Abstract:
Apparatus and methods for non-invasively determining the cardiac output or pulmonary capillary blood flow of a patient using partial re-breathing techniques. The apparatus includes a substantially instantaneously adjustable deadspace volume for accommodating differences in sizes or breathing capacities of various patients. The apparatus may be constructed of inexpensive elements, including one or more two-way valves, which render the apparatus very simple to use and inexpensive so that the unit may be employed as a disposable product. The method of the invention includes estimating the cardiac output or pulmonary capillary blood flow of a patient based on partial pressure of alveolar CO 2 , rather than on the partial pressure of end tidal CO 2 , as previously practiced. A computer program for calculating the cardiac output or pulmonary capillary blood flow of a patient is also disclosed.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
       [0001]    This application is a divisional of application Ser. No. 09/777,629, filed Feb. 6, 2001, pending, which is a continuation of application Ser. No. 09/262,510, filed Mar. 2, 1999, now U.S. Pat. No. 6,227,196, issued May 8, 2001, which is a continuation-in-part of application Ser. No. 08/770,138, filed Dec. 19, 1996. 
     
    
     
       BACKGROUND OF THE INVENTION  
         [0002]    1. Field of the Invention  
           [0003]    This invention relates to non-invasive means of determining cardiac output or pulmonary capillary blood flow in patients and, more specifically, to partial re-breathing systems and methods for determining cardiac output or pulmonary capillary blood flow in patients.  
           [0004]    2. Background of Related Art  
           [0005]    It is important in many medical procedures to determine or monitor the cardiac output or the pulmonary capillary blood flow of a patient. Cardiac output is the volume of blood pumped by the heart over a given period of time. Pulmonary capillary blood flow is the volume of blood that participates in gas exchange in the lungs. Techniques are known and used in the art which employ the use of catheters inserted into blood vessels at certain points (e.g., into the femoral artery, the jugular vein, etc.) to monitor blood temperature and pressure and to thereby determine the cardiac output or pulmonary capillary blood flow of the patient. Although such techniques can produce a reasonably accurate result, the invasive nature of these procedures has a high potential for causing morbidity or mortality.  
           [0006]    Adolph Fick&#39;s formula for calculating cardiac output, which was first proposed in 1870, has served as the standard by which other means of determining cardiac output and pulmonary capillary blood flow have since been evaluated. Fick&#39;s well-known equation, which is also referred to as the Fick Equation, written for carbon dioxide (CO 2 ), is:  
         Q   =       V     CO   2         (       C     v     CO   2         -     C     a     CO   2           )         ,                         
 
           [0007]    where Q is cardiac output, V CO   2  is the amount of CO 2  excreted by the lungs, or “CO 2  elimination,” and Ca CO     2    and Cv CO     2    are the CO 2  contents of arterial blood and venous blood, respectively. Notably, the Fick Equation presumes an invasive method (i.e., catheterization) of calculating cardiac output or pulmonary capillary blood flow because the arterial blood and mixed venous blood must be sampled in order to directly determine the CO 2  contents of arterial blood and venous blood.  
           [0008]    It has been shown, however, that by using the principles embodied in the Fick Equation, non-invasive means may be employed to determine cardiac output or pulmonary capillary blood flow. That is, expired CO 2  levels, measured in terms of fraction of expired gases that comprise CO 2  (f CO     2   ) or in terms of partial pressure of CO 2  (P CO     2   ), can be monitored and employed to estimate the content of CO 2  in the arterial blood. Thus, a varied form of the Fick Equation may be employed to estimate cardiac output or pulmonary capillary blood flow based on observed changes in f CO     2    or P CO     2   .  
           [0009]    An exemplary use of the Fick Equation to non-invasively determine cardiac output or pulmonary capillary blood flow includes comparing a “standard” ventilation event to a change in expired CO 2  values and a change in excreted volume of CO 2 , which is referred to as carbon dioxide elimination or CO 2  elimination (V CO   2 ), which may be caused by a sudden change in ventilation. Conventionally, a sudden change in effective ventilation has been caused by having a patient inhale or breathe a volume of previously exhaled air. This technique is typically referred to as “re-breathing.” 
           [0010]    Some re-breathing techniques have used the partial pressure of end-tidal CO 2  (Pet CO     2    or et CO     2   ) to approximate the content of CO 2  in the arterial blood of a patient while the patient&#39;s lungs act as a tonometer to facilitate the measurement of the CO 2  content of the venous blood of the patient.  
           [0011]    By further modification of the Fick Equation, it may be assumed that the CO 2  content of the patient&#39;s venous blood does not change within the time period of the perturbation. Thus, the need to directly calculate the CO 2  content of venous blood was eliminated by employing the so-called “partial re-breathing” method. (See, Capek et al., “Noninvasive Measurement of Cardiac Output Using Partial CO 2  Rebreathing,”  IEEE Transactions on Biomedical Engineering,  Vol. 35, No.  9 , September 1988, pp. 653-661 (hereinafter “Capek”).)  
           [0012]    The carbon dioxide elimination of the patient may be non-invasively 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 times the rate of flow over an entire breath. The volume of carbon dioxide inhaled and exhaled may each be corrected for any deadspace or for any intrapulmonary shunt.  
           [0013]    The partial pressure of end tidal carbon dioxide is also measured in re-breathing 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 (P A   CO     2   ) of the patient or, if there is no intrapulmonary shunt, the partial pressure of carbon dioxide in the arterial blood of the patient (Pa CO     2   ). Conventionally employed Fick methods of determining cardiac output or pulmonary capillary blood flow typically include a direct, invasive determination of Cv CO     2    by analyzing a sample of the patient&#39;s mixed venous blood. The re-breathing process is typically employed to either estimate the carbon dioxide content of mixed venous blood (in total re-breathing) or to obviate the need to know the carbon dioxide content of the mixed venous blood (by partial re-breathing) or determine the partial pressure of carbon dioxide in the patient&#39;s venous blood (Pv CO     2   ).  
           [0014]    Re-breathing processes typically include the inhalation of a gas mixture that includes carbon dioxide. During re-breathing, the carbon dioxide elimination of a patient typically decreases. In total re-breathing, carbon dioxide elimination decreases to near zero. In partial re-breathing, carbon dioxide elimination does not cease. Thus, in partial re-breathing, the decrease in carbon dioxide elimination is not as large as that of total re-breathing.  
           [0015]    Re-breathing can be conducted with a re-breathing circuit, which causes a patient to inhale a gas mixture that includes carbon dioxide. FIG. 1 schematically illustrates a conventional ventilation system that is typically used with patients who require assisted breathing during an illness, during a surgical procedure, or during recovery from a surgical procedure. The conventional ventilator system  10  includes a tubular portion  12  that may be inserted into the trachea of a patient by known intubation procedures. The end  14  (i.e., the end most distant from the patient) of the tubular portion  12  may be fitted with a Y-piece  16  that interconnects an inspiratory hose  18  and an expiratory hose  20 . Both the inspiratory hose  18  and expiratory hose  20  may be connected to a ventilator machine (not shown), which delivers air into the breathing circuit through the inspiratory hose  18 . A one-way valve  22  is positioned on the inspiratory hose  18  to prevent exhaled gas from entering the inspiratory hose  18  beyond the valve  22 . A similar one-way valve  24  on the expiratory hose  20  limits movement of inspiratory gas into the expiratory hose  20 . Exhaled air flows passively into the expiratory hose  20 .  
           [0016]    With reference to FIG. 2, an exemplary known re-breathing ventilation circuit  30  is shown. Re-breathing circuit  30  includes a tubular portion  32  insertable into the trachea of a patient by known intubation procedures. Gases may be provided to the patient from a ventilator machine (not shown) via an inspiratory hose  34  interconnected with tubular portion  32  by a Y-piece  36 . Tubular portion  32  and an expiratory hose  38  are also interconnected by Y-piece  36 . An additional length of hose  40  is provided in flow communication with the tubular portion  32 , between the tubular portion  32  and the Y-piece  36 , and acts as a deadspace for receiving exhaled gas. A three-way valve  42 , generally positioned between the Y-piece  36  and the opening to the additional length of hose  40 , is constructed for intermittent actuation to selectively direct the flow of gas into or from the additional length of hose  40 . That is, at one setting, the valve  42  allows inspiratory gas to enter the tubular portion  32  while preventing movement of the gas into the additional length of hose  40 . At a second setting, the valve  42  allows exhaled gas to enter into the expiratory hose  38  while preventing movement of gas into the additional length of hose  40 . At a third setting, the three-way valve  42  directs exhaled air to enter into the additional length of hose  40  and causes the patient to re-breathe the exhaled air on the following breath to, thereby, effect re-breathing and to cause a change in the effective ventilation of the patient.  
           [0017]    The change in CO 2  elimination and in the partial pressure of end-tidal CO 2  caused by the change in ventilation in the system of FIG. 2 can then be used to calculate the cardiac output or pulmonary capillary blood flow of the patient. Sensing and/or monitoring devices may be attached to the re-breathing ventilation circuit  30  between the additional length of hose  40  and the tubular portion  32 . The sensing and/or monitoring devices may include, for example, means  44  for detecting CO 2  concentration and means  46  for detecting respiratory flow parameters during inhalation and exhalation. These sensing and/or monitoring devices are typically associated with data recording and display equipment (not shown). One problem encountered in use of the conventional re-breathing system is that the volume of the deadspace provided by the additional length of hose  40  is fixed and may not be adjusted. As a result, the amount of deadspace provided in the circuit for a small adult to effect re-breathing is the same amount of deadspace available for a large adult to effect re-breathing, and the resulting changes in CO 2  values for patients of different sizes or breathing capacities, derived from fixed-deadspace systems, can produce inadequate evaluation of a patient&#39;s cardiac output or pulmonary capillary blood flow. Further, the three-way valve  42  of the system is expensive and significantly increases the cost of the ventilation device.  
           [0018]    During total re-breathing, the partial pressure of end-tidal carbon dioxide (Pet CO     2   ) is typically assumed to be equal to the partial pressure of carbon dioxide in the venous blood (Pv CO     2   ) of the patient, as well as to the partial pressure of carbon dioxide in the arterial blood (Pa CO     2   ) of the patient and to the partial pressure of carbon dioxide in the alveolar blood (P A   CO     2   ) of the patient. 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.  
           [0019]    In partial re-breathing, measurements during normal breathing and subsequent re-breathing are substituted into the carbon dioxide Fick equation. This results in a system of two equations and two unknowns (carbon dioxide content in the mixed venous blood and cardiac output), from which cardiac output or pulmonary capillary blood flow can be determined without knowing the carbon dioxide content of the mixed venous blood (Cv CO     2   ).  
           [0020]    Total re-breathing is a somewhat undesirable means of measuring cardiac output or pulmonary capillary blood flow because the patient is required to breathe directly into and from a closed volume of gases (e.g., a bag) in order to produce the necessary effect. Moreover, it is typically impossible or very difficult for sedated or unconscious patients to actively participate in inhaling and exhaling into a fixed volume.  
           [0021]    Known partial re-breathing methods are also advantageous over invasive techniques of measuring cardiac output or pulmonary capillary blood flow because partial re-breathing techniques are non-invasive, use the accepted Fick principle of calculation, are easily automated, and facilitate the calculation of cardiac output or pulmonary capillary blood flow from commonly monitored clinical signals. However, known partial re-breathing methods are somewhat undesirable because they are a less accurate means of measuring the cardiac output or pulmonary capillary blood flow of non-intubated or spontaneously breathing patients, may only be conducted intermittently (usually at intervals of at least about four minutes), and result in an observed slight, but generally clinically insignificant, increase in arterial CO 2  levels. Moreover, the apparatus typically employed in partial re-breathing techniques do not compensate for differences in patient size or breathing capacities. In addition, many devices employ expensive elements, such as three-way valves, which render the devices too expensive to be used as disposable units.  
           [0022]    Thus, there is a need for adjustable deadspace re-breathing apparatus that compensate for differences in the sizes or breathing capacities of different patients, that may be employed to provide a more accurate and continuous measurement of gases exhaled or inhaled by a patient, and are less expensive than conventional re-breathing apparatus and, thereby, facilitate use of the adjustable deadspace re-breathing apparatus as a single-use, or disposable, product. There is also a need for a more accurate method of estimating the cardiac output or pulmonary capillary blood flow of a patient.  
         SUMMARY OF THE INVENTION  
         [0023]    In accordance with the present invention, apparatus and methods for measuring the cardiac output or pulmonary capillary blood flow of a patient are provided. The apparatus of the present invention includes a deadspace (i.e., volume of re-breathed gases), the volume of which can be adjusted without changing airway pressure. The invention also includes methods of adjusting the volume of deadspace to obtain a more accurate cardiac output or pulmonary capillary blood flow value. A modified form of the Fick Equation may be employed with the adjustable deadspace volume to calculate the cardiac output or pulmonary capillary blood flow of the patient. The apparatus of the present invention also employs significantly less expensive elements of construction, thereby facilitating the use of the apparatus as a disposable product.  
           [0024]    The apparatus and methods of the present invention apply a modified Fick Equation to calculate changes in partial pressure of carbon dioxide (P CO     2   ), flow, and concentration to evaluate the cardiac output or pulmonary capillary blood flow of a patient. The traditional Fick Equation, written for CO 2  is:  
         Q   =       V     CO   2         (       C     v     CO   2         -     C     a     CO   2           )         ,                         
 
           [0025]    where Q is pulmonary capillary blood flow (“PCBF”), V CO     2    is the output of CO 2  from the lungs, or “CO 2  elimination,” and Ca CO     2    and Cv CO     2    are the CO 2  contents of the arterial blood and venous blood CO 2 , respectively. It has been shown in the prior work of others that cardiac output can be estimated from calculating the change in the fraction or volume of CO 2  exhaled by a patient and the partial pressure of end-tidal CO 2  as a result of a sudden change in ventilation. That can be done by applying a differential form of the Fick Equation, as follows:  
         Q   =         V     CO     2   1           (       C   v1     -     C   a1       )       =       V     CO     2   2           (       C     v   2       -     C     a   2         )           ,                         
 
           [0026]    where Ca CO     2    is the CO 2  content of the arterial blood of a patient, Cv CO     2    is the CO 2  content of the venous blood of the patient, and the subscripts  1  and  2  refer to measured values before a change in ventilation and measured values during a change in ventilation, respectively. The differential form of the Fick Equation can, therefore, be rewritten as:  
         Q   =             V     CO     2   1         -     V     CO     2   2               (       C   v1     -     C   a1       )     -     (       C   v2     -     C   a2       )                       or                 Q     =         Δ                   V     CO   2           Δ                   C     a     CO   2             =       Δ                   V     CO   2           s                 Δ                     Pet      CO     2               ,                         
 
           [0027]    where ΔV CO   2  is the change in CO 2  elimination in response to the change in ventilation, ΔCa CO     2    is the change in the CO 2  content of the arterial blood of the patient in response to the change in ventilation, ΔPet CO     2    is the change in the partial pressure of end-tidal CO 2 , and s is the slope of a CO 2  dissociation curve known in the art. The foregoing differential equation assumes that there is no appreciable change in venous CO 2  concentration during the re-breathing episode, as demonstrated by Capek. Also, a CO 2  dissociation curve, well known in the art, is used for determining CO 2  concentration based on partial pressure measurements.  
           [0028]    In previous partial re-breathing methods, a deadspace, which may comprise an additional 50-250 ml capacity of air passage, was provided in the ventilation circuit to decrease the effective alveolar ventilation. In the present invention, a ventilation apparatus is provided with a deadspace having an adjustable volume to provide a change in ventilation for determining accurate changes in CO 2  elimination and in partial pressure of end-tidal CO 2  that is commensurate with the requirements of patients of different sizes or breathing capacities. In one embodiment of the ventilation apparatus, selectively adjustable deadspace is provided into which the patient may exhale and from which the patient may inhale. Thus, the adjustable deadspace volume of the apparatus accommodates a variety of patient sizes or breathing capacities (e.g., from a small adult to a large adult). As a result, the patient is provided with a volume of re-breathable gas commensurate with the patient&#39;s size or breathing capacity, which decreases the effective ventilation of the patient without changing the airway pressure of the patient. Because airway and intra-thoracic pressure are not affected by the re-breathing method of the present invention, cardiac output and pulmonary capillary blood flow are not significantly affected by re-breathing.  
           [0029]    In an alternative method, the volume of deadspace may be effectively lessened by selectively leaking exhaled gas from the ventilation system to atmosphere or to a closed receptacle means during inspiration. Similarly, additional carbon dioxide may be introduced into the deadspace to increase the effective deadspace volume. Changing the effective deadspace volume in such a manner has substantially the same effect as changing the actual volume of the deadspace of the ventilation apparatus.  
           [0030]    The ventilation apparatus of the present invention includes a tubular portion, which is also referred to as a conduit, to be placed in flow communication with the airway of a patient. The conduit of the ventilation apparatus may also be placed in flow communication with or include an inhalation course and an exhalation course, each of which may include tubular members or conduits. In a common configuration, the inhalation course and exhalation course may be interconnected in flow communication between a ventilator unit (i.e., a source of deliverable gas mechanically operated to assist the patient in breathing) and the patient. Alternatively, however, a ventilator unit need not be used with the ventilation apparatus. For example, inhaled air and exhaled air may be taken from or vented to atmosphere. Other conventional equipment commonly used with ventilator units or used in ventilation of a patient, such as a breathing mask, may be used with the inventive ventilation apparatus.  
           [0031]    A pneumotachometer for measuring gas flow and a capnometer for measuring CO 2  partial pressure are provided along the flow path of the ventilation apparatus and, preferably, in proximity to the conduit, between the inhalation and exhalation portions of the ventilation apparatus and the patient&#39;s lungs. The pneumotachometer and capnometer detect changes in gas concentrations and flow and are preferably in electrical communication with a computer programmed (i.e., by software or embedded hardware) to store and evaluate, in substantially real time, the measurements taken by the detection apparatus. Other forms of detection apparatus may, alternatively or in combination with the pneumotachometer and the capnometer, be employed with the ventilation apparatus of the present invention.  
           [0032]    Deadspace having an adjustable volume is provided in flow communication with the conduit. In particular, the deadspace is in flow communication with the exhalation portion of the ventilation apparatus (e.g., the expiratory course), and may be in flow communication with the inhalation portion (e.g., the inspiratory course) of the ventilation apparatus. In one embodiment, the volume of the deadspace may be manually adjusted. Alternatively, electromechanical means may be operatively associated with the computer and with the deadspace to provide automatic adjustment of the volume of the deadspace in response to the patient&#39;s size or breathing capacity or in response to changes in the ventilation or respiration of the patient.  
           [0033]    In an alternative embodiment, a tracheal gas insufflation (“TGI”) apparatus is employed to provide the change in ventilation necessary to determine pulmonary CO 2  changes and to determine the cardiac output or pulmonary capillary blood flow of a patient in accordance with the differential Fick Equation disclosed previously. Tracheal gas insufflation apparatus are known, and are typically used to flush the deadspace of the alveoli of the lungs and to replace the deadspace with fresh gas infused through the TGI apparatus. That is, fresh gas is introduced to the central airway of a patient to improve alveolar ventilation and/or to minimize ventilatory pressure requirements. A TGI apparatus may be interconnected, for example, by means of a catheter, with a ventilator apparatus and includes a means of introducing fresh gas into the breathing tube and into the lungs of the patient. The TGI apparatus may be used in the methods of the present invention to determine baseline measurements of CO 2  elimination, partial pressure of end tidal CO 2 , or partial pressure of alveolar CO 2  during TGI. When the TGI system is turned off, a deadspace is formed by the patient&#39;s trachea and the endo-tracheal tube of the TGI apparatus, which facilitates measurement of a change in the partial pressure of CO 2  and in the amount of CO 2  eliminated by the patient that may be evaluated in accordance with the method of the present invention. Further, the catheter of the TGI apparatus may be variably positioned within the trachea of the patient to further adjust the deadspace volume.  
           [0034]    During re-breathing, the deadspace provided by the apparatus of the present invention facilitates a rapid drop in CO 2  elimination, which thereafter increases slightly and slowly as the functional residual lung gas capacity, which is also referred to as functional residual capacity or “FRC,” equilibrates with the increase in the partial pressure of CO 2  in the alveoli. Partial pressure of end tidal CO 2  increases at a slower rate than CO 2  elimination following the addition of deadspace, depending on alveolar deadspace and the cardiac output or pulmonary capillary blood flow of the patient, but then stabilizes to a new level. A “standard,” or baseline, breathing episode is conducted for a selected period of time immediately preceding the introduction of a deadspace into the breathing circuit (i.e., immediately preceding re-breathing) and CO 2  elimination and partial pressure of end tidal CO 2  values are determined based on measurements made during the “standard” breathing event. These values are substituted as the values V CO   2  and Ca CO     2    in the differential Fick Equation. Carbon dioxide elimination and partial pressure of end tidal CO 2  values are also determined from measurements taken for a predetermined amount of time (e.g., approximately thirty seconds) following the introduction of a deadspace (i.e., after the onset of re-breathing) during partial re-breathing to provide the second set of values (subscript 2 values) in the differential Fick Equation. Thus, the predetermined amount of time at which the second set of values are obtained may be about the same as the duration of partial re-breathing. The period of time during which partial re-breathing occurs and during which normal breathing occurs may be determined by the individual patient&#39;s size and breathing capacity. Additionally, the period of time between a re-breathing episode and a subsequent normal breathing episode may vary between patients, depending on a particular patient&#39;s size and breathing capacity.  
           [0035]    Cardiac output or pulmonary capillary blood flow may be determined in accordance with the method of the present invention by estimating the partial pressure of CO 2  in the alveoli or the content of the blood in capillaries that surround the alveoli of the lungs of a patient (Cc′ CO     2   ), or the alveolar CO 2  content (C A   CO     2   ), rather than basing the cardiac output or pulmonary capillary blood flow determination on the partial pressure of end-tidal CO 2 , as is typically practiced in the art. Partial pressure values that are obtained from CO 2  measurements are converted to a value for gas content in the blood using a CO 2  dissociation curve or equation, as known in the art. Thus, a more accurate cardiac output or pulmonary capillary blood flow value can be determined with alveolar CO 2  measurements than with partial pressure of end tidal CO 2  measurements.  
           [0036]    In addition, the accuracy of the cardiac output or pulmonary capillary blood flow measurement may be increased by correcting CO 2  elimination values to account for flow of CO 2  into the functional residual capacity of the lungs, which is the volume of gas that remains in the lungs at the end of expiration. The cardiac output or pulmonary capillary blood flow of the patient may then be determined by accounting for the functional residual capacity and by employing the values obtained in accordance with the method of the present invention, as well as other determined values, known values, estimated values, or any other values based on experiential data, such as by a computer processor in accordance with the programming thereof. Alternatively, cardiac output or pulmonary capillary blood flow may be estimated without accounting for functional residual capacity.  
           [0037]    The ventilation apparatus of the present invention may also employ inexpensive yet accurate monitoring systems as compared to the systems currently used in the art. The methods of the invention may include the automatic adjustment of the deadspace volume of the apparatus to accommodate patients of different sizes or breathing capacities or changes in the ventilation or respiration of a patient, and provides consistent monitoring with modest recovery time. Further, the present apparatus and methods can be used with non-responsive, intubated patients and with non-intubated, responsive patients.  
           [0038]    Other features and advantages of the present invention will become apparent through a consideration of the ensuing description, the accompanying drawings, and the appended claims. 
       
    
    
     BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS  
       [0039]    [0039]FIG. 1 is a schematic representation of a conventional ventilation system used to assist patient breathing;  
         [0040]    [0040]FIG. 2 is a schematic representation of a conventional re-breathing system;  
         [0041]    [0041]FIG. 3 is a schematic representation of a first embodiment of the ventilation apparatus of the present invention, illustrating a deadspace with an adjustably expandable volume;  
         [0042]    [0042]FIG. 4 is a schematic representation of an alternative embodiment of the present invention, wherein the re-breathing circuit is constructed with an evacuation valve;  
         [0043]    FIGS.  5 A- 5 C are schematic representations of another alternative embodiment of the present invention, wherein the inspiratory course and expiratory course of the breathing circuit are interconnected and the breathing circuit includes a two-way valve closeable across a flow path of the breathing circuit;  
         [0044]    [0044]FIG. 6 is a schematic representation of an alternative embodiment similar to the embodiment shown in FIGS.  5 A- 5 C, wherein the volumes of the inspiratory course and expiratory course of the breathing circuit are adjustably expandable;  
         [0045]    [0045]FIG. 7 is a schematic representation of another embodiment of the invention, wherein a series of valves is provided along the length of the inspiratory course and expiratory course of the breathing circuit to provide a selectable volume of deadspace dependent upon the size, breathing capacity, or changes in the ventilation or respiration of the patient;  
         [0046]    [0046]FIGS. 8A and 8B are schematic representations of another embodiment of the invention, wherein an evacuation valve is provided with a vent to atmosphere and to a receptacle or chamber, respectively;  
         [0047]    [0047]FIG. 9 is a schematic representation of a breathing circuit of the present invention that includes a tracheal gas insufflation apparatus, which can be used to provide a volume of deadspace;  
         [0048]    [0048]FIG. 10 is a schematic representation of human lungs, illustrating the concepts of parallel deadspace, alveolar deadspace and serial deadspace in the lungs of a patient;  
         [0049]    [0049]FIG. 11 is a flow diagram that illustrates the calculations made in the method of the present invention to determine cardiac output or pulmonary capillary blood flow by employing the measured values during both normal breathing and partial re-breathing; and  
         [0050]    [0050]FIG. 12 is a schematic representation of a variation of the ventilation apparatus of FIG. 7, including sections having selectively expandable volumes.  
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0051]    Ventilation Apparatus and Methods  
         [0052]    [0052]FIG. 3 illustrates a breathing circuit of the present invention, which is illustrated as a ventilation apparatus  50 , and which may be employed to determine the cardiac output of pulmonary capillary blood flow of a patient. Ventilation apparatus  50  comprises a tubular airway  52 , which is also referred to as an airway conduit or simply as a conduit, that may be placed in flow communication with the trachea or lungs of the patient. The present ventilation apparatus  50  may be placed in flow communication with the trachea of the patient by known intubation procedures or by positioning a breathing mask over the nose and/or mouth of the patient. Ventilation apparatus  50  may be used with unconscious or uncooperative patients needing ventilation assistance, and may be used with substantially equal efficacy with patients who are conscious. Ventilation apparatus  50  may also include an inspiratory hose  54 , which is also referred to as an inspiratory course or as an inspiration portion of the breathing circuit, and an expiratory hose  56 , which is also referred to as an expiratory course or as an expiration portion of the breathing circuit, both of which are in substantial flow communication with tubular airway  52 . The inspiratory hose  54  and the expiratory hose  56  may each be ventilated to atmosphere or operatively connected to a ventilator machine  55  to facilitate the delivery of air, breathing gases, or other breathing medium to the patient through the inspiratory hose  54 . The inspiratory hose  54  and expiratory hose  56  may each be joined in flow communication with the tubular airway  52  by means of a Y-piece  58 .  
         [0053]    An additional length of conduit or hose  60 , which provides a deadspace volume for receiving exhaled gas from the patient, is preferably in flow communication with the tubular airway  52 . Both ends of the additional length of hose  60  are preferably in flow communication with tubular airway  52 . The additional length of hose  60  is configured to be selectively expandable to readily enable the volume of deadspace to be adjusted commensurate with the size or breathing capacity of the patient, or commensurate with changes in the ventilation or respiration of the patient, such as an increased or decreased tidal volume or modified respiration rate. As suggested by FIG. 3, selective expansion of the deadspace may be accomplished by configuring the additional length of hose  60  to include an expandable section  62  made of, for example, a section of corrugated hose which can be lengthened or shortened by simply pulling or pushing the expandable section  62  substantially along its longitudinal axis  64 . The section of corrugated hose will preferably retain the length to which it is set until adjusted again. Other suitable means of providing adjustable expansion of the volume of the deadspace and, thus, methods of adjusting the volume of the deadspace of the breathing circuit are also available and within the scope of the present invention.  
         [0054]    A three-way valve  68  may be disposed along the flow path of tubular airway  52  between the two ends of additional length of hose  60  and selectively positioned to direct inspiratory gas into a deadspace  70  comprised of the additional length of hose  60  upon inhalation, to selectively prevent exhaled gas from entering the deadspace  70  during normal breathing, or to direct exhaled gas into deadspace  70  during re-breathing so that the patient will re-breathe previously exhaled gases or a gas including CO 2  from the deadspace  70 .  
         [0055]    A flow meter  72 , such as a pneumotachometer, and a carbon dioxide sensor  74 , which is typically referred to as a capnometer, may be exposed to the flow path of the ventilation apparatus, preferably between the tubular airway  52  and the additional length of hose  60 . Thus, the flow meter  72  and carbon dioxide sensor  74  are exposed to any air or gas that flows through ventilation apparatus  50 . The flow meter  72  detects gas flow through the ventilation apparatus  50 .  
         [0056]    A flow meter  72  of a known type, such as the differential-pressure type respiratory flow sensors manufactured by Novametrix Medical Systems Inc. (“Novametrix”) of Wallingford, Conn. (e.g., the Pediatric/Adult Flow Sensor (Catalog No. 6717) or the Neonatal Flow Sensor (Catalog No. 6718)), which may be operatively attached to a ventilation apparatus (not shown), as well as respiratory flow sensors based on other operating principles and manufactured or marketed by others, may be employed to measure the flow rates of the breathing of the patient.  
         [0057]    The carbon dioxide sensor  74  detects CO 2  levels and, therefore, facilitates a determination of changes in CO 2  levels that result from changes in the ventilation or respiration of the patient. The carbon dioxide sensor  74  and its associated airway adapter may be an “on airway” sensor, a sampling sensor of the type which withdraws a side stream sample of gas for testing, or any other suitable type of carbon dioxide sensor. Exemplary carbon dioxide sensors and complementary airway adapter include, without limitation, the Pediatric/Adult Single Patient Use Airway Adapter (Catalog No. 6063), the Pediatric/Adult Reusable Airway Adapter (Catalog No. 7007), or the Neonatal/Pediatric Reusable Airway Adapter (Catalog No. 7053), which are manufactured by Novametrix. Alternatively, combined flow and carbon dioxide sensors, as known in the art, may be employed.  
         [0058]    The data obtained by the flow meter  72  and by the carbon dioxide sensor  74  are preferably used to determine the cardiac output or pulmonary capillary blood flow of the patient. Accordingly, the flow meter  72  and carbon dioxide sensor  74  may be operatively associated with a computer  76  (e.g., by direct cable connection, wireless connection, etc.) programmed to store or analyze data from the flow meter  72  and the carbon dioxide sensor  74  and programmed to determine the cardiac output or pulmonary capillary blood flow of the patient from the stored or analyzed data.  
         [0059]    As previously described herein, the differential Fick Equation requires a change in the partial pressure of carbon dioxide and a change in carbon dioxide elimination to be induced in the patient in order to estimate the cardiac output or pulmonary capillary blood flow of the patient. As the patient re-breathes previously exhaled gas, the amount of CO 2  inhaled by the patient increases, thereby facilitating the evaluation of increased CO 2  levels during a change in effective ventilation, as compared to the CO 2  levels of the patient&#39;s breathing during normal ventilation. The re-breathing ventilation apparatus  50  of the present invention provides the ability to selectively adjust the volume of deadspace from which air is re-breathed in accordance with the size or breathing capacity of the patient, or in response to changes in the ventilation or respiration of the patient. For example, if the detected change in partial pressure of end tidal CO 2  is less than a threshold pressure (e.g., 1 mm Hg), or the change in CO 2  elimination is less than a threshold percentage or fraction (e.g., 20% or 0.2) of a baseline CO 2  elimination, then the deadspace volume may be increased by an appropriate amount (e.g., 20%). Similarly, if the detected change in partial pressure of end tidal CO 2  is greater than a threshold pressure (e.g., 12 mm Hg), or the change in CO 2  elimination is greater than a threshold percentage or fraction (e.g., 80% or 0.8) of the baseline CO 2  elimination, then the deadspace volume may be decreased by an appropriate amount (e.g., 20%).  
         [0060]    In an alternative embodiment of the re-breathing ventilation apparatus  50 ′ of the invention, as shown in FIG. 4, the expense of using a three-way valve may be eliminated by disposing an inexpensive two-way valve  78 ′ along the flow path of the additional length of hose  60 ′ and by positioning a flow restrictor  80  (e.g., a region of tubular airway  52  of decreased inner diameter) along tubular airway  52  between the inlet  82  and outlet  84  (i.e., the two ends) of the additional length of hose  60 ′. Thus, when the two-way valve  78 ′ is closed, inhaled and exhaled gases will be directed through the flow restrictor  80 . During re-breathing, the two-way valve  78 ′ is placed in an open position so that the exhaled air, encountering the flow restrictor  80 , follows the course of less resistance into the deadspace  70 ′. Inhaled, re-breathed air similarly follows the course of least resistance and flows from the deadspace  70 ′. As the optimal amount of air re-breathed by the patient may depend upon the size, breathing capacity, or changes in the ventilation or respiration of the patient, or on another factor, it may be desirable to adjust the deadspace  70 ′ at the expandable section  62 ′ to provide the necessary volume of deadspace for determining the cardiac output or pulmonary capillary blood flow of the patient.  
         [0061]    In another alternative embodiment of the ventilation apparatus  50 ″ of the present invention, as shown in FIGS.  5 A- 5 C, a shunt line  85  is positioned between the inspiratory course  54 ″ and the expiratory course  56 ″ to provide a selectively-sized deadspace  70 ″ in the re-breathing circuit. In the configuration of the embodiment shown in FIGS.  5 A- 5 C, the inspiratory course  54 ″ and expiratory course  56 ″ may comprise at least a part of the deadspace  70 ″. A two-way shunt valve  86 , positioned in the flow path of the shunt line  85 , selectively directs the flow of inspired and expired gas, dependent upon whether the shunt valve  86  is placed in an open position or a closed position. Thus, when the ventilation apparatus  50 ″ is configured for normal or baseline breathing, as depicted in FIG. 5A, exhaled air (represented by the shaded area) will enter the expiratory course  56 ″. During normal breathing, the shunt valve  86  is placed in the closed position. During a re-breathing episode, as depicted in FIG. 5B, the shunt valve  86  is placed in the open position, and exhaled gas may fill a portion of the inspiratory course  54 ″, substantially all of the expiratory course  56 ″, and the shunt line  85 , all of which serve as the deadspace  70 ″.  
         [0062]    The deadspace  70 ″ in the embodiment shown in FIGS.  5 A- 5 C may be rendered further expandable, as shown in FIG. 6, by structuring the inspiratory course  54 ″ with an expandable section  90  positioned between the shunt line  85  and the Y-piece  58 , and/or by structuring the expiratory course  56 ″ with an expandable section  92  positioned between the shunt line  85  and the Y-piece  58 . Thus, the deadspace  70 ″ can be selectively adjusted in accordance with the size or capacity of the patient, or responsive to operating conditions, by increasing or decreasing the volume of the expandable sections  90 ,  92  of the inspiratory course  54 ″ and expiratory course  56 ″, respectively. Shunt line  85  may similarly include a volume expandable section. As explained previously in reference to FIG. 3, any suitable adjustably expandable means may be employed as expandable sections  90 ,  92 . For example, as depicted in FIG. 6, the expandable sections  90 ,  92  may be fabricated from a corrugated plastic material, the length of which can be easily expanded or contracted and preferably substantially maintained until re-adjusted. The embodiment of FIG. 6 provides a particularly simple and inexpensive construction that may render it easy-to-use and facilitate its use as a disposable product.  
         [0063]    In yet another embodiment of the ventilation apparatus  50 ′″ of the present invention, as shown in FIG. 7, a plurality of shunt lines  85 ′″,  94 ,  96  is positioned between the inspiratory course  54 ′″ and the expiratory course  56 ′″, with each shunt line  85 ′″,  94 ,  96  including a two-way shunt valve  86 ′″,  98 ,  100 , respectively, disposed along the flow path thereof. In operation, the amount of deadspace  70 ′″ desired, according to the size or breathing capacity of the patient or other factors, may be selectively adjusted by permitting exhaled gas to move through any suitable combination of shunt lines  85 ′″,  94 ,  96 . For example, given a patient of average size or lung capacity, it may be appropriate to use shunt line  85 ′″ and shunt line  94  as potential deadspace  70 ′″. Thus, as the patient exhales in a re-breathing episode, the shunt valves  86 ′″,  98  associated with shunt line  85 ′″ and shunt line  94 , respectively, may be placed in an open position to permit exhaled and re-breathable gas to fill the expiratory course  56 ′″, the inspiratory course  54 ′″ between shunt line  94  and the Y-piece  58 , shunt line  85 ′″, and shunt line  94 . With a patient of larger size or greater lung capacity, it may be necessary to use the third shunt line  96  to provide sufficient deadspace  70 ′″ for re-breathing. Notably, each shunt valve  86 ′″,  98 ,  100  may be in electromechanical communication with the computer  76  (see FIG. 3) so that the computer may determine, from the carbon dioxide sensor  74  (see FIG. 3), for example, that a different volume of deadspace  70 ′″ is needed. The computer  76  may then direct the opening or closing of one or more of the shunt valves  86 ′″,  98 ,  100  to provide a sufficient volume of deadspace  70 ′″.  
         [0064]    Referring to FIG. 12, as a variation of the embodiment illustrated in FIG. 7, the ventilation apparatus  50 ′″ may also include selectively expandable sections  90 ′″,  92 ′″ similar to those shown in FIG. 6. Although expandable sections  90 ′″ and  92 ′″ are illustrated as being disposed along inspiratory course  54 ′″ and expiratory course  56 ′″, sections of expandable volume may also be disposed along other portions of the potential deadspace of the breathing circuit, such as along any of shunt lines  85 ′″,  94 , or  96 .  
         [0065]    In the several embodiments of the invention previously illustrated and described, the amount or volume of the deadspace has been selectively adjustable by providing means for adjusting the volume of the deadspace, such as by providing length-expanding means. It may be equally appropriate, however, to provide a change in ventilation, as required by the differential Fick Equation, by leaking some of the exhaled gas out of the system during the inspiration phase of a breath or by increasing the level of CO 2  in the deadspace, both of which provide an effective change in the volume of deadspace. Thus, as illustrated by FIG. 8A, the ventilation apparatus  50  of the present invention may include an evacuation element or component. The evacuation element may include an evacuation line  106  in flow communication with at least the expiratory course  56  of the ventilation apparatus  50 . The evacuation element includes a structure that permits gas or another breathing medium to flow into or out of the ventilation apparatus  50 , such as an evacuation valve  108 , which is also referred to as a valve, that, when opened, allows exhaled gas to escape the ventilation apparatus  50  through an orifice  110  positioned at the end of the evacuation line  106  or permits gas to be introduced into the ventilation apparatus  50 . Alternatively, a valve may be positioned in flow communication with ventilation apparatus  50  to facilitate the flow of gases therefrom.  
         [0066]    The volume of exhaled gas that should be leaked from the ventilation apparatus  50  or introduced therein during a re-breathing event, as well as the timing and duration of such leakage or introduction, may be determined by the computer  76  (see FIG. 3) in response to flow conditions, CO 2  conditions, the size or breathing capacity of the patient, or changes in the ventilation or breathing of the patient. In addition, the evacuation valve  108 , which may be in electromechanical communication with the computer  76 , may be selectively actuated by the computer  76  in accordance with the flow conditions, the CO 2  conditions, the size or breathing capacity of the patient, or changes in the ventilation or respiration of the patient.  
         [0067]    With reference to FIG. 8B, where a patient is anesthetized or is otherwise exhaling gas which is undesirable for venting to the atmosphere, a chamber or receptacle  112 , such as an expandable bag, may be disposed along the evacuation line  106  or otherwise in flow communication with the evacuation valve  108  to receive the exhaled gas leaked from the ventilation circuit.  
         [0068]    [0068]FIG. 9 schematically illustrates the use of a tracheal gas insufflation (TGI) apparatus  120  to provide the necessary deadspace in determining the cardiac output or pulmonary capillary blood flow of a patient. TGI apparatus  120  are typically used to ventilate sick patients who require the injection of fresh gas into their central airway to improve alveolar ventilation. TGI apparatus can be configured to provide continuous or phasic (e.g., only during inhalation) injections of gas. The TGI apparatus supplies gas, or an oxygen/gas mixture, to the lungs with every breath. As shown in FIG. 9, the TGI apparatus comprises an endotracheal tube  122 , which may be inserted into the trachea  124  of the patient by known intubation procedures. A catheter  126  extends through the endotracheal tube  122  and into the patient&#39;s lungs, typically just above the carina. Gas or an oxygen/gas blend is provided from a gas source  128  and is directed through gas delivery tubing  130  into the catheter  126 . A flow meter  132  disposed along gas delivery tubing  130  and in flow communication therewith may assist in determining the optimum amount of gas to be introduced into the lungs.  
         [0069]    An adaptor fitting  134  may be used to connect a ventilation apparatus  136 , such as the type previously described in reference to FIGS.  1 - 8 (B), to the TGI apparatus  120 . That is, the ventilation apparatus  136  may include a Y-piece  58  from which an inspiratory course  54  and an expiratory course  56  extend. The ventilation apparatus  136  may also include a flow meter  72  and a carbon dioxide sensor  74  disposed in flow communication therewith to collect data during normal breathing and during a re-breathing event. In the illustrated TGI apparatus  120 , the endotracheal tube  122  provides a volume of deadspace that may be required for re-breathing in addition to any deadspace volume provided by the ventilation apparatus  136 . In order to act as a deadspace, however, the TGI apparatus (i.e., the gas source  128  and flow meter  132 ) is preferably turned off, the amount of insufflation reduced, or the TGI apparatus otherwise disabled. Exhaled air is thereby allowed to flow into the endotracheal tube  122  and, preferably, through the Y-piece  58 . The endotracheal tube  122  and ventilation apparatus  136  or portions thereof may then serve as deadspace. The volume of deadspace provided by the TGI apparatus  120  may be further increased or decreased, as necessary, by varying the depth to which the catheter  126  is positioned in the patient&#39;s trachea.  
         [0070]    A computer  76  (see FIG. 3) to which the flow meter  72  and the carbon dioxide sensor  74  may be connected can be programmed to receive data from the flow meter  72  and the carbon dioxide sensor  74  and to analyze the data to determine or estimate the cardiac output or pulmonary capillary blood flow of the patient.  
         [0071]    Methods of Determining Cardiac Output or Pulmonary Capillary Blood Flow  
         [0072]    The determination of cardiac output or pulmonary capillary blood flow for a given patient may be based on data obtained with the flow monitor and the carbon dioxide sensor that are associated with the ventilation apparatus of the present invention. Raw flow and CO 2  signals from the flow monitor and the carbon dioxide sensor may be filtered to remove any artifacts, and the flow signals and CO 2  signals (e.g., data regarding partial pressure of CO 2 ) may be stored by the computer  76 .  
         [0073]    Each breath, or breathing cycle, of the patient may be delineated, as known in the art, such as by continually monitoring the flow rate of the breathing of the patient.  
         [0074]    For each breathing cycle, the partial pressure of end-tidal CO 2  carbon dioxide elimination (V CO   2 ), the fraction of inspired, or “mixed inspired,” CO 2  and the airway deadspace are calculated. End-tidal CO 2  is measured, as known in the art. Carbon dioxide elimination is typically calculated as the integral of the respiratory flow over a breathing cycle (in milliliters) multiplied by the fraction of CO 2  over the entire breath. The fraction of inspired CO 2  is the integral of CO 2  fraction times the air flow during inspiration, divided by the volume (in milliliters) of inspired gas.  
         [0075]    The values of V CO   2  and Pet CO     2    may be filtered by employing a median filter, which uses a median value from the most recent value of recorded V CO   2  and Pet CO     2    values and the two values that precede the most recent measured value, as known in the art.  
         [0076]    Preferably, when calculating V CO   2 , the V CO   2  value is corrected to account for anatomic deadspace and alveolar deadspace. With reference to FIG. 10, the lungs  150  of a patient may be described as including a trachea  152 , two bronchi  154  and numerous alveoli  160 ,  162 . The anatomic, or “serial,” deadspace of lungs  150  includes the volume of the trachea  152 , bronchi  154 , and other components of lungs  150  which hold gases, but do not participate in gas exchange. The anatomic deadspace exists approximately in the region located between arrows A and B. The so-called “shunted” blood bypasses pulmonary capillaries by way of an intrapulmonary shunt  165 .  
         [0077]    Lungs  150  typically include alveoli  160  that are in contact with blood flow and which can facilitate oxygenation of the blood, which are referred to as “perfused” alveoli, as well as unperfused alveoli  162 . Both perfused alveoli  160  and unperfused alveoli  162  may be ventilated. The volume of unperfused alveoli is the alveolar deadspace.  
         [0078]    Perfused alveoli  160  are surrounded by and in contact with pulmonary capillaries  164 . As deoxygenated blood  166  enters pulmonary capillaries  164 , oxygen binds to the hemoglobin molecules of the red blood cells of the blood, and CO 2  is released from the hemoglobin. Blood that exits pulmonary capillaries  164  in the direction of arrow  171  is referred to as oxygenated blood  168 . In alveoli  160  and  162 , a volume of gas known as the functional residual capacity (FRC)  170  remains following exhalation. The alveolar CO 2  is expired from a portion  172  of each of the alveoli  160  that is evacuated, or ventilated, during exhalation.  
         [0079]    The ventilated portion  178  of each of the unperfused alveoli  162  may also include CO 2 . The CO 2  of ventilated portion  178  of each of the unperfused alveoli  162 , however, is not the result of O 2  and CO 2  exchange in that alveolus. Since the ventilated portion  178  of each of the unperfused alveoli  162  is ventilated in parallel with the perfused alveoli, ventilated portion  178  is typically referred to as “parallel” deadspace (PDS). Unperfused alveoli  162  also include a FRC  176 , which includes a volume of gas that is not evacuated during a breath.  
         [0080]    In calculating the partial pressure of CO 2  in the alveoli (P A   CO     2   ) of the patient, the FRC and the partial pressure of CO 2  in the parallel deadspace in each of the unperfused alveoli  162  is preferably accounted for. FRC may be estimated as a function of body weight and of the airway deadspace volume by the following equation:  
           FRC=FRC −factor·(airway deadspace+offset value),  
         [0081]    where FRC-factor is either an experimentally determined value or is based on published data (e.g., “experiential” data) known in the art, and the offset value is a fixed constant which compensates for breathing masks or other equipment components that may add deadspace to the breathing circuit and, thereby, unacceptably skew the relationship between FRC and deadspace.  
         [0082]    The partial pressure of CO 2  in the parallel dead space (CO 2 PDS ) may be calculated from the mixed inspired CO 2  (Vi CO     2   ) added to the product of the serial deadspace multiplied by the end tidal CO 2  of the previous breath (Pet CO     2   (n−1)). Because the average partial pressure of CO 2  in the parallel deadspace is equal to the partial pressure of CO 2  in the parallel deadspace divided by the tidal volume (V t ) (i.e., the total volume of one respiratory cycle, or breath), the partial pressure of CO 2  in the parallel deadspace may be calculated on a breath-by-breath basis, as follows:  
                 P       CO   2                   PDS            (   n   )       =                [     FRC   /     (     FRC   +     V   t       )       ]     ·       P       CO   2                   PDS            (     n   -   1     )         +                          (       P   bar     ·     (       (     [       Vi     CO   2       +     deadspace   ·         Pet     CO   2            (     n   -   1     )       /     P   bar           )     ]     /                                        V   t     )     ·     [       V   t     /     (       V   t     +   FRC     )       ]       )     )     ,                               
 
         [0083]    where (n) indicates a respiratory profile parameter (in this case, the partial pressure of CO 2  in the parallel deadspace, P CO     2      PDS (n)) from the most recent breath and (n−1) indicates a respiratory profile parameter from the previous breath.  
         [0084]    The partial pressure of end-tidal CO 2 , which is assumed to be substantially equal to a weighted average of the partial pressure of CO 2  in all of the perfused and unperfused alveoli of a patient, may be calculated as follows:  
           Pet   CO     2     =®·P   A   CO     2   )+(1 −r ) P   CO     2 PDS   ,  
         [0085]    where r is the perfusion ratio, which is calculated as the ratio of perfused alveolar ventilation to the total alveolar ventilation, or (V A −V PDS )/V A . The perfusion ratio may be assumed to be about 0.95 or estimated, as known in the art. Alternatively, the perfusion ratio may be determined by comparing arterial P CO     2   , which measurement may be obtained directly from arterial blood and assumed to be substantially the same as alveolar P CO     2   , to end tidal P CO     2    values by rearranging the previous equation as follows:  
           r= ( Pet   CO     2     −P   CO     2 PDS   )/( P   A   CO     2     −P   CO     2 PDS   ).  
         [0086]    By rearranging the preceding Pet CO     2    equation, the alveolar CO 2  partial pressure of the patient may be calculated. Preferably, alveolar CO 2  partial pressure is calculated from the end-tidal CO 2  and the CO 2  in the parallel deadspace, as follows:  
           P   A   CO     2     =[Pet   CO     2   −(1 −r ) P   CO     2      PDS   ]/r.    
         [0087]    The alveolar CO 2  partial pressure may then be converted to alveolar blood CO 2  content (C A   CO     2   ) using an equation, such as the following:  
           C   A   CO     2   =(6.957·Hb cone +94.864)·ln(1+0.1933( P   A   CO     2   )),  
         [0088]    where C A   CO     2    is the content of CO 2  in the alveolar blood and Hb is the concentration of hemoglobin in the blood of the pulmonary capillaries. J. M. Capek and R. J. Roy,  IEEE Transactions on Biomedical Engineering  (1988) 35(9): 653 - 661 . In some instances, a hemoglobin count and, therefore, the hemoglobin concentration, are available and may be employed in calculating the CO 2  content. If a hemoglobin count or concentration is not available, another value that is based upon experiential or otherwise known data (e.g., 11.0 g/dl) may be employed in calculating the alveolar CO 2  content.  
         [0089]    In calculating V CO   2 , the FRC and alveolar deadspace of the lungs of a patient may be accounted for by multiplying the FRC by the change in end tidal partial pressure, such as by the following equation:  
           V   CO   2 corrected   =V   CO     2     +FRC×ΔPet   CO     2     /P   bar ,  
         [0090]    where ΔPet CO     2    is the breath-to-breath change in Pet CO     2   .  
         [0091]    Baseline Pet CO     2    and V CO   2  values, which are also referred to as “before re-breathing Pet CO     2   ” and “before re-breathing V CO   2 ,” respectively, occur during normal breathing and may be calculated as the average of a group of samples taken before the re-breathing process (e.g., the average of all samples between about 27 and 0 seconds before the start of a known re-breathing process). A V CO   2  value, which is typically referred to as “during re-breathing V CO   2 ,” is calculated during the re-breathing process. “During re-breathing V CO   2 ” may be calculated as the average V CO   2  during the interval of 25 to 30 seconds into the re-breathing period.  
         [0092]    The content of CO 2  in the alveolar blood during the re-breathing process may then be calculated by employing a regression line, which facilitates prediction of the stable, or unchanging, content of alveolar CO 2 . Preferably, P A   CO     2    is plotted against the breath-to-breath change in content of alveolar CO 2  (ΔC A   CO     2   ). A graph line that is defined by the plotted points is regressed, and the intersection between P A   CO     2    and zero ΔC A   CO     2    is the predicted stable content of alveolar CO 2 .  
         [0093]    Pulmonary capillary blood flow may then be calculated as follows:  
         Q   pcbf     =         [       before                 re        -        breathing                   V     CO   2         -     during                 re        -        breathing                   V     CO   2           ]       [       during                 re        -        breathing                   C     A     CO   2           -     before                 re        -        breathing                   C     A     CO   2             ]       .                           
 
         [0094]    Operation Logic of a Computer Program for Determining Cardiac Output or Pulmonary Capillary Blood Flow  
         [0095]    The operation logic of an exemplary computer program that directs the execution of the method of the present invention is briefly illustrated in the flow diagram of FIG. 11. The computer  76  (see FIG. 3) may be programmed to detect the end of an exhalation, at  200 , at which point the computer  76  collects data from the carbon dioxide sensor  74  and the flow meter  72  (see FIG. 3) and calculates Pet CO     2    V CO   2 , the fraction of inspired CO 2 , and the airway deadspace values at  202 . The computer  76  then calculates FRC, at  204 , according to the previously described equation, and in accordance with the program. The program also directs the computer  76  to correct the V CO     2    value, at  206 , in accordance with the previously described equation. At determined intervals of time (e.g., two seconds), the CO 2  and V CO   2  values are re-calculated, at  210 , to provide data samples at evenly spaced times, not on the respiratory rate, which may be variable. This technique is typically referred to as “re-sampling” the data.  
         [0096]    The computer  76 , in accordance with the program, then calculates the estimated partial pressure of CO 2  (P CO     2   ) in the parallel deadspace, at  212 , and calculates the estimated P CO     2    in the alveoli, at  214 , using the equations described previously. At that point, re-breathing is initiated, at  216 , and a deadspace volume is introduced in the re-breathing circuit. Again, the computer  76 , in accordance with the programming thereof, collects data from the carbon dioxide sensor  74  and the flow meter  72  (see FIG. 3) and, from that data, determines the change in V CO   2  and the change in partial pressure of alveolar CO 2  (P A   CO     2   ) induced by the introduction of the deadspace, at  218 . If the calculated change in V CO   2  is less than a predetermined minimum percentage (e.g., 20%) or exceeds a predetermined maximum percentage (e.g., 80%) of the baseline V CO   2 , or if the change in partial pressure of alveolar CO 2  is less than or exceeds predetermined threshold minimum and maximum pressures (e.g., 3 mm Hg or 20 mm Hg), determined at  220 , then the operator is notified to accordingly modify the volume of the partial re-breathing deadspace, at  222 . Baseline values may then be canceled, at  224  or  232 , then recalculated, as suggested by arrow  226  or arrow  234 . Alternatively, the computer  76  may signal mechanical or electromechanical means associated with the adjustable deadspace to automatically modify the volume thereof.  
         [0097]    Upon proper adjustment of the adjustable deadspace and the recalculation of baseline Pet CO     2   , V CO   2 , inspired CO 2  and airway deadspace values, the alveolar partial pressure (P A   CO     2   ) is converted by the software program to CO 2  content of the alveolar (pulmonary) capillaries (C A   CO     2    or Cc′ CO     2   ). The change in the CO 2  content of the alveolar blood induced by having the patient re-breathe a volume of previously exhaled gases from the deadspace is then calculated, at  236 . From these values, the cardiac output or pulmonary capillary blood flow of the patient may be calculated, at  238 , in accordance with the previously described equation or otherwise, as known in the art.  
         [0098]    Although the foregoing description contains many specifics, these should not be construed as limiting the scope of the present invention, but merely as providing illustrations of some of the presently preferred embodiments. Similarly, other embodiments of the invention may be devised which do not depart from the spirit or scope of the present invention. The scope of the invention is, therefore, indicated and limited only by the appended claims and their legal equivalents, rather than by the foregoing description. All additions, deletions and modifications to the invention as disclosed herein which fall within the meaning and scope of the claims are to be embraced thereby within their scope.