System and sensor for early detection of shock or perfusion failure and technique for using the same

RELATED APPLICATION

p-0002This application claims priority from U.S. Patent Application No. 61/009,736 which was filed Dec. 31, 2007 and is incorporated herein by reference in its entirety.

BACKGROUND

p-0003The present disclosure relates generally to medical devices and, more particularly, to a sensor placed on a mucosal tissue used for measuring physiological parameters of a patient.

p-0004This section is intended to introduce the reader to various aspects of art that may be related to various aspects of the present disclosure, which are described and/or claimed below. This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of the various aspects of the present disclosure. Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art.

p-0005In the field of medicine, doctors often desire to monitor certain physiological characteristics of their patients. Accordingly, a wide variety of devices have been developed for monitoring many such characteristics of a patient. Such devices provide doctors and other healthcare personnel with the information they need to provide the best possible healthcare for their patients. As a result, such monitoring devices have become an indispensable part of modern medicine.

p-0006In some instances, physicians may wish to have information about the clinical state of tissues that are not easily accessible, such as gastrointestinal tissue. For example, clinicians may wish to assess certain parameters of gastrointestinal tissue to determine whether a patient is in shock. Shock is a clinical syndrome characterized by decreased blood flow to the capillary beds. This condition typically occurs when arterial pressure and subsequently tissue blood flow decrease to a degree that the amount of delivered oxygen is inadequate to meet the metabolic needs of the tissue. During shock, the body directs blood to the heart and the brain, often at the expense of relatively less important organs such as the liver, skin, muscle, and gut. Prolonged shock may result in ischemia in tissues that have experienced diminished blood flow for a sufficient length of time. Ischemia in the gut may disrupt the normal intestinal barrier function, resulting in gut-derived bacteria and their endotoxins being able to move from the gut into other organs via the blood. This, in turn, may lead to toxemia or sepsis. Therefore, early detection of gut tissue damage may prevent the onset of shock or organ failure.

p-0007As prolonged gut hypoperfusion typically precedes gut ischemia, early detection of perfusion failure in the gut may prevent widespread tissue damage and may also reduce the incidence of toxemia or sepsis. Accordingly, physicians have developed methods for assessing hypoperfusion in the gut. However, these methods are associated with certain disadvantages. For example, assessing the hypoperfusion of gastrointestinal tissue by impedance spectroscopy may provide clinical information regarding shock, mucosal perfusion, or ischemia. This procedure involves insertion of an intestinal catheter, which is labor-intensive for a clinician to perform and uncomfortable for patients. An alternative technique uses an ion-sensitive field-effect transistor (ISFET) sensor to detect PCO₂in the gastric wall, which also correlates to the onset of shock. However, this technique is also invasive and involves direct contact with the gut.

p-0008Accordingly, a reliable, noninvasive monitor for gut perfusion failure may improve the diagnosis and management of patients with gut ischemia.

SUMMARY

p-0009Certain aspects commensurate in scope with the disclosure are set forth below. It should be understood that these aspects are presented merely to provide the reader with a brief summary of certain forms the disclosure might take and that these aspects are not intended to limit the scope of the disclosure. Indeed, the disclosure may encompass a variety of aspects that may not be set forth below.

p-0010There is provided a diagnostic physiological monitoring system that includes a first electrode capable of applying a current to an oral or nasal mucosa of a patient; a second electrode capable of detecting the applied current from the mucosa and output a value related to electrical impedance of the mucosa; and a monitor operatively coupled to the first electrode and the second electrode, wherein the monitor is capable of receiving the impedance value and performing an operation on the impedance value to determine a gastrointestinal tissue condition of the patient.

p-0011There is also provided a method that includes receiving an impedance measurement from at least two electrodes attached to an oral or nasal mucosa and analyzing the impedance measurement to determine a clinical condition including at least one of gut hypoperfusion, gut ischemia, shock, or organ failure.

p-0012There is also provided a method of asserting a shock treatment protocol, including attaching at least two electrodes to an oral or nasal mucosa, wherein the electrodes are configured to transmit an impedance measurement to a monitor that is operatively coupled to the electrodes; observing an alarm on the monitor, wherein the alarm is configured to indicate a shock condition by analyzing the impedance measurement; and proceeding with a shock treatment protocol.

p-0013There is also provided a sensor configured to detect gut ischemia that includes a first electrode capable of applying a current to an oral or nasal mucosa, a second electrode capable of detecting the applied current and output a value related to the impedance of the mucosa, a nonconductive sheet adapted to space the first electrodes and the second electrode at a generally fixed distance relative to one another, and a mucoadhesive layer disposed on a mucosal tissue-contacting side of the first electrode and the second electrode.

BRIEF DESCRIPTION OF THE DRAWINGS

p-0014Advantages of the disclosure may become apparent upon reading the following detailed description and upon reference to the drawings in which:

p-0015<figref idrefs="DRAWINGS">FIG. 1</figref> is a side view of an electrical impedance sensor showing a mucoadhesive layer attached to mucosal tissue according to an embodiment;

p-0016<figref idrefs="DRAWINGS">FIG. 2</figref> illustrates a perspective view of a patient with the sensor placed on buccal tissue for evaluation of tissue impedance according to an embodiment;

p-0017<figref idrefs="DRAWINGS">FIG. 3</figref> illustrates a perspective view of an electrical impedance sensor with two electrodes placed on a flexible non-conducting sheet according to an embodiment;

p-0018<figref idrefs="DRAWINGS">FIG. 4</figref> illustrates a perspective view of a monitoring system according to the present disclosure according to an embodiment;

p-0019<figref idrefs="DRAWINGS">FIG. 5</figref> a schematic view of the system of <figref idrefs="DRAWINGS">FIG. 4</figref>;

p-0020<figref idrefs="DRAWINGS">FIG. 6</figref> illustrates a flow chart for monitoring a patient according to an embodiment; and

p-0021<figref idrefs="DRAWINGS">FIG. 7</figref> illustrates a flow chart for monitoring a patient and administering a shock protocol according to an embodiment.

DETAILED DESCRIPTION

p-0022One or more embodiments of the present disclosure will be described below. In an effort to provide a concise description of these embodiments, not all features of an actual implementation are described in the specification. It should be appreciated that in the development of any such actual implementation, as in any engineering or design project, numerous implementation-specific decisions may be made to achieve the developers' specific goals, for example compliance with system-related and business-related constraints, which may vary from one implementation to another. Moreover, it should be appreciated that such a development effort might be complex and time consuming, but would nevertheless be a routine undertaking of design, fabrication, and manufacture for those of ordinary skill having the benefit of this disclosure.

p-0023According to various embodiments ensors and monitoring systems are provided herein that may detect gut ischemia by monitoring the electrical impedance of oral and/or nasal mucosal tissue. The electrical impedance of oral or nasal mucosal tissue may serve as an indicator of several gastrointestinal tissue conditions including gut ischemia, gut injury, gut hypoperfusion. Additionally, such sensors may be useful for predicting the onset of shock or organ failure. Generally, monitoring occurs while an electrical impedance sensor is secured to oral or nasal mucosal tissue, for example with a mucoadhesive. A sensor may be attached to any oral or nasal mucosal tissue that may be easily accessible to a healthcare worker, for example, buccal or sublingual tissue.

p-0024Generally, it is envisioned that electrical impedance sensors according to various embodiments may be appropriate for use in determining the electric impedance level in mucosal tissues. Electrical resistance of the mucosal tissue reflects the conducting properties of electrolytes and other components within the tissue, and the overall impedance reflects the interaction of these components within a complex tissue structure. As a result, electrical properties in tissue exhibit change as ischemia or perfusion failure occurs in the area. In the case of perfusion failure of internal organs, mucosal tissue in the gut and esophagus exhibit these changes as the condition advances. For example, as ischemic injury progresses, inflammatory mediators affect the membrane permeability of various cells within the gastrointestinal tissue. As a result, the balance of intracellular volume and extracellular volume changes as ischemia develops. The disruption of cell membrane permeability also affects cell transport and cell death. Each of these changes causes a shift in the electrical properties of the cells, and in turn the tissue, that may be assessed by measuring the electrical impedance of the tissue. Because the tissue of the gut is physically linked to the mucosal tissue of the upper gastrointestinal tract, hypoperfusion of the gut results in a corresponding reduction in blood flow to the mucosal tissue of the mouth and nose. Accordingly, impedance analysis of oral or nasal mucosal tissue may be useful in early detection of gut hypoperfusion.

p-0025According to various embodiments, sensors for measuring electrical impedance of mucosal tissue of the upper gastrointestinal tract may include one or more electrodes for measuring electrical impedance. For example, one or more electrodes may be secured inside the cheek or under the tongue. Further, the sensors as described herein are appropriate for use adjacent to or proximate to any mucosal surface, i.e. patient surfaces that include a mucous membrane or surfaces that are associated with mucus production. In addition to the oral mucosa, mucosal surfaces may include anal, respiratory (i.e. nasal) or urogenital surfaces. Additionally, oral or nasal mucosal impedance measurements may be part of a larger patient monitoring strategy that includes monitoring of health rate, blood pressure and/or blood oxygen saturation.

p-0026Electrical impedance sensors in accordance with the present disclosure may include one electrode for applying an electrical current and one electrode for detecting the voltage drop of the applied current as a result of the impedance of the tissue. In one embodiment, at least one current source electrode sends a small, high frequency sinusoidal current through the tissue. At least one detecting electrode measures the resulting voltage drop and phase lag of the sinusoidal current that has passed through the tissue. The electrodes may be disposable or reusable. In addition, the electrodes may be appropriate for short-term (e.g. minutes) or long-term (e.g. hours, days, or longer) monitoring. The electrodes may also be of various sizes or types depending upon the patient, measurement period, and other specifications. Generally, the impedance sensor includes at least one current sourcing electrode and at least one voltage detecting electrode. It should be noted that, in one embodiment, it may be appropriate to use an array of current source electrodes and detecting electrodes.

p-0027Turning now to the drawings, and referring to an embodiment in <figref idrefs="DRAWINGS">FIG. 1</figref>, sensor <b>10</b> is shown that includes current source electrodes <b>11</b> and voltage detection electrode <b>13</b>, with a mucoadhesive layer <b>12</b> on the skin contacting surface of the electrode. Not pictured is a monitoring device, which may be connected to sensor <b>10</b> by lead <b>14</b>. In the present embodiment, the mucoadhesive layer <b>12</b> affixes the sensor <b>10</b> to the oral mucosal tissue <b>16</b> of the patient. Components of sensor <b>10</b> and lead <b>14</b> may be made of any suitable material that may be generally suited to the aqueous environment of the mucous membrane, for example plastic. In other embodiments (not shown), it may be advantageous to package the electrodes in foil or other protective materials in order to protect the mucoadhesive layer <b>12</b> prior to use and to prevent drying out or oxidation of the mucoadhesive layer <b>12</b>.

p-0028The electrodes <b>11</b> and <b>13</b> may be of any suitable type for bioimpedance measurements, such as those offered for sale by Biopac Systems, Inc. (Goleta, Calif.). As should be appreciated, conductive gels (not pictured) may be used to enhance the electrical connection between the mucosal skin and the electrode. In an embodiment, a conductive gel may be used in a central area of the body of the electrode and may be surrounded by a mucoadhesive to ensure that the gel does not leak out from the electrode and to ensure that a conductive path to the electrode may be maintained. An alternative embodiment may include a gel substance that performs as both a mucoadhesive and a conductive gel.

p-0029In an embodiment, the sensor <b>10</b> may be secured to the oral or nasal mucosal tissue with a mucoadhesive or other suitable mounting device, such as a clip. The mucoadhesive layer may be applied to a flexible fabric or plastic non-conductive sheet which may be the portion of the electrode that may directly contact the mucosal surface. A secure mounting of the sensor to oral or nasal mucosal tissue with mucoadhesives reduces movement of the sensor, which may cause signal artifacts. Use of a mucoadhesive also prevents fluids or other substances from interfering with the sensor measurement while securing the sensor to the mucous tissue. The term mucoadhesive refers to a substance that sticks to or adheres to the mucous membrane by any number of mechanisms, for example, but not limited to the following: hydrogen-bonding, ionic interaction, hydrophobic interaction, van der Waals interaction, or combinations thereof.

p-0030In an embodiment, the mucoadhesive layer <b>12</b> may include a variety of mucoadhesive compositions to secure electrodes to mucosal tissue according to the present disclosure. As one of ordinary skill in the art may recognize, a mucoadhesive substance may be chosen that allows electrical signals to be conducted and received from the mucosal tissue to the electrodes. Suitable mucoadhesives include, but are not limited to hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethylcellulose, ethylcellulose, carboxymethylcellulose, dextran, guar gum, polyvinyl pyrrolidone, pectins, starches, gelatin, casein, acrylic acid polymers, polymers of acrylic acid esters, vinyl polymers, vinyl copolymers, polymers of vinyl alcohols, alkoxy polymers, polyethylene oxide polymers, polyethers, and any combination of the above.

p-0031In various embodiments, the mucoadhesive may be a biocompatible polymer, for example polyacrylic acid, that may be cross-linked with an acceptable agent to create an insoluble gel. The use of an insoluble gel may be desirable, particularly for long term monitoring, since it remains adhered to the mucosal tissue for relatively long periods of time. Cross-linked polyacrylic acid polymers, for example Noveon and Carbomer, may be appropriate for use for three to five days or longer. Noveon and Carbomer-based polymers are weak acids and contain many negatively-charged carboxyl-groups. The multiple negative charges on these polymers promote hydrogen-bonding between the polymers and the negatively charged mucin, a glycoprotein that mediates attachment of mucus to the epithelial lining. A mucoadhesive polymer may also include acrylic acid polymers (e.g. Carbopol® 940, also known as Carbomer® 940, Carbopol 934P and Carbopol® 980, products of BF Goodrich), methyl vinyl/maleic acid copolymers (e.g. Gantrez® S-97, a product of International Specialty Products), polyvinyl pyrrolidone also known as povidone (e.g. Plasdone® K-90, a product of International Specialty Products). These polymers impart relatively high viscosity at relatively low concentrations. They may be incorporated onto a sensor in amounts ranging from about 0.01% to about 10% by weight relative to the total composition. These viscosity modifying agents further act to improve the film adhesion of the composition to mucous membranes. Carbopol® 980, in one embodiment, may be 2-3% by weight of the total composition.

p-0032In an embodiment the mucoadhesive may be formulated as either a liquid or as a gel. If a liquid formulation may be desired, a relatively low concentration (e.g. 0.1-1%) of the mucoadhesive/viscosity modifying agent may be used. If a gel formulation is desired, a higher concentration (e.g. 1.5-4%) of the suitable viscosity modifying/mucoadhesive agent may be incorporated into the polymethacrylate/solvent vehicle for gel formation. The mucoadhesive may further comprise excipients e.g. plasticizers, flavorings, sweeteners and/or colorants. Examples of plasticizers include triethyl citrate, polyethylene glycol and glycerin. Such plasticizers may be present in amounts generally ranging from about 1% to about 10% by weight relative to the total composition. For example, glycerine may be present in the amount of about 1 to about 5% by weight. Polyethylene glycol and triethyl citrate may be used in the amount of about 5% to about 12%, in one embodiment.

p-0033<figref idrefs="DRAWINGS">FIG. 2</figref> illustrates the sensor <b>10</b> including the electrodes <b>11</b> and <b>13</b>, as placed inside the mouth of the patient <b>18</b> on the buccal tissue, according to an embodiment. The electrodes <b>11</b> and <b>13</b> may be suitably sized and shaped such that the patient <b>18</b> may easily close his or her mouth around the electrodes with minimal discomfort. The present embodiment shows two electrodes <b>11</b> and <b>13</b> that are not fixed in distance relative to one another. In this case, analysis of impedance measurements allows a variable distance between the electrodes. Such an embodiment may be appropriate for assessing changes in the electrical of the tissue over time. Once electrodes <b>11</b> and <b>13</b> are placed in the patient's mouth, impedance changes in the oral mucosa may be monitored. In such an embodiment, the collected impedance measurements may be assessed for changes that fall outside of a statistical deviation, which may signal the onset of hypoperfusion. For example, a running average of the impedance measurements may be calculated. If the running average changes at a rate faster than a predetermined threshold, an alarm may be activated.

p-0034An embodiment is shown in <figref idrefs="DRAWINGS">FIG. 3</figref> in which electrodes <b>11</b> and <b>13</b> are capable of being placed at a predetermined, fixed distance apart on the mucosal tissue. The embodiment uses a flexible non-conducting sheet <b>20</b> to maintain fixed spacing between the electrodes. The flexible non-conducting sheet may be made of any suitable material, such as plastic, neoprene, or rubber. A mucoadhesive layer (not pictured) may be placed on the tissue contacting surface of the non-conducting sheet to adhere the sensor to the mucosal tissue. In the embodiment, the electrical impedance data may be compared to a threshold or a reference value that has been empirically determined in order to assess if the impedance measurement is within an acceptable predetermined range. The electrodes <b>11</b> and <b>13</b> may be placed on the oral mucosa at a fixed distance that correlates to the distance at which the reference data was collected. For example, the electrical impedance of the oral mucosal tissue may be assessed prior to surgery to provide a reference value, and then the impedance may be spot-checked during a surgical procedure. In another embodiment the distance between the electrodes may be measured by a monitor. In the embodiment, the impedance value would be scaled, according to the measured distance, to correlate the measured impedance value with the distance at which the reference value was collected.

p-0035The diagram of <figref idrefs="DRAWINGS">FIG. 4</figref> shows a monitor <b>22</b>, which may be a component of an exemplary impedance monitoring system <b>24</b>. The system <b>24</b> may also include a sensor <b>10</b> with a lead <b>14</b>. The monitor <b>22</b> may be any suitable device for reading, recording, processing, and/or displaying the impedance measurement as well as the state of the gut tissue. A schematic view of the impedance monitoring system <b>24</b> is shown in <figref idrefs="DRAWINGS">FIG. 5</figref>. Sensor <b>10</b> may be connected to transmit an impedance measurement to monitor <b>22</b>. In the present embodiment, the monitor <b>22</b> may include an analog-to-digital converter <b>25</b> as well as a microprocessor <b>26</b>, which provides analysis of the measurement data. As will be appreciated by one of ordinary skill in the art, the measurement data may be stored in a memory <b>28</b> and may also be displayed on a display <b>30</b> as an alarm or by other graphical means. The display <b>30</b> may be part of the monitor <b>22</b> or it may be separate. Further, the monitor <b>22</b> may include a driver (not shown) to drive the current to the current source electrode <b>11</b>.

p-0036The monitor <b>22</b> may be capable of receiving signals from the sensor <b>10</b> related to the electrical impedance of a patient's mucosal tissue. The signals sent from the sensor <b>10</b> may include a code or other identification parameter that may allow the monitor <b>22</b> to select an appropriate software instruction for processing the signal. Based on the value of the received signals corresponding to voltage drop across the electrodes <b>11</b> and <b>13</b>, the microprocessor <b>26</b> may calculate the electrical impedance using various algorithms. The impedance Z may be calculated as the ratio of voltage (V) to current (I); i.e., Z=V/I. In addition, the memory <b>28</b> may contain comparison charts or tables for comparing measured impedance or measured impedance changes with clinically-derived impedance values that may correlate with specific disease states. In one embodiment, the processing algorithm may receive the voltage measurement and calculate a numerical indicator of the electrical impedance for display. In one embodiment, an algorithm may use as input electrical impedance data to output a more qualitative display output that correlates to a patient clinical condition.

p-0037In an embodiment, a threshold impedance value, based on reference data, may be established for the impedance measurement. As long as the measured impedance value remains well below the threshold value, the monitor <b>22</b> may illuminate a corresponding green light, indicating a “healthy” status. If the measurement value is within a predetermined range, e.g. within 5% of the threshold, then a yellow light may be illuminated, signaling a “warning” status. The “warning” range may correlate to an acceptable standard variance, as determined by statistical analysis of impedance data. Finally, if the measurement exceeds the threshold impedance, a red light may be displayed, indicating a clinical condition of gut hypoperfusion.

p-0038In an embodiment, the analysis of the impedance measurement data may include a threshold comparison to the raw data. Alternatively, the analysis may include a comparison of the threshold to a running average or mean of the measurement, to ensure that measurement errors do not result in false alarms. The aforementioned analysis may correspond to an embodiment where predetermined reference data may be used to establish a threshold impedance value. In another embodiment, the impedance data may be monitored for changes in value. In the corresponding embodiment, a threshold may be established for an alarm by a change that exceeds a certain percentage difference, as compared to a prior reading. Again, the impedance change data may use raw values, comparing successive readings, or the data may constitute a comparison of the running average to an average of prior data, to avoid false alarms.

p-0039<figref idrefs="DRAWINGS">FIG. 6</figref> is a flow chart of an embodiment of a perfusion failure monitoring system. In the embodiment, the impedance of the oral mucosal tissue of a patient may be measured (block <b>32</b>). Next, the measurement data may be analyzed to determine if perfusion failure is present by comparing the data to a threshold, for example (block <b>34</b>). If perfusion failure is present, then the clinician is notified of the condition (block <b>36</b>). For example, the clinician may be notified by an audible alarm and/or a flashing red light. If no perfusion failure is detected, then the impedance of the mucosal tissue may continue to be evaluated.

p-0040In one embodiment, the disclosed method of monitoring hypoperfusion in the gut may be used during a surgical procedure. In such an embodiment, a plurality of baseline measurements of the mean oral electrical impedance may be recorded, for example over a five or ten minute period prior to the surgery. These baseline measurements may then be used to compute a baseline value of mean oral electrical impedance as well as the standard variance. After the data are collected for determining the baseline value and the variance, the electrical impedance values of the oral mucosal tissue may be periodically measured between the electrode pair over the course of the surgery. The data representing these periodically measured impedance values may be compared against the stored baseline values, as shown in block <b>34</b>. If the measured electrical impedance varies from the baseline and standard variance, an alarm may be triggered to alert the surgeon to possible hypoperfusion in the gut, as discussed above.

p-0041<figref idrefs="DRAWINGS">FIG. 7</figref> shows a detailed example of an embodiment of the process that may lead to detection of hypoperfusion and a shock protocol that may be administered in response to the alarm. Initially, an oral mucosa monitoring system may be connected to a subject (block <b>38</b>). The impedance of the oral mucosal tissue may be then continuously monitored (block <b>40</b>). The impedance measurement may be analyzed as discussed above to determine the presence of perfusion failure (block <b>42</b>). If no perfusion failure is detected, then the tissue continues to be monitored. If perfusion failure is detected, then medical staff may be alerted to subsequently administer a shock protocol (block <b>44</b>). In the present embodiment, the first step of shock protocol may be to provide oxygen via airway management (block <b>46</b>). Subsequently, efforts are made control and limit the patient's bleeding (block <b>48</b>). The shock protocol may also include fluid replacement and therapy and/or antibiotic therapy (blocks <b>50</b>, <b>52</b>). As will be appreciated by one of ordinary skill in the art, the steps that may be performed during a shock treatment procedure may vary depending upon the stage of the patient's shock and guidelines provided by different healthcare institutions. One embodiment may include administration of Early Goal Directed Therapy (EGDT), such as the protocol described by Rivers et al in “Early goal-directed therapy in the treatment of severe sepsis and septic shock.” <i>N Engl J Med </i>2001; 345, 1368-1377, the text of which is incorporated by reference herein for all purposes.

p-0042While the disclosure may be susceptible to various modifications and alternative forms, embodiments have been shown by way of example in the drawings and have been described in detail herein. However, it should be understood that the embodiments are not intended to be limited to the particular forms disclosed. Indeed, the present disclosure may not only be applied to measurements of electrical impedance, but the disclosure may also be utilized for the measurement and/or analysis of other electrical properties of the tissue. Rather, the disclosure is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the disclosure as defined by the following appended claims. It will be appreciated by those working in the art that sensors fabricated using the present disclosure may be used in a wide variety of contexts.