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Patent Issued for Systems and Methods for Accurately, Substantially Noninvasively Determining Pulmonary Capillary Blood Flow Or Cardiac Output

August 25, 2014



By a News Reporter-Staff News Editor at Cardiovascular Week -- From Alexandria, Virginia, NewsRx journalists report that a patent by the inventors Orr, Joseph A. (Park City, UT); Kuck, Kai (Hamburg, DE), filed on February 3, 2006, was published online on August 12, 2014 (see also RIC Investments, LLC).

The patent's assignee for patent number 8801625 is RIC Investments, LLC (Murrysville, PA).

News editors obtained the following quote from the background information supplied by the inventors: "The present invention relates to methods for accurately, noninvasively measuring the pulmonary capillary blood flow (PCBF), cardiac output, and mixed venous carbon dioxide content of the blood of a patient. Particularly, the present invention relates to a method for noninvasively measuring pulmonary capillary blood flow or cardiac output that employs an algorithm to increase the accuracy of data upon which the pulmonary capillary blood flow or cardiac output measurement is based.

"Carbon dioxide elimination (VCO.sub.2) is the volume of carbon dioxide (CO.sub.2) excreted from the body of a patient during respiration. Conventionally, carbon dioxide elimination has been employed as an indicator of metabolic activity. Carbon dioxide elimination has also been used in rebreathing methods of determining pulmonary capillary blood flow and cardiac output.

"The carbon dioxide Fick equation: Q=VCO.sub.2/(CvCO.sub.2-CaCO.sub.2), (1) where Q is cardiac output, CvCO.sub.2 is carbon dioxide content of the venous blood of the patient, and CaCO.sub.2 is the carbon dioxide content of the arterial blood of the patient, has been employed to noninvasively determine the pulmonary capillary blood flow or cardiac output of a patient. The carbon dioxide elimination of the patient may be noninvasively measured as the difference per breath between the volume of carbon dioxide inhaled during inspiration and the volume of carbon dioxide exhaled during expiration, and is typically calculated as the integral of the carbon dioxide signal, or the fraction of respiratory gases that comprises carbon dioxide, or 'carbon dioxide fraction,' times the rate of flow over an entire breath.

"The partial pressure of end-tidal carbon dioxide (PetCO.sub.2 or etCO.sub.2) is also measured in rebreathing processes. The partial pressure of end-tidal carbon dioxide, after correcting for any deadspace, is typically assumed to be approximately equal to the partial pressure of carbon dioxide in the alveoli (PACO.sub.2) of the patient or, if there is no intrapulmonary shunt, the partial pressure of carbon dioxide in the arterial blood of the patient (PaCO.sub.2).

"Rebreathing is typically employed either to noninvasively estimate the carbon dioxide content of mixed venous blood (as in total rebreathing) or to obviate the need to know the carbon dioxide content of the mixed venous blood (by partial rebreathing). Rebreathing processes typically include the inhalation of a gas mixture that includes carbon dioxide. During rebreathing, the carbon dioxide elimination of the patient decreases to a level less than during normal breathing. Rebreathing during which the carbon dioxide elimination decreases to near zero is typically referred to as total rebreathing. Rebreathing that causes some decrease, but not a total cessation of carbon dioxide elimination, is typically referred to as partial rebreathing.

"Rebreathing is typically conducted with a rebreathing circuit, which causes a patient to inhale a gas mixture that includes carbon dioxide. FIG. 1 schematically illustrates an exemplary rebreathing circuit 50 that includes a tubular airway 52 that communicates air flow to and from the lungs of a patient. Tubular airway 52 may be placed in communication with the trachea of the patient by known intubation processes, or by connection to a breathing mask positioned over the nose and/or mouth of the patient. A flow meter 72, which is typically referred to as a pneumotachometer, and a carbon dioxide sensor 74, which is typically referred to as a capnometer, are disposed between tubular airway 52 and a length of hose 60 and are exposed to any air that flows through rebreathing circuit 50. Both ends of another length of hose, which is referred to as deadspace 70, communicate with hose 60. The two ends of deadspace 70 are separated from one another by a two-way valve 68, which may be positioned to direct the flow of air through deadspace 70. Deadspace 70 may also include an expandable section 62. A Y-piece 58, disposed on hose 60 opposite flow meter 72 and carbon dioxide sensor 74, facilitates the connection of an inspiratory hose 54 and an expiratory hose 56 to rebreathing circuit 50 and the flow communication of the inspiratory hose 54 and expiratory hose 56 with hose 60. During inhalation, gas flows into inspiratory hose 54 from the atmosphere or a ventilator (not shown). During normal breathing, valve 68 is positioned to prevent inhaled and exhaled air from flowing through deadspace 70. During rebreathing, valve 68 is positioned to direct the flow of exhaled and inhaled gases through deadspace 70.

"The rebreathed air, which is inhaled from deadspace 70 during rebreathing, includes air that has been exhaled by the patient (i.e., carbon dioxide-rich air).

"During total rebreathing, substantially all of the gas inhaled by the patient was expired during the previous breath. Thus, during total rebreathing, the partial pressure of end-tidal carbon dioxide (PetCO.sub.2 or etCO.sub.2) is typically assumed to be equal to or closely related to the partial pressure of carbon dioxide in the arterial (PaCO.sub.2), venous (PvCO.sub.2), or alveolar (PACO.sub.2) blood of the patient. Total rebreathing processes are based on the assumption that neither pulmonary capillary blood flow nor the content of carbon dioxide in the venous blood of the patient (CvCO.sub.2) changes substantially during the rebreathing process. The partial pressure of carbon dioxide in blood may be converted to the content of carbon dioxide in blood by means of a carbon dioxide dissociation curve, where the change in the carbon dioxide content of the blood (CvCO.sub.2--CaCO.sub.2) is equal to the slope (s) of the carbon dioxide dissociation curve multiplied by the measured change in end-tidal carbon dioxide (PetCO.sub.2) as effected by a change in effective ventilation, such as rebreathing.

"In partial rebreathing, the patient inhales a mixture of 'fresh' gases and gases exhaled during the previous breath. Thus, the patient does not inhale a volume of carbon dioxide as large as the volume of carbon dioxide that would be inhaled during a total rebreathing process. Conventional partial rebreathing processes typically employ a differential form of the carbon dioxide Fick equation to determine the pulmonary capillary blood flow or cardiac output of the patient, which do not require knowledge of the carbon dioxide content of the mixed venous blood. This differential form of the carbon dioxide Fick equation considers measurements of carbon dioxide elimination, CvCO.sub.2, and the content of carbon dioxide in the alveolar blood of the patient (CACO.sub.2) during both normal breathing and the rebreathing process as follows:

".times..times..times..times..times..times..times..times. ##EQU00001## where VCO.sub.2 B and VCO.sub.2 D are the carbon dioxide production of the patient before rebreathing and during the rebreathing process, respectively, CvCO.sub.2 B and CvCO.sub.2 D are the content of CO.sub.2 of the venous blood of the patient before rebreathing and during the rebreathing process, respectively, and CaCO.sub.2 B and CaCO.sub.2 D are the content of CO.sub.2 in the arterial blood of the patient before rebreathing and during rebreathing, respectively.

"Again, with a carbon dioxide dissociation curve, the measured PetCO.sub.2 can be used to determine the change in content of carbon dioxide in the blood before and during the rebreathing process. Accordingly, the following equation can be used to determine pulmonary capillary blood flow or cardiac output when partial rebreathing is conducted: Q=.DELTA.VCO.sub.2/s.DELTA.PetCO.sub.2. (3)

"Alternative differential Fick methods of measuring pulmonary capillary blood flow or cardiac output have also been employed. Such differential Fick methods typically include a brief change of PetCO.sub.2 and VCO.sub.2 in response to a change in effective ventilation. This brief change can be accomplished by adjusting the respiratory rate, inspiratory and/or expiratory times, or tidal volume. A brief change in effective ventilation may also be effected by adding CO.sub.2, either directly or by rebreathing. An exemplary differential Fick method that has been employed, which is disclosed in Gedeon, A. et al. in 18 Med. &Biol. Eng. &Comput. 411-418 (1980), employs a period of increased ventilation followed immediately by a period of decreased ventilation.

"The carbon dioxide elimination of a patient is typically measured over the course of a breath by the following, or an equivalent, equation: VCO.sub.2=.intg..sub.breathV.times.fCO.sub.2dt, (4) where V is the measured respiratory flow and fCO.sub.2 is the substantially simultaneously detected carbon dioxide signal, or fraction of the respiratory gases that comprises carbon dioxide or 'carbon dioxide fraction.'

"Due to the measured respiratory constituents upon which VCO.sub.2 and PetCO.sub.2 calculations are made, VCO.sub.2 typically responds to rebreathing about one breath before PetCO.sub.2 for the same breath. Accordingly, a VCO.sub.2 signal may lead a PetCO.sub.2 signal by about one breath. Thus, at a particular point in time, the VCO.sub.2 and PetCO.sub.2 signals do not correspond to one another. As these values are often used to noninvasively determine pulmonary capillary blood flow or cardiac output, the lack of correspondence between these values may lead to inaccuracies in the pulmonary capillary blood flow or cardiac output determination.

"In addition, measurements that are taken during spurious breaths, or breaths which do not provide information relevant to pulmonary capillary blood flow or cardiac output, may act as noise that introduces inaccuracy into the noninvasive pulmonary capillary blood flow or cardiac output determination.

"When equation (4) is employed to calculate the carbon dioxide elimination of the patient from the respiratory flow and carbon dioxide fraction measurements over an entire breath, such miscorrelation or noise-induced inaccuracies in either the expiratory flow, the inspiratory flow, or both may cause inaccuracies in the carbon dioxide elimination determination or inconsistencies between carbon dioxide elimination determinations.

"Accordingly, there is a need for a method of accurately, noninvasively calculating pulmonary capillary blood flow and cardiac output."

As a supplement to the background information on this patent, NewsRx correspondents also obtained the inventors' summary information for this patent: "The present invention includes a method for noninvasively measuring pulmonary capillary blood flow and cardiac output. The present invention includes the use of known rebreathing techniques to substantially noninvasively obtain carbon dioxide elimination (VCO.sub.2) and partial pressure of end-tidal carbon dioxide (PetCO.sub.2) measurements of a patient's breathing. These measurements may then be used to calculate pulmonary capillary blood flow or cardiac output of the patient by employing the following equation:

".DELTA..times..times..DELTA..times..times..DELTA..times..times..times..ti- mes..DELTA..times..times..times. ##EQU00002## where s is the slope of a standard carbon dioxide (CO.sub.2) dissociation curve, .DELTA.VCO.sub.2 is the change in the carbon dioxide elimination of the patient due to a change in effective ventilation, such as that caused by rebreathing, and .DELTA.CaCO.sub.2 and .DELTA.PetCO.sub.2 are the change in the content of carbon dioxide in the arterial blood of the patient and the change in the end-tidal partial pressure of carbon dioxide of the patient, respectively, due to the same change in effective ventilation. Alternatively, a standard carbon dioxide dissociation curve can be used to determine .DELTA.CaCO.sub.2 on the basis of the measured .DELTA.PetCO.sub.2.

"As an alternative to the use of the above equations to determine pulmonary capillary blood flow or cardiac output, the substantially noninvasive VCO.sub.2 and CaCO.sub.2 measurements can be related to each other in a linear fashion. This can be visually diagramed by plotting the VCO.sub.2 and CaCO.sub.2 measurements against one another on a two-dimensional (X-Y) line graph. The negative slope (-1.times.m) of the best-fit line through the data is approximately equal to the pulmonary capillary blood flow. The appropriate location and orientation of such a best-fit line may be calculated by linear regression or least squares. Depending on the correlation between the calculated best-fit line and the measured data, it may also be desirable to modify the data to provide a best-fit line that closely corresponds to the data.

"In one embodiment of the method of the present invention, the data can be modified by use of a known filter, such as a low-pass filter or a high-pass filter. Either digital or analog filters may be used. Either linear or nonlinear (e.g., median) filters may be used. By way of example, and not to limit the scope of the present invention, a low-pass filter may be applied to the measured VCO.sub.2 signal. As another example, a high-pass filter may be applied to the measured CaCO.sub.2 signal. Preferably, the filter and filter coefficient that are selected maximize the correlation between the measured VCO.sub.2 and CaCO.sub.2 signals.

"In another embodiment of the method of the present invention, the data points can be modified by clustering. That is, the data points that are grouped closest to other data points are assumed to most accurately represent the true VCO.sub.2 and CaCO.sub.2 of the patient. For example, the measured data with at least a predetermined number of close, or similar (e.g., within a specified threshold), data points is retained, while measured data with less than the predetermined number of close data points is discarded. The retained data points are assumed to be located on or near the best-fit line. In clustering, only these closely grouped sets of data points are considered in recalculating the best-fit line for the data and, thus, the negative slope (i.e., -1.times.m) of the best-fit line to determine the pulmonary capillary blood flow or cardiac output of the patient.

"Another embodiment of the method of the present invention includes modifying the data points that are most likely to be closest to an accurately placed and oriented best-fit line. Each data point, which has a carbon dioxide elimination component (e.g., a y-ordinate component) and a component based on an indicator of carbon dioxide content (e.g., an x-ordinate component), is evaluated on the basis of a predetermined minimum expected pulmonary capillary blood flow and a predetermined maximum pulmonary capillary blood flow. Lines, or the equations therefor, for both minimum expected and maximum expected pulmonary capillary blood flows are located so as to intersect at each data point. Then, the number of the other data points that are located between the two pulmonary capillary blood flow lines or equations is determined for each data point. Only those data points with a threshold number of other data points between the two intersecting lines are used in the determination of the location and orientation of the best-fit line through the data.

"Of course, any combination of methods of modifying data may be used to accurately determine the slope of the best-fit line through the measured VCO.sub.2 and PetCO.sub.2 data and, thus, to determine the pulmonary capillary blood flow or cardiac output of a patient.

"The best-fit line through carbon dioxide elimination and carbon dioxide content data may also be used to determine the mixed venous carbon dioxide content of the patient when partial rebreathing techniques are employed to obtain the data. As the mixed venous carbon dioxide content is assumed to equal the carbon dioxide content of the patient's blood when carbon dioxide elimination ceases (which does not occur during partial rebreathing), a best-fit line obtained by use of partial rebreathing techniques can be used to noninvasively determine carbon dioxide content and, thus, mixed venous carbon dioxide content when carbon dioxide elimination is set at zero.

"Other features and advantages of the present invention will become apparent to those of ordinary skill in the art through a consideration of the ensuing description, the accompanying drawings, and the appended claims."

For additional information on this patent, see: Orr, Joseph A.; Kuck, Kai. Systems and Methods for Accurately, Substantially Noninvasively Determining Pulmonary Capillary Blood Flow Or Cardiac Output. U.S. Patent Number 8801625, filed February 3, 2006, and published online on August 12, 2014. Patent URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=8801625.PN.&OS=PN/8801625RS=PN/8801625

Keywords for this news article include: Chemicals, Chemistry, Cardiology, Carbon Dioxide, RIC Investments LLC, Inorganic Carbon Compounds.

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Source: Cardiovascular Week


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