End-tidal gas estimation system and method

An apparatus and method of indicating the reliability of an end-tidal gas value that includes measuring a plurality of gas concentration values, measuring a plurality of ventilation values, determining an end-tidal gas value from the gas concentration values, determining the degree of ventilatory stability from the ventilation values, and providing an estimate of reliability of the end-tidal gas values using the degree of ventilatory stability.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention pertains to a method and apparatus for providing a reliable end-tidal carbon dioxide (CO2), end-tidal oxygen (O2), or other gas estimation.

2. Description of the Related Art

Respiratory gas monitoring systems typically comprise gas sensing, measurement, processing, communication, and display functions. Such systems are considered to be either diverting (i.e., sidestream) or non-diverting (i.e., mainstream). A diverting gas measurement system transports a portion of the sampled gases from the sampling site, which is typically a breathing circuit or the patient's airway, through a sampling tube, to the gas sensor where the constituents of the gas are measured. A non-diverting gas measurement system does not transport gas away from the breathing circuit or airway, but measures the gas constituents passing through the breathing circuit.

Conventional non-diverting gas measurement systems include gas sensing, measurement and signal processing required to convert the detected or measured signal (e.g., voltage) into a value that may be used by the host system. The gas measurement system communicates with the sample cell placed at the breathing circuit and comprises the components required to output a signal corresponding to a property of the gas to be measured. Placement of the sample cell directly at the breathing circuit results in a “crisp” waveform that reflects in real-time the partial pressure of the measured gas, such as carbon dioxide or oxygen, within the airway. The sample cell, which is also referred to as a cuvette or airway adapter, is located in the respiratory gas stream, obviating the need for gas sampling and scavenging as required in a diverting gas measurement system.

Conventional diverting gas measurement systems utilize a relatively long sampling plastic tube connected to an adapter in the breathing circuit (such as a T-piece at the endotracheal tube or mask connector) or a nasal catheter. The sample gas is continuously aspirated from the breathing circuit or the sample site through the sampling tube and into the sample cell within the monitor at sample flow rates ranging from 50 to 250 ml/min. The location of the sampling port in the breathing varies and may range anywhere from an elbow connected to an endotracheal tube to the wye connector.

Both diverting and non-diverting gas measurement systems include sensors that measure the concentration and/or partial pressure of at least one of the gas components in the sampled gas passing through the sample cell. Two of the most commonly measured gases of clinical importance are carbon dioxide and oxygen. Both diverting and non-diverting gas measurement systems utilize sensors to measure the constituent gases such as carbon dioxide and oxygen.

To measure these gases, electro-optical assemblies are often employed. In the case of a carbon dioxide sensor and a number of other gas sensors, these assemblies includes a source that emits infrared radiation having an absorption band for carbon dioxide. The infrared radiation is usually transmitted along a path that is normal to the flow path of the gas stream being analyzed. Photodetectors are arranged to receive and measure the transmitted radiation that has passed through the gas in the gas stream. Carbon dioxide within the sample gas absorbs this radiation at some wavelengths and passes other wavelengths. The transmitted radiation is converted to signals from which a processor calculates the partial pressure of carbon dioxide. In the case of an oxygen sensor, electrochemical or fluorescence based technologies are often employed.

Carbon dioxide and oxygen are expressed either as a gas fraction (FCO2and FO2) or partial pressure (PCO2and PO2). Capnography and oxygraphy, when used without qualification, refers to time-based capnography and oxygraphy. In addition to capnometry, capnography includes a plot of the instantaneous carbon dioxide concentration over the course of a respiratory cycle. From this plot, the cyclic changes can be visualized.

In a “textbook” capnogram2, an example of which is shown inFIG. 1, the capnogram comprises two segments: an “expiratory” segment4, and an “inspiratory” segment6. The expiratory segment consists of a varying upslope5athat levels to a constant or slight upslope5b. The inspiratory segment consists of a sharp downslope7athat settles to a plateau of negligible inspired carbon dioxide7b. However, other than the end-tidal partial pressure of carbon dioxide, which has been generally understood as the partial pressure of carbon dioxide at the end of expiration, only breathing frequency and a measure of inspiratory carbon dioxide levels are clinically reported. This is the case because only the transition between the expiratory and inspiratory segments can usually be well delineated from a capnogram.

Even then, only if there is substantially no rebreathing, does this transition correspond to the time of the actual beginning of inspiration as delineated by the flow waveform. The transition between inspiration and expiration cannot be readily discerned because of the presence of anatomic dead space that fills with inspiratory gas at the end of expiration. Although the oxygram is not in as widespread clinical use as capnograph, the same issues discussed above apply to the oxygram with the understanding that the oxygram can be considered an inverted version of the capnogram.

If flow is measured in addition to carbon dioxide, the volumetric capnogram can be determined. Similarly if flow is measured in addition to oxygen, the volumetric oxygram can be determined.FIG. 2illustrates the three phases of a volumetric capnogram. Phase I comprises the carbon dioxide free volume, while phase II comprises the transitional region characterized by a rapidly increasing carbon dioxide concentration resulting from progressive emptying of the alveoli. Phases II and III together are the carbon dioxide containing part of the breath, the effective tidal volume, VTeff. Phase III, the alveolar plateau, typically, has a positive slope indicating a rising PCO2. Using these three phases of the volumetric capnogram, physiologically relevant measures, such as the volumes of each phase, the slopes of phase II and III, and carbon dioxide elimination, as well as deadspace tidal volume and ratios of anatomic and physiologic deadspace can be determined.

One of the objectives when setting the level of mechanical ventilation for a patient is to reach and maintain a desired concentration of arterial carbon dioxide concentration (PaCO2). Because real-time access to PaCO2measurements is not easy, estimates from a capnogram are used to obtain a surrogate measure. Because of pulmonary shunting, i.e., a portion of the right heart cardiac output reaches the left atrium without having participated in gas exchange, the closest surrogate of PaCO2that can be obtained from the capnogram is alveolar CO2concentration (PACO2).

The end-tidal partial pressure of CO2(PetCO2), usually referred to as the end-tidal carbon dioxide, is used clinically, for example, to assess a patient ventilatory status and, as noted above, has been used by some as a surrogate for PaCO2. Similarly, the end-tidal partial pressure of O2(PetO2), which may be referred to as the end-tidal oxygen, is also used.

The medical literature is replete with conflicting articles regarding the relationship between PetCO2and PaCO2, as well as the relationship between changes in PetCO2and changes in PaCO2. On one hand, Nangia et al. notes that “ETCO2correlates closely with PaCO2in most clinical situations in neonates”. Similarly, Wu et. al. notes that “we recommend using mainstream capnography to monitor PetCO2instead of measuring PaCO2in the NICU.” On the other hand, Russell et al. studied ventilated adults and noted “trends in P(a-et)CO2magnitude are not reliable, and concordant direction changes in PetCO2and PaCO2are not assured.”

Researchers have considered maneuvers to improve ‘prediction’ of PaCO2. Tavernier et al. studied whether prolonged expiratory maneuvers in patients undergoing thoracoabdominal oesophagectomy improved the prediction of PaCO2from PetCO2and concluded that these maneuvers did not improve estimation. A commonly held belief among critical care physicians is that end-tidal CO2cannot be used as a surrogate for either arterial PCO2or changes in arterial PCO2. To complicate matters further Chan et al. noted that “mainstream PetCO2provided a more accurate estimation of PaCO2than side-stream measurement.”

If end-tidal PCO2could be reliably used as a surrogate for arterial CO2, arterial blood sampling could be reduced, applications that currently use intermittent blood sampling would become more clinically acceptable, and applications, such as closed loop control of ventilation (particularly non-invasive ventilation), would be more viable. Therefore, techniques for reliability and/or indicating the reliability of end-tidal PCO2estimations are desired.

SUMMARY OF THE INVENTION

Accordingly, it is an object of the present invention to provide a method of indicating the reliability of an end-tidal gas value that overcomes the shortcomings of conventional end-tidal CO2measurement techniques. This object is achieved according to one embodiment of the present invention by providing a method of indicating the reliability of an end-tidal gas value that includes measuring a plurality of gas concentration values, measuring a plurality of ventilation values, determining an end-tidal gas value from the gas concentration values, determining the degree of ventilatory stability from the ventilation values, and providing an estimate of reliability of the end-tidal gas values using the degree of ventilatory stability.

It is a further object of the present invention to provide an apparatus that indicates the reliability of an end-tidal gas value that overcomes the shortcomings of conventional end-tidal CO2measurement techniques. This object is achieved according to one embodiment of the present invention by providing an apparatus comprising a means for sensing a plurality of gas concentration values, means for sensing a plurality of ventilation values, means for determining an end-tidal value from the gas concentration values, means for determining the degree of ventilatory stability from the ventilation values, and means for providing an estimate of reliability of the end-tidal gas values using the degree of ventilatory stability.

DETAILED DESCRIPTION OF THE EXEMPLARY EMBODIMENTS

The present invention addresses the known problems with the studies to date including (a) the lack of a clear definition of end-tidal gas value, (b) how end-tidal gas values relate to arterial gas values in both ‘stable’ and ‘unstable’ ventilatory patterns, and, (c) an understanding of when end-tidal gas values will and won't be a reliable correlate of arterial and or alveolar gas values. The present invention addresses the need to provide more reliable end-tidal gas values. It should be noted that the while most of the present discussion takes place with reference to carbon dioxide (CO2), the methods described herein apply to other gases as well, including but not limited to respiratory gases, such as oxygen, nitrous oxide, nitric oxide, and other gases, such as anesthetic agents. To determine a more reliable end-tidal gas value, it is important to delineate properly the end-tidal gas value and to determine the reliability of that estimate.

An exemplary embodiment of a gas measurement system10suitable for use in the present invention is illustrated inFIG. 3. The illustrated exemplary embodiment of system10comprises a differential pressure flowmeter12, a flow signal unit16, a gas sensor14, a CO2signal unit18, a processor or processing unit20, and a data display22. System10can be used alone or in combination with mechanical ventilation of the patient. It can be a stand-alone monitoring system or integrated with a ventilator.

The exemplary device for respiratory flow measurement is differential pressure flowmeter12, which provides a pressure differential indicative of respiratory flow; the differential pressure being converted via pressure transducers in flow signal unit16to electrical signals representative of the relationship between respiratory flow and pressure differential. An exemplary differential pressure flowmeter is manufactured and sold by Respironics, Inc., Wallingford, Conn. However, any flow measurement devices may be utilized, including flow sensors based on other flow measurement techniques, such as optical, vanes, sonic, etc.

Sensors capable of measuring carbon dioxide content in a gas sample are well known. An exemplary device for measuring carbon dioxide content is a gas analyzer of the type employing non-dispersive infrared radiation, which presents data representing the % CO2(or pCO2) of a sample of exhaled breath. Other technologies used to measure the concentration of carbon dioxide, such as electrochemical technologies, Raman spectroscopy, and mass spectroscopy, can also be used in the present invention. The exemplary gas sensor14capable of measuring carbon dioxide content in a patient's exhaled breath is available from Respironics, Inc., Wallingford, Conn., under the trade name CAPNOSTAT®. It is to be understood, however, that other methods of measuring carbon dioxide content, either at the airway (non-diverting) or by removing a sample (diverting), may be used in the present invention.

FIG. 4illustrates one of the problems determining a repeatable and reliable end-tidal value with a plot of flow24, pressure,26and CO228as a function of time for two “breaths” with ventilator-patient asynchrony. The measured value of the PetCO2depends upon how PetCO2value is defined. For example, depending on how end-tidal CO2is determined, it could be reported as either 27, 30 or 31 mm Hg. InFIG. 4, PetCO2at position82is 27 mm Hg, at position84is 31 mm Hg, and at position86is 30 mm Hg. The end of expiration, as defined by the flow waveform (position82), results in an end-tidal value of 27 mm Hg. However, using the apparent expiration-inspiratory transition-position86from the capnogram alone results in PetCO2of 30 mmHg. On the other hand, if the largest value is used (position84) a PetCO2of 31 mm Hg is obtained.

Conventionally, the concentration towards the end of phase III of the time or volumetric capnogram is considered the good estimator of alveolar CO2concentration (i.e. PetCO2) and is usually determined on a breath-by-breath basis. As noted earlier, the simplest approach to determining PetCO2is simply to use the maximum value which would generally occur during phase III. Because extreme values are often sensitive to artifact or noise, other approaches may use an average over the last part of phase III, where the ‘last part’ can be defined either in terms of time or in terms of expiratory volume.

The present invention, unlike these other techniques, contemplates using the flow and/or pressure waveform to better delineate the end of expiration, especially, if significant rebreathing is present, so that the end-tidal gas value may be simply and repeatably determined. Similarly, because volume is the integral of flow, the volumetric capnogram may also be used as well to better delineate the end of expiration (see below). If the flow waveform or a surrogate is not available, the present invention contemplates using a waveform shape analysis to better delineate the end of expiration.

FIGS. 5 and 6are time-based and volumetric capnograms illustrating the potential difficulty of obtaining an end-tidal value from a time based capnogram alone.FIG. 5illustrates a phenomenon often seen in neonates with long expiratory pauses due to the I:E ratios of 1:8-1:10 during which very minor inspiratory efforts are made resulting in a capnogram that is difficult to interpret. Examining such a time-based capnogram makes it very difficult to determine an end-tidal value. However, comparing the time-based and volumetric-based capnograms inFIGS. 5 and 6allows for some clarity. Note that the ventilation-perfusion relationships of the lung are more accurately reflected in the slope of phase III by a volumetric capnogram than in that of a time-based capnogram in which the gradient of the phase III slope is usually less obvious and can be misleading. This may be because a smaller volume of expired gases (approximately the final 15%) often occupies half the time available for expiration, so that a similar change in the CO2concentration is distributed over a greater length of time in the time-based capnogram than in the volumetric capnogram.

InFIG. 6, the plot of the expired volume vs. the partial pressure of CO2during expiration clearly shows a plateau90from which an end-tidal value may be determined using a variety of methods. All of the parameters associated with volumetric capnography can also be determined. For example, the end-tidal gas value may be determined by computing the average PCO2value for the last X % of volume (such as 5 or 10%), fitting the curve, or a portion of it, to a model (physiologically based such as one based on Weibel model or empirical). Using a model based approach to fit the concentration-volume curve allows for potentially clinically relevant values to be determined.

In addition to the challenges already outline, one of the primary challenges in the determination and clinical use of PetCO2values comes from an implied assumption, that PetCO2represents the average value of the alveolar CO2concentration (PACO2). As CO2continues to pass from the blood into the alveolar gas phase during expiration, the alveolar CO2concentration rises during expiration. During inspiration, CO2free gas serves to dilute the alveolar gas and the alveolar CO2concentration decreases. The shape of the respiratory flow waveform (e.g., tidal volume, inspiratory to expiratory time ratio), the pulmonary capillary blood flow, the venous CO2concentration, the amount of deadspace, and the serial and alveolar deadspace affect the particular shape of the alveolar CO2concentration waveform. This shape, in turn, affects the average alveolar CO2concentration. The very last part of the expired volume that leaves the lungs, never reaches gas sensor14, but remains in the anatomical and apparatus (serial) deadspace.

The simulation shown inFIGS. 8A and 8B, which show simulated flow202, volume204, and alveolar CO2concentration206waveforms illustrate how this can affect the PetCO2and its relationship to average alveolar CO2concentration. Lines210and310in alveolar CO2concentration graphs206and306indicate the average alveolar concentration. Thickened lines220and320of alveolar CO2concentration graphs206and306illustrate portions of the alveolar waveform that is measured by gas sensor14in the form of a capnogram. End portions221and321of the thickened lines220and320are conventionally reported as PetCO2.

FIG. 8Aillustrates the waveforms that would be observed if there was no serial deadspace between the alveoli and gas sensor14. The resulting PetCO2value (end portion221) would overestimate average alveolar CO2in this simulation.FIG. 8Billustrates the waveforms which would be observed if there was a normal serial deadspace (e.g., 150 ml) between the alveoli and gas sensor14. The resulting PetCO2value (end portion321) would underestimate average alveolar CO2in this simulation. The step size of the alveolar CO2concentration graphs206and306are approximately 4 mmHg. Larger deadspaces and smaller tidal volumes can increase the difference between PetCO2and average alveolar CO2concentration. Also, this effect may increase noise in PetCO2signal due to breath-to-breath variations in tidal volumes of spontaneously breathing patients.

In patients who breathe through a face mask (instead of an endotracheal tube), the capnogram is additionally affected by the “smearing” effect of the face mask volume—again exacerbated by small or varying tidal volumes. This “smearing” effect is shown inFIGS. 9A and 9B. InFIG. 9A, the patient is breathing with through a mouthpiece resulting in alpha angle410of capnogram405, which is only slightly larger than 90 degrees. In addition, capnogram405has as a relatively flat phase III. InFIG. 9B, the same patient is breathing through a face mask resulting in alpha angle420of capnogram415that is more obtuse than angle410. In addition, phase III of capnogram415is more rounded than in capnogram405, primarily due to the dilution and mixing in the deadspace volume of the face mask. Generally, the differences between PetCO2and average alveolar CO2concentration are relatively small in most subjects (e.g., on the order of 2 or 3 mmHg) without serious ventilation-perfusion abnormalities. If, however, PetCO2is used to extract additional information, such as with partial CO2rebreathing maneuvers, these small differences may become significant.

The present invention contemplates approximating expiratory volumetric capnograms using mathematical functions. This is especially helpful when attempting to obtain a capnogram under adverse conditions, such as those noted above, as well as in the presence of large noise (physiological and instrumental). An exemplary mathematical function that may be used to approximate an expiratory volumetric capnogram is a power function of the following form:
invCO2=f×VEn,
where: invCO2═CO2−maxCO2, CO2is the expired CO2as measured by the gas sensor, VEis the expired volume, f and n are approximation parameters, and maxCO2is constant CO2value, which is another approximation parameter.

The approximation parameters f and n can be found by known numerical methods, including linear regression of natural log (invCO2) vs natural log (VE). The approximation parameter maxCO2can be found iteratively using known search algorithms or using more generalized least-squares algorithms than conventional linear regression.

FIG. 10shows an example of an original capnogram510approximated by a power regression curve520. A number of approaches are contemplated to determine an PetCO2-equivalent value from this power regression approximation. In general, the PetCO2value should be more representative of the alveolar CO2concentration, if the tidal volume is large. If the tidal volume is small, the power regression approximation may be used to extrapolate to what the capnogram value would have been at a larger expiratory volume. Alternatively, the power regression approximation may be used to report the PetCO2concentration at one constant expired volume for all breaths, regardless whether they are small or large.

The present invention contemplates that the model derived PetCO2values could be used replace conventionally determined PetCO2values in conventional CO2monitors, as well as replace conventionally determined PetCO2values for differential CO2Fick determination of pulmonary capillary blood flow. Other approximation functions, other than the power function described above, are contemplated as well. The approximation parameters may be found by methods known in the art including, but not limited to, linear regression, least square algorithms, artificial neural networks and iterative search algorithms. The algorithm to find the approximation parameters may also consider approximation results from previous breaths to make finding the approximation parameters for the current breath faster, less computationally expensive, and more accurate.

The present invention contemplates providing a better definition of when end-tidal CO2, however it may be determined, is a reliable/viable estimate of arterial CO2and when it is not a reliable/viable estimate of arterial CO2. This may be related to both the physiological status of the patient's cardio-pulmonary system and the recent pattern of ventilation, which may have significantly affected the lung and blood stores of the patient. Therefore, estimation of Vd/Vtphysiologic/alveolar or a surrogate to assess the degree of impairment and the assessment of the degree of disturbance to the CO2stores would permit the end-tidal CO2value to be determined and displayed with greater confidence.FIG. 7, which is discussed in greater detail below, illustrates an exemplary process and apparatus for providing an indication of when end-tidal CO2is or is not a reliable/viable estimate of arterial CO2.

The present invention also contemplates determining the degree of physiological impairment. Vd/Vt physiologic is preferably estimated using alveolar partial pressure of CO2(PACO2) (per its definition without the Enghoff modification). PACO2may be estimated by application of models to the volumetric capnogram as well as neural networks, genetic algorithms, and other approaches or combination of approaches. U.S. Pat. No. 5,632,281 describes an approach for arterial estimation that may be used for alveolar estimation. VDalv/VTalv may be used as well and Hardman et al. describes a method for estimating this ratio.

The present invention also contemplates determining the degree of disturbance. The degree of disturbance or ventilatory stability can be assessed by different methods. For example, assessment of the degree of disturbance to the CO2stores may be determined by the measurement of ventilation (with the use of a model) to better determine periods of ‘stability.’ Methods of estimating CO2stores may be found in U.S. Pat. No. 6,955,651 (“the '651 patent”), the contents of which are incorporated herein by reference. The tidal volume must be sufficient size relative to the anatomic deadspace. Functional anatomic deadspace may be estimated by methods known in the art such as Fowler's method. The reliability of the end-tidal value is further increased by applying criteria based on the expiratory flow rate for the breath from which the end-tidal measurement is taken. Application of these criteria will help allow the determination of a reliable end-tidal value

As noted above,FIG. 7illustrates an exemplary schematic embodiment of a gas measurement system100according to the principles of the present invention. Gas measurement system100illustrates the components of a system used to provide a reliable estimate of the end-tidal concentration of a gas. The gas concentration or partial pressure values (used interchangeably) are determined by gas measurement component110. This may be determined on a continuous or intermittent basis. Conventional gas concentration component provide data sampled at sampling rates from 25 to 100 samples/sec. Gas measurement component110corresponds, for example, to gas sensor14and CO2signal unit18inFIG. 1as discussed above.

Ventilation values measured at the airway or via other technologies are determined by ventilation measurement component120. Ventilation values includes, but are not limited to flow, volume, pressure, temperature, and humidity or any combination thereof. The ventilation values may be determined on a continuous or intermittent basis. Ventilation measurement component120corresponds, for example, to differential pressure flowmeter12and flow signal unit16. In an exemplary embodiment, the ventilation related values are determined by measurements of flow, volume, or surrogates thereof. Surrogates of flow derived from acoustic measurements from external surface sensors from companies, such as Andromed, are contemplated.

The gas concentration values from gas measurement component110and ventilation measurement component120are received by the end-tidal gas measurement component130. The present invention contemplates implementing end-tidal gas measurement component130via processing unit20ofFIG. 1. Characteristics of the received ventilation values are used by the end-tidal gas measurement component130to derive a more robust end-tidal gas value from the gas concentration values. For example, changes in the received ventilation values indicating the change from expiratory flow in the airway to inspiratory flow would be used to delineate in time the end of expiration. This may be obtained from the values of the flow, volume or surrogates thereof. For flow, the time of the zero crossing from expiratory flow (or zero flow in the case of a pause interval) to inspiratory flow may be used. For volume, the time from volume increasing (or flat) to decreasing may be used. Similarly, for acoustic measurements the change from expiratory to inspiratory flow can be determined by known methods.

Values from the ventilation measurement component120are also received by the ventilatory stability measurement component140. The present invention also contemplates implementing ventilatory stability measurement component140via processing unit20ofFIG. 1. Ventilatory stability may be determined by evaluating an historical record of ventilation values and assessing its stability. Time periods for assessment would vary based by the size of the gas stores of the gas in question. For CO2and O2, the gas stores that would be considered are both the lung and blood stores. The time interval that would be assessed would be based upon size of those stores which could be estimated via methods as disclosed the '651 patent as well as rules of thumb based upon patient size. Exemplary methods of determining the variability of the ventilation values over the time period for assessment include analysis of the distribution of tidal volume values and, if a period of significant hyperventilation or hypoventilation is observed during the assessment period, then the end-tidal value would be deemed less reliable. The present invention also contemplates that the ventilatory stability measurement component140would receive values from the gas measurement component110.

The estimates of ventilatory stability from the ventilatory stability measurement component140and the end-tidal values from end-tidal measurement component130are received by decision support system150. The present invention further contemplates implementing decision support system150via processing unit20ofFIG. 1. Using these values as well as other criteria, decision support system150determines the reliability of the end-tidal value. The reliability may be based simply on a threshold of ventilatory stability and may be indicated on the display of the host system numerically or graphically. The end-tidal number may be color coded to indicate its reliability such as red, yellow, green for unreliable, questionable, reliable, respectively. Based upon input from user or another system, decision support system150may be configured as a rule based system. For example, patient age as well as disease could permit physiological bounds (either fuzzy or hard bounds) to be used to indicate the reliability of the end-tidal value. It is also contemplated using measurement of Vd/Vt as noted earlier, in decision support system150to determine reliability of the end-tidal value. This could be simply an additional rule such as, in the case of Vd/Vt physiologic, if Vd/Vt physiologic >0.70 then the end-tidal CO2value is highly unreliable as surrogate of arterial CO2.