Patent Application
20100041970
1. Field of the Invention
The present invention concerns an implantable medical device of the type having an optical oxygen sensor that measures the level of oxygen in oxygenated blood, and that generates an oxygen measurement signal dependent on the level of oxygen.
Description of the Prior Art
Insufficiency of the lungs, like in Chronic Obstructive Pulmonary Disease (COPD), pulmonary edema due to Heart Failure, asthma, chronic bronchitis, emphysema and interstitial lung diseases have high prevalence adding extensive costs to the health care system and suffering for the patients. Therefore, it is a general fact that enhanced management of these patients would be useful.
In the following a number of publications are briefly discussed providing relevant background information in the field of diagnostic methods and apparatuses for detecting insufficiencies of the lungs.
United States Patent Application Publication No. 2003/0149367 relates to a system and method for evaluating risk of mortality due to congestive heart failure using physiological sensors. The method includes that arterial oxygen saturation is measured. Electrodes may be place in the left atrium for atrial pacing. It is mentioned that a combined pacemaker lead and physiological sensor can be used.
EP-1102198 relates to an automated collection and analysis patient care system and method for diagnosing and monitoring respiratory insufficiency and outcomes thereof. The system includes an implantable device for measuring the arterial oxygen saturation.
EP-1151718 relates to an apparatus for monitoring heart failure via respiratory patterns. An implantable device is adapted to measure the arterial oxygen saturation in order to detect changes in the breathing pattern.
U.S. Pat. No. 7,010,337 discloses method and apparatus for monitoring blood condition and cardiopulmonary function, where sensors located on a sensor carrier are placed adjacent one or more of a surgical patient's major thoracic blood-containing structures such as the aorta or pulmonary artery, and characteristics of the blood in the blood-containing structures are determined non-invasively by measuring transmission or reflection of light or other types of energy by the blood.
Further improvements of today's technology are needed in order to meet the increasing demands of devices that enable accurate and reliable detection of lung insufficiencies.
An object of the present invention is to provide a device that has improved capabilities regarding detection and monitoring of a patient's lung function, which may be related to Chronic Obstructive Pulmonary Disease (COPD), pulmonary oedema due to Heart Failure, asthma, chronic bronchitis, emphysema and interstitial lung diseases.
The above object is achieved in accordance with the present invention in an implantable medical device having an oxygen sensor that measures the level of oxygen in oxygenated blood in order to generate an oxygen measurement signal dependent on the level of oxygen, wherein the oxygen sensor performs the measurements in the heart, with regard to blood entering the left atrium of the heart, and wherein the obtained oxygen measurement signal is compared to a predetermined threshold level, and, as a result of the comparison, an indication signal is generated that indicates the lung functionality of the subject.
According to the present invention the degree of oxygen saturation of the blood oxygenized by the lungs, is monitored by an optical blood oxygen saturation sensor.
In particular the oxygen saturation measurement is performed when specified measurement criteria is fulfilled.
According to one embodiment the sensor is placed in or at the left atrium, which directly receives the oxygenized blood from the lungs. A preferred placement of the sensor is in the septum wall between the right and left atria.
An alternative placement is at the endocardium of the left atrium in order to minimise the risk of forming thrombosis.
According to another embodiment the oxygen sensor is mechanically integrated or co-assembled with a pressure sensor.
The sensor is connected to an implantable medical device (IMD). The device is provided with a measuring unit that measures the blood oxygen saturation detected by the oxygen sensor at suitable points in time. At a time, when the patient carrying this IMD, is at rest or asleep, the interference from other sources, that might disturb the sensor measurements, preferably is at a minimum. This is often the best choice of time to perform these measurements. The blood leaving the lungs has normally a high SaO2 value even during high patient workload.
According to an embodiment of the present invention, the degree of oxygen saturation of the blood oxygenized by the lungs is monitored by means of photoluminescence sensor utilizing photoluminescent molecules emitting light as a response to the concentration of oxygen in blood.
In embodiments of the invention, the oxygen sensor is a pO2 sensor, for example, a sensor as described in U.S. Pat. No. 5,431,172 sensitive to the levels of oxygen in arterial blood. It has been shown that the SvO2 and SaO2 values are correlated with the partial pressure of oxygen, pO2, in blood and thus SaO2 values may easily be calculated from measured pO2 values, and vice versa.
In case a lung problem evolves, which causes inadequate oxygenation, this will be measured by the sensor. SaO2 data will be stored and time marked in the IMD and analyzed. The stored data shall be used for diagnostic purposes and by the algorithm which will detect when the SaO2 values are below a certain limit for more than a certain period of time and at conditions which are recognized to give reliable sensor data. Normal patient activity will be recognized by data from an auxiliary sensor, such as an activity sensor. The SaO2 data should normally only be accepted when the activity sensor data indicate a patient at rest. In order to get reliable sensor data they shall be sampled at several times during this period of inactivity and the data shall be at about the same amplitude.
Disturbing influences, such as flying at a high altitude, may result in wrong interpretation of the status of the patient. Other auxiliary sensors, such as accelerometers and posture sensors, are then useful for being able to distinguish flying at high altitude from having impaired oxygenation in the lungs, e.g. by not performing blood oxygen saturation measurements if auxiliary sensors indicate that the patient is flying at a high altitude.
The present invention may also be used for detecting when a patient no longer may saturate the blood during exercise. This may be used for diagnostic purposes to show the physician at which work load this desaturation starts.
The usage of a SaO2 sensor in the left atrium may also be used together with saturation sensors in other parts of the heart or body of the patient. In many cases those algorithms using blood saturation sensors anticipate full saturation of the blood leaving the lungs. An example of that would be in a pacemaker provided with a rate responsive function based on the oxygen saturation in the right ventricle.
The SaO2 value may also be used for detecting impaired oxygenation in the lungs caused by pulmonary edema. The SaO2 sensor may not differentiate pulmonary edema from other lung diseases, but using impedance measurements internally over parts of thorax may indicate that such a condition is at hand.
SaO2-values may be transferred to e.g. databases and physicians using conventional telemetry communication and further on via internet on regular or planned occasions as well as when SaO2 alarm limits have been passed.
The oxygen saturation of blood is generally defined as the percentage of the hemoglobin binding sites that are occupied with an oxygen molecule. An SaO2 value in the range of 97-100% is considered normal, and an SaO2 value in the range of 92-97% indicates interstitial edema and should trigger an alarm to avoid pulmonary edema and hospitalization (this is further discussed below). An SaO2 value below 92% indicates pulmonary edema and the patient should immediately come to hospital.
As illustrated in
According to one embodiment of the present invention the implantable medical device is a heart stimulator which is illustrated in
The electrode lead provided with the optical sensor is adapted to be placed in the left atrium of the heart and in particular to perform measurements in the left atrium from a position reached from the right atrium via the septal wall between the right and left atrium of the heart. To firmly anchor and attach the distal tip within the septal wall the distal end of the electrode lead is provided with anchor means. The anchor means are schematically illustrated in the lower part of
As briefly mentioned above an indication signal is generated if the comparison indicates impaired lung functionality of the patient, e.g. to detect when a patient no longer may saturate the blood during exercise. In particular the indication signal is generated if the measurement signal is below a predetermined oxygen level threshold longer than a preset time period. A predetermined oxygen level threshold is 95% SaO2.
The threshold may naturally be set to any other value, depending on the purpose of the measurement. As stated above, normal values of SaO2 are typically 97-100% and if the value is below 92%, then the patient has severe problems.
In embodiments of the invention, the oxygen sensor is a pO2 sensor, for example, a sensor as described in U.S. Pat. No. 5,431,172 sensitive to the levels of oxygen in arterial blood. It has been shown that the SvO2 and SaO2 values are correlated with the partial pressure of oxygen, pO2, in blood and thus SaO2 values may easily be calculated from measured pO2 values, and vice versa.
In one embodiment of the present invention, the implantable medical device has an oxygen sensor, wherein the oxygen sensor is adapted to perform measurements inside the heart, of blood entering the left atrium of a patient's heart, to obtain a partial pressure of oxygen, pO2, dissolved in the blood, an SaO2 signal corresponding to the obtained pO2 signal is calculated, and the calculated SaO2 signal is compared to a predetermined threshold level and an indication signal is generated in dependence of this comparison, wherein said indication signal is indicative of the lung functionality of the patient.
With reference now to
Further, the sensor has a counter electrode (not shown) adapted to emit electrical current to the system and a reference electrode 24 adapted to sense an electrical potential in the blood or tissue to ensure a proper measurement potential. The sensor is connected to the implantable medical device via an implantable medical lead 26 including connections 27, 28 to the working electrode 22 and the reference electrode, respectively.
According to an embodiment, the sensor 20 is implanted transvenously and, as mentioned above, penetrates the septum 23 to place the outer surface of the working electrode 22 in contact with the blood in left atrium 30. The sensor is fastened to septum 30 by fixation means 31, for example, fixation plates or fixation elements.
Another embodiment of the present invention, a sensor for measuring the concentration of oxygen in blood by means of photoluminescence is arranged in the device for monitoring progression of heart failure in a human heart according to the present invention. Such a sensor is described in PCT/SE2007/000410 (“IMPLANTABLE DEVICES AND METHOD FOR DETERMINING A CONCENTRATION OF A SUBSTANCE AND/OR MOLECULE IN BLOOD OR TISSUE OF A PATIENT”), which is incorporated herein in its entirety by reference.
The sensor comprises a carrier in which photoluminescent molecules are embedded. The carrier is partially in contact with blood of a patient comprising oxygen for which the concentration shall be determined. The sensor further comprises a light source and a photo-detector which are optically connected to the carrier such that the light emitted from the light source can excite the photoluminescent molecules and such that the light emitted from the photoluminescent molecules in response to this excitation can be detected by the photo-detector. The carrier is selectively permeable to the oxygen molecules for which the concentration has to be determined such that oxygen molecules can diffuse from the region of the patient into the carrier. The photoluminescent molecules are selected to react with oxygen in the blood in such a manner that the characteristics of the light emitted from the photoluminescent molecules is altered because of the reaction. Depending on the concentration of oxygen molecules in the blood of the patient, the characteristics of the light emitted from the photoluminescent molecules will then be altered to different degrees. Thus, a determination of the concentration of oxygen in the blood of the patient is enabled.
In an embodiment, the light source and the photo-detector are directly arranged at a side of the carrier or in the carrier. In another embodiment, the light source and the photo-detector are optically connected to the photoluminescent molecules comprised in the carrier by means of optical fibers. The optical fibers may be arranged between the light source and the photoluminescent molecules and/or between the photo-detector and the photoluminescent molecules, which means that the light source and the photo-detector can be arranged at a certain distance from the analyzed region. The optical fibers are used to guide light from the light source and to guide light to the photo-detector, respectively.
In an embodiment, the light source and the photo-detector are fabricated on a same substrate using e.g. standard semiconductor technology. The carrier is then made of a material, such as a silicon adhesive, like e.g. the commercially available Rehau RAU-SIK SI-1511, containing the photoluminescent molecules and spread over the substrate. The substrate can then be used as a support for the light source, the photo-detector and the carrier. Such a substrate would also enable easy connection between the light source, the photo-detector and other components used to analyze the signal output of the photo-detector. The thickness of the adhesive film containing the photoluminescent molecules would typically be comprised between 0.03 and 3 mm.
In yet a further embodiment, the light source and the photo-detector can be fabricated on two separate substrates and joined together by means of the carrier, e.g. the silicon adhesive mentioned above, containing the photoluminescent molecules.
In an embodiment, a filter may be arranged in front of the photo-detector to select the range of wavelength that shall be transmitted to the photo-detector. In particular, the filter is used to eliminate the part of the excitation light emitted by the light source that is reflected by the photoluminescent molecules or by the carrier or carrier matrix.
In further embodiments, the carrier can be made as a material comprised in the group of silicone rubber (also known as polydimethylsiloxane), organosubstitute silicones such as poly(R—R′-siloxane) wherein R and R′ are one of the following {methyl, ethyl, propyl, butyl, “alkyl”, “aryl”, phenyl and “vinyl”} and not necessarily equal to each other, polyurethane, poly(1-trimethylsily-1-propyne), polystyrene, poly(methylmethacrylate), poly(vinyl chloride), poly(isobutylmethacrylate), poly(2,2,2-trifluoroethylmethacrylate), ethylcellulose, cellulose acetobutyrate, cellulose acetate, gas-permeable polytetrafluoroethylene and thermoplastic polyurethanes and copolymers, in which material the photoluminescent molecules are embedded. Further, these materials, in particular silicone rubber, thermoplastic polyurethanes and copolymers, gas-permeable polytetrafluoroethylene, are well adapted in the present invention since they are implantable biomaterials. In a particular embodiment, silicone rubber is well adapted if the sensor 1 is used to determine the concentration of oxygen in the region 10 since its permeability to oxygen is about ten times higher than in most polymeric materials, namely 6.95×1011 cm−2s−1Pa−1, which corresponds to a diffusion coefficient of about 1.45×10−5 cm2s−1.
The light source may be a solid state light source, preferentially a light emitting diode, which is advantageous since light emitting diodes are small and can therefore easily be incorporated in the sensor. Light emitting diodes are advantageous since the intensities, wavelengths, and time responses are controllable. Light emitting diodes can emit at various ranges, which generally extend from 390 nm to 1650 nm although not any wavelength of this range may be achieved.
The sensitivity of the photo-detector of the implantable sensor depends on the wavelength range at which the photoluminescent molecules emit. Generally, the range of wavelength at which photoluminescent molecules emit extend from 350 to 1800 nm, in particular in the range of 350-800 nm. Thus, the photo-detector shall be sensitive in this range of wavelength. As the wavelength at which selected photoluminescent molecules emit is known, the sensitivity of the photo-detector can be selected accordingly. As an example, oxyphors emit light at about 800 nm, which corresponds to near infrared. In this case, the photo-detector may be a commercially available planar InGaAs photodiode, which is sensitive to red and infrared light, i.e. in the spectral range of 800-1800 nm. Such a detector has a response time of up to 120 MHz, which is sufficiently rapid for measuring photoluminescent lifetimes and sufficiently quantitative for steady state measurements of intensities as well. The measurements of lifetimes and intensities will be described in more details later. In particular, the photo-detector may be one of the group comprised of a pn photodiode, a pin photodiode, a Schottky photodiode, an avalanche photodiode, a silicon photodiode, a planar InGaAs photodiode, a SiGe-based optoelectronic circuit and a InGaN/GaN multiple quantum well pn junction.
The photoluminescent molecules may be fluorescent molecules or phosphorescent molecules. Although it would be preferable to use fluorescent molecules as they are generally more stable over time, it is preferable to use phosphorescent molecules as phosphorescence leads to longer timescale, which then facilitates the design of the electronics in the sensor.
Since the sensor is designed to determine the concentration of oxygen in blood, it is preferable that the photoluminescent molecules are not sensitive to other gases than oxygen such as carbon monooxide which can also be found in blood. The photoluminescent molecules shall also be easily bounded to the material of the carrier, i.e. they should be compatible with the characteristics of the carrier.
Photoluminescent molecules that may be used to determined the concentration of oxygen are molecules comprised within the group of pyrene, pyrene derivatives (vinylpirene, methoxypyrene), a polyaromatic carrier, an ionic probe (ruthenium trisbypyridine) and Pd-tetra(4-carboxyphenyl)benzoporphin (Oxyphor). Additional examples are naphthalene derivatives (e.g. 2-dimethylamino-6-lauroylnaphthalene); polypyridyl complexes of transition metals, particularly Ruthenium, Osmium, or Rhenium containing fluorescent molecules {e.g. Ru(bipy)(3)(2+)(tris(2,2′-bipyridyl)ruthenium(II)chloride hexahydrate) and Ru(phen)(3)(2+)(tris(1,10-phenanthroline)ruthenium(II)chloride hydrate)}; fullerenes (C60 and C70); decacyclene; perylene and perylene derivatives (e.g.—perylene dibutylate); and metalloporphines especially Pt(II), Zn(II) and Pd(II) variants.
By including a pressure sensor in connection with the oxygen sensor as illustrated in
In combination with a heart stimulating means, both the oxygen saturation signal and a pressure signal may be used to control the stimulation rate.
The medical device comprises a pressure measurement interface means connected to the pressure sensor.
Different types of pressure sensors may be used. In
As in the embodiment illustrated in
As briefly mentioned above a further embodiment of the medical device comprises an auxiliary sensor adapted to generate an auxiliary measurement signal in dependence of a measurement influencing activity. The blood oxygen measurements are then performed when the auxiliary measurement signal fulfills specified measurement criteria. The reason to include an auxiliary sensor is to ensure that the oxygen measurements are performed with minimal disturbance or interference from other sources, e.g. when the patient is at rest or asleep.
The auxiliary sensor may be an activity sensor, a patient position sensor, or an impedance sensor. The impedance sensor preferably measures the impedance between the electrode lead and the conductive encapsulation of the implantable medical device.
The specified measurement criteria includes that the auxiliary measurement signal is below a specified level, or as an alternative, that the auxiliary measurement signal is above a specified level.
The following is an exemplary description of the function of the implantable medical device provided with an activity sensor, also functioning as a position sensor, and an impedance sensor as two auxiliary sensors.
Limit sensor values are initially set for activity and position, and limits are also set for persistence of activity and rest. The control means then starts to receive data from the position, activity and impedance sensors. Dedicated counters in the control unit are incremented as a result if detected rest and supine position, respectively, and when these counters have passed its respective limit, status flags are set to “1”. If both flags are “1” the SaO2 measurement starts and the measurement is performed as long as the status flags indicate that the measurement conditions are acceptable.
When the oxygen measurement is performed during a predetermined time interval, e.g. 10-30 minutes, an average value is determined and compare to a threshold as discussed above. If the average value is below the threshold an impedance measurement between electrodes in relevant position in thorax may be performed in order to confirm possible pulmonary edema. An alarm may then be generated via the telemetry communication means to an external device to alert the physician.
As an alternative, the measured SaO2 values are stored in a storage means in the control means to be further analyzed at a later follow-up procedure.
Although the present invention in particular relates to embodiments showing SaO2 measured parameters, other oxygen related parameters may be used such as pO2 as disclosed in U.S. Pat. No. 6,236,873 which is incorporated herein by reference. Measurement electrodes, adapted to perform pO2 measurements, are then included at the distal part of the electrode lead, and the control unit then includes specific hardware and/or software to handle the measurements.
Although modifications and changes may be suggested by those skilled in the art, it is the intention of the inventors to embody within the patent warranted heron all changes and modifications as reasonably and properly come within the scope of their contribution to the art.
| Number | Date | Country | Kind |
|---|---|---|---|
| PCT/SE2007/000289 | Mar 2007 | SE | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/SE07/01044 | 11/27/2007 | WO | 00 | 9/21/2009 |
