1-3.

DESCRIPTION

Organs, tissue, and fluid in a human body possess an ability to conduct electricity due to their components and environment. A body is composed of cells, fluid, and/or air compartments that include a mixture of electrically conductive and resistive components. The mixture of conductive and resistive components determines the electrical properties of a given environment or portion of a body. Impedance, as used herein, refers to the ability to resist electrical currents and consists of two components: resistance and capacitive reactance. Cells, fluid, and/or air spaces all contribute to the electrical impedance that a given location, environment, organ, or tissue exhibits. When physiological changes occur at a particular location in the body the electrical impedance at that location may be measurably altered.

Pleural, pulmonary or cardiac pathology has the potential to be rapidly detrimental to the health of patients if not fatal by affecting the function of the lungs, pleural space, heart and/or pericardium. No real-time continuous monitoring system that takes readings directly from the surface of the lung or pleural space or pericardium is currently available. Chest tubes are commonly in use in pleural, pulmonary, or cardiac pathology and come into direct contact with the lung, pleural space, or heart/pericardium, but these tubes are not being used as sensors or to gather data; alternatively, sensors placed within the pleural space or pericardium could function independently of chest tubes. Electrical impedance/resistance measurement can be used to identify pathologic changes to the lung/pleural space (e.g., pneumothorax) due to the inherent electrical resistance of the air-filled lung. Electrical impedance/resistance measurement can be used to identify pathologic changes to the heart/pericardial space due to the inherent electrical resistance patterns of the beating heart.

A pneumothorax is an abnormal collection of air or gas in the pleural space that causes an uncoupling of the lung from the chest wall. Like pleural effusion (liquid buildup in the pleural space), pneumothorax may interfere with normal breathing. A primary pneumothorax is one that occurs spontaneously without an apparent cause and in the absence of significant lung disease, while a secondary pneumothorax occurs in the presence of existing lung pathology. A pneumothorax can be caused by physical trauma to the chest, or as a complication of medical or surgical intervention. In some cases the amount of air in the chest increases markedly when a one-way valve is formed by an area of damaged tissue, leading to a tension pneumothorax. This condition is a medical emergency that can cause steadily worsening oxygen shortage and low blood pressure. Unless detected and reversed by effective treatment, these sequelae can progress and cause death. Symptoms typically include chest pain and shortness of breath. Diagnosis of a pneumothorax by physical examination alone can be difficult or inconclusive, so a chest radiograph or computed tomography (CT) scan is usually used to confirm its presence.

Because the lungs are an inherently electrically resistive organ owing to the presence of air within the pulmonary alveoli (lung air sacs), the measurement of electrical resistance/impedance from the lung has been suggested as a sensitive detector of lung pathology and devices which measure electrical resistance/impedance from the lung are presently commercially available. Sensors can be inserted in the pleural space (i.e., pleural sensors) and be coupled to a detector by a transmission lead. The transmission lead can connect one or more sensors to a measurement determining unit or detector. Sensors may transmit data to a microcontroller. The microcontroller can be configured to produce a therapeutic intervention when the impedance/resistance deviates beyond a pre-selected range or to monitor the impedance/resistance over time, thus detecting and correcting alterations in the environment surrounding a sensor. Thus, the microcontroller forms part of an impedance monitoring circuit.

In one embodiment, the sensor can include, but is not limited to one or more bare metal wires configured in such a way as to promote contact of the wires with the surface of the lung or with the surface of the chest wall, diaphragm, heart or pericardium.

In one embodiment, the sensor or sensors are embedded in a thoracostomy tube; such tubes are generally made of soft plastic or silicone material and typically have one or more perforations in the distal end of the tube to facilitate the evacuation of fluid and/or air from the pleural or pericardial space.

To demonstrate the utility of electrical impedance measurements obtained directly from the surface of the lung to monitor lung integrity, an electrical impedance sensor was constructed that could be embedded in a chest tube to be placed into the pleural space of an experimental animal. An example of such a sensor is pictured in FIG. 1-3. The sensor consisted of electrical contact points fashioned from temporary cardiac pacing wires (A&E Medical, Farmingdale, NJ; cat. #021-001) (FIG. 1 (1,2)) which were connected to connecting wires (FIG. 1 (3)) with the contact end of the pacing wires (FIG. 1 (1,2)) embedded in the exterior surface of the distal end of a silicone chest tube (Medline, Northfield, Ill; cat. #AXX100028) (FIG. 1 (4)). The outer electrodes (FIG. 1 (1)) were configured to deliver electrical current (I) between them while the inner electrodes (FIG. 1 (2)) were configured to measure the voltage drop (V) between them.

The connecting wires of the electrodes (FIG. 2 (3)) were brought along the outside of the length of the chest tube (FIG. 2 (4)) and connected to the impedance monitoring device (not shown) by the proximal pacing wire contact points (FIG. 2 (5)). The impedance measuring device (not shown) calculated impedance (Z) based on the formula: Z=V/I. Because the chest tube (FIG. 1 (4), FIG. 2 (4)) was made of silicone, an electrically non-conducting material, it functioned as an insulator to prevent the transmission of current between the electrodes in the absence of contact of the electrodes with tissue. Only in the case of all electrodes (FIG. 1 (1.2), FIG. 2 (1.2)) coming into contact with the same experimental animal tissue would current flow between them; without electrode tissue contact the current flow (I) would be zero rendering the measured value for impedance (Z) infinite. An alternative version of the sensor is shown in FIG. 3 and consisted of the bare pacing wire internal contact points (FIG. 3 (1.2)) embedded in an electrically insulating silicone cap (FIG. 3 (6)) and placed in the pleural space in contact with the lung surface and insulated against the chest wall of the experimental animal (not shown); the connecting wires of the electrodes (FIG. 3 (3)) were brought out of the experimental animal and connected to the impedance measuring device (not shown).

In order to provide a system that can continuously monitor a subject with a chest tube using impedance measurement (FIG. 1,2) or a free-standing intra-pleural impedance sensor (FIG. 3), the inventors previously have used a pig model of lung collapse to study and design an intervention system based on impedance measurements from a sensor positioned in the chest of an individual (illustrated in FIG. 4). This model consisted of two chest tubes located in the pleural space of the pig. One chest tube was meant to represent a conventional, therapeutic chest tube as used in human patients, i.e., which is connected to a suction device or alternatively only to a non-suction one way valve allowing any air present in the pleural space to be removed, maintaining full lung expansion. The second tube was used to introduce air into the pleural space at defined air-flows to mimic a pathologic air leak from the lung. The rationale for this model was that in human patients it is sometimes preferable from a clinical standpoint to provide suction via chest tubes in the pleural space to maintain full lung expansion while in other cases it is preferable not to use suction and place chest tubes simply to a one way valve allowing the natural motion of the lung to act as a pump to evacuate air out of the pleural space; this is due to the fact that suction therapy may be traumatic to the lung or impair lung healing in certain cases. However, it is not always clinically apparent which patients would benefit from which therapy and non-suction therapy carries a greater risk of allowing pneumothorax to develop. The inventors demonstrate that an intra-pleural electrical impedance sensor embedded in the therapeutic chest tube (FIG. 1, 2) or a convex portion of chest tube to orient the electrodes toward the lung (FIG. 3) could confirm full expansion of the lung, detect the development of lung collapse (pneumothorax), and identify successful resolution of pneumothorax with restoration of complete lung expansion in real time. These results would apply clinically to the scenario in which a patient with an air leak from the lung underwent a trial of transition from suction to non-suction therapy, experienced pneumothorax development, and was returned to suction therapy with resolution of the pneumothorax. This was confirmed by radiologic examination of the pig thorax in the presence of 4 liters per minute air leak and alternation of the therapeutic chest tube between suction therapy and non-suction therapy (FIG. 4). The functionality of such a device was based on the fact that when the therapeutic chest tube was set to suction therapy and the lung was fully expanded as verified by chest radiograph (FIG. 4 (7)), the electrodes embedded in the therapeutic chest tube were fully contacting the surface of the lung and therefore the electrical impedance value detected by the electrodes in the therapeutic chest tube was a finite value and had a very distinct sinusoidal pattern associated with the normal lung ventilation cycle (FIG. 4 (8)). When the therapeutic chest tube was transitioned to non-suction therapy at this level of air leak pneumothorax developed rapidly as verified by chest radiograph (FIG. 4 (9, arrow); under these conditions the impedance value measured by the intra-pleural electrodes became infinite as visualized by a flat-line or rail at the highest resistance value measurable by the impedance measuring device being observed in the resistance graph (FIG. 4 (10)). This flat-line was due to separation of the electrodes from the lung surface by the air insufflation into the pleural space and produced a very distinct signal readily differentiated from normal conditions (FIG. 4 (10)). When suction therapy through the therapeutic chest tube was restored, pneumothorax evacuation was achieved rapidly as confirmed by chest radiography (FIG. 4 (11)); this was associated with the rapid resolution of infinite impedance and restoration of the sinusoidal electrical impedance pattern associated with the normal lung ventilation cycle (FIG. 4 (12)).

A microprocessor can be used to electronically interpret the impedance signal and automatically alter the suction status of the chest tube. This would represent the clinical scenario of a patient with a chest tube who develops pneumothorax when clinicians are not present. In this case the system described herein would alter the suction status of the chest tube automatically based on the electronic recognition of an abnormal impedance pattern (e.g., a signal pattern similar to that shown FIG. 4 (10) and without the need for direct clinician oversight.

In certain aspects, the system can include, but need not be limited to the following components: (i) a microcontroller unit (MCU), (ii) a suction control circuit, and (iii) an impedance measurement circuit (see FIG. 2). The MCU could be any component or system that executes programmed instructions. The MCU can be coupled to the suction control circuit and the impedance measurement circuit. The MCU can include a computer processing unit (CPU) and storage devices, such as register or memory. The MCU can receive or fetch, or transmit data to or from the suction control circuit and the impedance measurement circuit, as well as process data received to generate one or more results that may result in communication of instructions to other components of the system. The CPU can be configured to execute an operating system (OS) and the applications of the system. According to certain embodiments the system can employ a graphical user interface for interaction with the microcontroller. According to certain implementations, the graphical user interface may include a touch screen, in addition to a rotating or sliding control button, or some other technology performing equivalent adjustment functions that complies with the required purposes. The graphical user interface may be provided with a patient monitoring and surveillance screen, which displays details of the elements according to various aspects to the present disclosure.

The suction control circuit could be any circuit or control mechanism that enables the MCU to control the suction level delivered to the patient. In certain aspects a negative pressure “vacuum” is needed to affect adequate flow and removal of undesirable air or fluids. A suction catheter can be placed in the appropriate position with one or several holes at the end thereby allowing flow of fluid or gas to the outside of the body. Not having accurate control of the vacuum source can pull tissue into the suction catheter leading to injury and or damage to the tissue. Bleeding, perforation, and death of tissue may ensue along with serious clinical harm. Accordingly, the MCU will be configured to control the vacuum source and provide the needed modulation of that vacuum source.

The impedance measurement circuit could be any method for measuring impedance. This includes both impedance measurement systems based on 2-electrode measurements, 3-electrode measurements, 4-electrode measurements or a system involving a greater number of electrodes.

One example of such system is one having a 4-wire impedance measurement (FIG. 5) such as that used to demonstrate feasibility. A known alternating current (AC) stimulation current is driven on the outer electrodes of the chest tube (I+, and I−). The resulting AC voltage is measured on the inner electrodes (V+, V−). The impedance (Z) is then calculated by the following equation: Z=V/I (see FIG. 5). For the purpose of this system the digital suction control circuit was implemented using a power metal-oxide semiconductor field-effect transistor (MOSFET). The power MOSFET can be modulated by the MCU at a duty cycle that adjusts the power delivered to the suction motor and therefore controls the amount of suction delivered to the patient. A 50% duty cycle results in 50% power delivery to the suction motor. A 100% duty cycle results in 100% power being delivery to the suction motor. The duty cycle and suction level delivered to the patient are directly related. In short, a higher duty cycle results in an increased suction level.

The amount of power delivered to the suction device is modulated by the MCU based on the impedance value detected by the impedance measurement circuit. When the lung is fully expanded, the chest tube lying next to the lung in the pleural space is completely in contact with the lung, meaning the electrodes in the chest are fully in contact with the surface of the lung. In this situation, the electrical impedance value detected by the electrodes is a finite value and has a very distinct sinusoidal pattern associated with the normal lung ventilation cycle. In this situation, the MCU will decrease power to the suction motor since suction is not needed in this situation because no pneumothorax is present and the normal ventilation movement of the lung will maintain lung expansion. When pneumothorax is present, the electrodes lose contact with the lung surface and the electrical impedance value becomes infinite (this is because current ceases to flow between the electrodes due to loss of contact with the lung surface or with the inner lining of the rib cage). In this situation, the MCU again modulates power to the suction motor based on the impedance value detected by the impedance measurement circuit; however, due to the MCU recognizing an infinite impedance value the MCU will deliver full power to the suction motor for the purpose of evacuating the pneumothorax. The MCU will maintain suction until it recognizes restoration of the normal ventilation impedance signal; at that point, depending on the programming, it will either maintain full power to the suction motor or attempt to decrease power to the suction motor as a means of minimizing the suction delivered to the pleural space to reduce lung trauma.

An example flow chart of the functionality of the MCU/chest tube suction device is diagrammed in FIG. 6. A graph showing experimental results of this MCU in a bench top model of pneumothorax is provided in FIG. 7. In FIG. 7, the initial resistance value is a finite value between 0-500 ohms (13); under these circumstances the MCU sets a low (PWM) percentage current to the suction pump because low suction is sufficient (14). In FIG. 7 (15), the resistance becomes infinite, representing the loss of contact of the lung with the sensor; this is indicated in this resistance monitoring device by a flat-line or rail at the negative of the maximum resistance detectable by the monitoring device (approximately −1600 ohms) though in other resistance measuring devices it would be the positive value of the maximum resistance detectable by that device. The response of the MCU to this flat-line resistance pattern is to begin increasing the PMW percentage to the suction pump to increase the duty cycle of the pump to increase the level of suction delivered (16). This continues to one hundred percent PMW to achieve maximum suction from the pump while the resistance value remains infinite (17). In FIG. 7 (18), the detected resistance returns to a finite value between 0-500 ohms representing a restoration of full lung expansion. In response to these conditions, the MCU begins to decrease the PWM to the suction pump to decrease the amount of suction delivered (19), representing the attempt by the MCU to identify the minimum amount of suction required to maintain a finite resistance value within a determined range, in this case between 0-500 ohms.

The 4-wire impedance measurement system depicted in FIG. 5 was tested in a porcine model of air leak similar to that described above in association with FIG. 4 to demonstrate the feasibility of such a system. A schematic of this animal model is shown in FIG. 8. FIG. 8 (20) indicates a chest tube with embedded electrodes as described in FIG. 1 and FIG. 2 with electrodes contacting the surface of the lung (FIG. 8 (21)) and with connecting wires (3) connecting to an impedance measurement circuit (22). The chest tube (20) was further connected by connecting tubing (23) to a digital suction device (24) which applied either active suction or non-suction one-way valve functionality to the chest tube (20). Not shown in this figure is a second chest tube which was placed to deliver air leak at determined rates to mimic an active air leak from the lung. The impedance measuring circuit was further connected to a microcontroller unit (MCU) (25) which in turn was connected to the digital suction device (24), This configuration allowed the impedance signal detected by the chest-tube embedded electrodes (20) to be communicated to the MCU (25) in order for the MCU to electronically determine suction versus non-suction therapy and/or the level of suction delivered by the digital suction device (24).

Graphs showing experimental results of this MCU/chest tube suction device in an animal model of pneumothorax are demonstrated in FIG. 9-12. For these experiments, the animal model described above for FIG. 8 was used consisting of two chest tubes located in the pleural space of a pig. One chest tube was meant to represent a conventional, therapeutic chest tube as used in human patients, which is connected to a one way valve and/or suction which allows any air present in the pleural space to be removed, maintaining full lung expansion; this chest tube also contained the embedded electrodes as described in FIG. 1 and FIG. 2 with electrodes contacting the surface of the lung (FIG. 8 (21). The second tube was used to introduce air into the pleural space at defined air-flows to mimic a pathologic air leak from the lung.

FIG. 9 shows experimental results of an experiment in which no air leak was present. In FIG. 9 the PMW of the MCU was initially set at approximately 55% (26) and a finite resistance value, normal respiratory resistance waveform (27) was detected by the pleural sensor. The programmed algorithm of the MCU then prompted a steady interval decrease in the PMW (28) until the PMW went to a value of 0% (29). At time point (30), a finite resistance value, normal respiratory resistance waveform was detected by the pleural sensor resulting in the MCU continuing a PMW of 0% according to the algorithm. This experiment demonstrated that, in the case of no pleural air leak, non-suction therapy can be successful at maintaining full lung expansion, that the intrapleural impedance sensor can accurately confirm full lung expansion, and that the measured impedance values can be transmitted to an MCU which in turn can command the suction device to maintain a PMW of 0% in the setting of full lung expansion in the absence of direct human intervention.

FIG. 10 shows experimental results of an experiment in which 1 liter/min air leak was present. In FIG. 10 the PMW of the MCU was initially set at approximately 50% (31) and a finite resistance value, normal respiratory resistance waveform (32) was detected by the pleural sensor. The programmed algorithm of the MCU then prompted a steady interval decrease in the PMW (33) until the PMW went to a value of 0% (34). At time point (35), a finite resistance value, normal respiratory resistance waveform was detected by the pleural sensor resulting in the MCU continuing a PMW of 0% according to the algorithm. This study demonstrates that, in the case of small air leaks, non-suction therapy can be successful at maintaining full lung expansion, that the intrapleural impedance sensor can accurately confirm full lung expansion, and that the measured impedance values can be transmitted to an MCU which in turn can command the suction device to maintain a PMW of 0% in the setting of full lung expansion in the absence of direct human intervention.

FIG. 11 shows experimental results of an experiment in which 4 liter/min air leak was present. In FIG. 11 the PMW of the MCU was initially set at approximately 55% (36) and a finite resistance value, normal respiratory resistance waveform (37) was detected by the pleural sensor. The programmed algorithm of the MCU then prompted a steady interval decrease in the PMW (38) until the PMW went to a value of 0% (39, arrow). At time point (40), infinite resistance and loss of the normal respiratory resistance waveform were detected by the pleural sensor resulting in the MCU returning to a PMW required to restore a finite resistance, normal respiratory resistance waveform (approximately 40%) (41) according to the programmed algorithm; this resulted in the restoration of the finite resistance, normal respiratory resistance waveform at time point (42). This experiment demonstrated that, in the case of moderate air leaks, non-suction therapy can be attempted to maintain full lung expansion but if the intrapleural impedance sensor identifies the failure of non-suction therapy, i.e. the development of pneumothorax, the infinite impedance values measured by the sensor can be transmitted to an MCU which in turn can command the suction device to restore suction therapy to re-establish a normal, finite respiratory impedance waveform in the absence of direct human intervention.

FIG. 12 shows experimental results of an experiment in which 6 liter/min air leak was present. In FIG. 12 the PMW of the MCU was initially set at approximately 55% (43) and a finite resistance value, normal respiratory resistance waveform (44) was detected by the pleural sensor. The programmed algorithm of the MCU then prompted a steady interval decrease in the PMW (45) until the PMW went to a value of 40% (46). At this level of PMW, however, the suction was no longer capable of evacuating the air introduced by the air leak and pneumothorax developed as indicated by infinite resistance and loss of the normal respiratory resistance waveform being detected by the pleural sensor (47). This resulted in the MCU increasing the PMW (48) according to the programmed algorithm back to approximately 50% (49) which was the amount of power required to restore a finite resistance, normal respiratory resistance waveform (50). According to the programmed algorithm, the restoration of a finite resistance, normal respiratory resistance waveform (50) resulted in the MCU attempting again to reduce PMW (51) as a means of reducing the amount of suction therapy delivered to the experimental animal to a level of about 40% PMW (52). However, as before, at this level of PMW, the suction was no longer capable of evacuating the air introduced by the air leak and pneumothorax again developed as indicated by infinite resistance and loss of the normal respiratory resistance waveform being detected by the pleural sensor (53). This resulted in the MCU increasing the PMW (54) according to the programmed algorithm back to approximately 50% (55) which was the amount of power required to restore a finite resistance, normal respiratory resistance waveform (56). This experiment demonstrated that, in the case of large air leaks, suction therapy can still be minimized to maintain full lung expansion but if the intrapleural impedance sensor identifies the failure at a certain point of reducing suction, i.e. the development of pneumothorax, the infinite impedance values measured by the sensor can be transmitted to an MCU which in turn can command the suction device to restore full suction therapy and that the MCU, according to the programmed algorithm will continue to try to identify the lowest amount of suction required to maintain a normal, finite respiratory impedance waveform in the absence of direct human intervention.

The 4-wire impedance measurement system depicted in FIG. 5 was also tested in a porcine model of regional lung ventilation to demonstrate the feasibility of such a system. A schematic of this animal model is shown in FIG. 13. FIG. 13 (20) indicates a chest tube with embedded electrodes as described in FIG. 1&2 with electrodes contacting the surface of the lung (FIG. 13 (21)) and with connecting wires (3) connecting to an impedance measurement circuit (22). The chest tube (20) was further connected to a suction device (not shown) to assure the maintenance of full lung expansion. The impedance measuring circuit was further connected to a microcontroller unit (MCU) (25) which in turn was connected to a mechanical ventilator (57) which was in turn delivering defined respiratory tidal volumes to the lung (21) via an endotracheal tube (58), The mechanical ventilator (57) had a built in capacity to identify the peak inspiratory pressure (P_IP) associated with each defined delivered tidal volume. Using the impedance values obtained by the impedance measurement circuit (22), the impedance amplitude defined by (R_P−R_T) and in turn the aeration index defined by (R_P−R_T)/(P_IP) could be calculated for each defined delivered tidal volume. This configuration allowed the impedance signal detected by the chest-tube embedded electrodes (20) and the peak airway pressure detected by the mechanical ventilator (57) to be communicated to the MCU (25) in order for the MCU to electronically determine optimal tidal volume delivery as a function of the maximization of the aeration index.

FIG. 14 shows experimental results of an experiment in an animal model of optimization of regional lung ventilation using the configuration illustrated in FIG. 13. For this experiment, the animal model consisted of the chest tube with embedded electrodes illustrated in FIG. 1-2 located in the pleural space of a pig being ventilated by a mechanical ventilator. The chest tube was meant to represent a conventional, therapeutic chest tube as used in human patients, i.e., which is connected to a one way valve and/or suction which allows any air present in the pleural space to be removed, maintaining full lung expansion. The electrodes in the chest tube were directed to face the surface of the lung and to be insulated away from the rib cage. The tidal volume delivered by the mechanical ventilator was modulated manually throughout a range from 250-1500 milliliters. At each tidal volume, the aeration index (AI) given by (R