1. Field of the Invention
The present invention relates generally to methods for noninvasively determining the pulmonary capillary blood flow or cardiac output of an individual. More specifically, the present invention relates to noninvasive methods for determining pulmonary capillary blood flow or cardiac output which account for correlation between parameters that have been measured during the same breath. In particular, the present invention includes methods for improving the correlation between carbon dioxide elimination and partial pressure of end-tidal carbon-dioxide measurements.
2. Background of Related Art
So-called “rebreathing” techniques have long been used to make noninvasive determinations of both pulmonary capillary blood flow and cardiac output. In rebreathing, the respiration of an individual is monitored during both “normal” breathing, which may be either spontaneous or ventilator-induced, and when a change in the effective ventilation of the individual has occurred or been induced. In particular, in conventional rebreathing techniques, the change in effective ventilation has been induced by causing a monitored individual to breathe air or a gas mixture with an increased level of carbon dioxide relative to the amount of carbon dioxide that was inhaled by the individual during “normal” breathing.
The carbon dioxide Fick equation has long been used to determine both pulmonary capillary blood flow and cardiac output. One form of the carbon dioxide Fick equation follows:{dot over (Q)}=VCO2/(cvCO2−caCO2),  (I)where {dot over (Q)} represents blood flow (e.g., cardiac output or pulmonary capillary blood flow), VCO2 is carbon dioxide elimination, cvCO2 is carbon dioxide content of the venous blood of the monitored individual, and caCO2 is the carbon dioxide content of the arterial blood of the monitored individual.
When rebreathing processes are employed, the various parameters of the carbon dioxide Fick equation are typically derived from two measured signals, a measurement of the volume or flow of carbon dioxide eliminated by the body (VCO2 and {dot over (V)}CO2, respectively), which represents gases that are present in the mouth, and a measurement of the partial pressure of end-tidal carbon dioxide (etCO2 or petCO2), which represents gases inside the lungs, at the alveoli. The petCO2 measurement correlates directly with a concentration of carbon dioxide in blood flowing past the alveoli of an individual (cACO2) and, therefore, is useful for determining caCO2 and cvCO2.
Rebreathing is often conducted with a rebreathing circuit, through which a patient may 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. Flow meter 72 and carbon dioxide sensor 74 communicate with one or more monitors 76, which are configured to monitor signals from flow meter 72 and carbon dioxide sensor 74, as known in the art. 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 (petCO2 or etCO2) is typically assumed to be equal to or closely related to the content of carbon dioxide in the arterial (caCO2), venous (cvCO2), or alveolar (cACO2) 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 (cvCO2) changes substantially during the rebreathing process. In total rebreathing, the carbon dioxide elimination (VCO2) of the patient decreases to about zero. 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 (cvCO2−caCO2) is equal to the slope(s) of the carbon dioxide dissociation curve multiplied by the measured change in end-tidal carbon dioxide (petCO2) as effected by a change in effective ventilation, such as rebreathing.
In partial rebreathing, the patient inhales gases that include elevated carbon dioxide levels (e.g., a mixture of “fresh” gases and gases that were 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. As carbon dioxide elimination (VCO2) is not decreased to zero during partial rebreathing and since the carbon dioxide content of the mixed venous blood is not known during partial rebreathing, 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. This differential form of the carbon dioxide Fick equation considers measurements of carbon dioxide elimination, cvCO2, and the content of carbon dioxide in the alveolar blood of the patient (cACO2) during both normal breathing and the rebreathing process as follows:                                                         Q              .                                      pcb              ⁢                                                           ⁢              BD                                =                                                                      V                  ⁢                  CO                                                  2                  ⁢                  B                                            -                                                V                  ⁢                  CO                                                  2                  ⁢                  D                                                                                    (                                                      c                                          vCO2                      ⁢                                                                                           ⁢                      B                                                        -                                      c                                          vCO2                      ⁢                                                                                           ⁢                      D                                                                      )                            -                              (                                                      c                                          aCO2                      ⁢                                                                                           ⁢                      B                                                        -                                      c                                          aCO2                      ⁢                                                                                           ⁢                      D                                                                      )                                                    ,                            (        2        )            where VCO2 B and VCO2 D are the carbon dioxide production of the patient before rebreathing and during the rebreathing process, respectively, cvCO2 B and CvCO2 D are the content of CO2 of the venous blood of the patient before rebreathing and during the rebreathing process, respectively, and caCO2 B and caCO2 D are the content of CO2 in the arterial blood of the patient before rebreathing and during rebreathing, respectively.
Again, with a carbon dioxide dissociation curve, the measured petCO2 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:{dot over (Q)}=ΔVCO2/sΔpetCO2.  (3)
Accordingly, a plot of VCO2 against petCO2 during both “normal” respiration and rebreathing is known to provide an indicator of the pulmonary capillary blood flow of an individual. The individual's pulmonary capillary blood flow is about equal to the negative slope (i.e., negative one multiplied by the slope) of the resulting line or curve.
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 petCO2 and VCO2 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 CO2, 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), includes a period of increased ventilation followed immediately by a period of decreased ventilation.
Carbon dioxide elimination (VCO2) is typically measured as the difference between the amount of carbon dioxide inhaled and the amount of carbon dioxide exhaled, with the amount of carbon dioxide exhaled usually being greater than that inhaled. The carbon dioxide elimination of a patient is typically measured over the course of a breath by the following, or an equivalent, equation:VCO2=∫breathV×fCO2dt,  (4)where V is the measured respiratory flow and fCO2 is the substantially simultaneously detected carbon dioxide signal, or fraction of the respiratory gases that comprises carbon dioxide or “carbon dioxide fraction”.
Prior to rebreathing, the amount of carbon dioxide eliminated (VCO2) by the patient, through his or her lungs, is much greater than the amount of CO2 inhaled by the patient. In rebreathing, although the amount of carbon dioxide inhaled by the individual and the amount of carbon dioxide exhaled by the individual both typically increase, the VCO2 measurement typically decreases. The difference between the amounts of carbon dioxide inhaled and eliminated is reduced by an amount that corresponds to the increased amount of carbon dioxide inhaled by the patient Detection of the change in VCO2 that may occur with changes in the effective ventilation of an individual may be somewhat delayed due to the dampening effect of the carbon dioxide stores of the individual's lungs. For example, at the beginning of rebreathing, a significant portion of the increased amount of carbon dioxide inhaled by the individual is absorbed by the carbon dioxide stores. If the amount of carbon dioxide inhaled during rebreathing is significantly increased, then a significant decrease will be seen in the difference between the amounts of carbon dioxide inhaled and eliminated, while this difference will be much less if the amount of carbon dioxide inhaled during rebreathing is only slightly greater than that inhaled during the patient's normal respiration.
VCO2 is the first of the two signals (i.e., VCO2 and petCO2) to accurately reflect rebreathing-induced changes. When rebreathing is initiated, the amount of carbon dioxide that is inhaled is increased. Prior to rebreathing, the lungs of the patient have been exposed to typical amounts of carbon dioxide, such as those experienced during normal respiration. Initially, some of the increased carbon dioxide that is inhaled during rebreathing is absorbed by the carbon dioxide stores of the lungs, including the functional residual capacity (FRC), which comprises stored gases, and lung tissues. Thus, only a portion of the increased amount of inhaled carbon dioxide initially makes its way to the alveoli, or air sacs, of the lungs, where gases exit and are absorbed by the blood. It only takes a short amount of time for the carbon dioxide stores of the lungs to equilibrate to the increased amount of carbon dioxide being inhaled. When such equilibration occurs, substantially all of the increase in the amount of carbon dioxide inhaled is realized in the alveoli. At that point in time, the full reduction in the difference between the amount of carbon dioxide inhaled by the patient and the amount of carbon dioxide eliminated by the patient may be noninvasively measured.
Assuming the increased amount of carbon dioxide inhaled by the individual is sufficient to quickly maximize the concentration of carbon dioxide in the carbon dioxide stores, the amount of carbon dioxide exhaled by the individual in the same breath may be used to accurately determine the VCO2 of the patient.
The partial pressure of end-tidal carbon dioxide (petCO2 or etCO2), after correcting for any deadspace, is typically assumed to be approximately equal to the partial pressure of carbon dioxide in the alveoli (PACO2) of the patient or, if there is no intrapulmonary shunt, the content of CO2 in the blood flowing past the alveoli (cACO2), as well as the CO2 content of oxygenated blood downstream from the alveoli (CaCO2).
The petCO2 measurement, which represents a measurement of carbon dioxide in the lungs of an individuals is typically not representative of the true gases that are present in the lungs at the time the measurement is taken. This is because, in rebreathing, the increased amount of carbon dioxide inhaled does not go directly to the alveoli. Rather, the carbon dioxide stores of the lungs, including the functional residual capacity (deadspace) and lung tissues, which do not participate directly in respiration, act as a buffer or filter. This filtering action includes the absorption and release of carbon dioxide in a manner that depends upon the amount of carbon dioxide in gases that are directly involved in respiration. Accordingly, when rebreathing first begins, a significant portion of the increased amount of carbon dioxide in the inhaled gases is initially absorbed into the carbon dioxide stores. Once the amount of carbon dioxide in the carbon dioxide stores and the amount of carbon dioxide in the “rebreathed” gases (including inspiratory and expiratory gases) equilibrate with one another, the amount of carbon dioxide within the lungs, including petCO2, may be accurately detected. The converse is also true: when “normal” respiration is recommended, the reduced amount of carbon dioxide in the expired gases is not immediately realized in an externally obtained, noninvasive respiratory measurement. Rather, carbon dioxide is released from the carbon dioxide stores of the lungs until the amount of carbon dioxide in the carbon dioxide stores equilibrates with the amounts of carbon dioxide in the inspiratory and expiratory gases. Only after such equilibration has taken place may accurate measurements of gases within the lungs, such as petCO2, be noninvasively obtained. Accordingly, at the start of both a rebreathing phase and “normal” breathing following a rebreathing phase, an immediate change in petCO2 is typically not seen.
Once the increase in the amount of inhaled carbon dioxide is realized at the level of the alveoli, the content of CO2 in the blood must increase correspondingly for carbon dioxide to be released from the blood as the blood flows past the alveoli. Thus, an additional period of time is required before the amount of carbon dioxide in the blood increases to a level which will facilitate release of the increased amount of carbon dioxide from the blood and an increase in the amount of carbon dioxide in the blood, which may be determined from a petCO2 measurement, may be detected. Thus, the accuracy of the petCO2, relative to the point in time at which the measurement is obtained relative to the initiation of rebreathing, lags behind the time-accuracy of the VCO2 measurement. This lag typically amounts to a period of time that corresponds to one or two breaths.
Following rebreathing, the amount of carbon dioxide inhaled by a patient is decreased. The carbon dioxide stores in the lungs equilibrate to the new amount of carbon dioxide being inhaled by releasing carbon dioxide. Consequently, while the carbon dioxide levels of the carbon dioxide stores of the lungs are equilibrating, the amount of carbon dioxide exhaled by the patient remains at an elevated level for a period of time following even a significant decrease in the amount of carbon dioxide inhaled by the patient.
Likewise, during equilibration of the carbon dioxide stores of a patient's lungs, the amount of carbon dioxide within the alveoli remains greater than that in the air or other gas mixture inhaled by the patient. Thus, carbon dioxide levels in the blood remain elevated. Once the carbon dioxide stores in the lungs of the patient begin to decrease and the amount of carbon dioxide within the alveoli begins to resemble the amount of carbon dioxide in the air or gases that have been inhaled by the patient, the high levels of carbon dioxide that have accumulated in the blood may be more readily released therefrom. Accordingly, following rebreathing, the amount of carbon dioxide in the blood flowing past the alveoli of the patient will initially remain high, as may be evidenced by relatively high petCO2 measurements. As the excess carbon dioxide that is trapped in the blood during rebreathing is gradually released therefrom, the amount of carbon dioxide in the alveolar blood of the patient decreases to a “normal” level.
It may be said that the carbon dioxide stores of a patient's lungs filter the petCO2 signal to a much greater extent than the VCO2 signal is filtered by the carbon dioxide stores. Because VCO2 signals typically respond to changes in the effective ventilation of a patient, such as rebreathing and nonrebreathing states, about one or two breaths before the petCO2 signal(s) for the same breath(s) will respond to such changes, VCO2 and petCO2 signals that are obtained during the same breath do not correlate well with one another. Accordingly, a VCO2 signal may lead a petCO2 signal by a time differential equal to the duration of about one or two breaths. Thus, at a particular point in time, the VCO2 and petCO2 signals do not correspond to one another. Stated another way, the accuracy of the petCO2 measurement lags that of the VCO2 measurement by a time duration equal to the length of a breath or two. 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.
The correlation between the petCO2 and VCO2 signals may be quantified by a so-called “correlation coefficient” (r2), where a value of 1 indicates complete correlation between the two signals and lesser values represent correspondingly lesser degrees of correlation. This is evidenced when VCO2 signals are plotted against caCO2 signals, such as the data shown in FIGS. 2A and 2B respectively, with the result appearing as an open loop, as depicted in the plot of FIG. 4, rather than the ideal straight line depicted in FIG. 3. As it is difficult to accurately assign a slope to a loop, it is difficult to accurately determine pulmonary capillary blood flow from a plot of noninvasively obtained petCO2-based caCO2 signals against VCO2 signals.
Upon the start of rebreathing, the flow of carbon dioxide eliminated at the mouth ({dot over (V)}MCO2) almost instantaneously drops to a lower level, while the plot of petCO2 goes through a transitional period before reaching the steady-state plateau at which it stays until the end of rebreathing. The trend plots of alveolar CO2 content (cACO2) and the volume of CO2 excreted from the blood into the alveoli ({dot over (V)}BCO2) from the carbon dioxide Fick equation (equation (1)) should follow the same shape (albeit inverted, due to the negative slope) as that of FIG. 3. However, VCO2 is not measured at the alveolar level ({dot over (V)}BCO2), but at the mouth ({dot over (V)}MCO2).
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 VCO2 of a 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 determination of VCO2 or inconsistencies between VCO2 determinations.
The inventors are not aware of a method for using a model of the lung which includes estimation, evaluation, or use of the carbon dioxide stores of the lung to transform, modify, or filter one or more noninvasively obtained respiratory signals to increase the correlation of each filtered or modified respiratory signal with at least one other noninvasively obtained respiratory signal.