Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
  • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
  • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
  • A61N1/3606—Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
  • A61N1/3611—Respiration control
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
  • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
  • A61N1/3601—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation of respiratory organs
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/08—Measuring devices for evaluating the respiratory organs
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/08—Measuring devices for evaluating the respiratory organs
  • A61B5/0816—Measuring devices for examining respiratory frequency
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/08—Measuring devices for evaluating the respiratory organs
  • A61B5/0826—Detecting or evaluating apnoea events
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/02—Details
  • A61N1/04—Electrodes
  • A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
  • A61N1/0551—Spinal or peripheral nerve electrodes
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
  • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
  • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
  • A61N1/36128—Control systems
  • A61N1/36135—Control systems using physiological parameters
  • A61N1/3614—Control systems using physiological parameters based on impedance measurement
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/48—Other medical applications
  • A61B5/4806—Sleep evaluation
  • A61B5/4818—Sleep apnoea
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
  • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
  • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
  • A61N1/36128—Control systems
  • A61N1/36135—Control systems using physiological parameters
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N1/00—Electrotherapy; Circuits therefor
  • A61N1/18—Applying electric currents by contact electrodes
  • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
  • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
  • A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
  • A61N1/36128—Control systems
  • A61N1/36146—Control systems specified by the stimulation parameters
  • A61N1/3615—Intensity

Definitions

• the present invention relates generally to implantable medical devices and more particularly to a device and method for controlling breathing and for treating Central Sleep Apnea.
• SDB Sleep Disordered Breathing
• CSA Central Sleep Apnea
• CHF Congestive Heart Failure
• the heart function of patients with heart failure may be treated with various drugs, or implanted cardiac pacemaker devices.
• the breathing function of patients with heart failure may be treated with Continuous Positive Air Pressure (CPAP) devices or Nocturnal Nasal Oxygen.
• CPAP Continuous Positive Air Pressure
• CPAP Continuous Positive Air Pressure
• Nocturnal Nasal Oxygen Nocturnal Nasal Oxygen.
• Phrenic nerve pacing as a separate and stand alone therapy has been explored for paralyzed patients where it is an alternative to forced mechanical ventilation, and for patients with the most severe cases of central sleep apnea.
• Ondine's Curse has been treated with phrenic nerve pacemakers since at least the 1970's.
• phrenic nerve pacemakers place an electrode in contact with the phrenic nerve and they pace the patient's phrenic nerve at a constant rate. Such therapy does not permit natural breathing and it occurs without regard to neural respiratory drive.
• SDB exists in two primary forms. The first is central sleep apnea (CSA) and the second is obstructive sleep apnea (OSA).
• CSA central sleep apnea
• OSA obstructive sleep apnea
• CSA patients also exhibit apnea but from a different cause. These CSA patients have episodes of reduced neural breathing drive for several seconds before breathing drive returns.
• the loss of respiratory drive and apnea is due to a dysfunction in the patient's central respiratory control located in the brain. This dysfunction causes the patient's breathing pattern to oscillate between too rapid breathing called hyperventilation and periods of apnea (not breathing).
• hyperventilation a dysfunction in the patient's central respiratory control located in the brain.
• This dysfunction causes the patient's breathing pattern to oscillate between too rapid breathing called hyperventilation and periods of apnea (not breathing).
• apnea not breathing
• Cheyne-Stokes breathing or CSR Cheyne-Stokes breathing
• Other patterns have been seen clinically as well including bouts of hyperventilation followed by hypopneas only.
• apnea-hypopnea index (a measure of the number of breathing disturbances per hour) has been found to correlate to a poor prognosis for the patient.
• the swings between hyperventilation and apnea characterized by central sleep apnea have three main adverse consequences, namely: large swings in arterial blood gases (oxygen and carbon dioxide); arousals and shifts to light sleep; and large negative swings in intrathoracic pressure during hyperventilation.
• the large swings in blood gases lead to decreased oxygen flow to the heart, activation of the sympathetic nervous system, endothelial cell dysfunction, and pulmonary arteriolar vasoconstriction.
• the device of the present invention can sense the patients breathing and it can distinguish inhalation or inspiration from exhalation or expiration.
• the device can periodically stimulate the phrenic nerve as required.
• the stimulation may be invoked automatically in response to sensed physiologic conditions.
• the device can stop the delivery of therapy in response to sensed conditions.
• the device can be prescribed and dispensed and the therapy delivered without regard to the sensed conditions. As a result, the device may be used to detect and intervene in order to correct episodes of sleep disordered breathing or the device may intervene to prevent episodes of sleep disordered breathing from occurring.
• the methods that are taught here may be used alone to treat a patient or they may be incorporated into a cardiac stimulating device where the respiration therapy is merged with a cardiac therapy.
• the therapy and its integration with cardiac stimulation therapy and the architecture for carrying out the therapy are quite flexible and may be implemented in any of several forms.
• the phrenic nerve stimulation may be carried out with a transvenous lead system lodged in one of the cardiophrenic vein a short distance from the heart.
• One or both phrenic nerves may be accessed with leads. Either one side or both (right and left) phrenic nerves may be stimulated.
• the phrenic nerve may be accessed through a large vein such as the jugular or the superior vena cava.
• a stimulation electrode may be place in the pericardial space on the heart, near the phrenic nerve but electrically isolated from the heart. Implementation of respiration detection may also take any of several forms.
• Transthoracic impedance measurement may be taken from electrodes implanted at locations in the body to measure or sense the change in lung volume associated with breathing.
• one or more implanted pressure transducers in or near the pleural cavity may be used to track pressure changes associated with breathing. Knowledge of breathing rates and patterns are useful in carrying out the invention but distinguishing reliably the inspiration phase from expiration phase is a breath is particularly important for timing the delivery of the stimulation.
• breathing has an inspiration phase followed by an expiration phase.
• Each breath is followed by a pause when the lungs are "still" before the next breath's inspiration.
• the device delivers phrenic nerve stimulation after the start of inspiration preferably toward the start of exhalation.
• the duration and magnitude of the stimulation is selected to "extend" the expiration phase or the respiratory pause of a naturally initiated breath.
• prolongation of a natural breath while keeping some air trapped in the lungs, delays the inspiration phase of next natural breath until the air trapped in the lungs is exhaled. For this reason our therapy has a tendency to lower the observed breathing rate.
• the stimulation maintains activation of the diaphragm long enough to mimic a patient holding their breath by not letting the diaphragm relax. This mechanism of action controls the rate of breathing by increasing the effective duration of each breath.
• Figure 1 is a schematic diagram
• Figure 2 is a schematic diagram
• Figure 3 is a schematic diagram
• Figure 4 is a schematic diagram
• Figure 5 is diagram showing experimentally derived physiologic data displayed in two panels A and B;
• Figure 6 is a schematic diagram showing physiologic data known in the prior art.
• Figure 7 is a schematic diagram showing physiologic data and device timing information.
• FIG. 1 is schematic diagram showing an implanted medical device (IMD) 101 implanted in a patient's chest for carrying out a therapeutic stimulation of respiration.
• IMD implanted medical device
• the patient has lungs shown in bold outline and indicated at 102 overlying the heart 103.
• the right phrenic nerve 104 passes from the head alongside the heart to innervate the diaphragm 106 at location 105.
• a transvenous lead 107 passes from the IMD 101 and passes through venous vasculature to enter the cardiophrenic vein 108 on the right side of the patient.
• the cardiophrenic vein 108 lies next to the phrenic nerve 104 along the heart.
• Electrical stimulation pulses supplied to the stimulation electrode 110 on lead 107 interact with the phrenic nerve to stimulate it and thus activate the diaphragm 106.
• a series of concentric circles 112 indicate electrical stimulation of the phrenic nerve.
• the stimulation electrode 110 lies far enough away from the heart 103 to avoid stimulating the heart 103.
• only one branch of the phrenic nerve 104 is stimulated and the other side of nerve is under normal physiologic control.
• a respiration electrode 114 on lead 107 cooperates with an indifferent electrode on the can of the IMD 101 to source and sink low amplitude electrical pulses that are used to track changes in lung volume over time.
• This well known impedance plethysmography technique is used to derive the inspiration and expiration events of an individual breath and may be used to track breathing rate.
• This impedance measurement process is indicated in the diagram by the dotted line 116 radiating from the electrode site of respiration electrode 114 to the IMD 101.
• Transvenous stimulation of the phrenic nerve from a single lead carrying an impedance measuring respiration electrode is a useful system since it permits minimally invasive implantation of the system. However other architectures are permissible and desirable in some instances.
• Figure 2 is a schematic diagram showing alternative electrode and lead placements for use in carrying out the stimulation regime of the invention.
• it may be easier or more suitable to access the phrenic nerve in the neck in the jugular vein at electrode location 200.
• Other potential locations for the stimulation electrodes are the large vessel (SVC) above the heart indicated by electrode 203. Unilateral stimulation is preferred but having multiple sites available may be used to reduce nerve fatigue. Non-venous placement is possible as well.
• a patch electrode in the pericardial space between the heart and within the pericardial sac is suitable as well, as indicated by electrode location 205.
• the insulating patch 206 isolates spaced electrodes 207 and electrode 208 from the heart.
• the lead 204 connects this bipolar pair of electrodes to the IMD 101.
• FIG. 1 shows a schematic diagram of a system for carrying out the invention.
• the system has an implanted portion 300 and an external programmer portion 301.
• the IMD 101 can provide stimulation pulses to the stimulation electrode 110.
• a companion indifferent electrode 306 may be used to sink or source the stimulation current generated in analog circuits 303.
• a portion of the exterior surface 302 of the IMD 101 may be used with respiration electrode 114 to form an impedance plethy sinograph.
• logic 305 will command the issuance of a train of pulses to the respiration electrode 114 and measure the amplitude of the signal as a function of time in circuits 304. This well known process can measure the respiration of the patient and find the inspiration phase and the expiration phase of a breath. Respiration data collected over minutes and hours can be logged, transmitted, and /or used to direct the therapy.
• the logic 305 commands the stimulation the phrenic nerve via the stimulation electrode 110 at a time after the beginning of the inspiration phase. Preferable the stimulation begins after the onset of exhalation. There is some flexibility in onset of stimulation.
• the shape of the stimulation pulses is under study and it may be beneficial to have the logic 305 command stimulation at higher amplitudes of energy levels as the stimulation progresses. It may also be desirable to have stimulation ramp up and ramp down during the therapy. It may prove desirable to stimulate episodically.
• the therapy may be best administered to every other breath or in a random pattern.
• the programmer may permit the patient to regulate the therapy as well. However in each case the stimulation of the diaphragm "stills" the diaphragm resulting in an amount of air trapped in at least one lung and extends the breath duration.
• the duration of the stimulation is under the control of logic 305. It is expected that the therapy will be dispensed with a fixed duration of pulses corresponding to breathing rate. It should be clear that other strategies for setting the duration of stimulation are within the scope of the invention.
• the breathing rate data can be used to set the stimulation duration to reduce breathing rate to a fraction of the observed rate.
• the therapy may also be invoked in response to detected high rate breathing or turned on at a fixed time of day. In a device where activity sensors are available the device may deliver therapy at times of relative inactivity (resting or sleeping).
• FIG. 4 shows a schematic diagram of an alternate partitioning of the system.
• the respiration sensing is carried out outside the patient with sensor 404, while the implanted portion 400 communicates in real time with an external controller 401 via coils 403 and 402.
• This respiration sensor 404 may be a conventional respiration belt or thermistor based system.
• Real time breathing data is parsed in the controller 401 and control signal sent to the IPG 101 to drive stimulation of the phrenic nerve via lead 107.
• This implementation simplifies IMD 101 portion for the system and may be useful for delivery of therapy to a resting or sleeping patient.
• Figure 5 is set forth as two panels. The data collected from an experimental animal (pig) is presented in the two panels and should be considered together. Panel 5B plots airflow into and out of the animal against time, while panel 5A plots volume against time. In the experiment the volume data was computed (integrated) from the airflow measurement. The two panels are two ways of looking at the same data collected at the same time. In each panel the dotted tracing 500 in 5B and 502 in panel 5 A represent the normal or natural or not- stimulated and therefore underlying breathing pattern of the animal. In panel 5 A the inspiration phase of tracing 502 is seen as segment 514. After tracing 502 peaks, the expiration phase begins as indicated by segment 516. The figure shows that along trace 502, the air that is inhaled is exhaled before 2 seconds has elapsed, as indicated by the dotted trace 502 returning to the zero volume level.
• Trace 504 is associated with the unilateral delivery of stimulation 508 to a phrenic nerve.
• the start of stimulation at time 518 is well after the start of inspiration and corresponds approximately to the reversal of airflow from inspiration to expiration as seen at time 518.
• the animal inhales more air seen by the "bump" 520 in the tracing 504 in panel 5B.
• a small increment in the total volume corresponding to this bump is seen at the same time in panel 5A.
• Of particular interest is the relatively flat tracing 522 corresponding to no significant change in lung volume during stimulation. Once stimulation terminates the lungs expel air as seen at volume change 524 in panel 5A corresponding to outflow labeled 512 in panel 5B.
• FIG. 6 shows a bout 601 of rapid breathing 603 followed by or preceded by apnea 602 events.
• This waveform is a presentation of Cheyne-Stokes respiration (CSR) well known in the prior art.
• CSR Cheyne-Stokes respiration
• the corresponding tracing of blood gas 607 indicates that the rapid breathing drives off blood carbon dioxide (CO2) as indicated the slope of line 606.
• CO2 blood carbon dioxide
• the ventilation drives the CO2 too low resulting in a loss of respiratory drive and an apnea event 602.
• the level of CO2 rises as indicated by the slope of line 604. Once a threshold is reached the cycle repeats.
• Figure 7 shows a schematic diagram showing the delivery of the inventive therapy in the context of a patient experiencing CSR respiration.
• the patient experiences several quick breaths 701 and then the device is turned on as indicated by the stimulation pulses 709.
• the device looks for a natural inspiration and waits until about the turn from inspiration to expiration, then the burst 709 of stimulation is delivered to a phrenic nerve.
• the stimulation delays breath 706.
• This next breath is also a candidate for the therapy and stimulation burst 710 is delivered to the phrenic nerve delaying breath 707.
• the device intervenes in breaths 707 and 708. It is expected that the lower rate breathing resulting from repeated application of the therapy will keep the CO2 level in a "normal" range 715 and prevent CSR.
• the therapy could also be invoked in response to a detected bout of CSR but this is not necessary and it is believed that keeping a patient out of CSR is the better therapy.
• the stimulation waveforms vary in Figure 7 with stimulation 710 rising in amplitude while stimulation 711 decreases in amplitude.
• stimulation 712 ramps up and then down during the therapy.
• the best waveform may vary from patient to patient or may vary over time.
• a refractory period typified by period 730 that may be implemented in the logic 302 to prevent the device from issuing the therapy too close in time to the last intervention.
• the refractory period effectively disables the deliver of therapy until the refractory period expires. This places an effective low rate on stimulated rate of breathing.
• the refractory may be fixed, programmable or adjusted based on sensed breathing rate.

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• 2006
  • 2006-11-17 EP EP06837985.8A patent/EP1960038B8/en active Active
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