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WO2006119546A1 - Methode capnodynamique pulmonaire pour une mesure non invasive continue d'une sortie cardiaque - Google Patents

Methode capnodynamique pulmonaire pour une mesure non invasive continue d'une sortie cardiaque Download PDF

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WO2006119546A1
WO2006119546A1 PCT/AU2006/000593 AU2006000593W WO2006119546A1 WO 2006119546 A1 WO2006119546 A1 WO 2006119546A1 AU 2006000593 W AU2006000593 W AU 2006000593W WO 2006119546 A1 WO2006119546 A1 WO 2006119546A1
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gas
subject
breath
blood flow
alveolar
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Philip John Peyton
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
    • A61B5/0205—Simultaneously evaluating both cardiovascular conditions and different types of body conditions, e.g. heart and respiratory condition
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/02—Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
    • A61B5/026—Measuring blood flow
    • A61B5/029—Measuring blood output from the heart, e.g. minute volume
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/08—Measuring devices for evaluating the respiratory organs
    • A61B5/083—Measuring rate of metabolism by using breath test, e.g. measuring rate of oxygen consumption
    • A61B5/0836—Measuring rate of CO2 production
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/08—Measuring devices for evaluating the respiratory organs
    • A61B5/087—Measuring breath flow

Definitions

  • the present invention relates to the measurement of cardiac output, in particular to a method and system for monitoring cardiac output of a subject, and a method and system for measuring effective pulmonary capillary blood flow (or non-shunt pulmonary blood flow), Qc , and total pulmonary blood flow (or cardiac output), Qt .
  • the invention allows the measurement of these parameters in a non-invasive manner, and to be measured breath by breath in a substantially continuous manner.
  • Cardiac output is the rate at which blood is pumped by the heart to the body. Along with the blood pressure, it fundamentally reflects the degree of cardiovascular stability and the adequacy of perfusion of vital organs. Knowledge of the cardiac output will not itself provide a diagnosis of a patient's condition, but can provide information useful in making a diagnosis. Monitoring cardiac output is most important where cardiovascular instability is threatened, such as during major surgery and in critically ill patients. In these situations "moment to moment" or continuous monitoring is most desirable, since sudden fluctuations and rapid deterioration can occur, for instance, where sudden blood loss complicates an operation.
  • the present invention provides a method for monitoring cardiac output of a subject, the method including: determining an effective pulmonary capillary blood flow of said subject at a first time on the basis of an effective pulmonary capillary blood flow of said patient at an earlier time, pulmonary uptake or elimination of a breathed gas species by said subject at said first time and said earlier time, partial pressures of said gas species in lungs of said subject at said first time and said earlier time, and a solubility of said gas species in blood of said subject.
  • the method includes measuring said net rates of pulmonary uptake or elimination of said gas species G at respective breaths of said subject.
  • the method includes measuring said partial pressures substantially at the end- tidal point of respective breaths of said subject.
  • the method includes performing said step of determining at successive breaths of said subject to provide breath-by-breath monitoring of said effective pulmonary capillary blood flow of said subject.
  • the method includes determining cardiac output of said subject at said first time by adding shunt blood flow of said subject to said effective pulmonary capillary blood flow.
  • the method includes determining said shunt blood flow of said subject.
  • said method includes measuring rates of change of alveolar partial pressures of said gas species, in lungs of said subject at each of said first time and said earlier time.
  • said step of determining includes determining (Qc k ) , the effective pulmonary capillary blood flow for a breath k, according to:
  • F 0 . and F 0 k are the net rates of pulmonary uptake or elimination of said gas species G at breaths i and k, respectively
  • Qc 1 is the effective pulmonary capillary blood flow for an earlier breath /
  • Cv 0 and Cv 0. are the mixed venous gas contents at breaths k and ft '
  • PE' Gk and PE' G are the alveolar (end-tidal) partial pressures of gas species G at breaths k and i
  • PB barometric pressure
  • Veffa is an effective lung volume of gas species G
  • S G is a partition coefficient for said gas species G in blood of said subject
  • dPE'oj/dt and dPEOk/dt are the rates of change of said partial pressures between successive breaths at the times of breaths i and k, respectively.
  • the method includes determining said effective pulmonary capillary blood flow of said patient at said earlier time on the basis of partial pressures of said gas species at respective breaths of said subject, rates of change of said partial pressures at said respective breaths, net uptakes or eliminations of said gas species in lungs of said subject at said respective breaths, a solubility of said gas species in blood of said subject, and an effective lung volume of said patient for said gas species; wherein an alveolar ventilation of said subject at an initial breath of said respective breaths is substantially different from an alveolar ventilation of said subject at a subsequent breath of said respective breaths.
  • alveolar ventilation of said subject is repeatedly alternated between a first level of alveolar ventilation maintained for a plurality of breaths, and a second level of alveolar ventilation maintained for a plurality of breaths.
  • the method includes determining said effective lung volume of said subject for said gas species on the basis of an effective pulmonary capillary blood flow of said patient, a solubility of said gas species in blood of said subject, rates of changes in alveolar partial pressures of said gas species in lungs of said patient at respective times, and net uptakes or eliminations of said gas species in lungs of said subject at respective times.
  • said rates of change and said net uptakes or eliminations are each determined at an initial time and a subsequent time, wherein alveolar ventilation of said subject at said initial time is substantially different from an alveolar ventilation of said subject at said subsequent step.
  • said effective lung volume is determined at one or more first breaths of a plurality of breaths at a changed level of alveolar ventilation.
  • the method includes repeatedly performing said step of determining said effective lung volume at a plurality of breaths of said subject.
  • said first level of alveolar ventilation constitutes a first half-cycle of a cyclic alternation of alveolar ventilation
  • said second level of alveolar ventilation constituting a second half-cycle of said cyclic alternation of alveolar ventilation
  • the method includes repeating steps (i) to (iii) to provide breath-by-breath monitoring of said effective pulmonary capillary blood flow.
  • the method includes determining a cardiac output of said subject on the basis of said effective pulmonary capillary blood flow to provide breath-by-breath monitoring of said cardiac output of said subject.
  • the method may be executed by a computer system having means for receiving gas species and gas flow data representing constituents, pressures and flow rates of gas inhaled and exhaled by said subject at said first time and said earlier time; and means for processing said gas species data to determine said effective pulmonary capillary blood flow of said subject at said first time.
  • the present invention also provides a system for monitoring cardiac output of a subject having components for executing the steps of any one of the above processes.
  • the present invention also provides a computer-readable storage medium having stored thereon program instructions for executing the steps of any one of the above processes.
  • the present invention also provides a system for monitoring cardiac output of a subject, including: means for receiving gas species and flow data representing constituents, pressures and flow rates of gas inhaled and exhaled by said subject at a first time and an earlier time; and means for processing said gas species and flow data and solubility data representing a solubility of said gas species in blood of said subject to determine an effective pulmonary capillary blood flow of said subject at said first time; wherein said effective pulmonary capillary blood flow of said subject at said first time is determined on the basis of an effective pulmonary capillary blood flow of said patient at said earlier time, pulmonary uptake or elimination of said breathed gas species by said subject at said first time and said earlier time, partial pressures of said gas species in lungs of said subject at said first time and said earlier time, and said solubility of said gas species in blood of said subject.
  • the system includes means for cyclically alternating alveolar ventilation of said subject between a first level of alveolar ventilation maintained for a plurality of breaths, and a second level of alveolar ventilation maintained for a plurality of breaths.
  • the system may also include means for operating a valve to selectively introduce a serial deadspace for gas breathed by said subject.
  • the system may further include a gas analyser for analysing gas breathed by said subject; and a gas flow device for determining flow of said gas breathed by said subject.
  • said subject may be a human being.
  • said gas species includes CO 2 .
  • the present invention provides a method for measuring the effective pulmonary capillary blood flow in a subject including:
  • PB barometric pressure
  • Veffo effective lung volume of gas G
  • S G is the solubility of gas G in blood.
  • Qc ,- is determined as follows.
  • the method may include a calibration step, made when the method makes a determination, that the cardiac output and lung gas exchange is sufficiently stable.
  • the calibration step is performed by solving the following "calibration equation" to obtain effective non-shunt pulmonary blood flow (Qc). For any two breaths / and j made at different levels of alveolar ventilation,
  • breaths / and j are sufficiently close in time to one another that CV Q and Qc can be assumed to have not changed substantially.
  • the invention provides a method for measuring the effective pulmonary capillary blood flow in a subject including:
  • PB barometric atmospheric pressure
  • Veffa is the effective lung volume of gas
  • G is the effective lung volume of gas
  • Sg is the solubility coefficient in blood of G
  • the continuity equation can be modified to allow for differences in the mixed venous gas content between breaths / and k.
  • the changes in alveolar ventilation can be introduced at arbitrary or discrete intervals to permit determination of the calibration equation to obtain Qc where cardiac output and lung gas exchange is stable, Preferably these changes are induced in a continuous alternating cyclic manner, so that computation of the calibration equation to obtain Qc can be done at every opportunity where cardiac output and lung gas exchange is stable.
  • a cycle comprises from 6 to 20 breaths of the subject, typically 12 breaths; a half cycle being half of this number of breaths.
  • a cycle comprises from 6 to 20 breaths of the subject, typically 12 breaths; a half cycle being half of this number of breaths.
  • any period of alveolar ventilation at a particular level can be considered to constitute a "half cycle" if it is followed and/or proceeded by a period of alveolar ventilation at a different level.
  • any two adjacent periods of alveolar ventilation at different levels can constitute a full cycle.
  • the method induces alternating cyclic changes in alveolar ventilation by the modulation of an automatic ventilator to alternate tidal volumes, overall rate, the inspiratory to expiratory ratio or the duration of end-expiratory pause, or by alternating the volume of serial deadspace in the breathing system using an automated valve or similar device.
  • breaths / andy occur within a single cycle, with breath i occurring in the first half cycle and breathy occurring in the second half cycle.
  • breaths i andy occur at periods within the half cycle during which washin or washout of G in the lung is minimised, as this minimises error in the determination of Qc due to any inaccuracy in estimation of Veffij. This will not normally occur until at least two or three breaths following a change in alveolar ventilation. The number of breaths required for stabilisation will be greater when there is a larger change in the level of alveolar ventilation or lower cardiac output.
  • the method may also include the step of determining effective lung volume ( Veff G ) with each breath and using the determined value Veff G when solving the calibration equation.
  • Veffg is determined by solving the following equation, hereinafter referred to as the "capacitance equation":
  • Veffg is calculated from the capacitance equation on one or more breaths immediately following the calibration equation, using the same input variables and the value for Qc determined by the calibration equation.
  • the continuity equation is used with each subsequent expired breath k, whenever the calibration equation is not used to determine effective non-shunt pulmonary blood flow (Qc k ) in terms of Qc ,- as described above.
  • Qc effective or "non-shunt" pulmonary capillary blood flow
  • Qs cardiac output
  • the gas species G can be an inert gas species administered to the patient by inhalation or otherwise.
  • the gas species G can be a physiological respired gas species, preferably carbon dioxide (CO 2 ).
  • CO 2 carbon dioxide
  • embodiments of the invention are hereinafter described with reference to the use of CO 2 as the gas G.
  • other physiological gas species can also be used.
  • the value of S in blood for CO 2 ( S QQ ) is determined by differentiating standard equations relating the content of CO 2 in blood to its partial pressure, as described below.
  • the method includes the use of a data averaging or smoothing function to determine the Qc or Qt of the subject.
  • one or more breathing systems for ventilating lungs of the subject ;
  • Ventilation adjustment means for rapidly adjusting alveolar ventilation between two or more levels
  • a rapid gas analyser and gas flow measuring device to allow measurement of alveolar (end- tidal) partial pressure and pulmonary uptake or elimination of a gas species G;
  • a data processor with inputs to receive data from the rapid gas analyser and gas flow measuring device, said processor being configured to determine Qc from gas species data received relating to a breath i taken at alveolar ventilation level / and a breath j taken at alveolar ventilation level/, levels / andy representing ventilation levels before and after an adjustment respectively, the determination being made according to the calibration equation:
  • PB barometric atmospheric pressure
  • Veffo is the effective lung volume of gas
  • G is the effective lung volume of gas
  • S G is a solubility coefficient in blood of G
  • processor is further configured to use the value of Q c determined from the calibration equation (Q c i ) and data received relating to a breath k, to determine the effective pulmonary capillary blood flow for breath k according to the continuity equation:
  • PB barometric pressure
  • Veffo effective lung volume of gas G
  • S G is the solubility of gas G in blood
  • said means may include one or more visual or audio display device(s).
  • the apparatus may have other components and the processor may have other functions to assist in the breath by breath measurement of effective pulmonary capillary blood flow or cardiac output.
  • the processor may also be configured to determine the effective lung volume of gas species G according to the capacitance equation described herein.
  • the apparatus may also have input means for inputting the haemoglobin content of the subject and the processor may also have an input for receiving data from a device for measuring arterial oxygen content, such as a pulse oximeter, and/or for measuring pH and/or arterial CO 2 partial pressure.
  • the apparatus or system preferably automatically displays and records relevant data in real time.
  • Figures 1 to 6 described below show typical measured input and determined output data for a subject where CO 2 is used as measurement gas G to continuously determine cardiac output Qt on a breath-by-breath basis in accordance with a preferred embodiment of the invention.
  • Figure 1 is a graph which depicts the measured expired tidal volume VE (in litres) with each breath of the measurement cycle, in accordance with a preferred embodiment of the invention in which cyclic variation in delivered tidal volume is used to produce cyclic changes in alveolar ventilation of the patient's lungs
  • Figure 2 is a graph which depicts the measured mean rate of elimination of CO 2 with each breath ( VE 00 in litres/min) over the same measurement cycle shown in Figure 1.
  • Figure 3 is a graph which depicts the measured end-expired (end-tidal) partial pressure of CO 2 (PE ( J Q in mmHg). over the same measurement cycle shown in Figure 1.
  • UPEQ 1 0 Figure 4 is a graph which depicts the determined rate of change of PE C ' O ( ), over
  • Figure 5 is a graph which depicts the determined cardiac output Qt (in litres/min) over the same measurement cycle shown in Figure 1, following adjustment of Qc for pulmonary shunt. The points at which the calibration and continuity equations are used are indicated.
  • Figure 6 depicts a capnography tracing (the expirogram for CO 2 ) over the same measurement cycle shown in Figure 1.
  • Figure 7 depicts a simulated measurement of cardiac output Qt over a 10 minute period in which a sudden drop in actual ("target") Qt takes place.
  • the graph shows that the continuity equation closely follows the target Qt .
  • the calibration equation does not accurately compute the cardiac output for the first 2 minutes following the change in Qt . This because the assumptions inherent in application of the calibration equation, that cardiac output is stable within a measurement cycle, do not hold true during the acute change in Qt .
  • Figure 8 is a schematic diagram of a system for monitoring cardiac output in accordance with one preferred embodiment of the present invention, wherein the system controls a ventilator to produce changes in alveolar ventilation.
  • Figure 9 is a graph of cardiac output data generated by the system, representing the cardiac output of an anaesthetised and ventilated sheep, together with simultaneous measurements made with an ultrasonic aortic or pulmonary artery flow probe in the sheep.
  • Figure 10 is a block diagram of a cardiac output monitor of the system.
  • Figure 11 is a flow diagram of a preferred embodiment of a method for monitoring cardiac output executed by the system.
  • Figure 12 is a schematic diagram of an alternative preferred embodiment of a system for monitoring cardiac output, in which the system controls the operation of a partial rebreathing valve and rebreathing loop to produce changes in alveolar ventilation by altering the volume of serial deadspace in the breathing circuit.
  • the capnodynamic method is the name that has been given to a new technique for automated and continuous determination of cardiac output (total pulmonary blood flow) on a breath-by-breath basis. It is non-invasive and is suitable for use in patients during anaesthesia or in critical care, who are intubated with either an endotracheal tube, endobronchial tube, or laryngeal mask airway or similar airway management device.
  • the method is based on the uptake or elimination of carbon dioxide (CO 2 ) and/or other gases by the lungs.
  • CO 2 carbon dioxide
  • the prefix capno used in this specification refers to use of measurement of CO 2 to determine cardiac output.
  • CO 2 is the preferred gas to measure since it is present under all physiological conditions.
  • other expired gases such as anaesthetic gases being administered to the patient, can be used instead, or at the same time. Consequently, the use of the prefix capno should not be understood as limiting the invention to the use of CO 2 .
  • the method is referred to as a method for monitoring cardiac output.
  • end-tidal partial pressure With every breath, the rate of elimination of CO 2 by the lungs, and consequently the partial pressure of CO 2 in gas expired from the lungs at the end of a breath, the end-expired partial pressure (referred to as end-tidal partial pressure), is measured in real time. These are the measured inputs used by the capnodynamic method.
  • the method can achieve quasi- continuous measurement of cardiac output by application, with each of a plurality of successive breaths, of the "continuity equation" described below. This measures change in cardiac output relative to a baseline measurement of cardiac output with its accompanying inputs.
  • the baseline cardiac output measurement may be obtained by a number of methods, but the preferred means is by application of the "calibration equation". This uses the same inputs as the continuity equation, but these are measured while the level of alveolar ventilation of the lungs is changed. This can be done one or more times, or continuously, repeatedly alternating between higher and lower levels of alveolar ventilation in a cyclic manner. Making a sudden change in alveolar ventilation also allows lung volume to be determined from the same measured inputs, using the "capacitance equation" described below.
  • capnodynamic method The underlying theory of the capnodynamic method is outlined below. The method has been developed with the assistance of theoretical computer modelling of lung gas exchange. An automated measurement system, which is suitable for use in patients, is also described below, together with the results of bench tests.
  • pulmonary capillary blood flow Qc is that part of the total pulmonary blood flow (cardiac output, Qt ) which engages in gas exchange with an inspired gas mixture in the lung.
  • Qc can be related to measured CO 2 elimination by the lungs V 00 by a variation of the Fick equation:
  • CC' CQ2 and Cv C o 2 are the fractional contents of CO 2 in pulmonary end-capillary and mixed venous blood, respectively. Since the pulmonary end-capillary blood and alveolar gas can be considered to be in equilibrium with one another, Cc 1 Co 2 can ⁇ e related to the content of CO 2 in the alveolar gas mixture if the solubility of CO 2 in blood is known, so that
  • PA COI is the alveolar partial pressure of CO 2 and PB is the atmospheric pressure corrected for the presence of water vapour at body temperature (47mmHg at 37 0 C).
  • S co is the blood-gas partition coefficient of CO 2 , a constant representing the solubility of CO 2 in blood under the conditions present in the patient at that time.
  • PE C ' O measured partial pressure of CO 2 in end-tidal gas
  • Equation (3) is not directly solvable, because CV QQ is a second unknown term.
  • CVQQ can only be directly measured by invasive mixed venous blood sampling via a pulmonary artery catheter. However, it can be estimated from changes in expired alveolar gas induced by certain unusual respiratory manoeuvres such as breath holding or rebreathing of expired gas (Defares 1958; Kim, Rahn and Farhi 1966; Russell et al 1990). Moreover, CV QQ can be eliminated from consideration under such conditions if two simultaneous equations of the form of (3) are generated, during which both Cv QQ and Qc are assumed to remain unchanged. This is known as the differential Fick approach (Capek and Roy 1988). If separate sets of measurements are made at times ti and t ⁇ under conditions that provide substantial changes in lung CO 2 elimination at these times, then it can be shown that
  • this equation allows Qc to be determined by changing the alveolar minute ventilation, which alters both V co and PE' QQ acutely.
  • This can be achieved a number of means.
  • the first method used in the past was to make a stepwise change in the respiratory rate (Gedeon et al 1980).
  • An alternative method, referred to as partial CO 2 rebreathing, is to introduce a change in the serial deadspace, while holding tidal volume constant, thereby effectively reducing the alveolar ventilation (Capek and Roy, 1988). This is the technique used by the NICO device (Novametrix, USA).
  • Tidal volume This volume of breath first passes through the length of the larger conducting airways of the lung, which do not contribute to gas exchange with the blood, and are collectively referred to as the “serial deadspace", with total volume VD.
  • a proportion of the inspired gas mixture is distributed to, and expired from, a separate alveolar gas compartment which is not in contact with the pulmonary blood, known as
  • V Q the volume of the gas G present in the lung
  • Veff G is the effective lung volume
  • PA G is the alveolar partial pressure of G.
  • Veff G is determined by the alveolar gas volume (VA) along with the volume of lung tissue (VL) and the solubility of the gas in lung tissue (SL 0 ), and therefore is different for gases of different solubilities.
  • a method for estimating Veff G is described below, or it can be determined from the capacitance equation (14) below.
  • V G Changes in V G can only occur due to changes in the rate of arrival of the gas G at the alveolar compartment in inspired gas and mixed venous blood and/or its removal in pulmonary end-capillary blood or expired alveolar gas.
  • rate of change of the dV G volume of G in the lung ( '-) is given by at
  • V G is the net rate by the patient of uptake of G from, or elimination of G to, an external breathing system ("gas exchange"), with each paired inspiration and expiration ("breath”).
  • a positive value for V G represents net uptake of G by the lung from the breathing system, and a negative value represents net elimination of G to the breathing system, with any given breath at time t.
  • Cv G is the fractional content of G in mixed venous blood.
  • S G is the blood gas partition coefficient of G (Ostwald coefficient, frequently designated by the symbol ⁇ ) which reflects the solubility of G in blood, and is known for most inert gases that can be administered to patients, including anaesthetic gases.
  • equation (8) the terms on the left hand side of equation (8) equal the mass balance of the gas G (net uptake or elimination) at the mouth, and represent uptake or elimination by the body of the gas G.
  • this the metabolic production rate of carbon dioxide by the body (V co t ody )-
  • Equation (8) contains three unknowns, Veff G Cv G and Qc .
  • the left hand terms are measurable non-invasively if, as stated above (in relation to CO 2 ), the end-tidal partial pressure ( PE 0 ) is used as a non-invasive approximation for PA 0 .
  • Veff G includes alveolar deadspace in the lung.
  • Equation (10) allows Qc to be determined as follows.
  • Successive measurements are taken of the relevant variables at two points in time, for example two separate breaths, before and after producing an acute change in V 0 and PE G ' .
  • Equation (12) is referred to herein as the calibration equation.
  • Veff G can be determined, if Qc is known, by transposing Equation (11) to solve for Veff G :
  • Equation (13) is referred to herein as the capacitance equation.
  • Veffa is best determined using measured data from the first breath of each half cycle immediately after determining Qc from Equation (12) (i.e., on breaths i+1 an ⁇ j+1), at which point dPE G /dt is greatest.
  • VeJf 0 is largely independent of Qc when applied at the appropriate time, for the reasons described below, so that the dominant term in the numerator of equation (13) is the first term, representing the measured gas exchange.
  • a mutual solution to equations (12) and (13) is obtained from an iterative method.
  • Qc at breath / ( Qc 1 ) can be determined as follows.
  • Equation (17) is referred to herein as the continuity equation.
  • Cv G can be estimated from equations (9) and (10) as:
  • Equations (17) and (18) are interdependent functions of each other, and can be solved iteratively.
  • the solution gives values for Qc k and Cv G , which represent the point of balance in the interdependent relationship between pulmonary blood flow and mixed venous gas content.
  • VeJf 0 can initially be estimated using one of the alternatives described below. This allows estimation of Qc using the calibration equation (12). VeJf 0 can subsequently be determined using the capacitance equation.
  • equations (11) to (18) ignore the presence of a difference between PA 0 and PE 0 , which arises from the presence of alveolar deadspace.
  • equation (4) and previously described differential Fick methods (Gedeon et al 1980, Capek and Roy, 1988), the capnodynamic method described herein shares the advantage that this difference largely cancels out in the denominator, since
  • V 0 is the difference in the volume of G inspired ( Vi 0 ) and that expired ( VE 0 ) with each breath, so that
  • V 0 VI 0 - VE 0 (19)
  • Vi 0 and VE 0 can be measured in a number of ways.
  • the ideal approach allows immediate measurement with each breath.
  • Total gas flow rate is measured using a pneumotachograph, or other device for the measurement of gas flow within a hollow tube (such as a differential pressure transducer, hot wire anemometer, turbine anemometer or other device).
  • Gas concentration is measured by sidestream sampling or inline measurement by a rapid gas analyser.
  • Suitable gas analysers include infrared absorption devices, photoacoustic devices, mass spectrometers, paramagnetic devices, Raman scatter analysers or other devices.
  • the volume of the gas G inspired and expired with each breath is obtained by multiplying flow by concentration point by point in time, and integrating the resultant waveform with respect to time. Accuracy is improved by compensating for transport delay (with sidestream sampling) and response time of the gas analyser. For example, if inspiration takes place between times tj and t 2 , and expiration between t ⁇ and t 3
  • Vl 1 and V ⁇ t are the measured total gas flow rates at time t during inspiration and expiration respectively.
  • P Q is the measured partial pressure of G at the point of gas sampling at time t.
  • Total gas flow measurement can be determined by measuring the concentration of a marker gas M fed into the gas stream at a known flow rate. This is usually an insoluble gas such as nitrogen, argon or sulphur hexafluoride, which is not taken up by the lungs. For example, the expiratory total gas flow rate at time t can be measured from
  • VE ⁇ is the known flow rate of the marker gas M
  • PEM t its measured partial pressure at time t.
  • the inspiratory total gas flow rate can be determined from a similar equation.
  • VE 1 can be determined by:
  • PEM 1 is the mean partial pressure of M in mixed expired gas.
  • This provides a mean expired flow measurement which may be more stable and accurate than the dynamic tidal flows determined by equations of the form of equation (20) to (22), because rapid signal sampling and more complex data processing can be dispensed with. However this can be expected to dampen the response of the gas exchange measurement to the breath by breath changes in gas exchange preferred for the capnodynamic method.
  • a potentially useful approximation for the volume of expired CO 2 with each breath can be obtained from the delivered tidal volume, adjusted for deadspace, and multiplied by the measured fractional concentration of alveolar CO 2 .
  • S G is known for most inert gases that can be administered to patients, including anaesthetic gases.
  • S 0 is a constant but may be modified by patient temperature; however S 0 can be adjusted for this. Values for S 0 for commonly available inert gases suitable for use in patients are set out in Tables 1 and 2 below.
  • PE Q ' can be measured at the end of each expired breath from a standard expirograph tracing for G.
  • a typical expirograph for CO 2 is shown in Figure 6.
  • the value of PE 0 is taken from a defined point on the plateau of the expirograph waveform, reflecting the end- expired (end-tidal) partial pressure of G. For CO 2 , this lies at or near the top of the curve for each breath.
  • Veff G is determined by the alveolar gas volume (VA) along with the volume of lung tissue ( VL ) and the solubility of the gas in lung tissue ( SL 0 ). It will therefore be different for gases of different solubilities. Determination of Veffa by the capacitance equation has been described above.
  • VT tidal volume
  • This flow of blood which engages in gas exchange with the inspired alveolar gas, is the "non-shunt” or "effective pulmonary capillary blood flow” Qc .
  • mixed venous blood that bypasses the alveolar gas compartment (“shunt” Qs ) will mix with this pulmonary end-capillary blood to form arterial blood, which travels to the body tissues as the cardiac output (Qt).
  • a gas species G enters the compartment in inspired gas and mixed venous blood and is removed from it in pulmonary end-capillary blood or expired alveolar gas.
  • VeJf 0 the effective volume of distribution of a gas in the lung, is determined by VA , VL and the solubility of the gas in lung tissue ( SL 0 ). These parameters can be estimated from body height, weight, sex and other patient demographic data and the known solubility of the gas in lung tissue.
  • the solubility coefficient of CO 2 in lung tissue has been measured to be approximately 2.7 (Sackner, Khalil and DuBois 1964).
  • the solubility coefficients of various other gases in lung tissue are listed in Tables 1 and 2 below. Where not specifically available, the blood/gas partition coefficient for the gas (S 0 ) provides a useful approximation of its lung tissue partition coefficient ( SL G ).
  • Veff G is modified by the presence of shunt, which can be significant in anaesthetised or critically ill patients.
  • Those areas of lung that contain shunted blood do not contribute to gas exchange, and therefore do not contribute to the effective volume of distribution of gas, such as CO 2 , which diffuses from blood into the alveolar gas compartment.
  • VL the volume of lung tissue
  • BSA body surface area
  • VA 0.825 5.18- /ft+ 0.11- - ⁇ r -23 -6.24 (A3) 3.34 ⁇ Ht
  • M is a modifier for the patient's sex: M is 3.34 for males and 2.86 for females.
  • the scaling factor 0.825 represents the decrease in lung volume that occurs in all patients when anaesthetised (Nunn 1993).
  • Equation (A3) provides a value for the patient's resting lung volume, but can be augmented further by an adjustment for the tidal volume (Vf).
  • VA is the time weighted mean of the value obtained from equation (A3) and that value can be augmented by VT, as follows:
  • VA VA + VT - (I- ⁇ ) (A4)
  • VA is the inspiratory to expiratory ratio of each breath, typically 1 :2 or 0.33.
  • VA is further modified by an adjustment (AVA) representing the proportion of alveolar gas volume contained in shunting areas of the lung.
  • AVA adjustment
  • the distribution of VL is assumed to parallel that of blood volume. Overall VL is roughly 5/6 of the blood volume, so that from Brudin:
  • Veff G VA - AVA + VL ⁇ SL 0 (A6)
  • Veffco 2 VA - A VA + VL .
  • the concentration of gas in the alveolar deadspace is always the same as in the inspired gas mixture, and does not alter in response the changes in alveolar ventilation or gas exchange.
  • PE G already reflects the volume weighted partial pressures of G from both alveolar and alveolar deadspace compartments, Veff G is not further reduced in proportion to the alveolar deadspace volume.
  • a standard method of measurement of Veff G is by insoluble inert gas dilution ("washin"). This is used in established methods for measurement of Qc by inert soluble gas uptake, such as acetylene or nitrous oxide rebreathing techniques (Cander and Forster 1959, Petrini et al 1978, Hook et al 1982, Gabrielsen et al 2002).
  • An insoluble gas which is not absorbed significantly by the blood, is administered simultaneously with the soluble gas.
  • the measured change in concentration of the insoluble gas reflects the dilution of the inspired gas mixture throughout the effective lung volume, enabling the determination of VA.
  • Estimation of VL is also required and this is done by other methods, such as extrapolation of soluble gas concentration change to time zero for the manoeuvre, to indicate uptake by lung tissues, which is assumed to be rapid compared with uptake by the blood.
  • Such techniques can be applied to estimation of Veff G , either as an initial "once off or as an intermittent manoeuvre, as part of a continuous cardiac output measurement system, such as the system described herein.
  • Pulmonary shunt (Qs I Qt) can be determined according to the traditional shunt equation. This determines Qs as a proportion of total pulmonary blood flow Qt , i.e., the shunt
  • Cc 1 ⁇ 2 , Ca Q2 and Cv 02 are O 2 fractional contents in "ideal" pulmonary end capillary blood, systemic arterial blood and mixed venous blood, respectively.
  • Cv 0 can be measured invasively from mixed venous blood sampling from a pulmonary artery catheter, which may be equipped with a photometric probe to measure mixed venous O 2 saturation Sv 0 .
  • Sv 0 or Cv 0 can be simply assumed or estimated.
  • the shunt fraction can be determined as follows (Peyton et al 2004):
  • V 0 ⁇ is the measured O 2 uptake by the lungs.
  • Cc'o and CQ Q can be determined or measured using minimally invasive methods.
  • Cd ' Q can be determined from "ideal" alveolar O 2 partial pressure ( PA Q2 ), obtained from the alveolar air equation:
  • PA ⁇ 2 Pl o 2 - ⁇ j ⁇ (AlO)
  • P ⁇ 02 can also be obtained from other equations, such as the modification of the alveolar air equation of Filley, Macintosh and Wright (Nunn 1993) which allows for the volume effects of uptake of other gases (such as nitrous oxide) during anaesthesia.
  • Cc 1 Q 2 is determined from P ⁇ 02 using one of a number of methods, such as that of Kelman
  • Ca Q can be estimated continuously and non-invasively from Sp 0 obtained from pulse oximetry, using the same equation:
  • a system for determining cardiac output as described herein can advantageously incorporate a pulse oximeter, with oximetry probe attached to the patient, and/or indwelling arterial oximetry or blood gas probe and processor, alongside a gas analyser, allowing continuous estimation of shunt fraction as described above. Greater accuracy may be obtained from arterial blood gas sampling to directly measure Cag 2 and/or Pa 02 .
  • V 0 can be measured directly by a similar method to that described above for V G using equations (19) to (23), but is most simply approximated from the measured mean VE 00 divided by an assumed value for the respiratory quotient (typically 0.8).
  • Total pulmonary blood flow Qt (cardiac output) is the sum of Qc and Qs .
  • Continuous measurement of Qt as described above allows continuous estimation of mixed venous O 2 saturation Sv 0 , a useful marker of tissue perfusion and the adequacy of O 2 delivery to the tissues. This is done by transposing the Fick equation for O 2 :
  • Sp 0 J 2 obtained from pulse oximetry, allows Sa 0 to be non-invasively measured for this purpose.
  • CO 2 is the preferred gas to measure, since it is present under all physiological conditions, and administration of the gas to the patient is not required. For this reason, the method is referred to as the "capnodynamic" method (the prefix capno refers to CO 2 ) in the described embodiment, although other expired gases can be used instead, or as well.
  • Inert gases have the advantage that they obey Henry's law i.e., that the relationship of partial pressure to content in solution in the blood is linear: that is, they have a linear dissociation curve, and the partition coefficient S for these gases is constant.
  • This is not the case for CO 2 which has an alinear dissociation curve in blood which is influenced by a number of physiological factors, including the patient's haemoglobin, temperature, oxygenation and acid-base status.
  • S co is in fact the slope of the tangent to the solubility curve for CO 2 at the operative point, and obtainable by a number of different methods. The preferred method is described below.
  • S COl quantitates the relationship between partial pressure of CO 2 in alveolar gas and the content of CO 2 in end-capillary blood. This relationship is the dissociation curve of CO 2 , and is affected by a number of physiological variables. These include the acid base status of the blood, reflected by the pH, Base excess and the plasma bicarbonate concentration (HCO 3 " ), as well as the blood temperature (T), haemoglobin (Hb) concentration. In addition, the carriage of CO 2 on haemoglobin has an interdependent relationship to the degree of oxygenation of the haemoglobin as measured by the arterial haemoglobin O 2 saturation (SpO 2 ).
  • the independent input variables are as follows:
  • PA QQ2 PA QQ2 partial pressure
  • Pdco 2 can be measured by arterial blood gas sampling, and this can be performed as an initial "once off measurement (since the degree of alveolar deadspace tends to remain fairly constant in an anaesthetised patient), which effectively "calibrates" the method for that patient.
  • This can be repeated intermittently with further sampling, or performed on a continuous basis using continuous arterial blood gas analysis via an indwelling arterial probe specifically designed for the purpose.
  • Such devices and probes for continuous arterial blood gas analysis are currently available and can be integrated into a cardiac output measurement system based on the capnodynamic method described herein.
  • Qc can be determined from uptake of one or more inert anaesthetic gases G and simultaneously determined from the elimination of CO 2 . It is also possible to use oxygen (O 2 ) as the measurement gas G because O 2 uptake (V 0 ) can be measured as described above in a similar manner to any other inspired gas.
  • O 2 oxygen
  • V 0 O 2 uptake
  • the use of O 2 presents greater difficulties for the determination of Qc by these equations due to the possibility of significant variations in the value of S for O 2 under different physiological conditions. This arises from the fact that O 2 carriage in the blood is almost entirely via its attachment to haemoglobin, and also from the highly alinear shape of the O 2 -haemoglobin dissociation curve.
  • a system for monitoring cardiac output includes a rapid gas analyser 804 (Datex Capnomac Ultima, Datex-Ohmeda, Finland), a gas flow transducer 806 (Validyne Corp, USA), a Fleisch pneumotachograph 808 (Hans Rudolf Corp, USA) (or other gas flow measurement device), including side stream gas concentration sampling port for the gas analyser 804, and a cardiac output monitor 810.
  • the system is also interconnected with a typical anaesthesia delivery system, including an anaesthesia machine 812, a ventilator 802 (Bear AV, 500, USA), and breathing circuit 813, connected to a common mouthpiece or other gas pathway of the breathing circuit, which is attached to a patient in order to provide gas to lungs 814 of the patient, and to receive exhaled gas from those lungs 814.
  • a typical anaesthesia delivery system including an anaesthesia machine 812, a ventilator 802 (Bear AV, 500, USA), and breathing circuit 813, connected to a common mouthpiece or other gas pathway of the breathing circuit, which is attached to a patient in order to provide gas to lungs 814 of the patient, and to receive exhaled gas from those lungs 814.
  • the cardiac output monitor 810 executes a method for monitoring cardiac output that determines at least Qc ; the effective pulmonary capillary blood flow of the patient, and preferably also the total cardiac output of the patient, on a quasi-continuous, breath-by- breath basis.
  • the cardiac output monitor 810 is a standard computer system such as an Apple 7200 personal computer manufactured by Apple Corporation, and the cardiac output monitoring method is implemented in software.
  • the computer 810 includes at least one processor 1002, random access memory 1004, at least one input/output interface 1006 for interfacing with the ventilator 802, the gas analyser 804, and the flow transducer 806, a keyboard 1008, a pointing device such as a mouse 1010, and a display 1011.
  • the cardiac output monitor 810 also includes the Labview 4.01 software development application 1012, available from National Instruments, USA, and the cardiac output monitoring method is implemented as one or more software modules developed using the Labview software application 1012, being the cardiac output modules 1014 stored on non-volatile (e.g., hard disk) storage 1016 associated with the computer system 810.
  • the various components of the cardiac output monitoring system can be distributed over a variety of locations and in various combinations, and that at least part of the cardiac output monitoring method could alternatively be implemented by one or more dedicated hardware components such as application-specific integrated circuits (ASICs).
  • ASICs application-specific integrated circuits
  • a system for monitoring cardiac output includes a length or loop of deadspace tubing opened to or closed from the breathing circuit by a partial rebreathing valve 1202 whose operation is controlled by the cardiac output monitor 810, via a valve controller 1204. Additionally, the gas analyser 804, gas flow transducer 806, and cardiac output monitor 810 are provided in a single housing or chassis 1206 to provide an integral, stand-alone cardiac output monitoring system that can be attached to any standard anaesthesia delivery system.
  • components 804, 806, and 810 are notionally the same as those in the previous embodiment shown in Figure 8, it will be apparent that when those components are combined within a single chassis 1208, it may alternatively be preferable to select alternative versions of these components to make the integrated stand-alone system more compact and to improve its ergonomics.
  • the pneumotachograph/gas sampling line 808 is positioned between the patient's lungs 814 and the partial rebreathing valve 1202, and consequently Equation (19) should be used to determine the uptake or elimination of CO 2 because the patient will rebreath a substantial amount of exhaled CO 2 with each inspired breath.
  • Equation (19) should be used to determine the uptake or elimination of CO 2 because the patient will rebreath a substantial amount of exhaled CO 2 with each inspired breath.
  • the partial rebreathing valve 1202 is alternatively located between the patient's lungs 814 and the pneumotachograph/gas sampling line 808, the simpler Equation (24) can be used because the amount of rebreathed CO 2 will be substantially reduced in this arrangement.
  • the cardiac monitor 810 receives gas analysis data from the rapid gas analyser 804, and gas flow data from the flow transducer 806.
  • the cardiac monitor 810 also generates and outputs ventilator control data to control the ventilator 802 and thereby the alveolar ventilation of the patient's lungs 814.
  • the ventilator could be independently configured to adjust the alveolar ventilation in a predetermined manner, and to provide an output signal to the cardiac monitor 810 to indicate these changes.
  • the cardiac output monitoring method begins at step 1102 by beginning the cyclic alternation of alveolar ventilation, and the periodic measurement of the partial pressure and volume of the gas species G of interest.
  • Total flow rates are measured by the flow transducer 806, which generates gas flow data and sends that data to the cardiac monitor 810.
  • the gas breathed by the patient is analysed by the rapid gas analyser 804, which generates gas analysis data, and sends that data to the cardiac monitor 810 for processing.
  • the gas flow data and the gas analysis data are generated and sent to the cardiac monitor 810 in real-time on a breath by breath basis.
  • the cardiac output monitor processes the gas analysis data to determine the partial pressure of the gas species G of interest (typically CO 2 ), and compares the partial pressure data for the current half cycle of ventilation with the previous half cycle.
  • a test is performed to determine whether the pattern of cyclic change in partial pressure appears to be stable, which would indicate that the effective pulmonary capillary blood flow is also stable. If this is the case, then at the last breath of the current half-cycle, Qc is determined using the calibration equation at step 1108. Since the current half-cycle is now complete, at step 1110, the next half-cycle is commenced by changing the level of alveolar ventilation. At the first breath of the new half-cycle, the effective lung volume of gas species G is determined using the capacitance equation at step 1112. As described above, the determination of Veffn ⁇ s performed at this point to produce the most accurate value.
  • the system determines the effective pulmonary capillary blood flow of the patient on a quasi-continuous, breath-by-breath basis.
  • the system also determines the shunt blood flow as described above, and adds the two values together to obtain updated values for the total cardiac output of the patient. These values are continually updated and displayed on the system monitor 1011 to allow medical or nursing staff to non-invasively monitor the patient's cardiac output during surgery, critical care, and other related procedures.
  • V G and PE 0 are produced by inducing sudden changes in the level of alveolar ventilation of the lungs on a continuous basis. This can be achieved in a number of ways. In patients who are undergoing controlled ventilation by an automated ventilator, such as patients under anaesthesia or in intensive care, a stepwise change can be made in the tidal volume, as shown in Figure 1. Alternative approaches are to alternate respiratory rate (either by alternating overall rate, I:E (inspiratory to expiratory) ratio or the duration of end-expiratory pause, or similar mechanism). These methods will generally require automated control of an electronic ventilator, as shown in the embodiment of Figure 8.
  • the alternative embodiment of the cardiac output monitoring system shown in Figure 12 produces changes in the level of the alveolar ventilation by intermittently introducing a volume of serial deadspace into the breathing system, by opening and closing a partial rebreathing valve 1202 attached to a length or loop of deadspace tubing. By altering VD, the level of alveolar ventilation is altered in the opposite direction. This method can be used in patients who are not undergoing controlled ventilation, but are breathing spontaneously.
  • V 0 and PE 0 by means other than altering alveolar ventilation, e.g., by intermittently adding a gas species G (CO 2 or other gas) to the inspired gas mixture to alter its inspired concentration, in which case equations of the form of (11) to (18) will apply instead.
  • G gas species
  • the cyclic alternation of alveolar minute ventilation between higher and lower levels is repeated on an ongoing basis for as long as cardiac output monitoring is required. This permits ongoing recalibration using the calibration equation as frequently as possible, provided that cardiac output and lung gas exchange are sufficiently stable (see timing considerations, below).
  • the higher and lower levels of alveolar ventilation are each considered to constitute a half cycle of the cyclic ventilation.
  • a stepwise change can be made in the alveolar ventilation level and maintained at that level for 6 breaths (half cycle), and then return to the previous level and maintained at that level for a further 6 breaths.
  • the total cycle length is therefore 12 breaths, but this can be varied to more or less.
  • each half cycle is limited by the magnitude of the change in CV Q induced by each change.
  • a persistent change in CV Q will produce progressively increasing errors in the values determined by both the calibration and continuity equations.
  • brief changes are expected to cause smaller fluctuations in Cv Q , but if too brief (fewer than 3 breaths or so), are likely to degrade the accuracy of the calibration equation.
  • the change in the alveolar ventilation is typically of the order of 50% or so (e.g., cyclic changes in tidal volume, or in the volume of serial deadspace in the breathing system, of 20OmL or so, or changes in respiratory rate of 5 breaths/min) although smaller or larger relative changes can be used.
  • the larger the change the greater the acute change in the variables measured to determine cardiac output ( V G and PE G ).
  • Improved accuracy and precision of the determined cardiac output are expected from this, although practical limitations apply to the size of the tidal volumes or breath to breath intervals that can be used safely in a patient.
  • the mean value of alveolar ventilation (midway between high and low levels) is preferably such that the overall minute ventilation remains at the desired level for the patient.
  • the rate of change of P Ej 3 can be estimated from the measured change of PE G ' over a series of 3 breaths whose duration is measured by a timer.
  • the pattern of change over the 3 breaths can be analysed using an appropriate least squares analysis technique, and assuming that the change follows an exponential washin/washout pattern, to obtain the
  • Figures 1 to 5 show typical data for the time course of changes in CO 2 elimination by the lungs for one measurement cycle.
  • the data was generated from a computer model of tidal gas exchange which incorporates realistic physiological distributions of ventilation and blood flow in the lung, giving typical values for pulmonary shunt and deadspace. Values for independent input variables were nominated which were typical for a ventilated patient.
  • the resting alveolar lung volume VA was 2.0 L
  • lung tissue volume VL was 0.6 L.
  • Sackner Sackner et al, 1964
  • the solubility coefficient of CO 2 in lung tissue ( SL CQ2 ) was taken to be 2.7. Tidal volume alternated between 400 and 600 mL/min at a rate of 10 breaths/min.
  • Cardiac output was 5.0 L/min.
  • Mean CO 2 production by the body was approximately 140 mL/min.
  • Shunt Qs was approximately 10% of the cardiac output. To represent realistic levels of measurement imprecision for measured parameters, a random noise function with specified standard deviation was superimposed on the output data.
  • Figure 1 shows the measured expired tidal volume VE with each breath.
  • the first 6 breaths of the half cycle (numbered 1 to 6) are at 400 mL tidal volume.
  • the next 6 breaths are at 600 mL, completing one measurement cycle.
  • Figure 2 shows the corresponding VE 00 values
  • Figure 3 the corresponding PE C ' O values
  • dPE C ' 0 the corresponding values.
  • dt the corresponding values
  • a first condition is that PE 0 for each breath remains stable within set limits (typically 0.5 mmHg for CO 2 ) for a given number of breaths or duration of time (typically over 10-12 breaths or approximately 1 minute).
  • the second condition is that, where cyclic alteration in alveolar ventilation is carried out in a continuing fashion, which will produce cyclic fluctuations in PE 0 , as illustrated in Figure 3, the pattern of change in measured PE Q ' within each half cycle is similar to that of the preceding half cycle. This is determined by comparing the shape of the curve PE 0 versus breath (see Figure 3) for each half cycle.
  • the curve for the current half cycle can be inverted and normalised at its first breath to match that from the preceding half cycle.
  • the curve for the current half cycle can be compared to the corresponding half cycle of the previous cycle. Stability in other indirect indicators of in cardiac output, such as blood pressure and V 0 measurement, can also be evaluated as well.
  • the calibration equation is used, to determine Qc . Where cyclic alteration in alveolar ventilation is carried out in a continuing fashion, this is done at the end of the current half cycle. Where ventilation has been stable, a cycle of alteration in alveolar ventilation is initiated first. For the calibration equation, breath i is at the end of the previous half cycle, and breath j at the end of the current half cycle. To improve the dP ⁇ ' reliability (precision) of the measurement, PE 0 , V G and — can be averaged over the
  • the capacitance equation (equation (13) for inspired gas G, or equation (26) for CO 2 ): The capacitance equation is used to determine Veff G at the start of each half cycle, on the breath immediately following of the last breath of the previous half cycle that was used to determine Qc from the calibration equation, assuming that Qc has not significantly changed between these successive breaths.
  • breath i+1 is the first breath of the previous half cycle
  • breath 7+ 7 the first breath of the current half dP ⁇ ' cycle, since washin or washout of G is fastest and therefore — [ s greatest at this point, dt as shown in Figure 4.
  • VeJf 0 is relatively insensitive to Qc at this point, since the difference between P ⁇ G at breaths /+/ and 7+ 7 tends to be relatively small, and the dominant term in the numerator of equation (12) is the term containing the measured V co .
  • VeJf 0 is a relatively stable physiological variable, a moving average of individual determinations of VeJf 0 can be made to improve its accuracy and precision.
  • the continuity equation (equation (17) for inspired gas G, or equation (27) for CO 2): For each breath k within the current half cycle, the continuity equation is used to determine Qc for that breath (Qc k ). Qc k is determined from the measured parameters for breath k and from Qc 1 and the measured parameters for breath i. Breath / can be any recent breath corresponding to when Qc was determined. Although the previous value of Qc is described herein as being determined by use of the calibration equation, it will be apparent that the value of Qc 1 could alternatively be determined using any method.
  • a moving average of Qc k can be used. Firstly, Qc k is averaged with the value from the identical point of the previous half cycle. Secondly, the last 3-6 such values are averaged. This process has the effect of delaying the responsiveness of the system to real-time changes in cardiac output, but provides substantially more stable results. Technical improvements in measurement of input parameters which reduce random measurement imprecision may allow shorter averaging or none at all, thereby improving the real-time responsiveness of the system.
  • Qt cardiac output
  • Qt cardiac output
  • Qs pulmonary shunt blood flow
  • Shunt blood flow is by definition that proportion of total pulmonary blood flow which does not engage in gas exchange with alveolar gas and so is not measured by techniques based upon lung gas exchange measurement.
  • lung shunt flow can be estimated by any one of a number of methods.
  • Total pulmonary blood flow Qt (cardiac output) is the sum of Qc and Qs .
  • FIG. 5 shows the determined cardiac output Qt for the measurement period. The breaths at which the calibration equation was evaluated are indicated (the end of each half cycle). The continuity equation was evaluated at all other breaths.
  • Figure 6 shows the simulated patient's capnography tracing over the measurement period. This is the expirogram for CO 2 partial pressure ( P cc , 2 ) measured at the level of the endotracheal tube in a ventilated patient. It shows the fluctuation in P co in real-time within each breath and from breath to breath and is a standard monitoring method for anaesthetised patients. It can be seen that the fluctuations in the end-tidal point ( PE C ' Q2 ) caused by the alternating tidal volume are only apparent upon close inspection. Any disturbance to the patient's normal cardio-respiratory function induced by the ventilatory manoeuvre will be negligible.
  • the calibration equation was evaluated at the end of each half cycle and the resulting values are shown ("calibration eq").
  • the continuity equation was evaluated with each breath. Both the raw Qt determined from the continuity equation (“continuity eq”) and with 6 breath averaging (“continuity eq averaged”) are shown.

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Abstract

L'invention concerne une méthode et un système pour surveiller la sortie cardiaque d'un sujet. La méthode et le système de l'invention sont destinés à mesurer un débit sanguin capillaire pulmonaire efficace (ou débit sanguin pulmonaire non shunté) et un débit pulmonaire total (ou sortie cardiaque) sur une base continue, respiration à respiration. Le débit sanguin capillaire pulmonaire efficace pour une respiration donnée est utilisé pour déterminer le débit sanguin capillaire pulmonaire efficace pour une respiration subséquente.
PCT/AU2006/000593 2005-05-06 2006-05-05 Methode capnodynamique pulmonaire pour une mesure non invasive continue d'une sortie cardiaque Ceased WO2006119546A1 (fr)

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Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009062255A1 (fr) * 2007-11-16 2009-05-22 Philip John Peyton Système et procédé de surveillance du débit cardiaque
EP2098163A1 (fr) * 2008-03-04 2009-09-09 Korea Advanced Institute of Science and Technology Procédé et appareil affichage pour déterminer de manière non invasive des propriétés pulmonaires en mesurant les gaz de la respiration et les gaz du sang
EP2138096A1 (fr) * 2008-06-03 2009-12-30 Nihon Kohden Corporation Système de mesure de débit et moniteur d'informations biologiques
WO2012077065A1 (fr) * 2010-12-10 2012-06-14 Koninklijke Philips Electronics N.V. Procédé et appareil pour déterminer la pression partielle de dioxyde de carbone dans le sang artériel
US8201557B2 (en) 2006-08-04 2012-06-19 Innovision A/S Method to compensate for the effect of recirculation of inert blood soluble gas on the determination of pulmonary blood flow in repeated inert gas rebreathing tests
EP2641536A1 (fr) 2012-03-21 2013-09-25 Maquet Critical Care AB Procédé de détermination continue et non invasive du volume pulmonaire efficace et du débit cardiaque
US9001049B2 (en) 2007-07-19 2015-04-07 Volkswagen Ag Method for determining the position of an actuation element, in particular a finger of a user in a motor vehicle and position determination device
WO2017105304A1 (fr) 2015-12-16 2017-06-22 Maquet Critical Care Ab Profil de ventilation pour détermination non invasive d'elv, d'epbf, du débit cardiaque et/ou de la teneur en co2 dans le sang veineux
WO2017192077A1 (fr) 2016-05-03 2017-11-09 Maquet Critical Care Ab Suivi par capnométrie du débit cardiaque ou du débit pulmonaire réel pendant une ventilation artificielle
WO2017192076A1 (fr) 2016-05-03 2017-11-09 Maquet Critical Care Ab Détermination du débit cardiaque ou du débit pulmonaire réel pendant une ventilation artificielle
WO2017200929A1 (fr) * 2016-05-15 2017-11-23 Covidien Lp Capnographie volumétrique du flux latéral
CN112426136A (zh) * 2014-08-27 2021-03-02 马奎特紧急护理公司 用于预测机械通气对象中流体响应性的方法和设备
CN112533533A (zh) * 2018-08-07 2021-03-19 罗斯特姆医疗创新有限公司 用于监测不与患者的通气肺相互作用的血流的系统和方法
WO2021118419A1 (fr) 2019-12-10 2021-06-17 Maquet Critical Care Ab Estimation de la saturation mêlée veineuse en oxygène

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6210342B1 (en) * 1999-09-08 2001-04-03 Ntc Technology, Inc. Bi-directional partial re-breathing method
US6217524B1 (en) * 1998-09-09 2001-04-17 Ntc Technology Inc. Method of continuously, non-invasively monitoring pulmonary capillary blood flow and cardiac output
EP1238631A1 (fr) * 2001-03-05 2002-09-11 Instrumentarium Corporation Procédé pour la détermination non-invasive des conditions circulatoires d'un sujet
US20030181820A1 (en) * 2000-02-22 2003-09-25 Orr Joseph A. Methods for accurately, substantially noninvasively determining pulmonary capillary blood flow, cardiac output, and mixed venous carbon dioxide content
US20040059239A1 (en) * 1996-12-19 2004-03-25 Jaffe Michael B. Apparatus and method for non-invasively measuring cardiac output

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040059239A1 (en) * 1996-12-19 2004-03-25 Jaffe Michael B. Apparatus and method for non-invasively measuring cardiac output
US6217524B1 (en) * 1998-09-09 2001-04-17 Ntc Technology Inc. Method of continuously, non-invasively monitoring pulmonary capillary blood flow and cardiac output
US6210342B1 (en) * 1999-09-08 2001-04-03 Ntc Technology, Inc. Bi-directional partial re-breathing method
US20030181820A1 (en) * 2000-02-22 2003-09-25 Orr Joseph A. Methods for accurately, substantially noninvasively determining pulmonary capillary blood flow, cardiac output, and mixed venous carbon dioxide content
EP1238631A1 (fr) * 2001-03-05 2002-09-11 Instrumentarium Corporation Procédé pour la détermination non-invasive des conditions circulatoires d'un sujet

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