CA2419622A1 - A new method of measuring cardiac related parameters non-invasively with spontaneous and controlled ventilation - Google Patents

Abstract

An improved method of apparatus for determining:
~, ~A, and calculating ~CO2, P~ CO2 - oxy, true P~ CO2, PaCO2, pulmonary shunt, anatomical dead space, and O2 saturation in mixed venous blood; which increases the accuracy of these determinations and calculations in relation to known methods and apparatuses and allows for full automation thereof if necessary by:
i) reading FGF to a sequential delivery circuit to create two sets of data for said determination utilizing the Fick equations; (or) ii) the P ET CO2 to PaCO2 gradient is calculated from two independently derived values in the same subject; (or) iii) utilizing the Kim-Rahn-Farhi technique a period of reducing FGF
simulates complete or partial breath holding, wherein the P ET CO2 of each breath is equivalent to a sequential alveolar sample;
thereby providing more relevant data to calculate desired parameters.

Description

a r TITLE OF THE INVENTION
A NEW METHOD OF MEASURING CARDIAC RELATED PARAMETERS NON-INVASIVELY WITH SPONTANEOUS AND CONTROLLED VENTILATION
FIELD OF THE INVENTION
This invention discloses a method that calculates aII of the Q regardless of shunt, calculates the shunt, anatomical and alveolar deadspace, true mixed venous Oa saturation, true mixed venous PC02, and PaC02. Furthermore the method can be performed in ventilated subjects, subjects breathing spontaneously, even with marked variations in their tidal volume and breathing frequency, or subjects undergoing surgery under anaesthesia. Subjects need not perform any respiratory manoeuvre such as hyperventilation or breath holding.
BACKGROUND OF THE INVENTION
1. ImporEance of cardiac output A physician's ability to determine a patient's cardiac output (Q, the volume of blood pumped by the heart each minute) is important in the assessment of critically ill patients. There are various devices and methods that provide a direct or indirect measure of Q (see table 2). The most common method used in clinical practice is thermo-dilution, established by Ganz et al 1. Commercially manufactured catheters (referred to as Swan-Ganz catheters, named after the inventors) contain multiple lumina, an embedded thermister, and a balloon at the tip. The method requires the insertion of the catheter through the skin to access a large central vein such as the internal jugular, subclavian, cephalic or femoral. When the balloon at the end of the catheter is inflated, the catheter tip is carried along with the flow of blood to the right ventricle of the heart and then into the pulmonary artery. The part of the catheter that remains outside the body has connections that can be attached to electrical sensors that determine the pressure and temperature in the pulmonary artery where the tip of the catheter is positioned. Calculation of Q requires the injection of a fixed volume of cool liquid of known temperature into a lumen of the catheter that has its opening part way along its length (usually in a part of the catheter in the right atrium). The thermister at the tip of the catheter will register changes in temperature as the cool liquid, carried by the blood, passes. The extent of dilution of the cold bolus of liquid by warm blood will determine the temporal profile of the temperature change at the tip of the catheter. This is referred to as the thermodilution method of measuring cardiac output (TD Q ) The popularity of TD Q stems from ease of use once the catheter is in place.
However, the placing and maintenance of the catheter entails considerable risk and expense. Insertion of the Swan-Ganz catheter is associated with complications that are frequently fatal such as puncture of the carotid or subclavian artery with associated internal haemorrhage or stroke, tension pneumothorax, rupture of the right ventricle, malignant arrhythmias (including fatal ventricular fibrillation), and rupture of the pulmonary artery. As a foreign body violating the skin barrier, a pulmonary artery catheter is a constant threat as a source of blood-born infection that is the greatest risk to heart valves, artificial joints, and other implants. Such 2o infections are medical disasters leading to severe morbidity and death.
Furthermore, the use of pulmonary artery catheters to measure TD ~ is very expensive as it requires admission to an intensive care facility where there is continuous presence of critical care nursing and medical staff. Despite these risks, it is still not the ideal method to measure Q as it tends to overestimates Q by as much as 10% compared to the Fick method (see below) and, for greatest accuracy, requires repeated measurements as its precision is poor. The variability of repeated single measurements is about 22% and can be reduced to 10% by repeated averages of 3 measurements 2. A single thermodilution measurement is considered to be plus or minus 33 % the true value G',,' Because of the expense and risks of keeping the catheters in place, they are removed as soon as practical, often within 24-48 hours of major heart surgery. Often they are removed while the information they provide can still be clinically useful and well before the patient is no longer at significant risk for relapse. If the patient's health deteriorates, a decision must be made as to whether to re-insert the catheter.
An automated non-invasive method of Q monitoring would be very useful in the following clinical scenarios:
a) Selected low risk patients now routinely undergoing pulmonary artery catheterization for infra- and postoperative monitoring.
b) Patients whose Q would be clinically important to know but in whom the risks and costs of insertion of a pulmonary catheter cannot be justified; this includes ward patients, outpatients or patients in the emergency department or doctor's office.
c) Patients who are too sick to warrant the added risk of pulmonary artery catheter insertion d) High and moderate cardiac risk patients undergoing minor and moderate non-cardiac surgical procedures e) Severely ill patients with non-cardiac disease.
f) Relatively healthy patients undergoing major stressful surgery.
g) Situations where Q is clinically indicated but there is no access to the expertise and critical care facilities required for the use of the pulmonary artery catheters.
h) Means of monitoring response to cardiovascular therapy such as for hypertension and heart failure.
i) As a non-invasive diagnostic test of cardio-pulmonary status.
j) As a means of assessing cardiovascular fitness.
Respite these many applications, non-invasive methods of ~ measurements have not obtained widespread clinical acceptance. The most commonly researched methods include ECG bio-impedance (Imhoff, 2000 3), and pulsed-wave Doppler esophageal sonography. These methods have good repeatability 4-ii and good limits of agreement with either thermodilution or Fick-based methods but only in some populations of subjects. Each method fails in certain patients groups with such pathologies as very high or low Q states as occur in surgical patients, septic shock, exercise or cardiogenic shock.
Table 1: Classification of methods of measuring (7 1. invasive a. extravascular (flow probe) b. intravascular i. invasive Fick ii. indicator dilution 1. thermodilution 2. coloured dyes 3. conductive indicators 2. Non invasive a. Doppler (external-ventricular volume, esophageal) b. Bioimpedence c. MRI
d. Respiratory based i. Foreign gas uptake (acetylene, carbon monoxide) ii. Equilibration with mixed venous PCOZ
1. complete equilibration 2. incomplete equilibration a. rebreathing b. breath hold iii. temporary steady state methods 1. differential Fick (Gedeon method) 2. constant inspired PCOZ (Fisher) iv. Breath holdlrespiratory quotient method 2. Background physiology and definition of terms Venous blood returns to the right side of the heart from the muscles and organs with reduced oxygen (Oz) and increased carbon dioxide (COz) levels. Blood from various parts of the body is mixed in the right side of the heart and pumped to the lungs via the pulmonary artery. The blood in the pulmonary artery is known as the mixed venous blood. In the lungs the blood vessels break up into a network of small vessels that surround tiny lung sacs known as alveoli. This net of vessels surrounding the alveoli provides a large surface area for the exchange of gases by diffusion along their partial pressure gradients. After a breath of air is inhaled into the lungs, it dilutes the COz left in the alveoli at the end of the previous expiration, thereby establishing a pressure gradient between the partial pressure of COz (PCOz) in the mixed venous blood (Pv COz) arriving at the alveoli and the alveolar PCOz (PACOz).
The COz diffuses into the alveoli from the mixed venous blood diminishing the PCOz in the blood, and increasing the PCOz in the alveoli until equilibrium is established between the PCOz in alveolar capillary blood and the PCOz in the alveoli. The blood then returns to the left side of the heart via the pulmonary vein and is pumped into the arterial system by the left ventricle. The PCOz in the arterial blood (PaCOz) is now the same as that in the alveoli. When the subject exhales, the gas at the very end of exhalation is considered to have come from the alveoli and thus simultaneously reflects the PCOz in the pulmonary capillaries and the alveoli; the PCOz in this gas is called the end-tidal PCOz (PETCOz).
The volume of gas breathed per minute, or minute ventilation ( VE ), expressed in L/min. The volume of breathed gas distributed to the alveoli (and thus contributing to gas exchange) is termed the alveolar ventilation ( TA ) and is also expressed in L/min. The part of VE that does not contribute to gas exchange is termed dead space ventilation. This is divided into the anatomical dead space which consists of the trachea and gas-conducting tubes leading from the mouth to the alveoli, and the alveolar dead space which is collectively the alveoli that are ventilated but not perfused with blood.
The VE during normal breathing provides the TlA that is required to eliminate the COz brought to the Iungs. VE is controlled by a feedback system to keep PaCOz at a set level of approximately 40 mmHg. Under steady state conditions, the rate at which COz is exhaled from the lungs ( hCOz ) is equal to the rate that it is brought to the lungs, which in turn is equal to the metabolic COz production. We define steady state as the condition where the flux of COz at the lungs is equal to the COz production and the YCOz, Pv COz and PaCOz remain steady. If the UCOz is diminished, the COz extraction from the mixed venous blood passing by the alveoli will be reduced resulting in an increase in the PaCOz when that blood reaches the arterial system. As the blood traverses the body, it will pick up additional COz and will return to the pulmonary artery with a higher PCOz than on its previous passage.
The time between the change in T~COz and re reappearance of the blood with raised PCOz in the mixed venous circulation is termed the rectrculatfo~c tirrte which is generally taken as 20-30 s in resting subjects.
3. The Fick equation The approach for respiratory-based methods for measuring Q non-invasively is described by the Fick equation, a mass balance of any substance across the lungs.
The Fick method was originally described fox Oz as a method for determining pulmonary blood flow. The Fick relation states that the Oz uptake by the lung is equal to the difference between the pulmonary artery and systemic arterial Oz contents times the Q . The blood contents originally had to be obtained invasively from blood samples. The same relation holds with respect to COz. The advantage of using COz as the tracer is that mixed venous and arterial blood contents of COz may be determined non-invasively. The Fick mass balance equation for COz is:

(CvC02 -CaC02 ) where Q is the cardiac output, V CO2 is the rate of elimination of CO2 at the lungs, Cv C02 and CaC02 are the mixed venous and systemic arterial contents of C02, respectively. V C02 can be measured by a timed collection of expired gas and measuring its PCO2 and volume. The term CaC02 can be calculated using an estimate of arterial PC02 (PaC02) as derived from the PCO2 of end tidal gas (PETC02). The hemoglobin concentration (easily obtained from a venous blood sample or a drop of blood from a finger prick) and the relation between blood and C02 content (available from standard physiology texts) are then used to calculate CaC02.
However, Cv COZ is difficult to estimate. The PC02 of mixed venous blood (Pv C02) is difficult to determine as true mixed venous blood is present only in the pulmonary artery, which is inaccessible from the surface. The air in the lungs is in intimate contact with mixed venous blood, but C02 diffuses rapidly from the mixed venous blood into the alveoli before an equilibrium is established. The PC02 of the expired gas therefore reflects this equilibrium PCOz and not the PC02 of mixed venous blood. The Pv C02 can be determined from expired gas only when there has been full equilibration with continuously replenished mixed venous blood or partial equilibration under controlled conditions that allow for back calculation of Pv C02 from the PC02 in expired gas. Hence during rebreathing, the alveolar gas is not refreshed and the mixed venous blood continuously passes the alveoli such that an equilibrium is established where the PCOZ reflect the PC02 in mixed venous blood.
However, even in this scenario, the PC02 is not that which exists in the pulmonary artery. Blood in the pulmonary artery has a relatively low P02. Because of the Haldane effect, the low POZ allows the CO2 to be carried by the hemoglobin at a relatively low PCO2. When the mixed venous blood is exposed to gas in the alveoli, 02 diffuses into the blood, binds to the hemoglobin and increases the PCOz for a given COz content on the hemoglobin (the complamentary aspect of the Haldane effect). All methods based on full or partial equilibration of alveolar gas with Pv COz take into account that the equilibration is to a virtual PCOz that would exist if the COz content of the hemoglobin were the same as in mixed venous blood but the hemoglobin were saturated with Oz. We refer to this as the oxygenated mixed venous PCOz (Pv COz-oxy). The relationship between PCOz and content of COz in blood is known, therefore Cv COz can be calculated from both the true Pv COz (as obtained, for example, from a pulmonary arterial blood sample) and Pv COz-oxy (as 1 o obtained by some of the non-invasive methods described below)1.

4. Rebreathing--equilibration method One method of measuring Pv COz-oxy was introduced by Collier in 1956, and is known as the equilibration method. A bag is pre-filled with a high concentration of COz (~10-13%) and the subject exhales and inhales rapidly to and from the bag and PCOz is monitored continuously at the mouth. The object of the test is to find the combination of bag volume and bag concentration of COz such that once the gas in the bag mixes with that in the lungs (the concentration of COz in the residual gas in the lung at the end of a breath in a healthy person is ~5.5°l°), the partial pressure of COz in the lung is equal to that in mixed venous blood. A flat PCOz tracing segment indicates that inspired and expired PCOz are equal. To identify the true Pv COz-oxy, the flat segment must occur within the first 3-4 breaths, before recirculation raises the Pv COz-oxy (see figure ~ The P~bC02-oxy does not really exist but is a virtual number created by instantaneously oxygenating mixed venous blood before and diffusion of COZ into the alveoli. The C~3C02 is the same in each.

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a Time {sec) 4.x.1 Advantages of the equilibration method:
The capnograph reading is of gas equilibrated with Pv COz-oxy and can be 5 considered a directly measured value as opposed to a value obtained from calculation or extrapolation.
4.2.2 Limitations of the equilibration method:
4.1.2.1 The COz concentration in the bag depends on bag size, the patient's lung 10 volume, and the Pv CO2-oxy---- the last being the unknown value.
'Therefore, the concentration of COz in the bag must be individualized to the patient and thus found by trial and error. The method is therefore difficult to automate fully.
4.1.2.2 In practice, since the characteristic of a suitable endpoint (the plateau of PCOz) is subjective, identification of a suitable plateau is difficult to automate.
4.1.2.3 The manoeuvre of rebreathing from a bag is difficult to perform in mechanically ventilated patients and is therefore not suitable for such patients.
4.1.2.4 Inhaling 10- 13 °!° COz is very uncomfortable and most people cannot tolerate it. It is particularly uncomfortable to someone who is short of breath or exercising.

4.1.2.5 The method requires an external source of C02. This makes testing equipment bulky and awkward.
4.1.2.6 The method requires that the subject hyperventilate in order to mix thoroughly the gas in the bag and the lungs before recirculation of blood takes place. This requirement limits the test to those subjects who can perform this manoeuvre and who can provide this degree of cooperation. This excludes patients who have severe lung disease, those who are too young, too confused or too ill to cooperate.
4.1.2.7 The test loads a considerable volume of C02 into the subject's lungs and at the same time prevents C02 from leaving the blood for the duration of the test. This has negative consequences for the subject:
4.1.2.7.1 Following the test, the subject must hyperventilate to eliminate the applied C02 load as well as the volume of metabolically-produced C02 not eliminated during the test. This may pose a considerable burden ~ 5 for some subjects with lung disease or exercising subjects who are already expending considerable effort to cope with their existing metabolic C02 load.
4.1.2.7.2 A period of hyperventilation following the test is required to eliminate the C02. This may be difficult for some subjects to perform and, consequently, they may experience respiratory distress for some time until their PC02 is decreased.
4.1.2.7.3 Repeated tests must be delayed until the extra COz is eliminated and the baseline state re-established.
4.1.2.7.4 The test itself may distress the subject and alter the Q .
5. Rebreathing - Exponential Method In this technique, a small amount of COz is placed in a bag and the subject asked to rebreathe from the bag. The PE'rC02s of successive breaths will rise in exponentially towards Pv C02-oxy. A rising exponential curve is then fit to the PETC02s of these breaths to predict an asymptotic value that is assumed to be the Pv COZ-oxy.

5.1 Advantages of the exponential method 5.1.1 There is no requirement for respiratory manoeuvres by the patient.
5.1.2 A smaller COZ load is placed on the subject in order to perform the test.
5.2 Limitations of the exponential method 5.2.1 This is an indirect test in which the Pv C02-oxy is not measured directly but calculated from data generated by a test.
5.2.2 As the metabolic production of COz is small compared to the size of the 1 o Lung and bag, the rise of PCOa occurs over a prolonged period. This severely limits the number of useful data points for accurate extrapolation from an exponential curve, before recirculation.
5.2.3 The most important limitation of this and other methods that use partial equilibration during rebreathing to extrapolate to an asymptote using a single exponential is that the assumptions underlying the method are incorrect. In fact, the method produces two different mathematical profiles: the one describing the washout of C02 from the lung into the bag is a decreasing exponential whereas the second describing the build-up of C02 released from the blood into the lung-bag mixture is an increasing exponential [~;l~iss ~, ~,'" "~~c, ~;~esxs. Only after the gases in the lung-bag system have become well mixed do the two exponentials resolve to a single exponential. By then, very few breaths (if any) that can provide suitable data for extrapolation from a single exponential can be taken before recirculation.
5.2.4 A continually rising Level of C02 makes this test unpleasant in conscious patients, especially in those exercising or very ill.
5.2.5 The manoeuvre of rebreathing from a bag is difficult to perform in mechanically ventilated patients and is therefore not suitable for such patients.

5.2.6 The method requires an external source of C02. This makes testing equipment bulky and awkward.
5.2.7 'The test loads a volume of C02 into the subject's lungs and at the same time prevents C02 from leaving the blood for the duration of the test.
Although the extent of the C02 load on the subject is less than with the equilibration method, the negative consequences for the subject, outlined in the section on the equilibration method discussed above, must be considered.
5.2.8 Priming the rebreathing bag with some C02 improves the predictive 1 o qualities of the asymptote since every data point lies closer to the asymptote, but the increased C02 concentrations increase the discomfort and the limitations approach those outlined above for the equilibration method.
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o ~-, Time (sec) 6.0 Calculating Q without first calculating I'v COa-oxy Gedeon in 1980 described a method of calculating Q in ventilated patients via a differential Fick method that circumvents the need to calculate Pv COz-oxy.
The underlying assumptions of the method are that Q and Pv COz will remain unchanged during a step change in lung COz elimination and alveolar PCOz (PACOz) lasting less than a recirculation time (about 30 seconds). Gedeon proposed reducing lung COz elimination by reducing either the tidal volume or respiratory frequency setting of the ventilator. As a modification of this method, Orr et al.
proposed leaving the ventilator settings unchanged and reducing lung COz elimination by temporarily interposing a dead space between the ventilator and the patient's airway resulting in a transient period of rebre;~thing previously exhaled gas.
6.1 'Theoretical basis of Gedeon method:
The method applies to a subject being ventilated under control conditions in which COz elimination and PE'rCOz are measured. A test manoeuvre consisting of a transient alteration in the COz elimination for a time less than a recirculation time is effected and the resulting "equilibrium" PEnCOz is noted. It is assumed that the Q
2o and Pv COz-oxy during the test are unchanged from control conditions. The Fick equation for these two conditions can be written as v co, cvco2 -cacoz Q= vco2, cvco2 - caco2 °
where V COz' is the COz flux at the lungs during the test and CaCOz' is the corresponding 'new arterial content of COz. These two equations can be combined to yield the differential form of Fick's equation:

Q- ?UC02 ?CaCOz Where D denotes a "difference in". Since the PaC02 and I'v C02-oxy lie on the same C02 dissociation curve, partial pressures of COs can be substituted for CO2 content to yield the following relation:
? U COZ
S * ?PaCO, where S is the slope of the CO2 dissociation curve. Like the conventional non-invasive COZ-based Fick method, the differential Fick method relies on predicting PaC02 through measurements of PETC02. However, instead of requiring a calculation of Pv C02-oxy, the differential Fick equation assumes no change in Pv C~02-oxy over the duration of the test, and uses the measured quantities V

and V CO2' and well as PaC02 and PaCO2' (from PETC02) to calculate the remaining unknown value in the equation: Q .
6.2 Advantages of Gedeon/~rr method 6.2.1 The main advantage is that Pv COZ does not need tc~ be calculated.
6.2.2 If the deadspace method is used to alter the V COz, then no change in breathing pattern is required.
6.2.3 The method can, theoretically, be fully automated. (In its present commercial form, the size of the interposed deadspace must still be altered manually).
6.3 Limitations of Gedeon/Orr method There are a number of limitations in applying Orr's method to spontaneously ventilating subjects.
6.3.1 In spontaneously breathing subjects, there is considerable breath-to-breath variation in breath size and breathing frequency resulting in a variation in PE'rCOz. This poses problems with respect to:

6.3.1.1 Identification of PETCOz and PETCOZ . Long periods of baseline measurements are needed in order to average the end tidal values and identify the PF'rCOz to be used as the baseline P~'rC02 in the differential Fick equation. The test phase cannot last for more than about 30 seconds (due to recirculation), typically 5 breaths. This leaves little time to determine an accurate average PE'rCOz'. During prolonged baseline periods of observation, the condition of the patient may change.
6.3.1.2 Calculation of V COz. The variations in PE'rCOz are related to variations in COz elimination but the relationship is not consistently reflected by the 1 o PE'rCOz. For example, assuming a subject breathing at rest with an average resting breath size, an interposed smaller breath may result in a lower PE'rCOz (due to a smaller contribution of alveolar gas to the end tidal sample) but the COz elimination from that breath will be diminished. Conversely, a larger breath may result in the same PE'rCOz as the resting breath but a greater volume of COz is eliminated. The commercial automated Gedeon method (NIC02, Novametrics Medical Systems, Wallingford, C'T, U.S.A.) measures the COz eliminated breath-by-breath and therefore must continuously average the values to measure V COz. The NIC02 method of calculating V COz by real-time integration of continuous measurements of flow (with a pneumotachometer) and COz concentration (with a capnograph) is fraught with potential for errors: a small error in the integration of these two signals with different time delays and time constants results in a much larger error in the calculation of V COz. In addition, the greater the variability of the breath size and COz concentrations, the longer the measurement time required for an accurate estimate of V COz.
6.3.2 Calculation of V COz'. Stable transient changes in V C Oz cannot be achieved in conscious spontaneously ventilating patients:
6.3.2.1 Interposing a deadspace and raising their PCOz will stimulate them to increase their V E until the V COz is restored.

6.3.2.2 Any change in breath size or frequency during a period of breathing, (a normal occurrence in spontaneously breathing people) changes the V COz of that period. During inspiration, the deadspace gas is inhaled first followed by fresh gas. A decrease in a breath size or frequency diminishes the volume of fresh gas inhaled (and thus the V COz for that breath). An increase in breath size or frequency will result in an increased volume of fresh gas delivered to the alveoli.
6.3.2.3 Each breath is an independent event and there is no inherent method to compensate in a subsequent breath for changes in V COz in any one breath.
1o For the method to be implemented, therefore, measures must be taken to ensure that breath size and frequency stay absolutely constant during the test.
The NIC02 method has no such built-in aspects. The method can therefore be used only in patients who are paralysed and mechanically ventilated.
6.3.3 Identification of PE'rC02-PaCOz gradient. The Gedeon and Orr methods require the establishment of a measured or assumed gradient between the PE'rCOz and the PaCOz. The variation in PE'rCOz is due to variations of distribution of fresh gas to various parts of the lung and any one breath does not reflect the overall state of COz exchange. On the other hand, such 2o variations are not reflected in the PaCOz which does reflect the overall exchange of COz and remains relatively constant. Therefore, variations in PE'rCOz also confound the quantification of the PE'rCOz-PaCOz gradient under control conditions. Although Orr provides a number of equations to correct for these limitations, these equations are empirical and do not necessarily apply to a particular patient. For example, they are applied indiscriminately whether or not there is irregular breathing.
The PE'rCOz-PaCOz gradient during the test phase when rebreathing occurs is unknown. In the presence of large alveolar deadspace (as commonly occurs in many ill patients) the PETCOz-PaCOz gradient will change during the rebreathing phase. Orr provides some equations to correct for this but since the volume of the alveolar deadspace is unknown, the applicability of the formula to any particular patient is unknown. This further diminishes the accuracy of calculating PaC02'.
Thus each of the terms required to calculate Q (V C02, V C02', PETC02, PE'rC02' and PaC02') by the Orr/NIC02/Gedeon method is difficult to implement and prone to errors in the presence of any variation in breath amplitude or breathing frequency as occurs in spontaneously breathing humans or animals.
6.3.~ The parameter calculated by the differential Fick method as practiced by Gedeon/ Orr/ Respironics is pulmonary blood flow - Q . Pulmonary blood flow may be less than Q when, for example, some of the Q is shunted from the right side of the circulation (superior vane cave, right atrium, right ventricle, pulmonary artery) into the left side of the circulation without passing through the lungs. This is referred to as '°shunt". About 5% of venous blood bypasses the lungs (termed shunted blood) in healthy adults.
Much larger shunts occur in many medical conditions such as congenital heart disease, surgical repair of some congenital heart disease, pneumonia, pulmonary edema, asthma, pulmonary atelectasis, adult respiratory distress syndrome, obesity, pregnancy, liver disease and others. The differential Fick method does not include shunted blood in the calculation of Q and other empiric corrections must be made to account for it.

7.0 Kirn-Itahn Farhi method 7.1 Theory:
A unique manoeuvre was proposed by Kim, Rahn and Farhi, (j. Appl. Physiol.
21(4):1388-44. 1966.) as a mechanism for calculating the oxygenated mixed venous PCO2 (Pv C02-oxy) as well as the true Pv CO2 and PaC02. The theory is based on a paradigm of taking a breath of Oz, holding the breath, and exhaling slowly over a period equal to the recirculation time. Over this time of exhalation, the C02 from the mixed venous blood will diffuse into the alveoli and 02 will be absorbed. The low P02 in the red blood cells in the mixed venous blood maximizes the volume of that can be carried by hemoglobin. In the alveoli, 02 diffuses into the red blood cells, raising the POZ and decreasing the affinity of hemoglobin for C02 (Haldane effect).
This releases COZ from the binding sites on the hemoglobin, making it available for diffusion into the alveoli. With breath holding, COZ will accumulate in the alveoli and the PCOz will rise until it no longer provides a gradient for diffusion from the blood. (This PCOZ is known as the oxygenated mixed venous PCO2 (Pv C02-oxy).) However, 02 will continue to be absorbed as long as the POZ in the alveoli is greater than that in the mixed venous blood. Relatively little C02 need diffuse into the alveoli to reach Pv C02-oxy compared to the volume of 02 that is available for absorption before the alveolar P02 is in equilibrium with that in the mixed venous blood. In other words, the equilibration of COz with the mixed venous blood will occur well before that of 02.
Since both Oz and C02 are contained in the same physical volume, the changes in concentrations of each gas over a short period will reflect the rates of absorption of that gas over the same period. Therefore, over a short period, the ratio of PC02 to P02 will reflect the RQ. The RQ will initially be highest at the beginning of the breath when the rate of C02 diffusion into the alveoli is maximal, and will approach 0 when the alveolar PC02 equals Pv C02-oxy. In vitro studies have shown that PAC02 equals the true Pv C02 when the RQ = 0.32 and equals PaCO2 when RQ is equal to the patient's steady state RQ.
7.2 Test method The method suggested for performing this test would require a subject to take a maximum breath of 100 % 02 and exhale very slowly and maximally. Over the course of this exhalation, expired gas is sampled and analyzed continuously for both and PC02. P02 is graphed vs. PC02 and the RQ is calculated from the instantaneous slope of tangent to the curves at various PC02 values as follows:
pQ - slope - (FeOz * slope) - FeCO
1- (Fe02 * slope) - FeC~Z
These RQ values are then plotted against their respective PC02 data points resulting in a linear relation as illustrated in figures 4 and 5 of T.S. Kin, H. Rahn, and L. E.
Farhi cited above.
7.3 Advantages of the method.
7.3.1 This is the only known non-invasive method by which true Pv C02 can be calculated.
7.3.2 The method provides an estimate of PaC02 not based on assuming a gradient between PETC02 and PaC02.
7.3.3 Data generated by the method can be used to calculate the 02 saturation of mixed venous blood.
7.4 Limitations of the Kim- Rahn-Farhi breath-hold method.
The main limitation of this method is that it requires the subject to have a large lung capacity, hold his breath, and exhale over a prolonged duration. Patients with conditions such as pulmonary fibrosis, pneumonia, adult respiratory distress syndrome, chronic obstructive lung disease, asthma, obesity, trauma, abdominal and chest surgery, mental obtundation, confusion, pregnancy and many others have marked limitations in their ability to take a large breath. Patients are required to cooperate with their duration of breath holding and rate of exhalation. Many patients who are ill, exercising subjects, children and others are unable to perform this satisfactorily. This method is very awkward to automate yr perform on ventilated patients.

8.0 Prior Disclosed Previous Fisher method 8.1 Theory In a steady state, if a subject breathes in a PCOz equal to Pv COz-oxy, there will be no gradient for gas exchange and the difference in PCOz between the inspired PCOz (PICOz) and the expired PCOz (PECOz) will be 0. The volume of COz diffusing into the alveoli will be maximal when the difference bet~~een PIC02 and PECOz is greatest, i.e., when the PICOz is 0. Since the change in alveolar PCOz (PACO2) varies directly as the volume of COz diffusing into the alveoli and the volume diffusing into the alveoli varies directly as the gradient, then the difference between the PICOz and PECOz will vary inversely as PICOz. In other words, graphing the difference between the PECOz and PICOz (PECOz - PICOz) vs. FICOz will result in a straight line.
Since subjects normally breathe room air (PrCOz equals 0 or Oz, the control PE'rCOz provides the first point on the graph. When subjects inhale gas with any constant value of PCOz, the PE'rCOz at the end of an equilibration period not exceeding the time for recirculation will provide a second data point which can be used to define the straight Line which crosses the X axis where PZCOz equals Pv COz-oxy.
8.2 Test method:
2o The subject breathes via a non-rebreathing valve. The inspiratory limb is provided with either fresh gas or test gas with any PCOz. To perform a test, the inspired gas is switched from control gas to test gas for about one recirculation time. The PICOz of the test gas, the PETCOz just before the test (when PrC02 was 0), and the PE'rCOz of the last breath before recirculation are used to calculate the Pv COz-oxy.
8.3 Advantages of the Prior Disclosed Previous Fisher method:
8.3.1 Any low inspired concentration of C02 such as 1 % is adequate to generate a data point; therefore the subject need not get a large COz Load.

8.3.2 This Fisher method extrapolates to the Pv CO2-oxy from a linear function and is therefore easier to calculate and more accurate than with the partial rebreathing test in which data points are fit to an exponential curve for extrapolation to an asymptote.
8.3.3 The PICOZ can be any value, so accurate mixtures of gases are not required.
8.3.4 Assuming arterial PCOz values can be obtained, the method measures total Q, not just pulmonary blood flow.
8.3.5 The subject need not carry out any respiratory manoeuvre such as breath 1 o holding or hyperventilation.
8.3.6 The method does not entail any rebreathing. Therefore, Oz levels remain stable throughout the test and supplemental 02 is not needed.
8.4 Limitations of the Prior Disclosed Previous Fisher anethocl.
8.4.1 Uniform breath size cannot be guaranteed :in spontaneously breathing subjects. A change of breath size or breathing frequency during the latter parts of the test phase will affect the PETC02 and thus the calculation of Pv CO?-oxy. Furthermore, as the subjects are inhaling gas that contains C02, they may be stimulated to take larger or more frequent breaths.
8.4.2 The test requires an external source of C02. This must be supplied via a tank of COZ and a gas blender or via a tank of pre-mixed gas. If more than one test gas is required, then arrangements to blend additional gases must be made or more than one additional gas tank is required.
This is inconvenient, costly, and adds complexity to the test method and additional bulk and weight to the test apparatus.
8.4.3 It is very complex to configure an automated system that works for both spontaneously breathing and mechanically ventilated patients.

8.4.4 There is no simple method to adapt currently available ventilators, anaesthetic machines or breathing circuits to provide a known and constant PIC02 for a fixed number of breaths.
8.4.5 The technique is difficult to adapt to anaesthetized patients breathing via a circle circuit in which both the test gas and the anaesthetic gases enter the circuit, especially in the presence of a C02 absorber filtering C02 from the circuit.
OBLECTS OF THE INVENTI~N
It is therefore a primary object of this invention to provide an improved method and apparatus for the purpose of determining cardiac output Q which may be utilized in ventilated subjects, subjects which breath spontaneously or subjects that are under controlled ventilation such as under surgical procedures.
It is yet a further object of this invention to provide an improved method and the apparatus related thereto for the purposes of determining alveolar ventilation and calculating V C02, Pv C02-oxy, true Pv CO~, PaC02, pulmonary shunt, anatomical dead space at a greater accuracy than prior known methods and apparatuses would provide.
It is yet another object of the invention to provide a method of calculating the oxygen saturation, a level of mixed venous blood (Sv 02) which may be utilized to reveal heart failure of septic shock in a patient or the like.
Further and other objects of the invention will become apparent to those skilled in the art when considering the following summary of the invention and the more detailed description of the preferred embodiments illustrated herein.

SUMMARY OF THE INVENTION
This invention discloses a method that calculates all of the Q regardless of shunt, calculates the shunt, anatomical and alveolar deadspace, true mixed venous Oz saturation, true mixed venous PC02, and PaC02. Furthermore the method can be performed in ventilated subjects, subjects breathing spontaneously, even with marked variations in their tidal volume and breathing frequency, or subjects undergoing surgery under anaesthesia. Subjects need not perform any respiratory manoeuvre such as hyperventilation or breath holding.
According to one aspect of the invention there is provided an improved method and apparatus for the purposes of determining Q and ~'~t and calculating 1lC~2, Pv COa-oxy, true Pv C02, PaCOz, pulmonary shunt, and anatomical dead space which increases the accuracy of these determinations in relation to known methods and apparatus and allows the full automation of the various methods disclosed herein for these determinations and calculations The new method:
1. is insensitive to changes in minute ventilation (V E), tidal volume or 2o respiratory frequency so that the method can be carried out in spontaneously breathing subjects;
2. is simplified and less expensive to construct compared to other automated methods of performing the differential Fick technique in that a. it does not require any valves be actively engaged in the patient circuit b. does not require a pneumotachgraph to measure .flows c. does not require manual adjustment of an interposed dead space (and thus can be totally automated);
d. The device will be the same for all sizes of adults (one size fits all) 3. will utilize new and original partial rebreathing circuits as disclosed in the figures;

4. the generation and presentation of data will be substantially the same for controlled (mechanical) ventilation and rebreathing so that the algorithms to perform the tests and analyze the data can be substantially the same;
5. will institute an equilibrium steady state within one recirculation time so that the value for end tidal PCO2 will be a true measured value rather than one requiring multiple corrections based on unsubstantiated assumptions;
6. will allow the measurement of a new steady state PETCO2 within one recirculation time and thus actualize the assumption underlying the Differential Fick approach that Pv COz is unchanged;
7. will minimize the interaction of change in tidal volume and the physiological dead space.
8. maintain the alveolar P02 white making pulmonary blood flow measurements;

9. make all calculations without a requirement to measure breath-by-breath volumes of inspired and expired CO2 or any flows of tidal gases.
According to one aspect of the invention there is provided an improved apparatus and method of identifying the alveolar ventilation ( vA ), substantially as illustrated and described herein preferably the TA so determined is utilized to calculate the T1C02 as VA x PETCO2.
In one embodiment the improved apparatus and method utilizes:
a) the Fisher E-I approach to determine Pv COZ-oxy (or) b) the Kim Rahn Farhi approach is used to determine i) Pv C02-oxy ii) true Pv C02 iii) PaC02 iv) true Pv C02 plus the information from a pulse oximeter to determine xruxed venous hemoglobin 02 saturation (or) c) the differential C02 Fick technique of Gedeon anal Orr is utilized to determine any combination of i) Pv CO2-oxy ii) Q
iii) V COz iv) V C02' v) PETCO2-PaC02 gradient determined using the PaCOa as determined by the Kim Rahn Farhi method from data collected while reducing the YCOz in order to perform the differential Fick method. (or) d) Q is determined via the Kim Rahn Farhi method performed during partial rebreathing using a C02 Fick method where the i) VCOZ is calculated with or without the new method as disclosed ii) CaC02 and Cv COZ are determined from the PaC02 and Pv COz ~ 5 respectively derived by the Kim Rahn Farhi method; (or) e) calculation of the respiratory quotient (RCS) is determined as PE'rC02 /
(PI02-PE02);
wherein said apparatus or method may be utilized for very accurate non-invasive determination of Q and the other indicated parameters.
According to yet another aspect of the invention there is provided an improved method of apparatus for determining:
Q, TIA, and calculating ~COz, Pv COz - oxy, true Pv C02, PaCOz pulmonary shunt, anatomical dead space, and 02 saturation in mixed venous blood; which increases the accuracy of these determinations and calculations in relation to known methods and apparatuses and allows for full automation thereof if necessary by:

i) reading FGF to a sequential delivery circuit to create two sets of data for said determination utilizing the Fick equations; (or) ii) the PETC02 to PaCO2 gradient is calculated from two independently derived values in the same subject; (or) iii) utilizing the Kim-Rahn-Farhi technique a period of reducing FGF
simulates complete or partial breath holding, wherein the P~rC02 of each breath is equivalent to a sequential alveolar sample;
thereby providing more relevant data to calculate desired parameters.
In yet another embodiment of the invention a ventilation circuit is provided comprising means for allowing/providing FGF to substantially equal TEA and substantially control TA, and in so doing provide for calculation of Q and other parameters as previously set out herein in the disclosure and figures.
In yet another embodiment there is provided a method and apparatus of determining Q and the other parameters disclosed by utilizing the circuits described and illustrated herein by reducing the FGF to said circuit independent of the breathing rate thereby allowing for calculations to be made via Fick equations, and or the Kim-Rahn-Farhi technique.
Preferably the method or apparatus previously described whexein the COa content as calculated from Pv COZ-oxy and true Pv CO2, may be utilized to determine the Oz saturation of mixed venous blood with known relations between C02 content, 02 saturation and PC02.
In one embodiment the method or apparatus disclosed may be utilized wherein the arterial 02 hemoglobin saturation, as determined by a non-invasive pulse oximeter which makes the measurement by shining infrared light through a finger, is utilized with the 02 saturation value in the pulmonary artery to calculate the fraction of shunted blood (assuming fully oxygenated blood in the end pulmonary capillary) thereof.
Preferably said method or apparatus is utilized to determine the fraction of shunted blood Qs, which in conjunction with determination of cardiac output Q~ may be used to determine Q n the pulmonary output via the relationship.
QT = Qr + Qs Preferably the method or apparatus disclosed wherein the 02 saturation of haemoglobin in mixed venous blood, as determined therewith, is utilized to reveal a condition in a patient such as septic shock, or heart failure.
BRIEF I7ESCRI1'TIOIV OF THE FIGURES
Figure 1 is an anesthesia via a circle circuit. The circuit is designed to efficiently deliver anesthetic gases to a patent. It does so by allowing the patient to rebreathe exhaled anesthetic gases but not COz.
Figure 2 is the Fisher Isocapnia Circuit. The circuit is designed to control the PC02 in expired gas (PETC02).
Figure 3 is similar to Figure 1 wherein the manifold remote from the patient.
Figure 4 is similar to Figure 3 used for a mechanically ventilated patient.
Figure 4B is prior art.
Figure 5 is the circuit for spontaneous ventilation.

Figure 6 is a co-axial version of new isocapnia circuit (CAIC).
Figure 7 is the new circuit and controlled ventilation.
Figure 8 is a new circuit with a co-axial extension and controlled ventilation.
Figure 9 is a circuit designed to deliver anesthetics.
DETAILED DESCRIPTION OF THE INVENTION
In reference to the above circuits (disclosed in previous document):
A device to measure Q and other parameters such as TA, VCOz, Pv C02-oxy, true Pv C02, PaC02, pulmonary shunt, and anatomical dead space, consisting of an apparatus comprising the following components:
a) a breathing circuit with characteristics that on exhalation, exhaled gas is kept separate from inhaled gas;
b) on inhalation, when V E is greater than fresh gas flow, the subject inhales fresh gas first and then inhales a reserve gas containing C02 that may be a 2o stored exogenous gas (the non-rebreathing circuit Fisher) or mostly previously exhaled gas;
c) any of the circuits contained in the Figures can be used but the preferred configuration is the FIC2-V-eo-ax (Figure 8), which we will refer to as the "preferred circuit";
d) gas sensors that monitor the COz with or without Oz concentrations in the gases at the patient-circuit interface and provide analogue signal outputs corresponding to the PC02 and POa in the gas;
e) a gas flow controller such as the Voltek gas flow controller (Voltek Enterprises, Toronto, Canada) consisting of a precise automated electronic 3o device that can controls the flow of one or more pressurized gases (such as oxygen, air, C02) singly or in combination in response to manual setting of dials or computer-generated instructions;
f) source of 02, and/or air with or without COz;
g) means to identify phase of breathing, said means may consist of pressure sensors or analysis by gas sensors;
h) machine intelligence consisting of a computer or logic circuit with input, output, and calculation functions;
i) input data consisting of operator-defined default values, output signals from gas and possibly pressure sensors, clock, and feedback information 1 o from flow and gas mixing controller;
j) output signals to gas flow and gas mixing controller and to screen;
k) calculations based on data from gas analyzers, feedback information from flow controller, and user-supplied default values;
1) control output signals to flow controllers according to a preset algorithm.
wherein said device may be utilized for non-invasive measurement and determination of Q and other parameters default values f --~ microprocessor Ga ~ ~'' w a1r U~
Gas sample line ~ gas flow to circuit Patient ~~ Breathing circuit This description may apply to any anaesthetic machine with the exception that 1) the breathing circuit we describe is different than any anaesthetic circuit. The sequential gas delivery circuit first provides fresh gas, then previously exhaled gas. This allows the circuit to compensate for changes in C02 elimination on any particular breath. For example, if there is a small breath, the unused fresh gas remains in the fresh gas reservoir and is available to provide the exact additional C02 elimination when a larger breath is taken or frequency of breathing increases subsequently. As a result, changes in V COZ can be instituted independent of breathing pattern.
2) Anesthetic machines do not automatically alter the fresh gas flows. Fresh gas flows are manually controlled by the anesthetist.
3) Anesthetic machines do not calculate V A and cannot calculate V CO2, and Q
.

4) Anesthetic machines cannot generate the data required to make the calculations for Q and its associated parameters because the circuit is inappropriate and the gas flows are not configured to be controlled by a computer.
5) The flowmeters on commonly used anesthetic machines are too imprecise and inaccurate to perform these tests and calculations. There is no need for such precision and accuracy of flow for routine clinical anesthetic care.
8.5 Method:
8.5.1 Set-up phase 8.5.1.1 Flow > VE
8.5.1.2 Access default values 8.5.1.3 Check pressure sensor during inspiration. If fresh gas reservoir collapsed, increase fresh gas flow (FGF) 8.5.1.4 Identify PETCOz from the PC02 tracing 8.5.2 Calibration phase 8.5.2.1 When in steady state institute test phase sequence for approximately the duration of one recirculation time.
8.5.2.1.1Decrease FGF to X L/min for approximately one recirculation time 8.5.2.1.2Return to FGF > VE
8.5.2.1.3Decrease FGF to Y L/min for approximately one recirculation time 8.5.2.1.4where X and Y are based on weight and CIE and calculated to be < ~1A.
8.5.2.2 identify PE'rC02 at the end of each test phase 8.5.3 Identify 1~A . Since flows X and Y are < VA, they will be the limiting factors that determine vA and thus 'VA will be equal to X and Y during the respective test phase. There is a linear relationship between ~A and the PE'rC02 at the end of the test phase. The fresh gas flow corresponding to the control PETC02 in this relationship is equal to the control VA.
In our previous patent / method of maintaining constant PaCOz and measurement of anatomic and alveolar dead space-US Patent Application Serial No. 10/135,655) we disclose a method of identifying the VA by progressively reducing the fresh gas flow from FGF= ~E until the PE'rC02 begins to rise. This point we called the "inflection point" and we defined as rIA as the FGF corresponding to the inflection point.
limitation of this method (2) The process can take a long time and is imprecise as there is an inherent variation in the PE'rC02 in spontaneously breathing subjects and it may be difficult to discern a consistent rise in PC02 without repeatedly raising and lowering the FGF.
(2) An irregular or changing breathing pattern during the test confounds the identification of the inflection point.
(3) Maintaining the FGF = VA becomes a problem if the ~1C02 increases as when the subject develops a fever or increases muscular activity.
Advantages of new method:
(1) The VA is readily identified by two tests of about 20-30s duration performed about 1 minute apart.
(2) The VA induced by the test is not affected by irregularities in ventilatory pattern (tidal volume and/or frequency) and is not dependent on the regularity of ventilation in the control phase as long as a control PE'rC02 can be identified.
(3) The algorithm maintains the FGF = VE so the FGF keeps pace with increases in VE ~
8.5.4 Differential Fick 8.5.4.1 CaIcuIate Q according to the differential Fick equation using VC02 and PE'rC02 data from test phase and control phase 8.5.4.2 Calculate Q according to the differential Fick equation using ~7C02 and PE'rC02 data from test phase and control phase and the PaC02 from the Kim Rahn Farhi method to identify the PE'rC02-PaCOz gradient Difference between this method and previous methods to perform the differential Fick:
(a) With the new method, the decrease in ~COz is performed by reducing the FGF to a sequential delivery circuit as opposed to insertion of a deadspace at the patient-circuit interface. As a result, if the subject increases his breathing rate or breath size, there is no 1 o change in VCOz and the calculations via the differential Fick equation are not affected.
(b) The ~COz is known using the VA (identified by the new or the previously disclosed method) and the PE'rC02, two robust and highly reliable measures. This is unlike the need for a pneumotachometer and the error-prone breath-by-breath analysis of ~COz required by previous art.
(c) VA is not identified with the previous differential Fick methods.
(d) The PETCOz to PaCOz gradient is calculated from two independently derived values in the same subject. In the previous 2o art, this gradient is calculated from empirical formulae derived from averaged values and do not necessarily relate to the subject.
Therefore our method provides more accurate values for VC02, VCOz' and PaCOz than the previous art.
8.5.5 Kim- Rahn-Farhi- (KRF) 8.5.5.I A period of reduced FGF simulates complete or partial breath holding. The PETCO2 of each breath is equivalent to a sequential alveolar sample in the KRF prolonged exhalation method. Use this more robust data to calculate true Pv CO2, Pv COz-oxy, PaC02 and hemoglobin Oz saturation in mixed venous blood using the KRF
method.

8.5.5.2 Q can be calculated using the Fick approach where the Pv COz-oxy and PaCOz are used to calculate the respective COz contents and the VCOz is as calculated from as disclosed in #3 above.
8.5.5.3 From the COz content as calculated from Pv COz-oxy in 5(a) and the true Pv COz, the Oa saturation of the mixed venous blood can be calculated with known relations between the COz content, Oz saturation and PCOz.
8.5.5.4 Information regarding the arterial Oz hemoglobin saturation (as read from a non-invasive commonly available pulse oximeter that makes 1 o the measurement by shining an infrared light through a finger), and the calculation of Oz saturation in the pulmonary artery (see 5(c)) can be used to calculate the fraction of shunted blood (assuming fully oxygenated blood in the end pulmonary capillary).
Our method of performing the KRF is an improvement over the previous art in that (a) Test is performed simultaneously with a test for differential Fick in spontaneously breathing subject.
(b) Data are pooled with the test as outlined above so calculation of V
2o CO~, is simultaneous to the other calculations. In the previous art, V
C02, calculation cannot be done during a breath hold or simulated breath hold by rebreathing.
(c) VCOz, measurement does not require a pneumotachometer which is expensive, cumbersome and error-prone. In the previous art, ~
C02, required for the calculation of Q required additional apparatus such as pneumatchometer or gas collection and volume measuring apparatus.

8.5.6 Fisher E-I test 8.5.6.1 Calculate VA from the calibration phase, set flow = VA if Fisher E-I
method is contemplated.
8.5.6.2 With FGF at VA, the FzCO2 is changed to any value for 5 breaths.
8.5.6.3 Pv C02-oxy is calculated using the PEC02 --PIC02 method described by Fisher.
Our method of the Fisher E-I test is an improvement over the previous art in that the effect of change in breath size on the equilibrium value of PE'rC02 is minimized by the sequential breathing circuit such that a larger breath delivers physiologically neutral previously expired gas instead of additional test gas.
~ 5 Measured Parameters for Cardiac ~~xt~ut SV02 - Nlixed venous blood Q - Cardiac output V02 _ Oxgen Consumption VC02 - Carbon Dioxide Consumption Qs / QT - Cardiac Shunt Total Cardiac Output RQ - Respiratory Quotation '702 ~7C02 VA - Alveolar Ventilation FRC - Functional Residal Capacity (after exhale) Dead Space - VD TOTAL (dead space total - includes alveolar dead VT space and dead space in trachea) vDAN - Anatomical dead space Ventilation value DESCRIPTION OF THE INVENTION
Anesthesia via a circle circuit (see figure 1) Fresh gas consisting of oxygen, with the possible addition of air and/ or nitrous oxide (N20), and possibly an anesthetic vapor such as isoflurane, desflurane or sevoflurane enters the fresh gas port (6) at a constant and known flow. The gas concentrations entering the circuit are set by the anesthesiologist. The patient inspires through the patient port (1) and draws fresh gas plus gas drawn from the 1 o gas reservoir bag (4) through the COz absorber (5) up the inspiratory limb (8).
During exhalation, the inspiratory valve (~ closes and the fresh gas passes through the C02 absorber (5) towards the gas reservoir bag. Expired gas flows down the expiratory limb (2) displacing gas into the gas reservoir bag (4). When the reservoir bag is full, the pressure in the circuit rises, opening the AhL (airway presslure relief) valve (9), and the rest of the expired gas exits the circuit through the APL
valve. Gas is sampled continuously at the patient port and is analyzed for concentrations of constituent gases. The inspiratory (2) and expiratory (8) limbs consist of tubing (T).
This circuit is designed to efficiently deliver anesthetic gases to a patient.
It does so by allowing the patient to rebreathe exhaled anesthetics gases but not COz.
Important characteristics to note:
1) The circuit is designed to be used as a partial rebreathing circuit. It has this characteristic when the fresh gas flow is less than minute ventilation ( VE ) where VE is defined as the volume of gas breathed per minute. Partial rebreathing i) results in inspired gas that is composed of mixtures of fresh gas and previously exhaled gas. Although fresh gas or previously exhaled gas may predominate during part of inhalation, the gases mix and cannot be separated.

Page 3~
ii) increases the efficiency of delivery of expensive anesthetic vapors as the vapor that had been exhaled on a previous breath can be re-supplied to the patient instead of being vented out of the circuit (through the APL
valve (9));
iii) requires the presence of a device that will filter out the carbon dioxide (C02) from the previously exhaled gas. An important function of breathing is to eliminate CO? from the body. If a CU2 filter, known as a C02 absorber, is present in the circuit, then all of the fresh gas inhaled is free of CO2 and the rate of elimination of CO2 is a function of VE , as is the case when breathing normally without a circuit. In that portion of previously exhaled gas that is inhaled, the C02 is filtered, but its anesthetic vapor is rebreathed as stated in (ii);
2) There are only two one-way valves, (3) and (7).
3) Note that if the CO2 absorber (5) is bypassed then the fresh gas and previously exhaled gases mix and COZ elimination becomes a function of the fresh gas flow until the fresh gas flow is increased to greater than VE , at which time C02 elimination becomes a function of VE .
4) The circuit is designed such that the valves and C02 absorber can be remote from the patient in order to allow for a maximal surgical field. If the surgery is on the chest or head and neck, there needs to be a minimum of tubing near the surgical field and there needs to be about 1-2 m of clearance between the anesthetic machine and the patient in order to give the nurses and surgeons a sufficiently large sterile field in which to work.
5) The length of the tubing (T) between the patient and the valve and C02 absorber manifold does not affect the function of the circuit.
The Fisher Isocapnia Circuit 1 (FICi), figure 2 During exhalation, gas passes from the patient port (10), through the expiratory one-way check valve (15) down the expiratory limb (16) into the expiratory reservoir bag (18). Excess gas exits the expiratory reservoir bag (18) at the opening (19) remote from the entrance. Fresh gas (gas containing no C02) enters the circuit at a constant flow via a fresh gas port (12). Is the inspiratory one-way check valve (11) is closed during exhalation, the fresh gas accumulates in the fresh gas reservoir bag (20).
During inhalation, fresh gas from the fresh gas flow and the fresh gas reservoir (20) passes through the inspiratory valve (11) and enters the patient. If the fresh gas flow is less than VE , the fresh gas reservoir bag (20) collapses and valve (17) in the bypass limb (13) opens, directing previously exhaled gas to the patient.
FICi is designed to control the PCO2 in expired gas (PE'rCO2).
Important characteristics of the circuit:
1) there are 3 valves.
2) during exhalation, it prevents mixing of exhaled gas with fresh gas 3) when minute ventilation ( VE ) exceeds fresh gas flow, both fresh gas and previously expired gas are inhaled in sequence - fresh gas first followed by mostly previously exhaled gas.
FICi compared to the anesthetic circuit (AC):
1. Control of C02 FICi: The precise and predictable control of the elimination of CO2 arises from the ability to sequence the delivery of gases. The gas that enters the lungs Iast (previously exhaled gas) is distributed to the anatomical deadspace.
The anatomical deadspace can contain some fresh gas and some previously exhaled gas depending on how much VE exceeds the fresh gas flow. If the VE exceeds the fresh gas flow sufficiently so that previously exhaled gas fills the anatomical deadspace, all the fresh gas (which was inhaled before the previously exhaled gas) will have passed the anatomical deadspace and been distributed to the alveoli. If at this point the fresh gas flow stays constant and the VE increases, the flow of fresh gas to the alveoli stays constant and only the flow of previously exhaled gas will vary with the CIE . As only the flow of fresh gas to the alveoli will determine the elimination of C02, varying VE
will not affect the rate of CO? elimination.
Stated another way, the alveolar ventilation , VA, that eliminates C02 is equal to the fresh gas flow whenever the fresh gas flow is less than the VE minus the ventilation distributed to the anatomical dead space.
AC: When the C02 absorber is in place, PErC02 is controlled by VE . If no C02 absorber is in place, the PETCOz is controlled by the fresh gas flow and VE . Since the fresh gas and the previously exhaled gas mix, fresh gas is distributed to both the alveoli and the deadspace. The actual VA that eliminates C02 will be Iess than or equal to the fresh gas flow. Since the flow of fresh gas to the alveoli will depend on the relative amounts of fresh gas flow and VE , YA and CO2 elimination cannot be precisely predicted from the fresh gas flow.
2. Mixing of gases 2o FICs: fresh gas and previously exhaled gases are kept separate in separate limbs and separate Yeservoir bags during exhalation. During inhalation, fresh gas enters the lungs first; if FGF is less than VE, thzs is followed by previously exhaled gas.
AC: fresh gas and previously exhaled gases mix in the C'.02 absorber and gas reservoir bag.
3. joining of previously expired gas and fresh gas FIC1: Occurs when the inspired volume exceeds the fresh gas reservoir volume, regardless of inspired flows.

AC: Occurs when the inspired flow exceeds fresh gas flow, regardless of the inspired volume.
4. Composition of inhaled gas FICz: Inhaled gas consists of fresh gas until the fresh gas reservoir collapses; it there consists of mostly expired gas.
AC: Inhaled gas consists of the gas mixture in the inspiratory limb of the circuit (8) between the inspiratory valve (7) and the patient port (1) followed by the fresh gas accumulated in the C02 absorber (5), followed by previously 1 o exhaled gas from the gas reservoir bag drawn through the COZ absorber.
5. Moving the manifold remote from the patient (as is required in the operating room and for some experiments).
FICZ: The fresh gas reservoir bag (20) and expiratory gas reservoir bag (18) can be moved remotely but the inspiratory valve (11), expiratory valve (15), or bypass valve (1~) must be kept close to the patient port (10) in order to retain the advantages of the FICi in maintaining isocapnia. Moving the valves and bypass limb distally from the patient will result in previously expired gas mixing with fresh gas in the inspiratory limb (14) before it is delivered to the patient. The precise sequential delivery of gases will be lost.
AC: Inspiratory (~) and expiratory (3) valves are remote from the patient.
Previously expired gas and fresh gas mix. There is no sequential delivery of gas.
6. Use to deliver anesthesia FICi: cannot be used with low fresh gas flow as the CO2 will build up. A CO2 absorber (typically 1-4 L in volume) on the bypass limb would make the manifold very bulky. Moving the bypass limb distally and adding a CO2 absorber would not have any advantages over the circle circuit with respect to delivery of anesthesia and would lose the advantages of the IC in maintaining isocapnia when the C02 absorber is out of the circuit.
7. Controlled ventilation:
FIC1: Is described for spontaneous ventilation only. We describe a modification of the circuit so that it can be used for controlled ventilation (Figure 4). The fresh gas reservoir bag (20) and expiratory gas reservoir bag (18) can be enclosed in a rigid air-tight container such that the inspiratory limb (14) enters the container via port (24) and expiratory limb (16) enters the 1 o container via port (25) such that the junctions of the outside of the limbs form an air-tight seal with the inside surface of the ports. A further port (22) is provided for attachment of tile Y piece of any ventilator (23). During the inspiratory phase of the ventilator, the pressure inside the container (21) rises putting the contents of the fresh gas reservoir bag (20) and the expiratory gas reservoir bag (18) under the same pressure. As the opening pressure of the inspiratory valve (11) is less than that of the bypass valve (1~, the fresh gas reservoir (20) will be emptied preferentially. When the fresh gas reservoir (20) is empty, the pressure in the container (21) and inside the expiratory gas reservoir (18) will open the bypass valve (17) and deliver the previously 2o expired gas to the patient. During the exhalation phase of the ventilator, the contents of the container (21) are opened to atmospheric pressure, allowing the patient to exhale into the expiratory gas reservoir (18) and the fresh gas reservoir bag to fill with fresh gas. Thus, fresh gas and previously exhaled gas are delivered sequentially during inhalation with controlled ventilation.
Previous art During controlled ventilation, the APL valve (309) is closed. In the exhalation phase, 3o the gas from the patient port (301) passes down the expiratory tubing (302) past the one-way expiratory valve (303) and into the common gas reservoir (312). When the common gas reservoir (312) is full, additional gas is vented through the spill valve (313) that contains a one-way valve (310). Fresh gas enters the fresh gas port (306) and flows into the C02 absorber (305), displacing gas that was in the C02 absorber (305) into the gas reservoir (312) or out of the spill valve (313). As the common gas reservoir (312) fills, it displaces gas from the rigid container ('311) out through the expiratory port (31~ of the ventilator Y piece (316).
During inhalation, the mushroom valve at the expiratory port of the ventilator Y
piece (31~ inflates, blocking off this port, and a volume of gas is delivered from the ventilator (315) into the rigid container (311). This displaces an equal volume of gas from the common gas reservoir (312) into the circuit. Fresh gas and previously exhaled gas from the gas reservoir bag (312) and CO2 absorber (305) pass the inspiratory one-way valve (306), travel down the inspiratory limb (308) towards the patient port (301).
The primary difference between the previous art (figure 4B) and our circuit is that with our circuit both an expired gas reservoir and a fresh gas reservoir are in the rigid box. In the presence of the disclosed configuration of 3 valves, such that the opening pressure of the bypass valve is greater than the opening pressure of the inspiratory valve, there will be sequential delivery of fresh gas, then previously exhaled gas, when VE exceeds fresh gas flow. This does not occur with the previous art, even if the C02 absorber is removed from the circuit.
Description of a new circuit to deliver fresh gas then previously exhaled gas sequentially A: Spontaneous ventilation:
The modification of FICi for controlled ventilation still has the limitation that the manifold must be kept close to the face. It is therefore the purpose of this application to further improve on the ventilated version of the FICi circuit by describing an isocapnia circuit that will maintain isocapnia by the sequential delivery of fresh and previously exhaled gas when VE exceeds fresh gas flow and will allow the placement of the manifold containing the valves and the fresh gas reservoir bag and the expiratory gas reservoir bag remote from the patient. This improvement will further reduce the bulk of tubing near the face by allowing the use co-axial tubing.
I. Description of the circuit for spontaneous ventilation Layout Patient (38) breathes via a Y connector (40). Valve (31) is an inspiratory valve and valve (33) is an expiratory valve. Valve (34) is a bypass limb valve that has an opening pressure greater than valve (31).
Function.
During exhalation, increased pressure in the circuit closes inspiratory valve (31) and bypass valve (35}. Gas is directed into the exhalation limb (39), past one-way valve (33) into the expiratory gas reservoir bag (36). Excess gas is vented via port (41} in expiratory gas reservoir bag (36). Fresh gas enters via port (30) and fills fresh gas reservoir (37}. During inhalation, inhalation valve (31) opens and fresh gas from the fresh gas reservoir (37) and fresh gas port (30) enter the inspiratory Iimb (32) and are delivered to the patient. If fresh gas flow is less than VE , the fresh gas reservoir (37) empties before the end of the breath, and continued respiratory effort results in a further reduction in pressure in the circuit. When the opening pressure of the bypass valve (35 ) is reached, it opens and gas from the expiratory gas reservoir (36) passes into the expiratory limb (39) and makes up the balance of the breath with previously exhaled gas.
Thus when fresh gas flow is Less than VE , the subject inhales fresh gas, then previously expired gas. As described by Fisher, this will maintain normocapnia independent of minute ventilation.

The new circuit maintains all of the functional advantages of the FICi circuit with respect to maintaining isocapnia independent of VE during spontaneous ventilation.
The circuit has additional advantages not attainable with the FICi such as ~) The circuit can retain all the advantages of sequential gas delivery while moving the gas reservoir bags and valves remote from the patient by extending the inspiratory and expiratory limbs or by the use of co-axial tubing, yet still be used with controlled ventilation (see below).
2) The lengths of the inspiratory and expiratory limb can be as long as desired 1 o without affecting the ability of the circuit to maintain isocapnia. (Note that connecting coaxial tubing to the patient port of FICi disrupts its ability to provide fresh gas and previously rebreathed gas sequentially when fresh gas flow is less than VE and would have the same effect as moving the bypass Iimb distally (discussed above)).
2. Description of co-axial version of new isocapnia circuit (CAIC~ (fig d) Layout Patient port (50) opens directly to the inspiratory limb (59) and expiratory limb (51) 2o without a Y connector. Valve (58) is an inspiratory valve and valve (52) is an expiratory valve. Valve (60) is a bypass limb valve that has an opening pressure greater than valve (58). f Function:
During exhalation, increased pressure in the circuit closes inspiratory valve (58) and bypass valve (60). Gas is directed into the exhalation limb (51), past one-way valve (52) into the expiratory gas reservoir bag (56). Excess gas is vented via port (55) in expiratory gas reservoir bag (56). Fresh gas enters via port (57) and fills fresh gas reservoir (56). During inhalation, inhalation valve (58) opens and fresh gas from the 3o fresh gas reservoir (56) and fresh gas port (57) enter the inspiratory limb (59) and are delivered to the patient. If fresh gas flow is less than VE , the fresh gas reservoir (56) empties before the end of the breath, and continued respiratory effort results in a further reduction in pressure in the circuit. When the opening pressure of the bypass valve (60) is reached, it opens and gas from the expiratory gas reservoir (54) passes info the expiratory limb (51) and makes up the balance of the breath with previously exhaled gas.
Thus when fresh gas flow is less than VE, the subject inhales fresh gas, then previously expired gas. As described by Fisher, this will maintain normocapnia independent of minute ventilation.
B: The new circuit and controlled ventilation (See figure 7) Our new circuit was described for spontaneous ventilation only. We describe a modification of the new circuit that will allow it to be used for controlled ventilation (Figure 7). The fresh gas reservoir bag (88) and expiratory gas reservoir bag (77) can be enclosed in a rigid air-tight container such that the inspiratory limb (84) enters the container via port (86) and expiratory Iimb (81) enters the container via port (74) such that the junctions of the outside of the limbs form an air-tight seal with the 2o inside surface of the ports. A further port (89) is provided for attachment of the Y
piece of any ventilator (73). During the inspiratory phase of the ventilator, the pressure inside the container (8~ rises, putting the contents of the fresh gas reservoir bag (88) and the expiratory gas reservoir bag (77) under the same pressure. As the opening pressure of the inspiratory valve (85) is Iess than that of the bypass valve (78), the fresh gas reservoir (88) will be emptied preferentially. When the fresh gas reservoir (88) is empty, the pressure in the container (87) and inside the expiratory gas reservoir (77) will open the bypass valve (78) and deliver the previously expired gas to the patient. During the exhalation phase of the ventilator, the contents of the container (87) are opened to atmospheric pressure, allowing the patient to exhale into the expiratory gas reservoir (77) and the fresh gas reservoir bag to fill with fresh gas. Thus fresh gas and previously exhaled gas are delivered sequentially during inhalation with controlled ventilation.
Previous art: The "bag in the box" method of controlled ventilation is well known.
The primary difference between the previous art (figure 4B) and our circuit is that with our circuit both an expired gas reservoir and a fresh gas reservoir are in the rigid box. In the presence of the disclosed configuration of 3 valves, such that the opening pressure of the bypass valve is greater than the opening pressure of the inspiratory valve, there will be sequential delivery of fresh gas then previously exhaled gas when VE exceeds fresh gas flow. This does not occur with the previous art, even if the C02 absorber is removed from the circuit. In addition, our circuit differs from the FIC1 modification for controlled ventilation in that our circuit will ~ 5 maintain isocapnia by the sequential delivery of fresh and previously exhaled gas and will allow the placement of the manifold containing the valves and the fresh gas reservoir bag and the expiratory gas reservoir bag remote from the patient and be connected to the patient via a co-axial tubing.
20 The new circuit with a co-axial extension arid controlled ventilation (See figure 8) Our new circuit with co-axial extension was described for spontaneous ventilation only. We describe a modification of the new circuit with co-axial extension that will allow it to be used for controlled ventilation (Figure 8). The fresh gas reservoir bag 25 (106) and expiratory gas reservoir bag (110) can be enclosed in a rigid air-tight container (105) such that the inspiratory limb (101) enters the container via port (103) and expiratory limb (114) enters the container via port (110) such that the junctions of the outside of the limbs form an air-tight seal with the inside surface of the ports.
(An alternate configuration is to have the full coaxial circuit entering the container 30 via a single port where the division of the inspiratory and expiratory limbs occurs inside the container. Valves (102), (213) and (215) would also be held inside the container.) A further port (107) is provided for attachment of the Y piece of any ventilator (108). During the inspiratory phase of the ventilator, the pressure inside the container (105) rises, putting the contents of the fresh gas reservoir bag (106) and the expiratory gas reservoir bag (210) under the same pressure. As the opening pressure of the inspiratory valve (102) is less than that of the bypass valve (115), the fresh gas reservoir (106) will be emptied preferentially. When the fresh gas reservoir (106) is empty, the pressure in the container (105) and inside the expiratory gas reservoir (110) will open the bypass valve (115) and deliver the previously expired 1 o gas to the patient. During the exhalation phase of the ventilator, the contents of the container (105) are opened to atmospheric pressure, allowing the patient to exhale into the expiratory gas reservoir (110) and the fresh gas reservoir bag to fill with fresh gas. Thus, fresh gas and previously exhaled gas are delivered sequentially during inhalation with controlled ventilation.
The additional advantage of this circuit over the previously described is that only one tube need be at the patient interface.
A circuit designed to deliver anesthetics It is the further purpose of this patent to describe an improved anesthetic circuit that can be used for the efficient delivery of anesthetics with Iow fresh gas flow or closed circuit with spontaneous ventilation and mechanical ventilation, and can also be used for:
1. precise control of C02 elimination independent of VE
2. accelerated elimination of anesthesia while maintaining normocapnia The circuit consists of the following components:
200 Patient port 2013 port connector 202 expiratory limb 203 expiratory valve 204cannister on bypass conduit that may be switched to be empty, contain COz absorbing crystals or zeolyte, charcoal or similar substance that filters anesthetic agents 205 bypass conduit.
206 one-way valve with opening pressure slightly greater than that of the inspiratory valve (219) 207 expiratory gas reservoir bag 208 port in rigid container for entrance of expiratory limb of circuit in an air-tight manner 209 exit port for expired gas from expired gas reservoir 210 a 2-way manual valve that can be turned so that the gas in the box (216) is continuous with either the ventilator Y piece (211) or the ventilation bag (212) and APL valve (213) assembly 212 the ventilator Y piece 212 the ventilation bag 213 APL valve 214 ventilation port of rigid box (216) 215 fresh gas reservoir 216 rigid box 227port in rigid container for entrance of inspiratory limb of circuit (220) in an air-tight manner 218fresh gasinlet 229inspiratory valve 220 inspiratory limb 221 bypass limb proximal to canister (204) Descriptions Function of the circuit as an anesthetic circuit:
During exhalation, increased pressure in the circuit closes inspiratory valve (219) and bypass valve (206). Exhaled gas is directed into the exhalation limb (202), past one-way valve (203) into the expiratory reservoir bag (20: ). Fresh gas enters via port (218) and fills the fresh gas reservoir (215). During inhalation, inhalation valve (219) opens and fresh gas from the fresh gas reservoir (215) and fresh gas port (218) enter 1 o the inspiratory limb (220) and are delivered to patient. If fresh gas flow is less than VE , the fresh gas reservoir (215) empties before the end of the breath;
continued respiratory effort results in a further reduction in pressure in the circuit.
When the opening pressure of the bypass valve (206) is reached, it opens and gas from the expiratory gas reservoir (20~ passes through a COa absorber (204) into the 7 5 rebreathing limb (221) and makes up the balance of the breath with partially rebreathed gas.
The rebreathed gas passes through the C02 absorber (204) but still contains expired 02 and anesthetic, which can both be safely rebreathed by the patient. In this respect, 2o the circuit in figure 9 functions like a circle anesthetic circuit in which the fresh gas flow containing 02 and anesthetic can be reduced to snatch the consumption or absorption by the patient.
Function of the circuit as an isocapnic hyperpnea circuit to eliminate anesthetics 25 or other volatile toxins:
During exhalation, increased pressure in the circuit closes inspiratory valve (219) and bypass valve (206). Exhaled gas is directed into the exhalation limb (202), past one-way valve (203) into the expiratory reservoir bag (20~. Fresh gas enters via port (218) and fills the fresh gas reservoir (215). During inhalation, inhalation valve (219) 30 opens and fresh gas from the fresh gas reservoir (215) and fresh gas port (218) enter the inspiratory limb (220) and are delivered to patient. If fresh gas flow is less than VE, the fresh gas reservoir (215) empties before the end of the breath;
continued respiratory effort results in a further reduction in pressure in the circuit.
When the opening pressure of the bypass valve (206) is reached, it opens and gas from the expiratory gas reservoir (20'~ passes through a gas filter {204) into the rebreathing limb (221) and makes up the balance of the breath with partially rebreathed gas.
The rebreathed gas passes through gas filter (204), which can be used to remove gases such as anesthetics or volatile hydrocarbons (depending on the choice of filter), but still contains expired Oz and COz, which can be used to maintain isocapnia independent of VE if the fresh gas flow is set to ~~. In this respect, the circuit in figure 9 functions like a non-rebreathing circuit described by Fisher, where rebreathed gas is cleared of an agent, rather than being delivered from a pressurized source.
Advantages of circuit over previous art:
1) It is comparable to the circle anesthesia circuit with respect to efficiency of delivery of anesthesia, and ability to conduct anesthesia with spontaneous ventilation as well as controlled ventilation.
2) It is often important to measure tidal volume and VE during anesthesia.
With a circle circuit, a pneumotach with attached tubing and cables must be placed at the patient interface, increasing the dead-space, bulk and clutter at the head of the patient. With our circuit, the pneumotachograph (or a spirometer if the patient is breathing spontaneously) can be placed at port (214) and thus remote from the patient.
3) Fisher (Accelerated elimination of anesthetic) taught a circuit that can be used to accelerate the elimination of anesthesia. However that required additional devices such as an external source of gas (reserve gas), a demand regulator, self-inflating bag or other manual ventilating device 3-way stopcock and additional tubing. Furthermore, he did not disclose a method whereby mechanical ventilation can be used. In fact it appears that it cannot be used - patients must be ventilated by hand for that method.
With this circuit, the canister (204) is made to contain an anesthetic gas absorbent such as zeolyte.
a) No other equipment is necessary: specifically, there is no requirement for an external source of gas or demand regulator;
b) the patient can be ventilated with the ventilation bag (212) already on the 1 o circuit or the circuit ventilator, or any ventilator; no other tubing or devices are required.
4) Circle circuit cannot deliver fresh gas and then previously exhaled gas sequentially. The ability to do so allows the fresh gas flow to precisely control the ~~. Such fine control may be required to make physiological measurements during anesthesia such as cardiac output (see next patent).
'With our circuit, if the canister (204) is bypassed, the circuit becomes the equivalent of the one described in fig ~ and fig 8 As many changes can be made to the various embodiments of the invention without departing from the scope thereof; it is intended that all matter contained herein be interpreted as illustrative of the invention but not in a limiting sense.

Claims (11)

1. An improved apparatus and method of identifying the alveolar ventilation (~A), substantially as illustrated and described herein.

2. The apparatus and method of claim 1 wherein the ~A so determined is utilized to calculate the ~CO2 as ~A × PETCO2.

3. The improved apparatus and method of claim 1 wherein:

a) the Fisher E-I approach to determine P~CO2-oxy (or) b) the Kim Rahn Farhi approach is used to determine i) P~CO2-oxy ii) true P~CO2 iii) PaCO2 iv) true P~CO2 plus the information from a pulse oximeter to determine mixed venous hemoglobin O2 saturation (or) c) the differential CO2 Fick technique of Gedeon and Orr is utilized to determine any combination of i) P~CO2-oxy u) ~

iii) ~CO2 iv) ~CO2' v) PETCO2-PaCO2 gradient determined using the PaCO2 as determined by the Kim Rahn Farhi method from data collected while reducing the ~CO2 in order to perform the differential Fick method. (or) d) ~ is determined via the Kim Rahn Farhi method performed during partial rebreathing using a CO2 Fick method inhere the i) ~CO2 is calculated with or without the new method as disclosed ii) CaCO2 and C~CO2 are determined from the PaCO2 and P~CO2 respectively derived by the Kim Rahn Farlni method; (or) e) calculation of the respiratory quotient (RQ) is determined as PETCO2 /
(PIO2-PEO2);

wherein said apparatus or method may be utilized for very accurate non-invasive determination of ~ and the other indicated parameters.

4. An improved method of apparatus for determining:
~, ~A, and calculating ~CO2, P~CO2- oxy, true P~CO2, PaCO2, pulmonary shunt, anatomical dead space, and O2 saturation in mixed venous blood; which increases the accuracy of these determinations and calculations in relation to known methods and apparatuses and allows for full automation thereof if necessary by:
i) reading FGF to a sequential delivery circuit to create two sets of data for said determination utilizing the Fick equations; (or) ii) the PETCO2 to PaCO2 gradient is calculated from two independently derived values in the same subject; (or) iii) utilizing the Kim-Rahn-Farhi technique a period of reducing FGF
simulates complete or partial breath holding, wherein the PETCO2 of each breath is equivalent to a sequential alveolar sample;
thereby providing more relevant data to calculate desired parameters.

5. A device to measure ~ and other parameters such as ~A, ~CO2, P~CO2-oxy, true P~CO2, PaCO2, pulmonary shunt, and anatomical dead space, consisting of an apparatus comprising the following components:

a) a breathing circuit with characteristics that on exhalation, exhaled gas is kept separate from inhaled gas;
b) on inhalation, when ~E is greater than fresh gas flow, the subject inhales fresh gas first and then inhales a reserve gas containing CO2 that may be a stored exogenous gas (the non-rebreathing circuit Fisher) or mostly previously exhaled gas;
c) any of the circuits contained in the Figures can be used but the preferred configuration is the FIC2-V-co-ax (Figure 8), which we will refer to as the "preferred circuit";
d) gas sensors that monitor the CO2 with or without O2 concentrations in the gases at the patient-circuit interface and provide analogue signal outputs corresponding to the PCO2 and PO2 in the gas;

e) a gas flow controller such as the Voltek gas flow controller (Voltek Enterprises, Toronto, Canada) consisting of a precise automated electronic device that can controls the flow of one or more pressurized gases (such as oxygen, air, CO2) singly or in combination in response to manual setting of dials or computer-generated instructions;

f) source of O2, and/ or air with or without CO2;
g) means to identify phase of breathing, said means may consist of pressure sensors or analysis by gas sensors;
h) machine intelligence consisting of a computer or Iogic circuit with input, output, and calculation functions;
i) input data consists of operator-defined default values, output signals from gas and possibly pressure sensors, clock, and feedback information from flow and gas mixing controller;
j) output signals to gas flow and gas mixing controller and to screen;
k) calculation based on data from gas analyzers, feedback information from flow controller, and user-supplied default values;
1) control output signals to flow controllers according to a preset algorithm.

wherein said device may be utilized for non-invasive measurement and determination of Q and other parameters.

6. A ventilation circuit comprising means for allowing/providing FGF to substantially equal VA and substantially control VA, and in so doing provide for calculation of Q and other parameters as previously set out herein in the disclosure and figures, for example, in relation to claim 4.

7. A method and apparatus of determining Q and the other parameters disclosed in claim 4 by utilizing the circuits described and illustrated herein by reducing the FGF to said circuit independent of the breathing rate thereby allowing for calculations to be made via Fick equations, and or the dim-Rahn-Farhi technique.

8. The method or apparatus of any previous claim wherein the CO2 content as calculated from P~ CO2-oxy and true P~ CO2, may be utilized to determine the saturation of mixed venous blood with known relations between CO2 content, O2 saturation and PCO2.

9. The method or apparatus of claim 8 wherein the arterial O2 hemoglobin saturation, as determined by a non-invasive pulse oximeter which makes the measurement by shining infrared light through a finger, is utilized with the saturation value in the pulmonary artery to calculate the fraction of shunted blood (assuming fully oxygenated blood in the end pulmonary capillary) thereof.

10. The method or apparatus of claim 9 utilized to determine the fraction of shunted blood ~ S, which in conjunction with determination of cardiac output ~
T
may be used to determine ~ p the pulmonary output via the relationship.

~ T = ~ P + ~ S

11. The method or apparatus of any previous claim wherein the O2 saturation of haemoglobin in mixed venous blood, as determined therewith, is utilized to reveal a condition in a patient such as septic shock, or heart failure.