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US20060217771A1 - Potassium monitoring - Google Patents

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Publication number
US20060217771A1
US20060217771A1 US11349058 US34905806A US2006217771A1 US 20060217771 A1 US20060217771 A1 US 20060217771A1 US 11349058 US11349058 US 11349058 US 34905806 A US34905806 A US 34905806A US 2006217771 A1 US2006217771 A1 US 2006217771A1
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response
muscle
patient
potassium
tissue
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Abandoned
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US11349058
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Orhan Soykan
Timothy Robinson
James Carney
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Medtronic Inc
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Medtronic Inc
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14546Measuring 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 analytes not otherwise provided for, e.g. ions, cytochromes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/103Detecting, measuring or recording devices for testing the shape, pattern, colour, size or movement of the body or parts thereof, for diagnostic purposes
    • A61B5/11Measuring movement of the entire body or parts thereof, e.g. head or hand tremor, mobility of a limb
    • A61B5/1107Measuring contraction of parts of the body, e.g. organ, muscle
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14507Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue specially adapted for measuring characteristics of body fluids other than blood
    • A61B5/1451Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue specially adapted for measuring characteristics of body fluids other than blood for interstitial fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14542Measuring 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 blood gases
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/145Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1468Measuring 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 chemical or electrochemical methods, e.g. by polarographic means
    • A61B5/1473Measuring 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 chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/45For evaluating or diagnosing the musculoskeletal system or teeth
    • A61B5/4519Muscles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/72Signal processing specially adapted for physiological signals or for diagnostic purposes
    • A61B5/7271Specific aspects of physiological measurement analysis
    • A61B5/7278Artificial waveform generation or derivation, e.g. synthesising signals from measured signals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128Control systems
    • A61N1/36135Control systems using physiological parameters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/362Heart stimulators
    • A61N1/365Heart stimulators controlled by a physiological parameter, e.g. heart potential
    • A61N1/36514Heart stimulators controlled by a physiological parameter, e.g. heart potential controlled by a physiological quantity other than heart potential, e.g. blood pressure
    • A61N1/36557Heart stimulators controlled by a physiological parameter, e.g. heart potential controlled by a physiological quantity other than heart potential, e.g. blood pressure controlled by chemical substances in blood
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/02Details of sensors specially adapted for in-vivo measurements
    • A61B2562/0219Inertial sensors, e.g. accelerometers, gyroscopes, tilt switches
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/05Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radiowaves
    • A61B5/053Measuring electrical impedance or conductance of a portion of the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Detecting, measuring or recording for diagnostic purposes; Identification of persons
    • A61B5/68Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6846Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive
    • A61B5/6847Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be brought in contact with an internal body part, i.e. invasive mounted on an invasive device
    • A61B5/686Permanently implanted devices, e.g. pacemakers, other stimulators, biochips
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142Pressure infusion, e.g. using pumps
    • A61M5/14244Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body
    • A61M5/14276Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body specially adapted for implantation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES 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
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168Means 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
    • A61M5/172Means 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
    • A61M5/1723Means 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128Control systems
    • A61N1/36146Control systems specified by the stimulation parameters
    • A61N1/36167Timing, e.g. stimulation onset

Abstract

In general, the invention is directed to methods and devices for determining a potassium ion concentration in the extracellular fluid of a patient. A system includes an electrode deployed in or near a tissue, such as a skeletal muscle, of the patient. A pulse generator supplies one or more stimulations to the tissue, and a sensor, such as an accelerometer, detects the response of the tissue to the stimulations. A processor determines a concentration of potassium ions in the extracellular fluid as a function of the response.

Description

    POTASSIUM MONITORING
  • [0001]
    This application claims the benefit of U.S. provisional application Ser. No. 60/650,497, filed Feb. 7, 2005, the entire content of which is incorporated herein by reference.
  • [0002]
    This application is related to U.S. patent application Ser. No. ______, attorney docket no. 1023-442US02/ P20657.01, filed Feb. 7, 2006, entitled “Ion Imbalance Detector,” the entire content of which is incorporated herein by reference.
  • TECHNICAL FIELD
  • [0003]
    The invention relates to systems and methods associated with monitoring physiological conditions, and in particular, to systems and methods associated with monitoring concentrations of ions in extracellular fluid.
  • BACKGROUND
  • [0004]
    The concentration of potassium ions, denoted [K+], in the extracellular fluid (ECF) of a patient is of clinical significance. Abnormal [K+] levels in the ECF can be a product of the pharmacological management of patients with heart failure. In general, [K+] in the intracellular fluid (ICF) of cardiac muscle or other tissue is high in comparison to [K+] in the ECF. When [K+] in the ECF becomes elevated, a reduced concentration gradient between ICF and ECF results. A reduction of the resting membrane potential is associated with the reduction in concentration gradient, often resulting in ectopic foci and arrhythmia.
  • [0005]
    A reduction in concentration gradient further affects the magnitude and duration of the action potential. The change in membrane potential caused by an action potential, which is about 120 mV in healthy cardiac muscle, can be reduced substantially. In addition, the duration of the action potential, which is about 250 milliseconds in healthy cardiac tissue, can be diminished.
  • [0006]
    [K+] can have additional clinical significance as well, and for some patients [K+] can be an important factor worth monitoring. For example, trauma patients, burn patients, diabetic patients with ketoacidosis, renal patients on dialysis, patients experiencing pulmonary edema, and cardiac arrest patients may have electrolyte fluctuations, particularly fluctuations of potassium ion concentrations. In addition, potassium ion retention accompanies the onset of some medical conditions, such as Addison's disease.
  • SUMMARY
  • [0007]
    In general, the invention is directed to methods and devices for determining a concentration of potassium ion in extracellular fluid of a patient. A system includes electrodes, and at least one of the electrodes is deployed in or near a tissue of the patient. The tissue may be a skeletal muscle, such as the pectoral muscle. A pulse generator supplies one or more stimulations to the tissue, and a sensor detects the response of the tissue to the stimulations. A processor determines a concentration of potassium ion as a function of the response.
  • [0008]
    As used herein, determining a concentration of potassium ions in extracellular fluid of the patient includes, but is not limited to, determining an absolute concentration, such as measuring or estimating a molarity. Determining a concentration of potassium ions can also include determining a relative concentration, such as a concentration with respect to a baseline. Furthermore, determining a concentration of potassium ions can include determining a change in concentration over time.
  • [0009]
    The invention can be implemented as a stand-alone potassium monitoring system. The invention can also be implemented in conjunction with an implantable medical device such as a cardiac pacemaker, cardioverter-defibrillator, patient monitor, drug pump or neurostimulator. The invention can be implemented as an external system or a system having external and implantable elements.
  • [0010]
    In one embodiment, the invention presents a system comprising a pulse generator configured to generate an electrical stimulation, an electrode configured to deliver the electrical stimulation to a tissue, such as a skeletal muscle, in a patient. The system further includes a sensor configured to detect at least one response of the tissue to the electrical stimulation, and a processor configured to determine a concentration of potassium ions in extracellular fluid of the patient as a function of the response. The processor can be configured to determine a concentration of potassium ions as a function of a sustained contraction of the tissue, for example, or a rippled contraction of the tissue, a rate of relaxation of the tissue, a pulse width of the response, the occurrence of summation in the response or the amplitude of the response. The system can be external, partially implantable or fully implantable.
  • [0011]
    In another embodiment, the invention is directed to a method that includes delivering an electrical stimulation to a tissue in a patient, detecting a response of the tissue to the electrical stimulation, and determining a concentration of potassium ions in extracellular fluid of the patient as a function of the response. The method can further include delivering a therapy to the patient as a function of the response.
  • [0012]
    In a further embodiment, the invention is directed to a method comprising delivering an electrical stimulation to a tissue in a patient, detecting at least one response of the tissue to the electrical stimulations and storing a relationship between a concentration of potassium ions in extracellular fluid of the patient and the response. This method is useful for calibrating a potassium monitoring system according to the invention.
  • [0013]
    Additional embodiments of the invention include computer-readable media comprising instructions that cause a programmable processor to carry out any of the methods of the invention.
  • [0014]
    The invention may result in one or more advantages. Compared to conventional techniques for detecting [K+], the invention offers convenience and supports long-term implantation. Tests that rely upon laboratory analysis of blood samples require that blood be drawn from the patient, and may not be available outside a hospital setting. Electrochemistry-based potassium sensors are implantable, but have not proven to be stable over long periods, and their performance degrades over time. Optical sensors for potassium typically call for periodic replacement of components, such as a disposable strip used for making measurements. By contrast, the invention can be implanted, can conveniently monitor potassium ion concentrations, and can remain reliable for extended periods of time.
  • [0015]
    In addition, the invention can be implemented within an IMD that delivers therapy, such as a pacemaker or drug pump, or supports other monitoring functions. Many patients experiencing heart failure, for example, can benefit from the implantation of an IMD that can monitor [K+] and apply one or more pacing therapies. The invention can offer the further advantage of implementation with one or more external elements, which can be deployed without surgery.
  • [0016]
    The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims.
  • BRIEF DESCRIPTION OF DRAWINGS
  • [0017]
    FIG. 1A is a schematic illustration of a human heart in conjunction with an exemplary implantable medical device and an exemplary electrode element according to an embodiment of the invention.
  • [0018]
    FIGS. 1B through 1E are schematic illustrations of an implantable medical device with alternate embodiments of electrode elements.
  • [0019]
    FIG. 1F is a schematic illustration of an exemplary external medical device and an exemplary electrode element according to an embodiment of the invention.
  • [0020]
    FIG. 2 is a schematic illustration of an implantation of an exemplary implantable medical device and an exemplary electrode element proximate to skeletal muscle.
  • [0021]
    FIG. 3 is a block diagram showing a system that can deliver one or more electrical stimuli to a tissue and determine a concentration of potassium ion in extracellular fluid as a function of the response to the stimuli.
  • [0022]
    FIGS. 4A and 4B are timing diagrams illustrating stimuli and the responses of skeletal muscle thereto, according to various embodiments of the invention.
  • [0023]
    FIG. 5 is a flow diagram illustrating a technique for calibrating a medical device to determine a concentration of potassium ion in extracellular fluid.
  • [0024]
    FIG. 6 is a flow diagram illustrating a technique for monitoring potassium ion concentration in extracellular fluid.
  • [0025]
    FIG. 7 is a schematic diagram of an experimental setup to test muscle contractions due to electrical stimuli.
  • [0026]
    FIG. 8 is a graph of exemplary data showing muscle force in various solutions of potassium versus time.
  • [0027]
    FIG. 9 is a graph of exemplary data showing contraction amplitude versus potassium concentration.
  • DETAILED DESCRIPTION
  • [0028]
    FIG. 1A is a schematic illustration of an exemplary embodiment of a system 10 that includes an implantable medical device (IMD) 12 in relationship to a heart 14 of a patient. IMD 12 is configured to be implanted in a human or animal body. As depicted in FIG. 1A, IMD 12 comprises a multi-chamber pacemaker having cardioversion and defibrillation capabilities. Although it can be advantageous to implement the invention with a multi-chamber pacemaker, the invention is not limited to the particular IMD shown. Furthermore, as discussed below, the invention need not be implemented as an implantable medical device. The invention can be implemented as a stand-alone potassium monitoring system, or in conjunction with a different type of implantable or external device such as a patient monitor, drug pump, muscle stimulator or neurostimulator.
  • [0029]
    A right ventricular lead 16 includes an elongated insulative lead body carrying one or more concentric coiled conductors separated from one another by tubular insulative sheaths. The distal end of right ventricular lead 16 is deployed in the right ventricle 18 of heart 14. Located adjacent the distal end of the lead body are one or more pace/sense electrodes 20, which are configured to deliver cardiac pacing and are further configured to sense depolarizations of right ventricle 18. A fixation mechanism 22 such as tines or a screw-in element, anchors the distal end in right ventricle 18. The distal end also includes an elongated coil electrode 24 configured to apply cardioversion or defibrillation therapy. Each of the electrodes is coupled to one of the coiled conductors within the lead body. At the proximal end of right ventricular lead 16 is a connector 26, which couples the coiled conductors in the lead body to IMD 12 via a connector module 28.
  • [0030]
    A right atrial lead 30 includes an elongated insulative lead body carrying one or more concentric coiled conductors separated from one another by tubular insulative sheaths corresponding to the structure of right ventricular lead 16. Located adjacent the J-shaped distal end of right atrial lead 30 are one or more pace/sense electrodes 32, which are configured to sense depolarizations of and deliver pacing stimulations to right atrium 34. As shown in FIG. 1A, an elongated coil electrode 36 is provided proximate to the distal end of right atrial lead 30, and is located in right atrium 34 and the superior vena cava 38. At the proximal end of the lead is a connector 40, which couples the coiled conductors in right atrial lead 30 to IMD 12 via connector module 28.
  • [0031]
    A coronary sinus lead 42 includes an elongated insulative lead body deployed in the great cardiac vein 44. The lead body carries one or more coiled conductors coupled to one or more pace/sense electrodes 46. Electrodes 46 are configured to deliver ventricular pacing to left ventricle 48 and are further configured to sense depolarizations of left ventricle 48. Additional pace/sense electrodes (not shown) may be deployed on coronary sinus lead 42 that are configured to pace and sense depolarizations of the left atrium 50. At the proximal end of coronary sinus lead 42 is connector 52, which couples the coiled conductors in coronary sinus lead 42 to connector module 28.
  • [0032]
    An exemplary electrode element 54A is coupled to the distal end of a lead 56. Lead 56 carries one or more conductors separated from one another by insulative sheaths. A connector 58 at the proximal end of the lead couples the conductors in lead 56 to IMD 12 via connector module 28.
  • [0033]
    In addition to connector module 28, IMD 12 comprises a housing 60 formed from one or more materials, including conductive materials such as stainless steel or titanium. Housing 60 may include insulation, such as a coating of parylene or silicone rubber, and in some variations, all or a portion of housing 60 may be left uninsulated. The uninsulated portion of housing 60 can serve as a subcutaneous electrode and a return current path for electrical stimulations applied via other electrodes.
  • [0034]
    In the embodiment shown in FIG. 1A, electrode element 54A includes two electrodes 62A and 62B. At least one of electrodes 62A and 62B is deployed in or near test tissue and delivers stimulation to the tissue, while the other provides a return current path. In the embodiment shown in FIG. 1A, electrodes 62A and 62B are button electrodes, but the invention encompasses other electrode types as well. The invention will be described in terms of stimulation of muscle cells, but the invention can encompass other test tissues as well. The test tissue can comprise a collection of autologous or non-autologous cells that are sensitive to [K+]. For example, the test tissue may be one of cardiac muscle, skeletal muscle, smooth muscle, nerve tissue, skin, or the like.
  • [0035]
    As described below, IMD 12 includes one or more implantable pulse generators (IPGs) (not shown in FIG. 1A) configured to generate stimuli to be delivered to one or more muscles of the patient via electrode element 54A. As described below, skeletal muscle is generally the most desirable tissue, because it is usually readily accessible and response of skeletal muscle can be readily related to [K+]. Furthermore, it may be desirable to stimulate skeletal muscles that do not get much use and are less prone to fatigue. The invention encompasses embodiments in which stimulation and response of other kinds of tissue can be related to [K+], but muscle tissue, such as skeletal muscle tissue is the exemplary tissue described herein.
  • [0036]
    Housing 60 may include one or more sensors (not shown in FIG. 1A) configured to detect at least one response of the stimulated muscle to the electrical stimulation or stimulations. In some embodiments, the sensor may be deployed elsewhere, such as on the distal end of lead 56. In general, the sensor detects the electromechanical response of the stimulated muscle. Examples of sensors will be described below.
  • [0037]
    In general, the distance between electrodes 62A and 62B can be a function of the pulse magnitude generated by an IPG, a target stimulation magnitude, and the kind of electrodes employed. For example, to deliver a stimulus with a field strength of 10 volts per centimeter (V/cm) using IMD 12, which is capable of producing 2 V pulses, electrodes 62A and 62B can be separated by two millimeters. The invention is not limited to any particular physical dimensions or stimulation magnitudes, however.
  • [0038]
    IMD 12 also includes one or more IPGs configured to generate pacing stimuli to be delivered to one or more chambers of heart 14. The IPGs that stimulate heart 14 may be, but need not be, the same IPG that generates muscle stimulations. IMD 12 further includes one or more processors (not shown in FIG. 1A) that regulate the delivery of pacing pulses. The processor in IMD 12 is configured to apply a variety of pacing modes, including therapies that may be beneficial for patients suffering from heart failure, such as cardiac potentiation therapy (CPT) or cardiac resynchronization therapy (CRT). CPT generally involves electrically stimulating one or more heart chambers to induce post-extrasystolic potentiation, and CRT involves delivering pacing pulses to one or both ventricles to synchronize ventricular contractions.
  • [0039]
    FIG. 1B is a schematic illustration of IMD 12, with an alternate embodiment of an electrode element 54B. In the embodiment depicted in FIG. 1B, electrode element 54B, like electrode element 54A, is coupled to the distal end of lead 56, which carries one or more conductors separated from one another by insulative sheaths and is coupled to connector module 28 via connector 58. Electrode element 54B includes two electrodes 62C and 62D, which deliver electrical stimulation to muscle, or other tissue sensitive to [K+], and provide a return current path.
  • [0040]
    Electrode element 54B resembles a pace/sense electrode, such as pace/sense electrode 32 in FIG. 1A, in that electrode element 54B includes a tip electrode 62C and a ring electrode 62D. Dimensions of electrode element 54B may be comparable to those of conventional pace/sense electrodes. Although not shown in FIG. 1B, the distal end of lead 56 may include one or more fixation mechanisms configured to prevent or reduce lead migration.
  • [0041]
    FIG. 1C is a schematic illustration of IMD 12, with another alternate embodiment of an electrode element 54C. In the embodiment depicted in FIG. 1C, electrode element 54C includes an electrode 62E deployed at the distal end of lead 56, and another electrode 62F in the body of housing 60. Housing electrode 62F can be deployed at any site in housing 60. Lead electrode 62E is configured to generate an intense electrical field at the site of stimulation. A point at the distal end of lead electrode 62E causes the electric field to be more intense at the point, which can improve the likelihood of stimulation of muscle tissue or other tissue sensitive to [K+]. The distal end of lead 56 may include one or more fixation mechanisms configured to prevent or reduce lead migration.
  • [0042]
    FIG.1D is a schematic illustration of IMD 12, with an additional alternate embodiment of an electrode element 54D. Electrode element 54D includes an electrode 62G deployed on a fixed mount 64. In the embodiment depicted in FIG. 1D, fixed mount 64 is coupled to connector module 28, but fixed mount 64 may also be deployed elsewhere on IMD 12. Exemplary electrode 62G, like electrode 62E in FIG. 1C, is configured to generate an intense electrical field at the site of stimulation. Another electrode 62H is deployed in the body of housing 60.
  • [0043]
    As discussed below, some implantations if IMD 12 may place IMD 12 in direct contact with muscle such as skeletal muscle. The embodiment depicted in FIG. 1D may be desirable in such implantations, as electrodes 62G and 62H can be deployed without leads.
  • [0044]
    FIG. 1E is a schematic illustration of IMD 12, with a further alternate embodiment of an electrode element 54E. Electrode element 54E includes two electrodes 621 and 62J deployed in housing 60. In a variation of this embodiment, housing 60 may include an array of three or more electrodes. As with the embodiment shown in FIG. 1D, the embodiment shown in FIG. 1E may be desirable in implantations in which IMD 12 is implanted in direct contact with muscle or other [K+] sensitive tissue.
  • [0045]
    FIG. 1F is a schematic illustration of a further embodiment of the invention, in which one or more elements are external and are not configured to be implantable in a human or animal body. In the embodiment depicted in FIG. 1F, external medical device 65 includes one or more IPGs (not shown in FIG. 1F) configured to generate stimuli to be delivered to one or more muscles of the patient via electrode element 66. Examples of medical devices that can be configured to generate stimuli to be delivered to muscles via an electrode element are a Transcutaneous Electrical Nerve Stimulation (TENS) unit, an Electronic Muscle Stimulation (EMS) unit and an electro-acupuncture unit. The invention is not limited to such medical devices, however. Medical device 65 or electrode element 66 may also include one or more sensors (not shown in FIG. 1F) configured to detect an electromechanical response of the stimulated muscle to the electrical stimulation or stimulations. In a variation, a sensor module distinct from device 65 or electrode element 66 may be deployed on the patient's skin to detect the electromechanical response.
  • [0046]
    Electrode element 66 is coupled to medical device 65 via lead 67. Electrode element 66 includes two electrodes 68A and 68B, which deliver electrical stimulation to muscle, or other tissue sensitive to [K+], and provide a return current path. In the example of FIG. 1F, electrodes 68A and 68B are deployed externally with adhesive pads 69A and 69B, which adhere to the skin. Electrodes 68A and 68B may deliver an electrical stimulation to any of several tissues, especially skeletal muscles located beneath the skin. Although the embodiment shown in FIG. 1F is completely external with no implantable elements, the invention encompasses embodiments that have external and implantable elements.
  • [0047]
    The invention is not limited to the particular embodiments depicted in FIGS. 1A through 1F. For purposes of discussing the invention and its operation, the description below will focus principally upon implantable embodiments, and in particular, the embodiment depicted in FIG. 1A. Further, as discussed above, the invention is not limited to stimulation of skeletal muscle tissue, or stimulation via leads or electrodes that are separate from the leads or electrodes used to deliver therapeutic stimulation. For example, in some embodiments, [K+] may be determined by detecting the response of cardiac muscle to the therapeutic pacing stimuli delivered to heart 14. In this manner, [K+] may be determined directly in the organ of interest without the use of an additional stimulation pulse or stimulation lead.
  • [0048]
    FIG. 2 is a schematic illustration of an exemplary implantation in a patient 70 of the apparatus depicted in FIG 1A. Right ventricular lead 16, right atrial lead 30 and coronary sinus lead 42 are deployed in heart 14 via access through a vein such as the subclavian vein (not shown). Electrode element 54A and lead 56, by contrast, do not enter the cardiovascular system in the illustrated embodiment.
  • [0049]
    Rather, electrode element 54A is deployed proximate to skeletal muscle. In the exemplary implantation depicted in FIG. 2, electrode element 54A is deployed proximate to the sternal portion 72 and clavicular portion 74 of the Pectoralis major. The invention also supports implantations in which electrode element 54A is deployed proximate to other skeletal muscles or other tissue sensitive to [K+]. When a surgeon implants IMD 12 in a pocket, such as a pocket proximate to the Pectoralis major according to a conventional implantation procedure, the surgeon can deploy electrode element 54A proximate to a desired skeletal muscle. Electrode element 54A may include a fixation mechanism such as a loop or Dacron mesh that allows the surgeon to anchor electrode element 54A in place with suture.
  • [0050]
    As shown in FIG. 2, housing 60 of IMD 12 is deployed in contact with pectoral muscles 72 and 74. A conventional implantation technique for some implantable devices, such as a pacemaker, provides for deploying IMD 12 in direct contact with pectoral muscle. In such implantations, embodiments such as those depicted in FIGS. 1D and 1E may be feasible.
  • [0051]
    FIG. 3 is a block diagram illustrating components of an exemplary system 10 such as the system depicted in FIG. 1A. Electrode element 54A includes electrodes 62A and 62B, which are configured to deliver one or more electrical stimulations to a muscle or other tissue sensitive to [K+]. In a typical embodiment, one of electrodes 62A and 62B introduces a stimulation from IMD 12 to a skeletal muscle, and the other of electrodes 62A and 62B provides the return current path.
  • [0052]
    In the embodiment shown in FIG. 3, IMD 12 includes a sensor 80 that detects the electromechanical response of the muscle to the stimulations delivered by electrodes 62A and 62B. Sensor 80 can detect the mechanical response, the electrical response, or both. Examples of mechanical responses are muscle tension, muscle strength, muscle density, muscle length and pressure generated by the muscle. Sensor 80 can be deployed inside housing 60 of IMD 12 or outside housing 60. Sensors such as an optical sensor could be configured to respond to one or more of these mechanical responses. An accelerometer, which responds to muscle movement, is another example of a sensor that can detect a mechanical response. In some embodiments of IMD 12, an accelerometer may be provided inside housing 60 to detect patient activity or posture. Such an accelerometer could also detect a mechanical response of stimulated muscle. In an external implementation such as that depicted in FIG. 1F, an accelerometer may be disposed in device 65, in electrode element 66, or as a separate module deployed on the patient's skin. Further examples of sensors that can detect a mechanical response are a pressure sensor and a piezoelectric sensor.
  • [0053]
    Sensor 80 can also be configured to detect an electrical response. In some embodiments of the invention, electrodes 62A and 62B not only deliver electrical stimulations to the muscle, but also convey the electrical response to sensor 80. An example of a sensor that detects an electrical response is an impedance sensor.
  • [0054]
    A pulse generator 82 in IMD 12 generates the stimulations that are delivered to the skeletal muscle via electrodes 62A and 62B. Pulse generator 82 may be, but need not be, the same component that generates pacing stimulations that are delivered to heart 14. Pulse generator 82 operates under the control of processor 84. Processor 84 can be embodied in one or more forms, such as a microprocessor, digital signal processor, application specific integrated circuit or full custom integrated circuit. In addition to controlling pulse generator 82, processor 84 receives and analyzes signals detected via sensor 80 that are indicative of the response of the muscle to the stimulations, and determines a concentration of potassium ions in extracellular fluid (ECF) of the patient as a function of the signals. As discussed in more detail below, [K+] in the ECF affects the response of the muscle or other tissue being monitored.
  • [0055]
    As used herein, determining a concentration of potassium ions in ECF of the patient can include determining an absolute concentration, such as measuring or estimating the molarity of potassium ions. Determining a concentration of potassium ions can also include determining a relative concentration, such as a concentration with respect to a baseline. Furthermore, determining a concentration of potassium ions can include determining a change in concentration over time. In practice, monitoring a change in concentration over time has clear clinical advantages.
  • [0056]
    Processor 84 controls the scheduling of stimulations. Processor 84 may be configured to deliver the stimulations and monitor [K+] when the patient is in bed, for example. Processor 84 may also be configured to deliver the stimulations and monitor [K+] a predetermined number of times each day.
  • [0057]
    Processor 84 may further be configured to determine whether conditions are suitable for delivering stimulations and monitoring [K+]. For example, it may be desirable to monitor [K+] once a day when the patient is inactive, particularly when the patient's muscles or other tissues are relaxed and when there is less likelihood of extraneous motion that could affect sensor 80. When the patient is physically active, the physical activity can interfere with the monitoring of [K+]. Processor 84 may receive a signal from sensor 80 or from another sensor that generates a signal as a function of patient activity, such as an accelerometer. On the basis of the signal, processor 84 may determine whether the patient is too active or whether conditions are otherwise unsuitable for monitoring. When processor 84 determines that conditions are unsuitable, processor 84 may defer delivering stimulations and may reschedule the stimulations for a later time.
  • [0058]
    In addition, processor 84 may be programmed to deliver the stimulations and monitor [K+] in response to an event. An exemplary event that could trigger delivery of stimulations and monitoring of [K+] is an arrhythmia. When IMD 12 is a pacemaker or other device configured to treat arrhythmia, IMD 12 may apply therapy to treat the arrhythmia, then deliver the stimulations and monitor [K+], to determine whether potassium ion concentration might be contributing to the arrhythmia. Processor 84 can further be configured to control delivery of pacing therapy to heart 14. Another exemplary triggering event is the detection of a low level of physical activity indicative of the onset of rest or sleep.
  • [0059]
    Alternatively, processor 84 may be programmed to deliver the stimulations and monitor [K+] to predict an arrhythmia. In this manner, IMD 12 may detect poor regulation of [K+] and allow a physician to modify patient medication or suggest alternative diets. Exemplary medications may include anti-arrhythmic drugs, potassium channel inhibitors, or diets that include potassium sources such as bananas. In some embodiments, IMD 12 may notify the patient of unsafe [K+] with an audible sound or stimulation so that the patient may take precautions before the arrhythmia.
  • [0060]
    In the embodiment depicted in FIG. 3, IMD 12 includes a memory element 86 configured to store information about potassium ion concentration. Memory element 86 can store information such as the time when electrical stimulations were administered, the frequency of the stimulations, the muscle's response to the stimulations, and the determined potassium ion concentration. Memory element 86 can also store a history of such monitoring, and can store information concerning the change in [K+] over time.
  • [0061]
    Further, memory element 86 may store instructions that cause a programmable processor, such as processor 84, to carry out techniques for monitoring potassium ion concentration. Memory element 86 may include but is not limited to read-only memory, random access memory, Flash memory, EPROM and a magnetic or optical storage medium, or any combination thereof.
  • [0062]
    When processor 84 determines that [K+] in ECF is elevated to the point that heart function may be adversely affected, or when processor 84 determines that [K+] in ECF is rising to a point of concern, processor 84 may take action. Processor 84 may, for example, send a notification via an input/output element 88. Input/output element 88 comprises one or more elements that relay the message to the patient, the patient's physician, or any other person or monitoring device. Input/output element 88 can include, for example, a radio frequency (RF) transmitter, an inductive coil transmitter or an audible alarm. For example, input/output element 88 may issue a warning to patient 12 if the determination of [K+] is above or below a predetermined threshold.
  • [0063]
    Additionally, whether or not a determination that patient function may be adversely affected has been made, input/output element 88 may transmit data stored by memory element 86, i.e. [K+] or system 10 status data, to another computing device such as a notebook computer, hand held computer, physician programmer, personal computer, or network server. The data may be transmitted for analysis and/or storage. In the case of a network server, the data may be further forwarded to a hospital, clinic, manufacturer of IMD 12, or another location where the data may be analyzed or stored.
  • [0064]
    When processor 84 determines that [K+] in ECF is of concern, processor 84 can also control the delivery of therapy via a therapy element 90. Therapy element 90 can include, for example, an implantable drug delivery device that delivers a drug to the patient. The drug may be a diuretic, for example. As the patient's body loses water due to increased urinary output, the patient's arterial blood pressure declines, reducing the workload of heart 14. In addition, increased urinary output enhances [K+] elimination. Therapy element 90 can work in concert with input/output element 88. For example, therapy element 90 can administer a drug while input/output element 88 can notify the patient that the patient should take an action, such as contacting his physician or controlling the potassium in his diet. In addition, input/output element 88 may issue a warning to patient 12 if the determination of [K+] is above or below a predetermined threshold.
  • [0065]
    Therapy element 90 can also encompass elements that pace heart 14 via leads 16, 30 and 42, or any combination thereof, as depicted in FIGS. 1A and 2. In general, however, pacing therapies would probably not be applied to address or control [K+]. Although pacing therapies such as cardiac resynchronization and bi-ventricular pacing may be of benefit to patients having heart failure, such pacing therapies would not ordinarily be administered in response to elevated [K+]. Some pacing therapies can cause [K+] to become even more elevated. Accordingly, although it is unlikely that processor 84 would apply pacing therapies to address elevated [K+], processor 84 may monitor [K+] to determine whether such pacing therapies ought to be employed or discontinued. In other words, processor 84 may monitor [K+] to determine whether pacing therapies are likely to be safe and effective.
  • [0066]
    FIGS. 4A and 4B are timing diagrams that illustrates exemplary techniques by which processor 84 can determine a concentration of potassium ion in ECF as a function of the response of skeletal muscle to stimulations from an electrode element such as electrode elements 54A-E. Each stimulus may have an amplitude of about two to twenty volts, for example, and a pulse width of about 0.1 to 1.0 milliseconds. Stimulus line 100 shows the timing of stimuli generated by pulse generator 82 delivered to the skeletal muscle via electrodes such as electrodes 62A-62J. Response line 104 depicts a response of skeletal muscle to the stimulations in an environment where [K+] is low relative to concentrations in ICF. In other words, response line 104 depicts a response of skeletal muscle in a “normal” patient. By contrast, response line 104 depicts a response of skeletal muscle in a patient having elevated [K+]. A patient having elevated [K+] is not normal and is at risk of heart failure.
  • [0067]
    For purpose of illustration, the response is depicted as muscle tension. Other responses, such as muscle motion or muscle length, may also be evaluated, although the response waveforms may look different from those in FIGS. 4A and 4B. In addition, the response waveforms may look different from those in FIGS. 4A and 4B depending upon the muscle or other tissue being stimulated. For example, in embodiments that monitor the response of nervous tissue to the stimulation as a means for monitoring [K+], the response waveform may include one or more action potentials.
  • [0068]
    Stimuli can be delivered in a range of frequencies, such as from about 10 Hz to about 150 Hz. A first set of stimuli 106 at a low frequency produces similar but distinct responses in normal [K+] and elevated [K+] environments. Contractions 108 in a normal muscle and contractions 110 in a muscle in an environment of elevated [K+] are indicated by muscle tension as a function of time. In comparison to one another, contractions 108 in a normal muscle have a longer duration and may also exhibit some summation. In the example of FIG. 4A, contractions 108 also exhibit a greater amplitude. In contrast, contractions 110 in an elevated [K+] environment are of a smaller amplitude, a shorter duration and exhibit little or no summation.
  • [0069]
    A second set of stimuli 112 at a higher frequency produces distinct responses in normal [K+] and elevated [K+] environments as well. Contractions 114 in a normal muscle exhibit marked summation. The muscle approaches tetanus, but, as depicted in FIG. 4, the frequency of stimulation is too low to produce a sustained tetanic response. Instead, muscle contractions 114 exhibit “ripples” or wavering, rather than the sustained contraction of tetanus. In contrast with contractions 114, contractions 116 in an elevated [K+] exhibit little or no summation.
  • [0070]
    A third set of stimuli 118 at an even higher frequency produces contractions 120 in a normal muscle that show a tetanic response. In particular, muscle tension rises steadily to a maximum and levels off. Contractions 122 in an elevated [K+] environment, by contrast, exhibit summation, but the rise in tension is rippled and tension is not sustained. In other words, stimuli 118 produce a sustained response 120 in a normal [K+] environment, but produce a rippled response 122 in an elevated [K+] environment.
  • [0071]
    The frequency of third set of stimuli 118 can be used to distinguish a normal [K+] environment from an elevated [K+] environment. The distinction can be achieved in a number of ways. For example, an analog or digital highpass filter may be employed to detect whether a ripple is present. Fourier or wavelet analysis may be used to detect the presence of high frequency components. Template matching or other morphological analysis may be performed. Other forms of analog or digital signal analysis may be used to detect the presence of a rippled response.
  • [0072]
    A fourth set of stimuli 124 at an even higher frequency produces contractions 126 in a normal muscle and contractions 128 in an elevated [K+] environment that are similar, in that both exhibit a tetanic response. Consequently, stimuli at this frequency would be less desirable for distinguishing a normal [K+] environment from an elevated [K+] environment.
  • [0073]
    FIG. 4B shows additional distinction techniques. A set of stimuli 130 evokes responses 132, 134 similar to responses 120, 122 in FIG. 4A. In FIG. 4B, the quantity of interest is the decline of the response following cessation of stimulation, which indicates how fast the stimulated muscle relaxes. In FIG. 4B, the decline is indicated by angles α and β of lines tangent to the responses. In general, the response returns to resting more quickly in an elevated [K+] environment and more slowly in a normal [K+] environment, so angle β is generally larger and indicative of a greater slope than angle α. Another measurement of the decline of the response is the fall time, i.e., the time for the response to decrease from one value to another. Fall time can be determined by measuring the time it takes for the response to fall from its peak value to half its peak value, for example, or the time it takes for the response to fall from ninety percent of its peak value to ten percent of its peak value. The signal decays more quickly in elevated [K+] environment and more slowly in a normal [K+] environment, so the fall time in the elevated [K+] environment is smaller than the fall time in a normal [K+] environment. Processor 84 may detect the rate of muscle relaxation with any analog or digital technique, such as taking a difference at discrete points, measuring the time between high and low values, or differentiating the response waveform.
  • [0074]
    It may be possible to observe the decline with a single stimulus. Stimulus 136 evokes responses 138, 140. In addition to monitoring fall time or slope as described above, processor 84 may detect the pulse width or action potential duration of the response. Because the response returns to resting more quickly in an elevated [K+] environment than in a normal [K+] environment, the pulse width of the in an elevated [K+] environment is narrower than in a normal [K+] environment. The narrower pulse width is associated with the shorter refractory period in an elevated [K+] environment. Narrower pulse width in an elevated [K+] environment has been demonstrated with both cardiac muscle and skeletal muscle.
  • [0075]
    A set of stimuli 142 illustrates another distinction technique. This process includes delivering pairs of stimuli separated by different time intervals. In FIG. 4B, the initial pair of stimuli is separated by a very short interval, and subsequent pairs are separated by larger intervals. In an elevated [K+] environment, the response will exhibit a two-peak ripple at a smaller interval than in a normal [K+] environment. Processor 84 can detect the presence of the two-peak ripple using any signal processing technique, including techniques mentioned above.
  • [0076]
    Another distinction technique is to “sweep” through a range of frequencies, as illustrated by set of stimuli 148. In a normal [K+] environment, the response 150 exhibits more rapid summation and reaches a sustained response in a shorter time. In contrast, the response 152 in an elevated [K+] environment is slower to exhibit summation and sustained response. Processor 84 can detect the onset of rapid summation and sustained response any signal processing technique, including techniques mentioned above.
  • [0077]
    The signals depicted in FIGS. 4A and 4B are for purposes of illustration and the invention is not limited to signals of this type. Instead of measuring tension, as depicted in FIGS. 4A and 4B, sensor 80 could respond to muscle motion or muscle length, for example. In other embodiments, other signals may be measured in other tissue sensitive to [K+], such as action potentials in nerve tissue.
  • [0078]
    As FIG. 4A shows, it may be more difficult to distinguish whether [K+] is low or elevated when stimulations are applied at high frequencies. Further, the frequency at which a normal [K+] environment can be distinguished from an elevated [K+] environment may vary from patient to patient. Accordingly, a patient who has received IMD 12 may undergo one or more tests to calibrate muscle response to [K+] or other tissue response to [K+].
  • [0079]
    FIG. 5 illustrates an exemplary calibration procedure. Although FIG. 5 illustrates an example embodiment related to monitoring muscle tissue, the illustrated technique may be applicable to calibration for monitoring of other [K+] sensitive tissues, such as nerve tissue.
  • [0080]
    In a laboratory setting, while conditions are suitable for stimulating the muscle and observing the response, IMD 12 delivers one or more electrical stimulations to the muscle of the patient via the electrodes (160). The stimulations may be delivered according to a particular parameter, such as a known frequency. For purposes of illustration, it is assumed that the stimulation parameter is a known frequency of stimulation, and that the initial known frequency is a low frequency. It is further assumed that the characteristic of interest is whether the muscle exhibits a sustained tissue response.
  • [0081]
    IMD 12 detects the response of the muscle to the stimulations (162) and performs signal analysis to determine whether stimulations at the known frequency produce a tissue response (164). If not, the frequency may be changed (166), e.g., increased, and the testing may be performed again (160). At some point, the patient will exhibit a rippled response, and at a higher frequency the patient will exhibit a sustained response.
  • [0082]
    At substantially the same time, the patient has his ECF [K+] measured by conventional laboratory techniques. Data concerning [K+] are then correlated to data pertaining to the patient's response to stimulation at one or more frequencies. In one embodiment, IMD 12 receives the data concerning measured [K+], and processor 84 performs the correlation. In another embodiment, another processor performs the correlation, and the relationship is supplied to processor 84 via input/output element 88.
  • [0083]
    IMD 12 stores the relationship between a known [K+] and the patient's response (168). In this way, a baseline measurement of [K+] can be established for the patient. Future determinations of [K+] can be measured against the baseline. If, at later time, the patient exhibits a sustained response at lower frequency, then [K+] has declined in comparison to the baseline. Conversely, if the later patient exhibits a sustained response at higher frequency, then [K+] has increased with respect to the baseline.
  • [0084]
    Although FIG. 5 illustrates calibration by observing sustained response, calibration may also be performed using other responses. Other responses can include, for example, the rate of relaxation following cessation of stimulation, the pulse width of a response, the occurrence of summation in the response, the amplitude of a response, or any combination thereof.
  • [0085]
    As part of the calibration, IMD 12 may deliver stimuli at different amplitudes. By iterative experimentation, IMD 12 can discover what amplitude of stimulation will produce a response. IMD 12 may be programmed to adjust the amplitude of stimulation as appropriate.
  • [0086]
    FIG. 6 is a flow diagram illustrating a technique for monitoring ECF potassium ion concentration and for delivering therapy in response to a determination of ECF potassium ion. concentration. When, for example, processor 84 determines that it is time for a scheduled monitoring or when processor 84 detects a triggering event that can activate monitoring, processor 84 initiates the monitoring process (170). Before actually conducting the monitoring, however, processor 84 determines whether the conditions are suitable for monitoring (172). An illustrative situation in which conditions might not be suitable for monitoring is a situation in which the patient has a high level of physical activity. When a signal from an activity sensor indicates that the patient is physically active, it may be difficult to monitor [K+] accurately. When processor 84 determines that conditions are not suitable for monitoring, processor 84 can defer monitoring to a later time (174).
  • [0087]
    IMD 12 delivers one or more electrical stimulations to the tissue of the patient (176). The stimulations may include a set of stimulations delivered at a known frequency or a set of stimulations that sweep through a range of frequencies. IMD 12 detects the response of the tissue to the stimulations (178). Although not depicted in FIG. 6, stimulations and detection (176, 178) may be repeated. For example, a later set of stimulations may be repeated at a known frequency that is different from an earlier set of stimulations.
  • [0088]
    On the basis of the detections, processor 84 determines a concentration of potassium ions in ECF of the patient (180). As noted above, this determination can include determining an absolute concentration, determining a relative concentration or determining a change in concentration, or any combination thereof.
  • [0089]
    On the basis of the determination of a concentration of potassium ions in ECF, processor 84 further determines whether action should be taken. In the example FIG. 6, the action in question is whether therapy is indicated (182). When therapy is indicated, processor 84 controls therapy element 90 to deliver therapy to the patient (184). The invention is not limited to instances in which IMD 12 takes action in the form of administration of therapy. Other kinds of action include transmitting a notification via input/output element 88 or changing how often IMD 12 monitors [K+].
  • [0090]
    The results of the determination (180), and the delivery of therapy, if any, may be recorded in memory 86 (186). Among other purposes, data stored in memory are useful for monitoring the change in [K+] over time and for documenting the response of the patient to therapy.
  • EXAMPLE 1
  • [0091]
    FIG. 7 is a schematic diagram illustrating an experimental setup that was used to test muscle contractions due to electrical stimuli. As shown in FIG. 7, mouse skeletal muscle 202 was held between clamps 208 and 210 in a chamber 190. Clamp 210 was connected to a wall of chamber 190 by a support structure 206 while clamp 208 was connected to force transducer 212. Force transducer 212 was connected to support structure 204, which was attached to chamber 190. Chamber 190 was contained within bath 188. Electrical stimulator 192 provided electrical stimuli to muscle 202 through electrodes 198 and 200. Electrodes 198 and 200 were coupled to electrical stimulator 192 by wires 194 and 196, respectively.
  • [0092]
    In the experiment described in FIGS. 7-9, bath 188 was set to 37 degrees Celsius, and chamber 190 was filled with potassium buffer that was controlled to provide varying concentrations of potassium ions to determine how muscle 202 contracts with electrical stimuli in the presence of differing potassium ion concentrations. Muscle 202 was an isolated mouse skeletal muscle. Force transducer 212 was a strain gauge. Biphasic electrical stimuli was delivered to muscle 202 via electrodes 198 and 200 in order to trigger isometric contractions in the muscle. A computing device monitors the measurements from force transducer 212 in real-time or offline. The experimental setup described in FIG. 7 may be varied to determine contraction forces from other tissues or using other devices.
  • [0093]
    FIG. 8 is a graph of experimental data showing muscle force in various solutions of potassium versus time. Graph 214 shows electrical stimuli 216 and 218 in conjunction with measured forces of muscle 202 of FIG. 7. Broken line 220 represents contractions when [K+] equals 2 millimoles (mM), solid line 222 represents contractions when [K+] equals 4 mM, and dotted line 224 represents contractions when [K+] equals 10 mM. Contraction force was highest when [K+] equaled 2 mM, which is a lower [K+] than the normal potassium ion concentrations for a mouse. A medium level of force was generated with electrical stimuli when [K+] equaled 4 mM, and the lowest levels of force was generated when [K+] equaled 10 mM. Normal [K+] of a mouse is approximately 4 mM.
  • [0094]
    In the experiment, a burst electrical stimulation consisting of 5 pulses with a frequency of 50 Hz were applied to muscle 202. Pulses were biphasic with anodic and cathodic pulse durations of 1 millisecond (ms), and 18 ms of pause between each pulse.
  • [0095]
    FIG. 9 is a graph of experimental data showing contraction amplitude versus potassium concentration. Graph 226 displays contraction amplitudes in Volts according to three different electrical stimuli frequencies. Volts may be translated into force measurements by a calibration procedure. Solid line 228 and included closed boxes are representative of 50 Hz stimulation, broken line 230 and included open boxes are representative of 100 Hz stimulation, and dotted line 232 and included closed circles are representative of 150 Hz stimulation.
  • [0096]
    The [K+] was varied in the sequence of 4 mM, 10 mM, 4 mM, 2 mM, and 4 mM. The results showed that the amplitude of the force generated by muscle 202 may be determined by the [K+] when the stimulation frequency 50 Hz and 100 Hz. In addition, stimulation at 150 Hz may also be used to determine [K+] in skeletal muscle, but was less sensitive to [K+] than the other frequencies tested. Other frequencies not tested in the experiment of FIGS. 7-9 may also be useful for electrical stimulation.
  • [0097]
    In some embodiments, other tissues may be tested and may respond similarly as the mouse skeletal muscle. Other frequencies and [K+] may also be tested, while the exemplary conditions provided herein are only a small sample of [K+] that may be detected with electrical stimulation.
  • [0098]
    The invention may produce one of more advantages. In comparison with conventional implantable potassium sensors such as electrochemistry-based potassium sensors or optically based sensors, the invention supports long-term implantation. Conventional potassium sensors have proven to be unstable over extended periods. Some sensors require a periodic replacement of a sensing element, and other sensors lose sensitivity when the body naturally encapsulates the implanted elements. Some sensors also can be rejected by the body of the patient.
  • [0099]
    IMDs such as those described above, however, have proven to be well tolerated in the long term. Rejection rates are low. Further, the IMD can respond to encapsulation by increasing the voltage of stimulations to provoke a response.
  • [0100]
    The stimulations need not be painful. In practice, the patient may very likely experience a tingle. The tingle may be uncomfortable, but it would probably not be painful as long as stimulations are adjusted to a voltage that provokes a response and is not excessive. Further, as discussed above, the stimulations may be therapeutic stimulation of, for example, cardiac muscle or nervous tissue, that would have otherwise been delivered to the patient whether or not [K+] was monitored. There may further be an element of convenience to the patient, as the patient may reduce the number of tests that rely upon blood samples.
  • [0101]
    IMDs such as those described above can be implanted using conventional, well-established surgical techniques. In the case of an IMD that delivers pacing or other heart therapies, an electrode configured to deliver an electrical stimulation to a tissue may be deployed as part of conventional device implantation technique, with little or no additional incision or trauma to the patient. Many patients experiencing heart failure may benefit from the implantation of an IMD that combines pacing therapies and potassium monitoring capability.
  • [0102]
    In addition, the invention supports embodiments that include one or more external elements, which may offer further advantages. A patient may receive the embodiment depicted in FIG. 1F, for example, without surgery. An external electrode element, such as that depicted in FIG. 1F, may be deployed at several sites on the body of the patient without surgery. An external electrode element may also be readily redeployed from one site to another.
  • [0103]
    Various embodiments of the invention have been described, but the invention is not limited to these particular embodiments. Although the invention has been depicted in the context of a pacemaker having one or more leads configured to deliver pacing stimuli to a heart, the invention can also be implemented in conjunction with other implantable and external devices. The invention can be implemented with a neurostimulator that includes a lead configured to deliver a pacing stimulation to a nerve, or a drug pump that includes a pump configured to deliver a drug to the patient from a reservoir. The invention may also be implemented as a standalone potassium monitor.
  • [0104]
    The invention may be embodied in a computer-readable medium with instructions that cause a programmable processor to carry out the techniques described above. A “computer-readable medium” includes but is not limited to read-only memory, Flash memory, EPROM and a magnetic or optical storage medium. The medium may comprise instructions for causing a programmable processor to control a pulse generator to deliver an electrical stimulation to a muscle in a patient, for example, or receive from a sensor a signal indicative of a response of the tissue to the electrical stimulations. These and other embodiments are within the scope of the following claims.

Claims (36)

  1. 1. A system comprising:
    a pulse generator configured to generate an electrical stimulation;
    an electrode configured to deliver the electrical stimulation to a tissue in a patient;
    a sensor configured to detect a response of the tissue to the electrical stimulation; and
    a processor configured to determine a concentration of potassium ions in extracellular fluid of the patient as a function of the response.
  2. 2. The system of claim 1, wherein the tissue is at least one of skeletal muscle, smooth muscle, cardiac muscle, nerve tissue, or skin.
  3. 3. The system of claim 1, wherein the processor is further configured to determine a concentration of potassium ions in the extracellular fluid of the patient by at least one of determining an absolute concentration of potassium ions in the extracellular fluid, determining a relative concentration of potassium ions in the extracellular fluid or determining a change in concentration of potassium ions in the extracellular fluid over time.
  4. 4. The system of claim 1, wherein the pulse generator is further configured to generate a set of electrical stimulations.
  5. 5. The system of claim 4, wherein the pulse generator is configured to generate a set of electrical stimulations at a known frequency.
  6. 6. The system of claim 4, wherein the processor is further configured to control the timing of the set of electrical stimulations generated by the pulse generator.
  7. 7. The system of claim 1, wherein the processor is further configured to determine a concentration of potassium ions in the extracellular fluid as a function of at least one of a sustained contraction of the tissue, a rippled contraction of the tissue, a rate of relaxation of the tissue, a pulse width of the response, the occurrence of summation in the response or the amplitude of the response.
  8. 8. The system of claim 1, wherein the electrode is a first electrode, the system further comprising a housing and a second electrode in the housing.
  9. 9. The system of claim 1, wherein the sensor comprises at least one of an optical sensor, an accelerometer, a pressure sensor, a piezoelectric sensor or an impedance sensor.
  10. 10. The system of claim 1, wherein the processor is further configured to control delivery of pacing therapy to a heart of the patient.
  11. 11. The system of claim 1, further comprising a lead configured to couple the electrode to the pulse generator.
  12. 12. The system of claim 1, wherein the system further comprises at least one of a lead configured to deliver a pacing stimulation to a heart, a lead configured to deliver a pacing stimulation to a nerve, or a pump configured to deliver a drug from a reservoir.
  13. 13. The system of claim 1, wherein at least one of the pulse generator, electrode, sensor and processor is configured to be implanted in a human or animal body.
  14. 14. The system of claim 1, wherein the processor monitors the concentration of potassium ions to predict an arrhythmia.
  15. 15. A method comprising:
    delivering an electrical stimulation to a tissue in a patient;
    detecting a response of the tissue to the electrical stimulation; and
    determining a concentration of potassium ions in extracellular fluid of the patient as a function of the response.
  16. 16. The method of claim 15, wherein the tissue is at least one of skeletal muscle, smooth muscle, cardiac muscle, nerve tissue, and skin.
  17. 17. The method of claim 15, wherein determining the concentration of potassium ions in the extracellular fluid of the patient comprises least one of determining an absolute concentration of potassium ions in the extracellular fluid, determining a relative concentration of potassium ions in the extracellular fluid or determining a change in concentration of potassium ions in the extracellular fluid over time.
  18. 18. The method of claim 15, wherein determining the concentration of potassium ions in the extracellular fluid of the patient comprises least one of detecting a sustained contraction of the tissue, detecting a rippled contraction of the tissue, detecting a rate of relaxation of the tissue, detecting a pulse width of the response, detecting the occurrence of summation in the response or detecting the amplitude of the response.
  19. 19. The method of claim 15, further comprising delivering a therapy to the patient as a function of the response.
  20. 20. The method of claim 15, wherein the electrical stimulation is a first electrical stimulation and the response is a first response, the method further comprising:
    delivering a second electrical stimulation to the tissue;
    detecting a second response of the tissue to the second electrical stimulation; and
    determining a change in concentration of potassium ions in the extracellular fluid of the patient as a function of the first and second responses.
  21. 21. The method of claim 15, further comprising:
    detecting a triggering event; and
    delivering the electrical stimulation in response to the triggering event.
  22. 22. The method of claim 15, further comprising:
    determining whether conditions are suitable for determining the concentration of potassium ions; and
    delivering the electrical stimulation when the conditions are suitable.
  23. 23. The method of claim 15, further comprising monitoring the concentration of potassium ions to predict an arrhythmia.
  24. 24. The method of claim 15, further comprising at least one of recording information relating to the determination, or issuing a warning to at least one of the patient or a caregiver based upon the determination.
  25. 25. The method of claim 15, further comprising transmitting information relating to the determination to another device.
  26. 26. A computer-readable medium comprising instructions that cause a programmable processor to:
    control a pulse generator to deliver an electrical stimulation to a tissue in a patient;
    receive from a sensor a signal indicative of a response of the tissue to the electrical stimulations; and
    determine a concentration of potassium ions in extracellular fluid of the patient as a function of the response.
  27. 27. The medium of claim 26, wherein the tissue is at least one of skeletal muscle, smooth muscle, cardiac muscle, nerve tissue, or skin.
  28. 28. The medium of claim 26, the instructions further causing the processor to determine the concentration of potassium ions in the extracellular fluid by determining a change in concentration of potassium ions in the extracellular fluid over time.
  29. 29. The medium of claim 26, the instructions further causing the processor to determine the concentration of potassium ions in the extracellular fluid by at least one of detecting a sustained contraction of the tissue, detecting a rippled contraction of the tissue detecting a rate of relaxation of the muscle, detecting a pulse width of the response, detecting the occurrence of summation in the response or detecting the amplitude of the response.
  30. 30. The medium of claim 26, the instructions further causing the processor to control delivery of a therapy to the patient as a function of the response.
  31. 31. The medium of claim 26, further comprising instructions that cause the programmable processor to monitor the concentration of potassium ions to predict an arrhythmia.
  32. 32. A method comprising:
    delivering an electrical stimulation to a tissue in a patient;
    detecting a response of the tissue to the electrical stimulations; and
    storing a relationship between a concentration of potassium ions in extracellular fluid of the patient and the response.
  33. 33. The method of claim 32, wherein the electrical stimulation is a first electrical stimulation and the response is a first response, the method further comprising:
    delivering a second electrical stimulation to the tissue;
    detecting a second response of the tissue to the second electrical stimulation; and
    determining a concentration of potassium ions in the extracellular fluid of the patient as a function of the first and second responses.
  34. 34. The method of claim 33, wherein determining the concentration of potassium ions in the extracellular fluid of the patient comprises determining a change in concentration of potassium ions in the extracellular fluid over time.
  35. 35. A computer-readable medium comprising instructions that cause a programmable processor to:
    control a pulse generator to deliver an electrical stimulation to a tissue in a patient;
    receive from a sensor a signal indicative of a response of the tissue to the electrical stimulations; and
    store a relationship between a concentration of potassium ions in extracellular fluid of the patient and the response.
  36. 36. The medium of claim 35, wherein the instructions further cause the processor to:
    receive data concerning a measured concentration of potassium ions in the extracellular fluid; and
    correlate the measured concentration with the response.
US11349058 2005-02-07 2006-02-07 Potassium monitoring Abandoned US20060217771A1 (en)

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Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060241709A1 (en) * 2005-02-07 2006-10-26 Medtronic, Inc. Ion imbalance detector
US20100114210A1 (en) * 2008-10-31 2010-05-06 Medtronic, Inc. Implantable medical device lead connection assembly
WO2010051492A1 (en) * 2008-10-31 2010-05-06 Medtronic, Inc. Implantable medical device including a plurality of lead connection assemblies
US20100137929A1 (en) * 2008-10-31 2010-06-03 Medtronic, Inc. Implantable medical device including a plurality of lead connection assemblies
US7809441B2 (en) 2006-05-17 2010-10-05 Cardiac Pacemakers, Inc. Implantable medical device with chemical sensor and related methods
WO2012148784A2 (en) 2011-04-29 2012-11-01 Medtronic, Inc. Method and device to monitor patients with kidney disease
US8926542B2 (en) 2011-04-29 2015-01-06 Medtronic, Inc. Monitoring fluid volume for patients with renal disease
US9131865B2 (en) 2013-10-17 2015-09-15 Medtronic, Inc. Method and apparatus for cardiac function monitoring
US9138157B2 (en) 2013-10-17 2015-09-22 Medtronic, Inc. Method and apparatus for cardiac function monitoring
US9421382B2 (en) 2013-12-13 2016-08-23 Medtronic, Inc. Method and apparatus for monitoring of patient medication compliance
US9456755B2 (en) 2011-04-29 2016-10-04 Medtronic, Inc. Method and device to monitor patients with kidney disease
US9526822B2 (en) 2013-02-01 2016-12-27 Medtronic, Inc. Sodium and buffer source cartridges for use in a modular controlled compliant flow path
US9707328B2 (en) 2013-01-09 2017-07-18 Medtronic, Inc. Sorbent cartridge to measure solute concentrations
US9713668B2 (en) 2012-01-04 2017-07-25 Medtronic, Inc. Multi-staged filtration system for blood fluid removal
US9713665B2 (en) 2014-12-10 2017-07-25 Medtronic, Inc. Degassing system for dialysis
US9827361B2 (en) 2013-02-02 2017-11-28 Medtronic, Inc. pH buffer measurement system for hemodialysis systems
US9848778B2 (en) 2011-04-29 2017-12-26 Medtronic, Inc. Method and device to monitor patients with kidney disease
US9855379B2 (en) 2013-02-02 2018-01-02 Medtronic, Inc. Sorbent cartridge configurations for improved dialysate regeneration
US9872949B2 (en) 2013-02-01 2018-01-23 Medtronic, Inc. Systems and methods for multifunctional volumetric fluid control
US9895479B2 (en) 2014-12-10 2018-02-20 Medtronic, Inc. Water management system for use in dialysis

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20080172107A1 (en) * 2007-01-11 2008-07-17 Mcginnis William J Stand alone osteogenic stimulus device and method of using
US7734349B2 (en) * 2007-07-18 2010-06-08 Cardiac Pacemakers, Inc. Osmometric heart monitoring device and methods
US8864677B2 (en) * 2008-03-13 2014-10-21 Cardiac Pacemakers, Inc. Systems and methods for myocardial ischemia detection

Citations (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4374382A (en) * 1981-01-16 1983-02-15 Medtronic, Inc. Marker channel telemetry system for a medical device
US4556063A (en) * 1980-10-07 1985-12-03 Medtronic, Inc. Telemetry system for a medical device
US4750494A (en) * 1981-05-12 1988-06-14 Medtronic, Inc. Automatic implantable fibrillation preventer
US5127404A (en) * 1990-01-22 1992-07-07 Medtronic, Inc. Telemetry format for implanted medical device
US5305745A (en) * 1988-06-13 1994-04-26 Fred Zacouto Device for protection against blood-related disorders, notably thromboses, embolisms, vascular spasms, hemorrhages, hemopathies and the presence of abnormal elements in the blood
US5683432A (en) * 1996-01-11 1997-11-04 Medtronic, Inc. Adaptive, performance-optimizing communication system for communicating with an implanted medical device
US6052622A (en) * 1998-02-12 2000-04-18 Pacesetter Ab Heart stimulator with an evoked response detector
US6230059B1 (en) * 1999-03-17 2001-05-08 Medtronic, Inc. Implantable monitor
US6321101B1 (en) * 1997-10-29 2001-11-20 Pacesetter Ab Method and device for determination of concentration
US6363279B1 (en) * 1996-01-08 2002-03-26 Impulse Dynamics N.V. Electrical muscle controller
US6602399B1 (en) * 2000-03-22 2003-08-05 Max-Planck-Gesellschaft Zur Forderung Der Wissenchaften E.V. Signal recording of a receptor-effector-system by an extracellular planar potential-sensitive electrode
US20040019312A1 (en) * 2002-07-19 2004-01-29 Childers Robert W. Systems and methods for performing peritoneal dialysis
US6711439B1 (en) * 2002-02-14 2004-03-23 Pacesetter, Inc. Evoked response variability as an indicator of autonomic tone and surrogate for patient condition
US20050236330A1 (en) * 2000-12-22 2005-10-27 Fresenius Medical Care Deutschland Gmbh. Method for determining concentration; a dialyser
US7077819B1 (en) * 1998-12-24 2006-07-18 Fresenius Medical Care Deutschland Gmbh Method for determining the distribution volume of a blood component during an extracorporeal blood treatment and device for carrying out the method
US20070066928A1 (en) * 2005-09-22 2007-03-22 Jean-Michel Lannoy Automation and optimization of CRRT treatment using regional citrate anticoagulation
US20070175827A1 (en) * 2006-02-02 2007-08-02 Cardiac Pacemakers, Inc. Cardiac rhythm management device and sensor-suite for the optimal control of ultrafiltration and renal replacement therapies
US20080021337A1 (en) * 2006-07-24 2008-01-24 Dan Li Cardiac signal display and event detection using multiresolution z-score transform
US20100168546A1 (en) * 2005-03-10 2010-07-01 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US20110077574A1 (en) * 2009-09-30 2011-03-31 Medtronic, Inc. System and method to regulate ultrafiltration
US20110130666A1 (en) * 2009-11-30 2011-06-02 Yanting Dong Enhanced reporting of pathological episodes

Family Cites Families (155)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1189458A (en) 1967-09-27 1970-04-29 Nat Res Dev Improvements in or relating to dialysers
US3669878A (en) 1968-12-02 1972-06-13 Health Education And Welfare U Treatment of dialysate solution for removal of urea
US3669880A (en) 1969-06-30 1972-06-13 Cci Aerospace Corp Recirculation dialysate system for use with an artificial kidney machine
DE2239254C2 (en) 1970-12-30 1983-08-04 Organon Teknika Corp., Oklahoma City, Okla., Us
US3850835A (en) 1971-11-08 1974-11-26 Cci Life Systems Inc Method of making granular zirconium hydrous oxide ion exchangers, such as zirconium phosphate and hydrous zirconium oxide, particularly for column use
US3884808A (en) 1973-06-20 1975-05-20 Res Dev Systems Inc Wearable, self-regenerating dialysis appliance
US4060485A (en) 1975-06-09 1977-11-29 I T L Technology, Inc. Dialysis apparatus
US4581141A (en) 1978-02-27 1986-04-08 Purdue Research Foundation Dialysis material and method for removing uremic substances
US4371385A (en) 1981-04-28 1983-02-01 Cobe Laboratories, Inc. Deaerating liquid
US4381999A (en) 1981-04-28 1983-05-03 Cobe Laboratories, Inc. Automatic ultrafiltration control system
US4650587A (en) 1982-09-09 1987-03-17 Akzona Incorporated Ammonia scavenger
US4460555A (en) 1983-08-25 1984-07-17 Organon Teknika Corporation Ammonia scavenger
US4685903A (en) 1984-01-06 1987-08-11 Pacesetter Infusion, Ltd. External infusion pump apparatus
US4678408A (en) 1984-01-06 1987-07-07 Pacesetter Infusion, Ltd. Solenoid drive apparatus for an external infusion pump
US4562751A (en) 1984-01-06 1986-01-07 Nason Clyde K Solenoid drive apparatus for an external infusion pump
EP0202710B1 (en) 1985-05-15 1992-02-05 ENIRICERCHE S.p.A. Zirconium phosphate and method for its preparation
DE3785147T2 (en) 1986-11-07 1996-09-19 Asahi Chemical Ind Regenerated cellulose membrane and processes for their preparation.
US4828693A (en) 1987-09-22 1989-05-09 Baxter Travenol Laboratories, Inc. Water pressure regulator for hemodialysis apparatus
GB8722854D0 (en) 1987-09-29 1987-11-04 Hardy S M Implantable artificial kidney
US5080653A (en) 1990-04-16 1992-01-14 Pacesetter Infusion, Ltd. Infusion pump with dual position syringe locator
US5097122A (en) 1990-04-16 1992-03-17 Pacesetter Infusion, Ltd. Medication infusion system having optical motion sensor to detect drive mechanism malfunction
FR2687307B1 (en) 1992-02-14 1999-06-04 Lascombes Jean Jacques Device for preparing a solution for medical use.
US5284470A (en) 1992-11-02 1994-02-08 Beltz Alex D Wearable, portable, light-weight artificial kidney
US5302288A (en) 1993-03-19 1994-04-12 Zimpro Environmental, Inc. Treatment of highly colored wastewaters
DE4321927C2 (en) 1993-07-01 1998-07-09 Sartorius Gmbh Filter unit with degassing
US5591344A (en) 1995-02-13 1997-01-07 Aksys, Ltd. Hot water disinfection of dialysis machines, including the extracorporeal circuit thereof
US5944684A (en) 1995-08-31 1999-08-31 The Regents Of The University Of California Wearable peritoneum-based system for continuous renal function replacement and other biomedical applications
US6048732A (en) 1996-10-16 2000-04-11 Board Of Regents, The University Of Texas System Receptor and method for citrate determination
EP0906768B1 (en) 1997-10-02 2004-02-25 St. Jude Medical AB Evoked response detector and a heart stimulator with such a detector
US6088608A (en) 1997-10-20 2000-07-11 Alfred E. Mann Foundation Electrochemical sensor and integrity tests therefor
WO1999037342A1 (en) 1998-01-21 1999-07-29 Gambro Ab Safety arrangement for a dialysis machine and method of activating the safety arrangement
US6197197B1 (en) 1998-04-23 2001-03-06 Dialysis Systems, Inc. Method for fluid delivery in a dialysis clinic
US6058331A (en) 1998-04-27 2000-05-02 Medtronic, Inc. Apparatus and method for treating peripheral vascular disease and organ ischemia by electrical stimulation with closed loop feedback control
US6554798B1 (en) 1998-08-18 2003-04-29 Medtronic Minimed, Inc. External infusion device with remote programming, bolus estimator and/or vibration alarm capabilities
CA2345439C (en) 1998-10-29 2005-08-09 Minimed, Inc. Compact pump drive system
US6248093B1 (en) 1998-10-29 2001-06-19 Minimed Inc. Compact pump drive system
US6254567B1 (en) 1999-02-26 2001-07-03 Nxstage Medical, Inc. Flow-through peritoneal dialysis systems and methods with on-line dialysis solution regeneration
US6274103B1 (en) 1999-03-26 2001-08-14 Prismedical Corporation Apparatus and method for preparation of a peritoneal dialysis solution
WO2000057935A1 (en) 1999-03-30 2000-10-05 Gambro Lundia Ab Method, apparatus and components of dialysis system
JP4903311B2 (en) 1999-04-30 2012-03-28 チルドレンズ ホスピタル メディカル センター Hemofiltration system and method based on the monitored patient parameters, supervisory control device and blood adaptive control of the filter pump hemofiltration
US20010041869A1 (en) 2000-03-23 2001-11-15 Causey James D. Control tabs for infusion devices and methods of using the same
US6676608B1 (en) 2000-04-19 2004-01-13 Cheetah Medical Ltd. Method and apparatus for monitoring the cardiovascular condition, particularly the degree of arteriosclerosis in individuals
WO2001085295A3 (en) 2000-05-05 2002-04-04 Hemocleanse Inc Use of magnetic particles or other particles having relatively high density in a fluid for mixing and/or leak detection
US6589229B1 (en) 2000-07-31 2003-07-08 Becton, Dickinson And Company Wearable, self-contained drug infusion device
US7033498B2 (en) 2000-11-28 2006-04-25 Renal Solutions, Inc. Cartridges useful in cleaning dialysis solutions
US6627164B1 (en) 2000-11-28 2003-09-30 Renal Solutions, Inc. Sodium zirconium carbonate and zirconium basic carbonate and methods of making the same
CA2470339C (en) 2000-12-12 2007-07-17 Jurag Separation A/S A method and apparatus for isolation of ionic species by electrodialysis
WO2002053209A1 (en) 2000-12-27 2002-07-11 Philips Japan, Ltd. Biological information and blood treating device information control system, biological information and blood treating device information control device, and biological information and blood treating device information control method
US6960179B2 (en) 2001-11-16 2005-11-01 National Quality Care, Inc Wearable continuous renal replacement therapy device
US7387734B2 (en) 2001-11-23 2008-06-17 Gambro Lundia Ab Method of operating a dialysis machine
US6878283B2 (en) 2001-11-28 2005-04-12 Renal Solutions, Inc. Filter cartridge assemblies and methods for filtering fluids
US20030114787A1 (en) 2001-12-13 2003-06-19 Victor Gura Wearable peritoneal dialysis system
US7153286B2 (en) 2002-05-24 2006-12-26 Baxter International Inc. Automated dialysis system
JP2005533560A (en) 2002-07-19 2005-11-10 バクスター インターナショナル インコーポレイテッド System and method for performing peritoneal dialysis
WO2004009156A3 (en) 2002-07-19 2004-05-06 Baxter Int Systems and methods for peritoneal dialysis
US7144384B2 (en) 2002-09-30 2006-12-05 Insulet Corporation Dispenser components and methods for patient infusion device
US7128727B2 (en) 2002-09-30 2006-10-31 Flaherty J Christopher Components and methods for patient infusion device
US20040099593A1 (en) 2002-11-25 2004-05-27 Potito De Paolis Concurrent dialysate purification cartridge
EP1592494B1 (en) 2003-01-07 2009-06-24 NxStage Medical, Inc. Batch filtration system for preparation of sterile replacement fluid for renal therapy
US7276042B2 (en) 2003-01-23 2007-10-02 National Quality Care, Inc. Low hydraulic resistance cartridge
US7330750B2 (en) 2003-04-25 2008-02-12 Instrumentarium Corp. Estimation of cardiac death risk
US8026729B2 (en) 2003-09-16 2011-09-27 Cardiomems, Inc. System and apparatus for in-vivo assessment of relative position of an implant
US20050065760A1 (en) 2003-09-23 2005-03-24 Robert Murtfeldt Method for advising patients concerning doses of insulin
JP4691503B2 (en) 2003-10-28 2011-06-01 バクスター・インターナショナル・インコーポレイテッドBaxter International Incorp0Rated For medical fluid system, improved priming method and apparatus integrity and hydraulic head height
US7744553B2 (en) 2003-12-16 2010-06-29 Baxter International Inc. Medical fluid therapy flow control systems and methods
EP1701752B1 (en) 2003-12-24 2016-05-18 Chemica Technologies, Inc. Dialysate regeneration system for portable human dialysis
DE102004013814A1 (en) 2004-03-20 2005-10-13 B. Braun Medizintechnologie Gmbh A method for allowing operator inputs to a medical device
US7776210B2 (en) 2004-06-09 2010-08-17 Renal Solutions, Inc. Dialysis system
EP1773427B1 (en) 2004-07-23 2014-01-15 Gambro Lundia AB A machine for extracorporeal treatment of blood
US7356366B2 (en) 2004-08-02 2008-04-08 Cardiac Pacemakers, Inc. Device for monitoring fluid status
WO2006071532A1 (en) 2004-12-28 2006-07-06 Renal Solutions, Inc. Method of synthesizing zirconium phosphate particles
US7756572B1 (en) 2005-01-25 2010-07-13 Pacesetter, Inc. System and method for efficiently distinguishing among cardiac ischemia, hypoglycemia and hyperglycemia using an implantable medical device and an external system
US8903492B2 (en) 2005-02-07 2014-12-02 Medtronic, Inc. Ion imbalance detector
US20060195064A1 (en) 2005-02-28 2006-08-31 Fresenius Medical Care Holdings, Inc. Portable apparatus for peritoneal dialysis therapy
JP4726045B2 (en) 2005-04-08 2011-07-20 日機装株式会社 Hemodialysis apparatus
WO2006120417A3 (en) 2005-05-06 2007-01-18 Imi Vision Ltd Fluid processing apparatus
US7686787B2 (en) 2005-05-06 2010-03-30 Medtronic Minimed, Inc. Infusion device and method with disposable portion
US7674231B2 (en) 2005-08-22 2010-03-09 Massachusetts Institute Of Technology Wearable pulse wave velocity blood pressure sensor and methods of calibration thereof
US20100137693A1 (en) 2005-11-01 2010-06-03 Fresenius Medical Care Holdings, Inc. Methods and systems for patient care
DE102005060866B4 (en) 2005-12-20 2009-01-15 Bruker Biospin Gmbh Combined Titration and pH electrode for the preparation of liquid test samples in particular for NMR spectroscopy
WO2007089855A3 (en) 2006-01-30 2008-07-24 Univ California Peritoneal dialysis methods and apparatus
US7785463B2 (en) 2006-03-17 2010-08-31 Children's Hospital Medical Center Extracorporeal renal replacement modeling system
US8366316B2 (en) 2006-04-14 2013-02-05 Deka Products Limited Partnership Sensor apparatus systems, devices and methods
US8292594B2 (en) 2006-04-14 2012-10-23 Deka Products Limited Partnership Fluid pumping systems, devices and methods
US20070255125A1 (en) 2006-04-28 2007-11-01 Moberg Sheldon B Monitor devices for networked fluid infusion systems
EP2056900B1 (en) 2006-08-16 2014-01-15 Triomed AB System for regeneration of a fluid
US7887502B2 (en) 2006-09-15 2011-02-15 University Of Florida Research Foundation, Inc. Method for using photoplethysmography to optimize fluid removal during renal replacement therapy by hemodialysis or hemofiltration
WO2008036011A1 (en) 2006-09-19 2008-03-27 Gambro Lundia Ab Estimation of propensity to symptomatic hypotension
US8183046B2 (en) 2007-01-11 2012-05-22 The Board Of Trustees Of The University Of Illinois Temperature resistant pH buffers for use at low temperatures
US7967022B2 (en) 2007-02-27 2011-06-28 Deka Products Limited Partnership Cassette system integrated apparatus
KR20170003718A (en) 2007-02-27 2017-01-09 데카 프로덕츠 리미티드 파트너쉽 Hemodialysis apparatus and methods
US8409441B2 (en) 2007-02-27 2013-04-02 Deka Products Limited Partnership Blood treatment systems and methods
US8042563B2 (en) 2007-02-27 2011-10-25 Deka Products Limited Partnership Cassette system integrated apparatus
CA2693303C (en) 2007-07-20 2017-11-07 Mayo Foundation For Medical Education And Research Natriuretic polypeptides
US7981082B2 (en) 2007-08-21 2011-07-19 Hospira, Inc. System and method for reducing air bubbles in a fluid delivery line
WO2009026603A1 (en) 2007-08-31 2009-03-05 Zentrum Für Biomedizinische Technologie Der Donau-Universität Krems Method for detecting the ion concentrations of citrate anti-coagulated extracorporeal blood purification
US20090101577A1 (en) 2007-09-28 2009-04-23 Fulkerson Barry N Methods and Systems for Controlling Ultrafiltration Using Central Venous Pressure Measurements
US8580112B2 (en) 2007-11-16 2013-11-12 Fresenius Medical Care Holdings, Inc. Dialysis systems and methods
US8889004B2 (en) 2007-11-16 2014-11-18 Fresenius Medical Care Holdings, Inc. Dialysis systems and methods
CN104307210B (en) 2008-01-18 2017-09-29 弗雷塞尼斯医疗保健控股公司 Removing carbon dioxide gas from the dialysis fluid circuit device
US8019406B2 (en) 2008-03-10 2011-09-13 Biotronik Crm Patent Ag Apparatus and method to assess the risk of R-on-T event
CA2717890A1 (en) 2008-04-30 2009-11-05 Gambro Lundia Ab Hydrophobic deaeration membrane
US8882700B2 (en) 2008-05-02 2014-11-11 Baxter International Inc. Smart patient transfer set for peritoneal dialysis
US8233973B2 (en) 2008-05-02 2012-07-31 Spacelabs Healthcare, Llc Methods for detection of cardiac arrhythmias
US8220643B2 (en) 2008-06-06 2012-07-17 Fresenius Medical Care Holdings, Inc. Urea sorbent
RU2525205C2 (en) 2008-06-23 2014-08-10 Темасек Политехник Flow system of dialysis device and portable dialysis device
US9821105B2 (en) 2008-07-01 2017-11-21 Baxter International Inc. Nanoclay sorbents for dialysis
US8057679B2 (en) 2008-07-09 2011-11-15 Baxter International Inc. Dialysis system having trending and alert generation
US8696626B2 (en) 2008-07-30 2014-04-15 Claudia F. E. Kirsch Debubbler
EP2163272B1 (en) 2008-09-15 2014-06-25 B. Braun Avitum AG Device to early predict the Kt/V parameter in kidney substitution treatments
US8409444B2 (en) 2008-09-30 2013-04-02 Fresenius Medical Care Holdings, Inc. Acid zirconium phosphate and alkaline hydrous zirconium oxide materials for sorbent dialysis
JP5848128B2 (en) 2008-09-30 2016-01-27 フレセニウス メディカル ケア ホールディングス インコーポレーテッド Covalently immobilized enzymes and a method of manufacturing the same
US8640887B2 (en) 2008-10-03 2014-02-04 Fresenius Medical Care Holdings, Inc. Zirconium phosphate particles having improved adsorption capacity and method of synthesizing the same
CN102202702B (en) 2008-11-03 2014-05-21 弗雷泽纽斯医疗保健控股有限公司 Portable peritoneal dialysis system
CA2754522A1 (en) 2009-03-06 2010-09-10 Baxter International Inc. Hemodialysis and peritoneal dialysis systems having electrodeionization capabilities
CA2766597A1 (en) 2009-07-01 2011-01-06 Board Of Regents, The University Of Texas System Methods of determining the presence and/or concentration of an analyte in a sample
US8404091B2 (en) 2009-08-27 2013-03-26 Baxter International Inc. Dialysis treatment devices for removing urea
US20110066043A1 (en) 2009-09-14 2011-03-17 Matt Banet System for measuring vital signs during hemodialysis
US8518260B2 (en) 2009-10-01 2013-08-27 Fresenius Medical Care Holdings, Inc. Method of controlling diffusive sodium transport in dialysis
US9132219B2 (en) 2010-04-16 2015-09-15 Baxter International Inc. Therapy prediction and optimization of serum potassium for renal failure blood therapy, especially home hemodialysis
WO2011140268A3 (en) 2010-05-04 2012-05-31 C-Tech Biomedical, Inc. Dual mode hemodialysis machine
EP2576453A2 (en) 2010-05-24 2013-04-10 Baxter International Inc. Systems and methods for removing hydrogen peroxide from water purification systems
US8784668B2 (en) 2010-10-12 2014-07-22 Fresenius Medical Care Holdings, Inc. Systems and methods for compensation of compliant behavior in regenerative dialysis systems
US9694125B2 (en) 2010-12-20 2017-07-04 Fresenius Medical Care Holdings, Inc. Medical fluid cassettes and related systems and methods
WO2012115771A3 (en) 2011-02-25 2013-03-14 Medtronic, Inc. Systems and methods for therapy of kidney disease and/or heart failure using chimeric natriuretic peptides
KR101529414B1 (en) 2011-03-21 2015-06-16 감브로 룬디아 아베 An apparatus for extracorporeal blood treatment
US20120258546A1 (en) 2011-04-08 2012-10-11 Life Technologies Corporation Automated On-Instrument pH Adjustment
EP2701580A2 (en) 2011-04-29 2014-03-05 Medtronic, Inc. Method and device to monitor patients with kidney disease
EP2701758A1 (en) 2011-04-29 2014-03-05 Medtronic, Inc. Multimodal dialysis system
US9848778B2 (en) 2011-04-29 2017-12-26 Medtronic, Inc. Method and device to monitor patients with kidney disease
US9132217B2 (en) 2011-04-29 2015-09-15 Medtronic, Inc. Multimodal dialysis system
US9456755B2 (en) 2011-04-29 2016-10-04 Medtronic, Inc. Method and device to monitor patients with kidney disease
US8926542B2 (en) 2011-04-29 2015-01-06 Medtronic, Inc. Monitoring fluid volume for patients with renal disease
US9724458B2 (en) 2011-05-24 2017-08-08 Deka Products Limited Partnership Hemodialysis system
CA2840715A1 (en) 2011-07-29 2013-02-07 Baxter International Inc. Sodium management for dialysis systems
EP2739325B1 (en) 2011-08-02 2017-10-04 Medtronic, Inc. Hemodialysis system having a flow path with a controlled compliant volume
WO2013025844A3 (en) 2011-08-16 2013-05-02 Medtronic, Inc. Modular hemodialysis system
WO2013028809A3 (en) 2011-08-22 2013-05-16 Medtronic, Inc. Dual flow sorbent cartridge
JP5099464B1 (en) 2011-12-29 2012-12-19 富田製薬株式会社 Preparation apparatus and process for the preparation of bicarbonate ion concentration variable of the dialysate, bicarbonate ion concentration variable dialysis agent, and bicarbonate ion concentration variable dialysis system
EP2800591B1 (en) 2012-01-04 2016-01-13 Fresenius Medical Care Holdings, Inc. Method and system of enhancing removal of toxic anions and organic solutes in sorbent dialysis
EP2800592A4 (en) 2012-01-04 2015-02-25 Medtronic Inc Multi-staged filtration system for blood fluid removal
EP2809374B1 (en) 2012-02-02 2017-12-27 Quanta Dialysis Technologies Limited Dialysis machine
EP2814535A1 (en) 2012-02-14 2014-12-24 Quanta Fluid Solutions Ltd Dialysis machine
US9610392B2 (en) 2012-06-08 2017-04-04 Fresenius Medical Care Holdings, Inc. Medical fluid cassettes and related systems and methods
US9500188B2 (en) 2012-06-11 2016-11-22 Fresenius Medical Care Holdings, Inc. Medical fluid cassettes and related systems and methods
US9162021B2 (en) 2012-10-22 2015-10-20 Baxter International Inc. Integrated water testing system and method for ultra-low total chlorine detection
US9138520B2 (en) 2012-10-22 2015-09-22 Baxter International Inc. Total chlorine water detection system and method for medical fluid treatments
JP2014097224A (en) 2012-11-15 2014-05-29 Tatsunori Kato Dialysis unit and method for measuring access recirculation rate
US20140158623A1 (en) 2012-12-10 2014-06-12 Medtronic, Inc. Sodium management for hemodialysis
US20140158588A1 (en) 2012-12-10 2014-06-12 Medtronic, Inc. pH AND BUFFER MANAGEMENT SYSTEM FOR HEMODIALYSIS SYSTEMS
US9399090B2 (en) 2012-12-10 2016-07-26 Medtronic, Inc. Potassium loaded ion-exchange material for use in a dialysate regeneration system
EP2950836A4 (en) 2013-02-01 2016-11-16 Medtronic Inc Sorbent cartridge to measure solute concentrations
US9707328B2 (en) 2013-01-09 2017-07-18 Medtronic, Inc. Sorbent cartridge to measure solute concentrations
US9526822B2 (en) 2013-02-01 2016-12-27 Medtronic, Inc. Sodium and buffer source cartridges for use in a modular controlled compliant flow path
US9827361B2 (en) 2013-02-02 2017-11-28 Medtronic, Inc. pH buffer measurement system for hemodialysis systems

Patent Citations (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4556063A (en) * 1980-10-07 1985-12-03 Medtronic, Inc. Telemetry system for a medical device
US4374382A (en) * 1981-01-16 1983-02-15 Medtronic, Inc. Marker channel telemetry system for a medical device
US4750494A (en) * 1981-05-12 1988-06-14 Medtronic, Inc. Automatic implantable fibrillation preventer
US5305745A (en) * 1988-06-13 1994-04-26 Fred Zacouto Device for protection against blood-related disorders, notably thromboses, embolisms, vascular spasms, hemorrhages, hemopathies and the presence of abnormal elements in the blood
US5127404A (en) * 1990-01-22 1992-07-07 Medtronic, Inc. Telemetry format for implanted medical device
US6363279B1 (en) * 1996-01-08 2002-03-26 Impulse Dynamics N.V. Electrical muscle controller
US5683432A (en) * 1996-01-11 1997-11-04 Medtronic, Inc. Adaptive, performance-optimizing communication system for communicating with an implanted medical device
US6321101B1 (en) * 1997-10-29 2001-11-20 Pacesetter Ab Method and device for determination of concentration
US6052622A (en) * 1998-02-12 2000-04-18 Pacesetter Ab Heart stimulator with an evoked response detector
US7077819B1 (en) * 1998-12-24 2006-07-18 Fresenius Medical Care Deutschland Gmbh Method for determining the distribution volume of a blood component during an extracorporeal blood treatment and device for carrying out the method
US6230059B1 (en) * 1999-03-17 2001-05-08 Medtronic, Inc. Implantable monitor
US6602399B1 (en) * 2000-03-22 2003-08-05 Max-Planck-Gesellschaft Zur Forderung Der Wissenchaften E.V. Signal recording of a receptor-effector-system by an extracellular planar potential-sensitive electrode
US20050236330A1 (en) * 2000-12-22 2005-10-27 Fresenius Medical Care Deutschland Gmbh. Method for determining concentration; a dialyser
US6711439B1 (en) * 2002-02-14 2004-03-23 Pacesetter, Inc. Evoked response variability as an indicator of autonomic tone and surrogate for patient condition
US20040019312A1 (en) * 2002-07-19 2004-01-29 Childers Robert W. Systems and methods for performing peritoneal dialysis
US20100168546A1 (en) * 2005-03-10 2010-07-01 Dexcom, Inc. System and methods for processing analyte sensor data for sensor calibration
US20070066928A1 (en) * 2005-09-22 2007-03-22 Jean-Michel Lannoy Automation and optimization of CRRT treatment using regional citrate anticoagulation
US20070175827A1 (en) * 2006-02-02 2007-08-02 Cardiac Pacemakers, Inc. Cardiac rhythm management device and sensor-suite for the optimal control of ultrafiltration and renal replacement therapies
US20080021337A1 (en) * 2006-07-24 2008-01-24 Dan Li Cardiac signal display and event detection using multiresolution z-score transform
US20110077574A1 (en) * 2009-09-30 2011-03-31 Medtronic, Inc. System and method to regulate ultrafiltration
US20110130666A1 (en) * 2009-11-30 2011-06-02 Yanting Dong Enhanced reporting of pathological episodes

Cited By (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060241709A1 (en) * 2005-02-07 2006-10-26 Medtronic, Inc. Ion imbalance detector
US9289165B2 (en) 2005-02-07 2016-03-22 Medtronic, Inc. Ion imbalance detector
US8903492B2 (en) 2005-02-07 2014-12-02 Medtronic, Inc. Ion imbalance detector
US7809441B2 (en) 2006-05-17 2010-10-05 Cardiac Pacemakers, Inc. Implantable medical device with chemical sensor and related methods
US20120197231A1 (en) * 2006-05-17 2012-08-02 Cardiac Pacemakers, Inc Implantable medical device with chemical sensor and related methods
US8126554B2 (en) * 2006-05-17 2012-02-28 Cardiac Pacemakers, Inc. Implantable medical device with chemical sensor and related methods
US8571659B2 (en) * 2006-05-17 2013-10-29 Cardiac Pacemakers, Inc. Implantable medical device with chemical sensor and related methods
US8200335B2 (en) 2008-10-31 2012-06-12 Medtronic, Inc. Implantable medical device lead connection assembly
WO2010051492A1 (en) * 2008-10-31 2010-05-06 Medtronic, Inc. Implantable medical device including a plurality of lead connection assemblies
US8290593B2 (en) 2008-10-31 2012-10-16 Medtronic, Inc. Implantable medical device including a plurality of lead connection assemblies
WO2010051495A1 (en) * 2008-10-31 2010-05-06 Medtronic, Inc. Implantable medical device lead connection assembly
US20100114210A1 (en) * 2008-10-31 2010-05-06 Medtronic, Inc. Implantable medical device lead connection assembly
US20100137929A1 (en) * 2008-10-31 2010-06-03 Medtronic, Inc. Implantable medical device including a plurality of lead connection assemblies
US9750862B2 (en) 2011-04-29 2017-09-05 Medtronic, Inc. Adaptive system for blood fluid removal
US8926542B2 (en) 2011-04-29 2015-01-06 Medtronic, Inc. Monitoring fluid volume for patients with renal disease
US9456755B2 (en) 2011-04-29 2016-10-04 Medtronic, Inc. Method and device to monitor patients with kidney disease
US9848778B2 (en) 2011-04-29 2017-12-26 Medtronic, Inc. Method and device to monitor patients with kidney disease
WO2012148784A3 (en) * 2011-04-29 2012-12-20 Medtronic, Inc. Method and device to monitor patients with kidney disease
US9192707B2 (en) 2011-04-29 2015-11-24 Medtronic, Inc. Electrolyte and pH monitoring for fluid removal processes
WO2012148784A2 (en) 2011-04-29 2012-11-01 Medtronic, Inc. Method and device to monitor patients with kidney disease
US9302036B2 (en) 2011-04-29 2016-04-05 Medtronic, Inc. Blood fluid removal system performance monitoring
US9700661B2 (en) 2011-04-29 2017-07-11 Medtronic, Inc. Chronic pH or electrolyte monitoring
US8951219B2 (en) 2011-04-29 2015-02-10 Medtronic, Inc. Fluid volume monitoring for patients with renal disease
US9642960B2 (en) 2011-04-29 2017-05-09 Medtronic, Inc. Monitoring fluid volume for patients with renal disease
US9713668B2 (en) 2012-01-04 2017-07-25 Medtronic, Inc. Multi-staged filtration system for blood fluid removal
US9707328B2 (en) 2013-01-09 2017-07-18 Medtronic, Inc. Sorbent cartridge to measure solute concentrations
US9526822B2 (en) 2013-02-01 2016-12-27 Medtronic, Inc. Sodium and buffer source cartridges for use in a modular controlled compliant flow path
US9872949B2 (en) 2013-02-01 2018-01-23 Medtronic, Inc. Systems and methods for multifunctional volumetric fluid control
US9855379B2 (en) 2013-02-02 2018-01-02 Medtronic, Inc. Sorbent cartridge configurations for improved dialysate regeneration
US9827361B2 (en) 2013-02-02 2017-11-28 Medtronic, Inc. pH buffer measurement system for hemodialysis systems
US9138157B2 (en) 2013-10-17 2015-09-22 Medtronic, Inc. Method and apparatus for cardiac function monitoring
US9131865B2 (en) 2013-10-17 2015-09-15 Medtronic, Inc. Method and apparatus for cardiac function monitoring
US9421382B2 (en) 2013-12-13 2016-08-23 Medtronic, Inc. Method and apparatus for monitoring of patient medication compliance
US9713665B2 (en) 2014-12-10 2017-07-25 Medtronic, Inc. Degassing system for dialysis
US9895479B2 (en) 2014-12-10 2018-02-20 Medtronic, Inc. Water management system for use in dialysis

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US20150032023A1 (en) 2015-01-29 application
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US8903492B2 (en) 2014-12-02 grant
US9289165B2 (en) 2016-03-22 grant

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