improved insulin dosing algorithms and to the improvement in other treatment decisions, since insulin delivery protocols might be improved if insulin were to be delivered based in part on an individual patient's ability to use that insulin effectively.
  • This patient's ability can be determined, for example, by measuring blood glucose at different sites within the patient's body, and then determining insulin dosing based at least in part on the differences in blood glucose levels measured at those different sites.
  • a substantial difference in those two levels - blood glucose in the vessel upstream of the brain being higher than blood glucose downstream of the brain - would then indicate that the patient' s brain was consuming that glucose effectively, and thus making good use of the insulin being delivered to the patient.
  • a small difference, on the other hand, would indicate that the patient's brain was not using glucose effectively, thus that the current delivery of insulin was not having a good effect, and therefore that an alternative rate insulin delivery or another mode of treatment would be more appropriate.
  • the goal of such a scheme would be to deliver insulin to increase the patient' s consumption of glucose as long as the patient is hypoglycemic. If it is determined on the other hand, that increasing the level of insulin does not increase glucose consumption, then the delivery of insulin should not be increased further, because the patient would experience no benefit from such an increase. Insulin would thus be delivered only to the extent that it would be determined currently to be having a substantial positive effect in that particular patient. Similar measurements could be made, for example, both in the patient's blood and the patient's urine, with dosing algorithms or other treatment decisions based appropriately on differences between the two measured levels, rates of change of those levels or their differences, or similar values measured by the system.
  • FIG. 6 presents multiple views, FIGs. 6A-6N showing a screen of the display device of the system previously described, and how the display screen may change over time.
  • the screen shows chart 600, a readout for EGV 602, a readout and a "touch" adjustment panel 604 for insulin levels, and a touch menu button 606.
  • estimated glucose values are shown graphically as points 608.
  • Historical and the most current insulin levels are shown with solid line 610, and recommended insulin levels are shown with dotted line 612.
  • time is shown on horizontal axis 620 and glucose level is shown on vertical axis 640.
  • the display also shows glucose limit lines defining the acceptable range of values for this patent, a high limit line 650 and a low limit line 660.
  • the insulin dosage is set to 5.0 units per hour and the EGV for the patient is gradually dropping.
  • FIG. 6E the system has increased the recommended insulin dose to 5.5 units per hour.
  • a caregiver must confirm this new recommended dose for the processor to cause the delivery device to change the infusion rate.
  • the caregiver confirms the dose in FIG. 6F by pressing a soft key with a finger 680.
  • a pointing device such as a mouse could also be used to position and activate a "virtual" finger or otherwise provide input to the system.
  • the dose has increased to the recommended level of 5.5 units per hour.
  • FIGs. 61 and 6J the recommended insulin dose has changed to 4.5 and then 4.0 units per hour, respectively.
  • the recommended dose has now been calculated at 3.5 units per hour, and a caregiver has confirmed this dose and it is being administered in FIG. 6L and 6M.
  • the recommended does has now been calculated to be 4.0 units per hour.

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Abstract

La présente invention concerne un procédé et un système destinés à l'administration d'agent thérapeutique sur la base de valeurs d'analyte de patient stockées. Ledit système peut recommander un dosage, et un fournisseur de soins peut facilement mettre en œuvre un schéma posologique classique en réponse à cette recommandation. En variante, ledit système peut fournir l'agent thérapeutique automatiquement, avec ou sans entrée utilisateur supplémentaire. L'analyte de patient peut être du glucose dans le sang représenté par une valeur de glucose estimée, et l'agent thérapeutique peut être de l'insuline. Ledit système peut éventuellement comprendre diverses améliorations dans le calcul d'un dosage, par exemple en utilisant des niveaux de confiance, une différence entre une valeur estimée de glucose dans les artères et une valeur estimée de glucose dans les veines, un taux de changement d'une valeur estimée de glucose, une différence entre une valeur centrale estimée de glucose et une valeur estimée périphérique de glucose, et une détermination du niveau de contamination de capteur.
PCT/US2013/049124 2012-07-03 2013-07-02 Administration d'agent thérapeutique sur la base de valeurs d'analyte de patient stockées WO2014008288A1 (fr)

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US201261667856P 2012-07-03 2012-07-03
US201261667571P 2012-07-03 2012-07-03
US61/667,856 2012-07-03
US61/667,571 2012-07-03
US201361772959P 2013-03-05 2013-03-05
US61/772,959 2013-03-05

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CN107530032A (zh) * 2015-04-29 2018-01-02 比格福特生物医学有限公司 操作输液泵系统

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US20080306435A1 (en) * 2007-06-08 2008-12-11 Dexcom, Inc. Integrated medicament delivery device for use with continuous analyte sensor
US20090105658A1 (en) * 2005-12-28 2009-04-23 Abbott Diabetes Care, Inc. Infusion sets for the delivery of a therapeutic substance to a patient
US20100016700A1 (en) * 2008-07-18 2010-01-21 Lifescan, Inc. Analyte measurement and management device and associated methods

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Publication number Priority date Publication date Assignee Title
US20020115958A1 (en) * 1999-10-22 2002-08-22 Nyhart Eldon H. Manufacturing methods for an apparatus for the controllable modification of compound concentration in a tube
US20030156143A1 (en) * 1999-12-07 2003-08-21 University Of Utah Anesthesia drug monitor
US20090105658A1 (en) * 2005-12-28 2009-04-23 Abbott Diabetes Care, Inc. Infusion sets for the delivery of a therapeutic substance to a patient
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US20100016700A1 (en) * 2008-07-18 2010-01-21 Lifescan, Inc. Analyte measurement and management device and associated methods

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CN107530032A (zh) * 2015-04-29 2018-01-02 比格福特生物医学有限公司 操作输液泵系统

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