Method of measuring cardiac related parameters non-invasively via the lung during spontaneous and controlled ventilation

Abstract

A method of identifying alveolar ventilation (V.sub.A) in a subject, the method comprising: (1) using a breathing circuit which, at exhalation, keeps exhaled gas separate from inhaled gas and at inhalation, when a first gas set (FGS) flow is less than the subject's minute ventilation (V.sub.E), results in a subject inhaling FGS first and then a second gas set (SGS), for the balance of inhalation; (2) setting the FGS flow at a rate greater that V.sub.E; (3) measuring an end tidal CO.sub.2 concentration at a steady state; (4) progressively lowering the FGS flow until a time equal to a recirculation time of CO.sub.2 in the subject; and (5) deriving V.sub.A as the rate of FGS flow at the intersection between an average PETCO.sub.2 in a steady state and a line fit to the PETCO.sub.2 values after the rise in PETCO.sub.2 values begins until the recirculation time.

Claims

1. A method of identifying alveolar ventilation (V.sub.A) in a subject, the method comprising: (1) using a breathing circuit configured to: i. on exhalation by the subject, keep exhaled gas substantially separate from inhalation gas, and ii. on inhalation by the subject, when a first gas set (FGS) flow is less than a minute ventilation (V.sub.E) of the subject, first provide FGS flow to the subject, and then provide a balance of the V.sub.E of the subject that is substantially a second gas set (SGS); (2) setting the FGS flow into the breathing circuit at a rate greater than the V.sub.E of the subject; (3) measuring an end tidal CO.sub.2 concentration (PETCO.sub.2) in a steady state; (4) progressively lowering the FGS flow into the circuit, either breath by breath or continuously, until after a time equal to a recirculation time of CO.sub.2 within the subject after a rise in PETCO.sub.2 values above a threshold value is observed; and (5) deriving V.sub.A as the rate of FGS flow at a point of the intersection between two lines comprising: (a) an average PETCO.sub.2 in steady state; and (b) a straight line fit to the PETCO.sub.2 values after the rise in PETCO.sub.2 values begins until the recirculation time.

Description

BRIEF DESCRIPTION OF THE FIGURES

(1) FIG. 16: PCO.sub.2 vs. time tracing during a rebreathing equilibrium test for determining oxygenated mixed venous PCO.sub.2

(2) FIG. 17: PCO.sub.2 vs. time tracing during exponential method of finding oxygenated mixed venous PCO.sub.2

(3) FIG. 1 is a SGDB Circuit as taught by Fisher in U.S. Pat. No. 6,622,725 referred to herein as the Fisher circuit.

(4) FIG. 2 is similar to FIG. 1 wherein the reservoir bags are remote from the patient.

(5) FIG. 9 is a new circuit for use with spontaneous ventilation.

(6) FIG. 3 is similar to FIG. 9 wherein bypass limb, bypass valve, and passive expiratory valve are replaced by an active expiratory valve.

(7) FIG. 5 is similar to FIG. 1 wherein an active valve has been added to the inspiratory limb to prevent mixing of FGS with SGS during inhalation.

(8) FIG. 10 is similar to FIG. 9 wherein an active valve has been added to the inspiratory limb to prevent mixing of FGS with SGS during inhalation.

(9) FIG. 6 is similar to FIG. 1 wherein an active valve has replaced the passive inspiratory valve.

(10) FIG. 11 is similar to FIG. 9 wherein an active valve has replaced the passive inspiratory valve.

(11) FIG. 4 is similar to FIG. 3 wherein an active valve has replaced the passive inspiratory valve.

(12) FIG. 7 shows a modification of any of the circuits shown in FIGS. 1, 2-6, 9-11 for use with a mechanically ventilated patient.

(13) FIG. 8 shows the preferred embodiment modified for use on ventilated patients.

(14) FIG. 13 is a modification of the above circuits to include co-axially arranged inspiratory and expiratory limbs between the valves and the patient.

(15) FIG. 14 shows the preferred embodiment of the cardiac output circuit where inspiratory and expiratory limbs are co-axially arranged with the circuit of FIG. 5A.

(16) FIG. 15 is a new circuit designed to allow measurement of cardiac output while delivering anesthetics or removing volatile agents from a patient.

(17) FIG. 12 shows a detail of a circuit design where the passive valves are surrounded by the exhaled gas reservoir

(18) FIG. 18: Apparatus for non-invasive cardiac output apparatus consisting of a breathing circuit, gas sources, gas flow controllers, gas concentration sensors, and microprocessor capable of receiving and storing analog and digital input from sensors and operators, storing and following a decision tree, and generating output signals to a computer screen and to flow controllers.

(19) FIG. 19: Flow diagram describing automated sequence of events performed by the non-invasive cardiac output apparatus in order to automatically generate and record data non-invasively and calculate {dot over (Q)} and other physiologic parameters.

(20) FIG. 20 is a schematic of a standard anesthetic circle system herein provided as reference for discussion of disclosed system. Gas entering the anesthetic circuit consisting of oxygen, with the possible addition of air and/or nitrous oxide (N.sub.2O), 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 gas reservoir bag (4) through the CO.sub.2 absorber (5) up the inspiratory limb (8). During exhalation, the inspiratory valve (7) closes and the fresh gas passes through the CO.sub.2 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 APL (airway pressure 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).

(21) FIG. 21: A detail of the computer screen output of an automated analysis of test finding {dot over (V)}.sub.A by progressive reduction in SGF flow method in a subject is illustrated in FIG. 21. The figure illustrates that progressive reduction of SGF (labelled “FGF” in the figure) results in a distinct inflection point when either PETCO.sub.2 or PETO.sub.2 is graphed as a function of SGF.

DETAILED DESCRIPTION OF THE INVENTION

(22) Detailed Description of the Apparatus

(23) Referring now to FIG. 18, an apparatus is shown with the following components: 1) a breathing circuit (1800), said breathing circuit preferably has the characteristic that, on exhalation by a subject (1801), exhaled gas is kept separate from inhaled gas and on inhalation, when VE is greater than the flow of a first gas set (FGS) into the circuit, the subject inhales FGS gas first and then inhales a second gas set (SGS) gas, preferably said SGS containing CO2 and where SGS may be mostly previously exhaled gas. Any SGDB circuit can be used to greater or lesser benefit, according to its characteristics. We provide below detailed descriptions of several alternate configurations and outline their particular advantages and drawbacks with respect to measuring Q and related parameters outlined above. 2) a gas sample line (1802) leading to a gas analyzer (1804) that monitors the concentration of gases, for example CO2, O2, at the patient-circuit interface 28 and outputs preferably an electric signal corresponding to the concentrations (for example if the gases of interest are O2 and CO2, the “#17500 O2 and CO.sub.2 analyzer set” (Vacumed, Ventura Calif., USA)) 3) a precise gas flow controller (1806), preferably one that can control the flow of one or more pressurized gases (such as oxygen, air, CO2) singly or in combination, and that can be set manually or via an automated system such as via machine intelligence (for example, the Voltek gas flow controller by Voltek Enterprises, Toronto, Canada); 4) a source of FGS (1810), preferably containing O2 and/or air with or without CO2; 5) means (1812) to identify phase of breathing, for example using electronic pressure sensors with tubing to sample pressures at the patient-circuit interface (1814) or in other locations in the circuit and generating electrical signal corresponding to the sensed pressures. Such means will provide electrical signal (1816). Phase of breathing can also be determined from analysis of gas sensor output by machine intelligence. 6) a computer or machine intelligence (1818) which records, stores, analyzes signals from gas analyzer (204) and pressure transducer (if present), contains a predetermined set of instructions regarding the analysis of data such as calculation of {dot over (Q)} and physiologic parameters, determination of phase of respiration, display of information on a computer screen, and control of gas flow controller (200) including the timing, sequence and flow of gas. 7) wherein said device may be utilized for non-invasive measurement and determination of {dot over (Q)} and other parameters such as {dot over (V)}A, {dot over (V)}CO.sub.2, PvCO.sub.2-oxy, true PvCO.sub.2, PaCO.sub.2, pulmonary shunt, and anatomical dead space

(24) Detailed Description of Breathing Circuits

(25) FIG. 9 shows a breathing circuit which provides sequential delivery of the FGS followed by the SGS when {dot over (V)}E exceeds FGSF, with the manifold containing the valves and the FGS reservoir bag and the expiratory gas reservoir bag remote from the patient. This improvement reduces the bulk of the patient manifold, and eliminates the possibility of the SGS mixing with the FGS due to vigorous exhalation.

(26) Referring to FIG. 9, Patient (38) breathes via a Y connector (40). Valve (31) is an inspiratory valve and valve (33) is an expiratory valve. Valve (35) is a bypass valve in the bypass limb (34) that bypasses the expiratory valve (33) and has an opening pressure greater than inspiratory valve (31). Valves (35, 33) may be close to or distal from the patient manifold as desired, as long as they are on the expiratory limb (39). However, in the preferred embodiment, they are distal to the patient to reduce the bulk of the patient manifold. Inspiratory valve (31) may be close to, or distal from, the patient manifold as desired, as long as it is on the inspiratory limb (32). In the preferred embodiment, it is distal to the patient as well. FGS enters the circuit via port (30).

(27) Function:

(28) 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). FGS enters via port (30) and fills FGS reservoir (37). During inhalation, inhalation valve (31) opens and FGS from the FGS reservoir (37) and FGS port (30) enter the inspiratory limb (32) and are delivered to the patient. If FGSF is less than {dot over (V)}E, the FGS 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 SGS.

(29) Thus when FGSF is less than {dot over (V)}E, the subject inhales FGS, then SGS, and no contamination of FGS occurs.

(30) FIG. 3 shows an alternate embodiment of the circuit illustrated in FIG. 9 where the passive expiratory valve (33) and expiratory bypass limb (34), and expiratory limb bypass valve (3S) are replaced with a control valve that is triggered by the collapse of the inspiratory reservoir. Referring to FIG. 3, a control valve (401) is placed in the expiratory limb (16) anywhere along its length between the patient port (10) and the expiratory reservoir bag (18). When the patient's VE exceeds the FGSF during inspiration the reservoir bag (20) collapses. This is detected by pressure sensing means (405) through port (406) as an acute reduction in pressure. Pressure sensing means (405) could be an electronic pressure transducer capable of detecting changes 2 cm H.sub.2O pressure, for example. Immediately afterwards, valve (401) is then opened by control means (403), which could be an electronic signal for activating a solenoid valve, for example, leading to depressurization and collapse of a balloon valve, as is known to those skilled in the art, resulting in SGS is being inhaled for the balance of inhalation. During exhalation, patient exhales through expiratory tube (16) past valve (401) into the SGS reservoir (18). At end of exhalation, as detected by pressure sensing means (405) as a reduction of pressure, valve (401) is closed by control means (403), which could be an electronic signal for toggling a solenoid valve, for example, leading to pressurization and inflation of a balloon valve, as is known to those skilled in the art.

(31) While the circuits of FIG. 9 and FIG. 3 present the advantages over the Fisher circuit of reducing the bulk of the patient manifold, and eliminating the possibility of the SGS mixing with the FGS due to vigorous exhalation, they still have the following drawback: When FGS reservoir (20, 37) is emptied and the patient is breathing SGS for the balance of an inspiration, the circuit does not deliver SGS alone but a mixture of SGS and FGS. The FGS continues to flow into the circuit and is drawn by inhalation past one-way inspiratory valve (31, 3) and allows FGS gas to be inhaled from the inspiratory limb (32,14). To optimize the generation of data required to measure of cardiac output, it is necessary to redirect the FGS into the FGS reservoir (37, 20) for the balance of inhalation after the initial collapse of the FGS reservoir. This would prevent mixing of FGS with SGS during the period of inhalation where the patient breathes SGS. This limitation of circuits illustrated in FIGS. 9 and 3 with respect to measuring cardiac output are shared with the Fisher circuit.

(32) FIG. 5 shows an improved circuit that prevents contamination of the SGS by FGS when SGS is being delivered to the patient. Referring to FIG. 5. FGS control valve (400) is added to the inspiratory limb (14) at some point between the FGS port (12) and the inspiratory valve (11). Pop-off valve (425) is connected to the inspiratory limb on the side of the FGS control valve (400) that is proximal to the inspiratory reservoir bag (425). During exhalation, gas passes from the patient port (10), through the expiratory one-way check valve (1S) 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. FGS enters the circuit at a constant flow via a fresh gas port (12). As the inspiratory one-way check valve (11) is closed during exhalation, the fresh gas accumulates in the fresh gas reservoir bag (20). During inhalation, FGS entering from the port (12) and the FGS reservoir (20) passes through the inspiratory valve (11) and enters the patient. If the FGSF is less than {dot over (V)}E, the FGS reservoir bag (20) collapses, as detected by pressure sensing means (405) connected to pressure sensing port (406). FGS control valve (400) is closed via valve control means (403), and valve (17) in the bypass limb (13) opens, directing previously exhaled gas to the patient. When the FGS control valve (400) is closed, any FGSF entering the circuit during the balance of inspiration is directed only to the FGS reservoir bag (20) and not to the patient, who is receiving SGS for the balance of inspiration. FGS control valve (400) may be re-opened any time from the beginning of expiration to just before the next inspiration. FGS control valve (400) may be any type of valve, and is preferably an active valve such as a balloon valve, known to those skilled in the art, that can be controlled by automated means. The pop-off valve (425) opens when the reservoir bag (20) is full to prevent the reservoir bag (20) from overfilling.

(33) The circuit illustrated in FIG. 10 is similar to that in FIG. 9 but has the addition of a FGS control valve (400), together with pressure sensing means (405) and port (406), and valve control means (403), added to the inspiratory limb of the circuit (32) distal to the one-way inspiratory valve (31) and proximal to the FGS inflow port (30). Similarly, a FGS control valve, together with pressure sensing means and port, and valve control means, may be added to the inspiratory limb (14) of the circuit illustrated in FIG. 3 positioned distal to the one-way inspiratory valve (31) and proximal to the FGS inflow port (12) to achieve the same result, namely, prevention of contamination of SGS by FGS when {dot over (V)}E exceeds FGSF and the FGSF reservoir bag is emptied.

(34) We present two additional circuits that are configured by adding FGS control valve (400) together with pressure sensing means (405) and port (406), and valve control means (403), to the Fisher circuit and the circuit illustrated in FIG. 9 and removing the passive one way inspiratory valve (11, 31), as shown in FIGS. 6 and 11 respectively. These circuits function identically to those illustrated in FIGS. 5 and 10 with respect to complete separation of FGS and SGS during inhalation. In such a circuit, during inspiration, FGS control valve (400) is open until FGSF reservoir bag (20, 37) is emptied, then it is closed so that any additional FGSF entering the circuit during the balance of inspiration is directed only to the reservoir bag (20) and not to the patient. As the patient continues to inspire, bypass valve (17, 35) opens allowing the patient to inhale SGS for the balance of inspiration.

(35) Another embodiment of each of the circuits whereby the valves can be remote from the patient without loss of sequential delivery of FGS and SGS, such as those illustrated in FIGS. 9, 3, 10, 11, 4, 8, is the replacement of separate inspiratory limbs and expiratory limbs with co-axially arranged inspiratory and expiratory limbs as shown in FIG. 13. FIG. 14 shows the preferred embodiment of the invention: The circuit valves are configured as in the circuit illustrated in FIG. 10 with the improvement of co-axially arranged inspiratory (59) and expiratory (51) limbs. The limbs (51, 59) are co-axial so that one limb is contained within the other for some length of tubing, with the limbs separating at some point along its length, such that the expiratory limb (51) leads to the exhaled gas reservoir (54) and the inspiratory limb (59) leads to the FGS reservoir (56). This has two important advantages over the circuit of FIG. 9: 1. A single tube is connected to the patient interface making it easier to manage sick patients 2. The heat contained in the expiratory limb (51) warms the FGS entering through the inspiratory limb (59). 3. If the inner tube is of a material that allows moisture to pass through it but not gas, such as Nation, will promote moisture exchange as well, so that FGS will become slightly moisturized and more comfortable for the patient to breathe if the SGS is moist. It should be understood that co-axial tubing may be used with any of the SGDB circuits described herein.

DESCRIPTION OF A PREFERRED EMBODIMENT

(36) Referring to FIG. 14, Patient port (50) opens directly to the inspiratory limb (59) and expiratory limb (51) without a Y connector, where the limbs are arranged coaxially. Valve (31) is an inspiratory valve and valve (33) is an expiratory valve. Valve (35) is a bypass valve in the bypass limb (34) that bypasses the expiratory valve (33) and has an opening pressure greater than inspiratory valve (31). Valves (35, 33) are preferably distal from the patient on the expiratory limb (51) to reduce the bulk of the patient interface. Inspiratory valve (31) is also preferably distal from, the patient on the inspiratory limb (59). FGS enters the circuit via port (30). FGS control valve (400) is on the inspiratory limb (59) between port (30) and inspiratory valve (31). FGS reservoir bag (37) is connected to inspiratory limb (59) distal to the patient, past port (37). SGS reservoir bag (36) is distal to the patient on the expiratory limb (51) past expiratory valve (33) and bypass valve (35). Excess expiratory gas vents to the atmosphere via port (41). Pressure sensing means (405) is connected to pressure sensing port (406) which is connected to the patient port (50), and valve control means (403). Pressure sensing port (406) may be connected to the co-axial inspiratory (59) and expiratory limb arrangement (51) anywhere along its length between the inspiratory valve (31) and the patient port (50) or between the expiratory valve (33) and the patient. Pop-off valve (425) is connected to the inspiratory limb on the side of the FGS control valve (400) that is proximal to the inspiratory reservoir bag (425).

(37) Function:

(38) During exhalation, increased pressure in the circuit closes inspiratory valve (31) and bypass valve (35). Gas is directed into the exhalation limb (51), 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). FGS enters via port (30) and fills FGS reservoir (37). During inhalation, inhalation valve (31) opens and FGS from the FGS reservoir (37) and FGS port (30) enter the inspiratory limb (59) and are delivered to the patient. If FGSF is less than {dot over (V)}E, the FGS 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 SGS. The emptying of FGS reservoir bag (37) is detected by pressure sensing means (405) such as an electronic pressure transducer, known to those skilled in the art, connected to pressure sensing port (406), and FGS control valve (400) such as a balloon valve known to those skilled in the art, is closed via valve control means (403) such as access to gas pressure controlled by an electronically toggled solenoid valve known to those skilled in the art. When the FGS control valve (400) is closed, any additional FGSF entering the circuit during the balance of inspiration is directed only to the FGS reservoir bag (20) and not to the patient, who is inhaling only SGS for the balance of inspiration. FGS control valve (400) may be re-opened any time from the beginning of expiration, as sensed by the reverse of pressure by the pressure sensing means (405), to just before the next inspiration, also sensed by pressure changes in the breathing circuit. Pop-off valve (425) prevents the FGS reservoir bag (20) from overfilling when FGS exceeds {dot over (V)}E.

(39) Thus when FGSF is less than {dot over (V)}E, the subject inhales FGS, then SGS, and no contamination of SGS with FGS occurs.

(40) Use of Circuits for Ventilated Patients

(41) Any of the SGDB circuits disclosed herein as well as the Fisher circuit can be used for a patient under controlled ventilation by enclosing the FGS reservoir (20) and exhaled gas reservoir (18) within a rigid container (21) with exit ports for the inspiratory limb of the circuit (24) and expiratory limb of the circuit (25) and port for attachment to a patient interface of a ventilator (22) as illustrated in FIG. 7. In FIG. 7, the inspiratory limb (500) represents the inspiratory limb of any of the SGDB circuits herein described, and expiratory limb (501) corresponds to the expiratory limb of any of the SGDB circuits herein described. The FGS reservoir bag (20) and expiratory gas reservoir bag (18) are enclosed in a rigid air-tight container such that the inspiratory limb (500) enters the container via port (24) and expiratory limb (501) enters the 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 the Y piece of any ventilator (23). Detachment from the ventilator allows the circuit to be used with a spontaneously breathing patient. During the inspiratory phase of the ventilator, the pressure inside the container (21) rises putting the contents of the FGS reservoir bag (20) and the expiratory gas reservoir bag (18) under the same pressure. Since the opening pressure of the inspiratory valve is less than that of the bypass valve for circuits using passive bypass valves (for example those shown in FIGS. 1, 2, 9, 11, 10, 6, and 5, the FGS reservoir (20) will be emptied preferentially. When the FGS reservoir (20) is empty, the pressure in the container (21) and inside the expiratory gas reservoir (18) will open the bypass valve (35, 17, 206) and begin emptying exhaled gas reservoir (18) delivering SGS to the patient. For circuits using an actively engaged control valve (400) in the inspiratory limb of the circuit, a valve opening detection means (407) such as an electronic circuit that is broken by the opening of the valve when the valve is part of a closed electronic circuit, not shown, detects opening of the one way valve (35, 17, 206) in the exhalation bypass limb. The FGS control valve (400) is then closed, directing FGS into the FGS reservoir bag until the collapse of the FGS reservoir during the next inspiratory phase.

(42) During the exhalation phase of the ventilator, the ventilator's expiratory valve is opened and contents of the container (21) are opened to atmospheric pressure, allowing the patient to exhale into the expiratory gas reservoir (18) and the FGS to flow into the FGS reservoir bag (20). Thus, the FGS and SGS are inhaled sequentially during inhalation with controlled ventilation without mixing of FGS with SGS at any time.

(43) FIG. 8 shows the ventilator configuration described above as used with the preferred circuit shown in FIG. 14. This is the preferred embodiment for ventilated patients.

(44) The primary difference between the standard anesthetic circle circuit of the prior art (FIG. 20) and the circuits disclosed herein is that with the circuits disclosed herein, both a SGS reservoir (18) and a FGS reservoir (20) are in the rigid box. With the valve configurations disclosed herein, there will be sequential delivery of the FGS, then the SGS, when {dot over (V)}E exceeds the FGSF. This does not occur with the standard anesthetic circle circuit, even if the CO2 absorber is removed from the circuit.

(45) Circuit for Calculation of {dot over (Q)} and Related Physiologic Parameters while Modifying Second Gas Set

(46) FIG. 15 shows the preferred circuit for measuring cardiac output while maintaining the ability to modify the SGS. The circuit consists of the following components:

(47) TABLE-US-00001 200 patient port 201 three-port connector 202 expiratory limb 203 expiratory valve 204 canister on bypass conduit that may be switched to be empty, contain CO.sub.2 absorbing crystals, zeolyte, charcoal or similar substance that filters anesthetic agents, or hopcalite for filtering carbon monoxide 205 bypass conduit. 206 one-way bypass valve with opening pressure slightly greater than that of the inspiratory valve (219) 207 SGS 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 rigid box (216) is continuous with either the ventilator Y piece (211) or the manual ventilation assembly consisting of ventilating bag (212) and APL valve (213) 211 the ventilator Y piece 212 the ventilation bag 213 APL valve 214 ventilation port in rigid box (216) 215 FGS reservoir 216 rigid box 217 port in rigid container for entrance of inspiratory limb of circuit (220) in an air-tight manner 218 FGS inlet port 219 inspiratory valve 220 inspiratory limb 221 bypass limb proximal to canister (204) 400 active FGS Control valve 403 valve control means 407 bypass valve opening sensing means

(48) Function of the Circuit as an Anesthetic Circuit:

(49) For spontaneous ventilation, 3-way valve (210) is open between rigid container (216) and manual ventilation assembly consisting of ventilation bag (212) and APL valve (213). When the patient exhales, 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 (207). FGS enters via port (218) and fills the FGS reservoir (215). During inhalation, inhalation valve (219) opens and FGS from the FGS reservoir (215) and FGS port (218) enter the inspiratory limb (220) and are delivered to patient. If FGSF is less than {dot over (V)}E, the FGS 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 exceeded, it opens and gas from the expiratory gas reservoir (207) passes through the canister (204) into the rebreathing limb (221) and makes up the balance of the breath with SGS. The opening of bypass valve (206) is detected by valve opening sensing means (407) signals are sent to close FGS control valve (400) by activating valve control means (403). When the FGS control valve (400) is closed, any additional FGSF entering the circuit during the balance of inspiration is directed only to the FGS reservoir bag (215) and not to the patient. When valve (400) is closed patient receives only SGS for the balance of inspiration. FGS control valve (400) may be re-opened any time from the beginning of expiration to just before the next inspiration. Phase of ventilation is sensed by sensor (407).

(50) For the purposes of functioning as an anesthetic delivery circuit, part of the FGS entering the circuit would be the anesthetic vapor, for example Desflurane, and the canister (204) would contain CO.sub.2 absorbent material. The SGS passes through the canister (204) but still contains expired O.sub.2 and anesthetic, which can both be safely rebreathed by the patient. In this respect, the circuit in FIG. 15 functions like a circle anesthetic circuit in which the FGSF containing O.sub.2 and anesthetic can be reduced to match the consumption or absorption by the patient. However, by bypassing the canister (204), the circuit can be used for measuring cardiac output.

(51) If the canister (204) is filled with hopcalite it can be used to remove carbon monoxide from the patient, since the SGS still contains expired O.sub.2 and CO.sub.2. If the canister (204) is filled with zeolite it can be used to remove volatile agents such as anesthetics from the patient.

(52) 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 pneumotach (or a spirometer if the patient is breathing spontaneously) can be placed at port (214) and thus remote from the patient. 3) Sasano (Anesth Analg 2001; 93:1188-1191) taught a circuit that can be used to accelerate the elimination of anesthesia. However that circuit 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, Sasano 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 the apparatus and method disclosed herein, there is no requirement for an additional external source of gas or demand regulator; 4) the patient can be ventilated with the ventilation bag (212) already on the circuit or the circuit ventilator, or any ventilator; no other tubing or devices are required. 5) Circle circuits cannot deliver FGS and then SGS sequentially. Such control is required to make physiological measurements such as cardiac output during anesthesia.

(53) With the circuit of FIG. 15, if the canister (204) is bypassed, the circuit becomes the equivalent of the one described in FIG. 9 with the addition of the ventilator apparatus shown in FIG. 7. With the circuit of FIG. 15, box (216) could be opened to atmosphere instead of connected to a ventilator, and the circuit could be used with spontaneously breathing patients for measuring cardiac output while modifying SGS.

(54) It should be recognized to those skilled in the art that various embodiments of the invention disclosed in this patent application are possible without departing from the scope including, but not limited to: a) using multiple inspiratory and expiratory limbs in combination provided that: i) the inspiratory and expiratory limbs are kept separate except at a single point prior to reaching the patient where they are joined ii) each limb has the corresponding valves as in the arrangement above, and iii) the valves have the same relative pressures so as to keep the inspired gas delivery sequential as discussed above. b) using active valves, for example electronic, solenoid, or balloon valves, instead of passive valves, provided said valves are capable of occluding the limbs, and means is provided for triggering and controlling said active valves. The advantage of active valves is more precise control. The disadvantage is that they are more costly. c) replacing reservoir bags with extended tubes or other means for holding gases d) surrounding valves in exhalation limb and/or in the inspiratory limb of circuit with the exhaled gas reservoir causing them to be surrounded by warm exhaled air and prevent freezing and sticking of valves in cold environments. e) Changing the composition of FGS and SGS to change alveolar concentrations of gases other than CO.sub.2, for example O.sub.2. By analogy to CO2, with respect to O.sub.2: alveolar PO.sub.2 is determined by FGS flow and the PO.sub.2 of FGS. When PO.sub.2 of SGS is the same as the PO.sub.2 in the alveoli, inhaling SGS does not change flux of O.sub.2 in the alveoli. Therefore, those skilled in the art can arrange the partial pressure of component gases in FGS and SGS and the flows of FGS such that they can achieve any alveolar concentration of component gases independent of {dot over (V)}E, as long as {dot over (V)}E exceeds sufficiently flow of FGS.

(55) 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.

(56) To clarify the function of the automated cardiac output device, we will contrast it to a standard anaesthetic machine which has the same configureation of listed components. 1) The preferred SGDB circuits we describe differ from any anaesthetic circuit. The SGDB circuit first provides the FGS, then the SGS. This allows the circuit to compensate for changes in CO.sub.2 elimination on any particular breath. For example, during a small breath, the unused FGS remains in the FGS reservoir and is available to provide the exact additional {dot over (V)}A for each gas in the set when a larger breath is taken or frequency of breathing increases subsequently. As a result, changes in {dot over (V)}CO.sub.2 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 anesthesiologist. 3) Anesthetic machines do not calculate {dot over (V)}A and cannot calculate {dot over (V)}CO.sub.2, and {dot over (Q)}. 4) Anesthetic machines cannot generate the data required to make the calculations for {dot over (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.

(57) 9.0 Method of generating data required to make calculations of {dot over (Q)} and related physiologic parameters (see FIG. 19):

(58) Cardiac Output can be measured in several ways according to the methods and apparatus disclosed herein. These include:

(59) 9.1 Set-Up Phase 9.1.1 Set Flow of FGS>{dot over (V)}E 9.1.2 Access default values 9.1.3 Check pressure sensor or PCO.sub.2 sensor during inhalation. If fresh gas reservoir collapsed or CO.sub.2 is detected during inhalation, increase FGS flow until the reservoir until reservoir does not collapse fully and no CO.sub.2 is detected during inhalation 9.1.4 Identify PETCO.sub.2 from the CO.sub.2 gas analyzer

(60) 9.2 Find {dot over (V)}A Via One of Two Methods: 9.2.1 Calculate {dot over (V)}A by inducing two reductions in FGS flow below {dot over (V)}A without first identifying {dot over (V)}A by following the following steps: 9.2.1.1 Calculate a preliminary minimum {dot over (V)}A for the subject based on body weight, temperature, sex and other parameters known to those skilled in the art. 9.2.1.2 Provide luxuriant FGS flow greater than the patient's resting {dot over (V)}E until steady state PETCO.sub.2, is reached 9.2.1.3 Impose a VA by setting FGS Flow below assumed {dot over (V)}A, to {dot over (V)}A.sup.x preferably just below the calculated preliminary {dot over (V)}A, for a time less than or equal to a recirculation time, and measure PETCO.sub.2.sup.x, the end tidal CO.sub.2 concentration during equilibrium if an equilibrium end tidal value is reached within a recirculation time, otherwise it is the equilibrium value of end tidal CO.sub.2 as extrapolated from the exponential rise in end tidal CO.sub.2 values within the recirculation time. 9.2.1.4 Set FGS flow above V.sub.E until steady state PETCO.sub.2 is reached as identified by a less than a threshold change in PETCO.sub.2 over a designated time period. The actual thresholds and time periods are user defined according to the circumstances of the test and can be determined by those skilled in the art. 9.2.1.5 Impose a {dot over (V)}A by setting FGS Flow below assumed {dot over (V)}A, to {dot over (V)}A.sup.y where {dot over (V)}A.sup.y is less than calculated preliminary minimum {dot over (V)}A and not equal to {dot over (V)}A.sup.x, for a time approximately equal to a recirculation time, about 30 s at rest. Measure PETCO.sub.2.sup.x, the end tidal CO.sub.2 concentration during equilibrium if an equilibrium end tidal value is reached within a recirculation time, otherwise it is the equilibrium value of end tidal CO.sub.2 as extrapolated from the exponential rise in end tidal CO.sub.2 values within the recirculation time. 9.2.1.6 On a graph of PETCO.sub.2 vs FGS flow, plot the points (PETCO.sub.2.sup.y, {dot over (V)}A.sup.y) and (PETCO.sub.2.sup.x, {dot over (V)}A.sup.x). Extrapolate the line formed by connecting these two point to intersect a horizontal line at PETCO.sub.2=resting PETCO.sub.2. The FGS flow at the intersection point is determined to be {dot over (V)}A. 9.2.2 Progressive Reduction of FGS flow method of finding {dot over (V)}A: 9.2.2.1 Use FGS that preferably has no CO.sub.2 9.2.2.2 Wait for steady state as indicated by less than a threshold change in PETCO.sub.2 over a designated time period. The actual thresholds and time periods are user defined according to the circumstances of the test and can be determined by those skilled in the art. 9.2.2.3 When in steady state, reduce FGS flow by a small fixed flow, for example 0.1 L/min, preferably at regular intervals of time or after each breath. Alternate flow reduction rates could be used, and the reduction need not be linear in time. 9.2.2.4 When PETCO.sub.2 begins to rise above a threshold value which is approximately the mean steady state PETCO.sub.2, continue the reduction in the FGS flow for a time approximately equal to one recirculation time. 9.2.2.5 After approximately one recirculation time, usually about 30 s, raise FGS flow above resting {dot over (V)}E. A relation of PETCO.sub.2 vs FGS flow is calculated and two lines of best fit are calculated, one for the set of steady state PETCO.sub.2 values, and one for the set of raised PETCO.sub.2 values above the mean of the steady state values. The FGS flow corresponding to the intersection of said lines corresponds to {dot over (V)}A. FIG. 21 illustrates that progressive reduction of SGF (labelled “FGF” in the figure) results in a distinct inflection point when either PETCO.sub.2 or PETO.sub.2 is graphed as a function of SGF. We define the SGF corresponding to this inflection point as equal to {dot over (V)}A. 9.2.2.6 These two methods of finding {dot over (V)}A are physiologically equivalent and one may have some advantages over the other in particular clinical or research circumstances. The Progressive Reduction method should be contrasted with the method for calculating {dot over (V)}A taught by Preiss et al. (Canadian Patent Application 2346517). In that method, while fresh gas flow into a sequential gas delivery circuit was reduced stepwise, after each reduction, the subject was observed for several breaths looking for an exponential rise in PETCO.sub.2. The Preiss method requires continued breathing at each fresh gas flow looking for development of a new steady when fresh gas flow falls below {dot over (V)}A. This process is very time consuming and is unlikely to be tolerated by most patients. If, in the attempt to shorten the time for finding the fresh gas flow below {dot over (V)}A the fresh gas flow reduction are large, resolution of critical fresh gas flow is lost. If the steps are small, when the fresh gas flow is just barely less than {dot over (V)}A, it will be difficult to discern the small rise in PETCO.sub.2 from the normal variation in PETCO.sub.2. The progressive breath-by-breath reduction in FGS flow disclosed herein results in a rapid linear rise in PETCO.sub.2 and fall in PETO.sub.2, both of which can be used to identify the FGS flow corresponding to {dot over (V)}A as illustrated in FIG. 21.

(61) 9.3 Calculations with the Differential Fick Equation

(62) There are two methods of calculating cardiac output with the Differential Fick equation. (It is understood that the general methods are disclosed without the details well known to those skilled in the art of the multiple standard corrections for temperature, moisture, barometric pressure and the like): 9.3.1 Find {dot over (V)}A by the Progressive Reduction of FGS flow method of finding {dot over (V)}A: 9.3.1.1 Find {dot over (V)}A 9.3.1.2 Set FGS Flow={dot over (V)}A and calculate {dot over (V)}CO.sub.2 using the equation {dot over (V)}CO.sub.2={dot over (V)}A×FETCO.sub.2. 9.3.1.3 Impose a transient step change in {dot over (V)}A to {dot over (V)}A′ for a time approximately equal to a recirculation time, about 30 s at rest, by changing FGS flow to a value below {dot over (V)}A. To fully automate the process, select a {dot over (V)}A′ that will be below the {dot over (V)}A. Calculate {dot over (V)}CO.sub.2′={dot over (V)}A′×FETCO.sub.2′. Where FETCO.sub.2′ is the fractional end tidal CO.sub.2 concentration during equilibrium if an equilibrium end tidal value is reached within a recirculation time, otherwise it is the equilibrium value of end tidal CO.sub.2 as extrapolated from the exponential rise in end tidal CO.sub.2 values within the recirculation time. 9.3.1.4 Calculate {dot over (Q)} according to the differential Fick equation using {dot over (V)}CO.sub.2, {dot over (V)}CO.sub.2′, and CCO.sub.2 and CCO.sub.2′ where CCO2 and CCO.sub.2′ are the contents of CO.sub.2 of end capillary blood as calculated from PETCO.sub.2, and PETCO.sub.2′ using known relationships between PETCO.sub.2, and other characteristics related to the blood such as hemoglobin concentration, temperature oxygen partial pressure and other parameters that are accessible or can be used as default values by those skilled in the art. 9.3.1.5 Calculate {dot over (Q)} according to the differential Fick equation using {dot over (V)}CO.sub.2 and PETCO.sub.2 data from steady state phase and step change phase and the PaCO.sub.2 from the Kim Rahn Farhi method. This allows the identification of the PETCO.sub.2—PaCO2 gradient without an arterial blood sample. 9.3.2 Generate required data by inducing two reductions in FGS flow below {dot over (V)}A without first identifying {dot over (V)}A by following the following steps: 9.3.2.1 Calculate a preliminary minimum {dot over (V)}A for the subject based on body weight, temperature, sex and other parameters known to those skilled in the art. 9.3.2.2 Provide luxuriant FGS flow greater than the patient's resting {dot over (V)}E until steady state PETCO.sub.2 is reached 9.3.2.3 Impose a {dot over (V)}A and hence a {dot over (V)}CO.sub.2 by setting FGS Flow below preliminary calculated {dot over (V)}A, to {dot over (V)}A.sup.x preferably just below the preliminarily calculated {dot over (V)}A, for a time less than or equal to a recirculation time, and calculate {dot over (V)}CO.sub.2.sup.x using the equation {dot over (V)}CO.sub.2.sup.x={dot over (V)}A.sup.x×FETCO.sub.2.sup.x where FETCO.sub.2 is the fractional end tidal CO.sub.2 concentration during equilibrium if an equilibrium end tidal value is reached within a recirculation time, otherwise it is the equilibrium value of end tidal CO.sub.2 as extrapolated from the exponential rise in end tidal CO.sub.2 values within the recirculation time. 9.3.2.4 Set FGS flow above V.sub.E until steady state PETCO.sub.2 is reached as identified by a less than a threshold change in PETCO.sub.2 over a designated time period. The actual thresholds and time periods are user defined according to the circumstances of the test and can be determined by those skilled in the art. 9.3.2.5 Impose a transient step change in {dot over (V)}A to {dot over (V)}A.sup.y where {dot over (V)}A.sup.y is less than calculated {dot over (V)}A and not equal to {dot over (V)}A.sup.x, for a time approximately equal to a recirculation time, about 30 s at rest. Calculate {dot over (V)}CO.sub.2.sup.y={dot over (V)}A.sup.y×FETCO.sub.2.sup.y. FETCO.sub.2.sup.y is the end tidal CO.sub.2 concentration during equilibrium if an equilibrium end tidal value is reached within a recirculation time, otherwise it is the equilibrium value of end tidal CO.sub.2 as extrapolated from the exponential rise in end tidal CO.sub.2 values within the recirculation time. 9.3.2.6 Calculate {dot over (Q)} according to the differential Fick equation using {dot over (V)}CO.sub.2.sup.x, {dot over (V)}CO.sub.2.sup.y, and and CCO.sub.2.sup.x and CCO.sub.2.sup.y where CCO.sub.2.sup.c and CCO.sub.2.sup.y are the contents of CO.sub.2 of end capillary blood as calculated from PETCO.sub.2.sup.x, and PETCO.sub.2.sup.y using known relationships between PETCO.sub.2, and other characteristics related to the blood such as hemoglobin concentration, temperature oxygen partial pressure and other parameters that are accessible or can be used as default values by those skilled in the art. 9.3.2.7 Calculate {dot over (Q)} according to the differential Fick equation using {dot over (V)}CO.sub.2 and PETCO.sub.2 data from steady state phase and step change phase and the PaCO.sub.2 from the Kim Rahn Farhi method to identify the PETCO.sub.2—PaCO.sub.2 gradient. This allows the identification of the PETCO.sub.2—PaCO.sub.2 gradient without an arterial blood sample.

(63) Difference between this method and previous methods to perform the differential Fick: (a) With the new method, the decrease in {dot over (V)}CO.sub.2 is performed by reducing the FGF to a SGDB 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 change in {dot over (V)}CO.sub.2 and the calculations via the differential Fick equation are not affected. (b) The {dot over (V)}CO.sub.2 is known using the {dot over (V)}A (identified by one of the new or the previously disclosed method) and the PETCO.sub.2, two robust and highly reliable measures. This is unlike the need for a pneumotachymeter and the error-prone breath-by-breath analysis of {dot over (V)}CO.sub.2 required by previous art. (c) {dot over (V)}A is not identified with the previous differential Fick methods. (d) The PETCO.sub.2 to PaCO.sub.2 gradient is calculated from two independently derived values in the same subject. In the previous art, this gradient is calculated from empirical formulae derived from averaged values and do not necessarily apply to the subject.

(64) Therefore our method provides more accurate values for {dot over (V)}CO.sub.2, {dot over (V)}, CO.sub.2′ and PaCO.sub.2 than the previous art.

(65) 9.4 Kim-Rahn-Farhi 9.4.1 A period of reduced FGS flow simulates complete or partial breath holding. The PETCO.sub.2 of each breath is equivalent to a sequential alveolar sample in the KRF prolonged exhalation method. The substitution of sequential PETCO.sub.2 values for sequential samples from a single exhalation is used to calculate true PvCO.sub.2, PvCO.sub.2-oxy, PaCO.sub.2 and hemoglobin O.sub.2 saturation in mixed venous blood SvO.sub.2 using the Kim Rahn Farhi method. 9.4.2 {dot over (Q)} can be calculated using the Fick approach where the PvCO.sub.2-oxy and PaCO.sub.2 as calculated by the Kim Rahn Farhi method are used to calculate the respective CO.sub.2 contents using methods well known to those skilled in the art, and the {dot over (V)}CO.sub.2 is as calculated from {dot over (V)}A and FETCO.sub.2 as derived in the sequence of steps described above. 9.4.3 Mixed venous O.sub.2 hemoglobin saturation are calculated as follows. {dot over (V)}O.sub.2 is calculated from {dot over (V)}O.sub.2={dot over (V)}A×(FIO.sub.2−FETO.sub.2) where FIO.sub.2 and FETO.sub.2 are the fractional concentration of inspired and end tidal O.sub.2 respectively. Using {dot over (V)}O.sub.2, {dot over (Q)} as calculated by Differential Fick or Kim Rahn Farhi or Fisher Method, end capillary O.sub.2 oxygen content (assuming end capillary blood is fully saturated with oxygen), Mixed venous O.sub.2 saturation can be calculated from the standard Fick equation. 9.4.4 Information regarding the arterial O.sub.2 hemoglobin saturation (SaO.sub.2) (as read from a non-invasive commonly available pulse oximeter that makes the measurement by shining an infrared light through a finger), and the SvO.sub.2 can be used to calculate the fraction of shunted blood ({dot over (Q)}s) (assuming fully oxygenated blood in the end pulmonary capillary) by using the following equation

(66) $\stackrel{.}{Q}s=\frac{\left(\mathrm{SP}{O}_2\right)\stackrel{.}{Q}t-\left(\mathrm{Sa}{O}_2\right)\stackrel{.}{Q}p}{S\stackrel{\_}{v}{O}_2}$

(67) Our method of performing the Kim Rahn Farhi 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 CO.sub.2, is simultaneous to the other calculations. In the previous art, the {dot over (V)}CO.sub.2, calculation cannot be done during a breath hold or simulated breath hold by rebreathing. (c) {dot over (V)}CO.sub.2, measurement does not require a pneumotachymeter which is expensive, cumbersome and error-prone. In the previous art, {dot over (V)}CO.sub.2, required for the calculation of {dot over (Q)} required additional apparatus such as pneumatchymeter or gas collection and volume measuring apparatus.

(68) 9.5 Fisher E-I Test 9.5.1 Calculate {dot over (V)}A from the calibration phase, set FGS flow={dot over (V)}A. 9.5.2 With FGS Flow at {dot over (V)}A, the PCO.sub.2 in the FGS is changed to any value and held at that value for a time approximately equal to a recirculation time, about 30 s at rest. 9.5.3 PvCO.sub.2-oxy is calculated using the PETCO.sub.2−PICO.sub.2 method described by Fisher.

(69) 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 PETCO.sub.2 is minimized by the SGDB circuit such that a larger breath delivers physiologically neutral previously expired gas instead of additional test gas.

(70) 10.0 Method of Finding {dot over (V)}E Using Progressive Reduction of FGS Flow:

(71) 10.1 Use FGS that Preferably has No CO.sub.2

(72) 10.2 Wait for steady state as indicated by less than a threshold change in PETCO.sub.2 over a designated time period. The actual thresholds and time periods are user defined according to the circumstances of the test and can be determined by those skilled in the art.

(73) 10.3 When in steady state, reduce FGS flow by a small fixed flow, for example 0.1 L/min, preferably at regular intervals of time or after each breath. Alternate flow reduction rates could be used, and the reduction need not be linear in time.

(74) 10.4 Using a means for measuring pressure within the FGS reservoir in the breathing circuit, for example a pressure transducer, monitor when the FGS reservoir bag first collapses. {dot over (V)}E is the FGS flow rate when the reservoir bag first collapses.

(75) 11.0 Method for Measuring Anatomical Dead Space

(76) 11.1 Measure {dot over (V)}E and {dot over (V)}A using any of the methods disclosed above

(77) 11.2 Measure the respiratory rate, preferably using the apparatus for cardiac output disclosed herein.

(78) 11.3 Calculate Anatomical Dead Space {dot over (V)}DAN=({dot over (V)}E−{dot over (V)}A)/respiratory rate

(79) 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.

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