Interpretation of gas levels measured via breath, blood and skin after different breath-holding times

Abstract

A method or device for assaying physiological gas levels in a human, comprising: repeatedly measuring a gas in samples of breath or blood, or continuously measuring the gas through the skin or fingernail, while he or she holds his or her breath for a specified time interval (BHt) before each measurement, wherein these time intervals are selected from the group consisting of BHt=0, 4-6, 20-25 and 35-40 seconds, and recording the results to form a series of values including at least one measurement at BHt=35-40 which is treated as representing the average gas level in all the tissues of the body (T) at that time, to determine if the individual is net inhaling, net exhaling or in equilibrium with the gas.

Claims

1. A method for assaying physiological gas levels, comprising: a) repeatedly measuring a gas level in a human who has held his or her breath for a specified time interval (BHt) before each measurement, wherein at least two and up to four time intervals are selected from the group consisting of BHt=0, 4-6, 20-25 and 35-40 seconds, b) recording the results of the measurements of the gas level of step “a)” to form a series of values including at least one measurement at BHt=35-40, which is treated as the average gas level in all tissues of the body, including the lungs, arteries and veins; c) calculating differences between the recorded results of step “b)” that represent relative estimates of the level of the gas in lungs minus tissues, arteries minus veins, arteries minus tissues, and/or veins minus tissues; d) interpreting the recorded results of step “b)” and the calculated results of step “c)” to determine if the gas is being net inhaled or absorbed versus net exhaled or excreted, and at what relative rate; wherein the gas levels measured in step “a)” are measured in end-tidal (ET) samples of exhaled breath with a sensing device, and wherein BHt=0 is measured and treated as representing the level of the gas in the lungs (L), BHt=5 is measured and treated as representing the level of the gas in the arteries (A), BHt=20 is measured and treated as representing the level of the gas in the veins (V) and BHt=35 is measured and treated as representing the average of the gas in all tissues (T), including L, A and V.

2. The method of claim 1, wherein the gas levels measured in step “a)” are measured in end-tidal (ET) samples of exhaled breath with a gas sensing device.

3. The method of claim 2, wherein the gas is selected from the group consisting of O2, CO2, NO, NO2, SO2, O3, H2, and H2S.

4. The method of claim 1, wherein the level of the gas in lungs minus tissues (L−T) and the level of the gas in arteries minus veins (A−V) are calculated and interpreted to determine if Carbon Monoxide (CO) gas is being net absorbed or excreted from the human.

5. The method of claim 4, wherein the gas is selected from the group consisting of O2, CO2, NO, H2, and H2S.

Description

DETAILED DESCRIPTION OF THE INVENTION

(1) Many devices can measure gas levels in humans and are suitable for the present invention. They include transcutaneous monitors, pulse oximeters and pulse CO-oximeters that measure oxygen, carbon dioxide and/or carbon monoxide continuously via non-invasive sensors placed over skin or fingernails. They do not generally specify any breath holding times and assume the user is breathing normally while being monitored.

(2) Devices also exist that measure gases at only one time. These generally do not specify breath holding time, (e.g arterial and venous blood gases, breath alcohol), or require only one specified breath holding time (e.g. 15 s in Bedfont's breath CO analyzers, 20 s in others). They also generally specify only one type of sample (mouth, upper respiratory, or end-tidal) and one route of sampling (via nose or mouth for breath testing, over particular types of tissue such as finger tips, ear lobes, or neonatal heels for TC testing).

(3) Some devices give the option to change the length of an audio-visual BHt countdown but no option for comparing the result of one BHt against another (such as Bedfont's Toxco).

(4) Devices designed to calculate a human's resting or basal metabolic rate specify a breath holding time and display a calculated measure that is based in part on the difference between inhaled and exhaled CO.sub.2 and/or O.sub.2 at rest. But they do not display the actual level of either gas.

(5) Devices exist that require users to first inhale a gas mixture, hold their breath for a fixed time (e.g. 10 s) and then exhale into the device. The device calculates and displays a result based in part on the difference between the inhaled and exhaled concentrations. The most widely used example is a pulmonary medicine test called the ‘Diffusing Capacity of the Lung for Carbon Monoxide.’ DLCO was introduced in 1950s and is now widely used by a variety of methods for inhaling CO and then breath holding before exhaling, none of which are hardware or device specific. DLCO devices do not display actual level of CO exhaled or the net difference from inhaled, just a calculated DLCO statistic that also depends on many other variables.

(6) According to the present invention, the above devices may be modified to automatically record and track results, including the clinically important gaps (differences) between values measured at specific breath-holding times, and alert users whenever any of the tracked variables is outside published normal ranges and/or the user's own historical normal ranges for measurements at approximately the same time of day. Gas metabolism varies throughout the day and after meals, so users tracking daily trends should retest themselves at approximately the same time of day and with the same number of hours since their last meal.

EXAMPLES OF THE PRESENT INVENTION

(7) Representative methods of the invention are described below in four parts. The first three parts address the estimate of CO in L, A, V and T via breath, skin and blood measurements, while the fourth addresses how the present method can be extended to the measurement of other gases besides CO.

(8) Part 1—Method for Measuring and Interpreting the Concentration of Gases Exhaled after Different Breath Holding Times: Carbon Monoxide [CO] Via Breath

(9) CURRENT STATE OF THE ART: Breath gas analyzers are designed to be used with a single breath hold time (BHt) to estimate either venous or arterial COHb but not both, and not the level of CO in the lungs or the average CO level in all tissues. As such, they cannot determine whether an individual is net inhaling or net excreting CO.

(10) GOAL: To assess CO levels in lungs, arteries, veins and the average of all tissue and whether individual is net inhaling CO, net exhaling CO, or in equilibrium.

(11) METHOD: by varying the breathholding time from 0 to 35-40 seconds, measurements can be made that represent the level of CO in the lungs, arteries, veins and the average of all tissues. For consistency, all measurements must be done while a subject is in the same position, either supine (for highest readings) or seated (lower). Standing is not recommended because some subjects may get dizzy, wobble or faint while holding their breath.

(12) APPLICATION: Method of the invention can be used with any device able to measure CO in intervals of whole ppm or tenths of ppm starting from zero in an ET breath sample. The device or an associated application running on another device must be able to display all measured CO levels and preferably to record and track them over time as well, although a user can do this manually. No changes to the hardware of existing devices are needed, but software and firmware may be adapted to offer users the ability to use the method, calculate the results, display and track them over time.

(13) STEP 1. MEASURE CO IN END-TIDAL BREATH SAMPLES FOUR TIMES: at BHt=0, 5, 20 and 35 seconds in that order. These measurements capture the relative concentrations of CO in Lungs (L), Arteries (A), Veins (V), and average of all Tissues (T), respectively. Results can be recorded and tracked manually by user and/or automatically by device and associated software. If the user cannot hold his or her breath for 35 seconds, the results of the results of the first three tests at BHt=0, 5 and 20—or even any two of these three tests—are enough to evaluate if CO is being abnormally net inhaled or exhaled.

(14) Example 1: Real data collected 1 minute after a single normal inhalation and exhalation by mouth of CO (approximately 500 ppm) with the subject standing: L=84, A=24, V=20, T=19, all in ppm.

(15) STEP 2. CALCULATE GAPS (differences) between CO levels in lungs and tissues, and between arteries and veins. These gaps indicate CO uptake versus CO excretion or when the gaps are both zero, dynamic equilibrium. They can be calculated manually by the user of the device or calculated by the firmware or software in the device or an associated application. To track results, manual users of the method (or the device automatically) should record the date and time of all measurements

(16) LUNG-TISSUE GAP=L−T=ΔLT=CO in Lungs minus CO in Tissues (using Example 1: ΔLT=84−19=+65)

(17) ARTEREO-VENOUS GAP=A−V=ΔAV=CO in Arteries minus CO in Veins (using Example 1: ΔAV=24−20=+4)

(18) Example 2. Re-testing of the subject in Example 1 above 10 minutes after the CO exposure gave L=15, A=15, V=16, T=16.

(19) LUNG-TISSUE GAP=L−T=ΔLT=CO in Lungs minus CO in Tissues (using Example 2: ΔLT=15−16=−1)

(20) ARTEREO-VENOUS GAP=A−V=ΔAV=CO in Arteries minus CO in Veins (using Example 2: ΔAV=15−16=−1)

(21) STEP 3. INTERPRET RESULTS

(22) 3A. Regarding the Values of L, A, V and T:

(23) In non-smokers, the typical healthy range of CO is below 7 ppm in L, A, V and T. If the CO level in any one compartment is significantly higher than all the others at any time, the others will either gradually rise to meet it (if the endogenous and/or exogenous CO exposure continues unabated for hours), or if the exposure stops, the highest level will fall quickly along with all the others to some new level of dynamic equilibrium that is lower than all of them.

(24) In smokers, even several hours after smoking L, A, V and T may all contain up to 10-25 ppm CO. During smoking and other acute CO exposures, the lung compartment is the highest and may contain hundreds of ppm above the other compartments In Examples 1 and 2 above, L, A, V and T were all >6 immediately after, as well as 10 minutes after the CO exposure stopped, indicating unhealthy CO levels in all compartments. The lung level started 3 times greater than arterial and 4 times greater than venous. The average of all tissues shows that the CO exposure was not long enough for the body to reach equilibrium with the level of CO being inhaled.

(25) 3B. Regarding the Values of the ΔLT and ΔAV Gaps:

(26) In non-smokers and smokers when not smoking, the healthy stable range for ΔLT and ΔAV gaps are each 0-3 ppm. This is due to continuous production of endogenous CO in healthy lungs that enters tissues via arterial blood but which does not all come out via venous blood.

(27) It is considered unhealthy if either or both gaps are >3, which is common in smokers while smoking. A gap indicates disequilibrium with very recent or current exogenous CO poisoning still being absorbed into the body faster than it can be excreted. In Example 1 above, both gaps are greater than 3, with ΔLT=65 and ΔAV=4.

(28) It is also considered unhealthy if either or both gaps are negative (<0). Negative values indicate disequilibrium and unhealthfully high levels of CO coming out of tissues due to prior exogenous and/or endogenous CO exposures that have not yet been fully metabolized to CO.sub.2 and/or excreted. In Example 2 above, 10 minutes after exposure both ΔLT and ΔAV gaps were −1.

(29) 3C. Regarding the Relative Magnitude of the ΔLT and ΔAV Gaps:

(30) When ΔLT=ΔAV the lung-tissue and arterial-venous gaps are the same size, but the interpretation depends on whether these gaps are zero, positive or negative.

(31) If Δ=0 (both gaps are zero) it indicates a stable equilibrium of CO in the body with CO in air, which is healthy when L, A, V and T are all below 7, but not if they are all much higher.

(32) If Δ>0 (both gaps are positive, as in Example 1) it indicates a net uptake of CO from the lungs into tissues. This may be the result of inhaled exogenous CO and/or higher than normal endogenous production of CO in the lungs. If the CO exposure continues, both gaps will remain positive until equilibrium is reached (at A=0), but if CO exposure stops, both gaps will reverse within one hour, cross zero and then remain negative until a new equilibrium is reached.

(33) If Δ<0 (both gaps are negative, as in Example 2) it indicates a net respiratory excretion of CO from tissues which, if breathing CO-free air, should gradually get smaller until a new equilibrium is reached.

(34) When ΔLT and ΔAV are both positive but not equal (as in Example 1) it indicates disequilibrium, with more CO being absorbed from the lungs and arteries into tissues than coming out of the body. Note that such disequilibria usually balance out within a few minutes to hours after CO exposure stops depending on the level and duration of exposures.

(35) When ΔAV and ΔLT are both negative but not equal, it indicates disequilibrium, with more CO being excreted from tissues through veins to lungs than entering tissues from arteries.

(36) Part 2—Method for Measuring and Interpreting the Concentration of Gases Exhaled after Different Breath Holding Times: Example of CO Via Skin or Nails with Pulse CO-Oximetry™

(37) CURRENT STATE OF THE ART: Masimo's Rainbow® line of pulse CO-oximeters™ with SET® are designed to be used without any breath holding via a sensor placed over a fingernail, earlobe or heel to measure the percentage of total hemoglobin in arterial blood that is bound to CO in the form of % COHb and to display this as % SpCO® (percent of Hb saturated with CO). The manufacturer does not specify that the measure is arterial, and most independent researchers who have studied the device mistakenly compared the results to venous COHb values on the mistaken assumption that arterial and venous values are always equal or close enough to not make a significant difference. Devices that measure and display % SpCO can alternately display the functional percent oxygen saturation (% SpO.sub.2) by toggling from one screen to another.

(38) GOAL: To assess relative % SpCO® levels in lungs, arteries, veins and the average of all tissues, and whether a subject is net inhaling or net exhaling CO or in dynamic equilibrium, using either the earlobe or fingertip sensor.

(39) METHOD: Measure % SpCO® and % SpO.sub.2 with a pulse CO-oximeter™ using either earlobe or fingertip sensor while seated or supine from BHt=0 while breathing normally in and out via the nose and then while holding one's breath for 35 to 40 seconds. As the blood continues circulating during breathholding, the arterial blood measured under the skin sensor at BHt=0 is followed by blood coming from the lungs, then the veins, and finally from the average of all tissues.

(40) The analysis for skin measurements is thus quite different from those breath measurements described above. For consistency, all skin CO measurements should be done while the subject is in the same position, either supine, for highest readings, or seated, and after a consistently large inhalation via the nose. CO measurements made while standing are lowest and not recommended because some subjects may get dizzy, wobble or even faint while breath holding.

(41) APPLICATION: Method of the invention can be used with any device able to measure % SpCO® and % SpO.sub.2 continuously via skin sensors on an earlobe or fingertip and display results in intervals of tenths of percent starting from zero. The device or an associated application running on another device must be able to display the measured levels % SpCO® and % SpO.sub.2 levels and preferably to record and track them over time as well, although a user can do this manually by toggling back and forth between the screens. No changes to the hardware of existing devices are needed, but software and firmware may be adapted to offer users the ability to use the method, calculate the results, display and track them over time.

(42) STEP 1. MEASURE % SpCO® and % SpO.sub.2 levels with an earlobe or fingertip sensor while seated or supine at rest and breathing in and out via the nose without any breath holding (BHt=0). These are both arterial levels. An earlobe sensor is recommended because blood from the lungs reaches the earlobe more quickly than it does the fingertip but either will work. Then start holding the breath and monitor the automatically recorded % SpCO® and % SpO.sub.2 levels as the breath holding time increases. Some devices (such as the Masimo Radical-7™) allow users to see both the CO and O.sub.2 display on the same screen while others (such as the Masimo Rad-57™ and Rad-87™) require toggling back and forth between two display screens.

(43) STEP 2. PLOT RESULTS manually on paper or view in Masimo software with BHt on x-axis from 0 at least 35-40 seconds and the % SpCO® and % SpO.sub.2 levels on the Y-axis (either combined or separate does not matter, but easier to interpret results if combined).

(44) STEP 3. IDENTIFY TIME TO PEAK % SpO.sub.2.

(45) The time interval from BHt=0 until the maximum level of % SpO.sub.2 is defined as Lt. This is the time it took the richly oxygenated blood that was in the lung at the start of breathholding (after a deep inhalation) to circulate to the site of the skin measurement.

(46) STEP 4. INTERPRET % SpCO® VALUES AT VARIOUS BREATH HOLDING TIMES

(47) 4A. The level of % SpCO® in arterial blood (A) is that measured at BHt=0.

(48) 4B. The relative % SpCO® level in the lungs (L) is measured at BHt=Lt (from Step 3).

(49) 4C. The relative % SpCO® level in the veins (V) is measured at some point between BHt=Lt and BHt=35-40. Although the exact BHt that best estimates the level of % SpCO® in veins cannot be predicted, it occurs approximately 10-15 seconds after Lt.

(50) 4D. The relative average of % SpCO® in all tissues (T) is measured at BHt=35-40.

(51) 4E. In non-smokers, the typical healthy range of arterial % SpCO® at BHt=0 is below 2%, and the level in the average of all tissues should be the same or lower. If the CO level in any one compartment is significantly higher than all of the others at any time, the others will either gradually rise to meet it (if the endogenous and/or exogenous CO exposure continues unabated for hours), or if the exposure stops, the highest level will fall quickly along with all the others to some new level of dynamic equilibrium that is lower than all of them.

(52) 4F. In smokers while they are smoking, A>T with respect to % SpCO®. Thereafter, T>A and both typically remain in the range of 5-10% even hours after smoking. Levels above 5% and 10% in non-smokers and smokers, respectively, are considered acute CO poisoning and should be treated immediately. If chronic, any level over 2% or more in non-smokers is unhealthy.

(53) STEP 5. INTERPRET % SpCO® LINE FROM BHt=0 TO BHt=35-40.

(54) Because the data displayed by pulse CO-oximetry™ devices are continuous, interpretation focuses on the slope of the correlation between BHt and % SpCO from BHt=0 to BHt=35-40 rather than on at any particular times in between. This relationship can be seen at a glance from the shape of the line that connects whatever intermediate values were plotted in Step 2. When the % SpCO® line: 5A. stays flat, it indicates CO is in equilibrium with A=L=V=T without any net inhalation or exhalation. 5B. starts rising and keeps rising, it indicates the CO in A<L<V<T. This is the result of having more CO in tissues than blood or lungs due to prior exogenous CO exposures and/or to increased endogenous production and/or to decreased metabolism of CO in tissues. The upper limit of % COHb associated with endogenous CO-related disorders such as rheumatoid arthritis is approximately 4%, so any level above this indicates continued CO poisoning of tissues from some earlier high level of exogenous CO exposure. 5C. starts falling and keeps falling, it indicates the CO in A>L>V>T. This is the result of a relatively brief but high level of exposure to exogenous CO that recently ended, as might be seen in someone just rescued from inhaling smoke in a fire. The lungs have started to clear but more CO is still in arteries than in either tissues or veins. 5D. starts rising but then reverses and keeps falling, it indicates the CO level originally in either the lungs or veins was higher than that in the arteries, such that L>A>T>V or V>L>A>T. The former could be the result of abnormally high endogenous CO production in the lung, and/or current exogenous CO poisoning, while the latter could be due to similar high endogenous CO in non-lung tissues and/or the balance of CO left in tissues from some prior CO poisoning(s). To determine which is the case, examine the % SpCO® line at time=Lt, when the % SpO.sub.2 measure peaks (from Step 3). If the early CO and O.sub.2 peaks coincide at BHt=Lt, then the CO peak is clearly from the lung fraction. But if the CO peak occurs more than a few seconds (e.g. 5 seconds) later than the % SpO.sub.2 peak arriving from the lung, it must be from the venous fraction that follows. 5E. starts falling but then reverses and rises, it indicates the CO level originally in either the lungs or the veins was lower than that in the arteries, such that A>L<V<T or A>L>V<T. The former could be the result of recent exogenous CO exposure that just ended, with the highest CO level now in tissues, while the latter indicates current CO poisoning. To determine which is the case, examine the % SpCO® line at time=Lt, when the % SpO.sub.2 measure peaks (from Step 3). If the early CO minimum and O.sub.2 maximum coincide at BHt=Lt, then the low CO level is clearly from the lung fraction and A>L<V. But if the CO minimum occurs more than a few seconds (e.g. 5 seconds) later than the % SpO.sub.2 peak arriving from the lung, it must be from the venous fraction that follows and then A>L>V<T

(55) Part 3—Method for Measuring and Interpreting the Concentration of Gases Exhaled after Different Breath Holding Times: Example of CO Via Blood

(56) CURRENT STATE OF THE ART: Blood samples are taken from an artery or vein but rarely both for determination of the percent carboxyhemoglobin (% COHb) while the patient is seated or supine. No breath holding time is specified, so some people are breathing normally when blood is drawn while others may be holding their breath or hyperventilating due to anxiety about the blood drawing procedure. The blood sample(s) is then analyzed for COHb with a CO-oximeter, gas chromatograph, or other instrument capable of making this measurement with resolution of at least 0.1%. (Each 1% COHb in blood is equivalent to approximately 6 to 7 ppm.) As with % SpCO® measurements, most clinicians and researchers are under the misimpression that arterial and venous % COHb are equal or close enough not to make a clinically significant difference, and so they rarely test both.

(57) GOAL: To assess the % COHb levels in the average of all tissues (T) and either the arteries (A) or the veins (V) and from these two measures, to determine whether an individual is net absorbing CO [from blood into tissues], net excreting CO [from tissues to blood], or in dynamic equilibrium.

(58) METHOD: By taking two blood samples from one skin puncture at BHt=0 and BHt=35-40 seconds, measurements can be made of the level of CO in either the arteries (A) or veins (V), depending which is sampled, and the average of all tissues (T). Blood testing does not allow a meaningful estimate of the lung CO level but this is not needed to interpret the A−T and T−V gaps. Either one of which is sufficient to determine if the individual is net absorbing or excreting CO from his or her tissues. But since even one skin puncture is invasive, painful, and not without risk, embodiments of the invention that require only non-invasive measurements of breath or skin are preferred.

(59) APPLICATION: The method can be used with any device that can measure COHb in a blood sample. No changes to the hardware of existing devices are needed, but software changes may be incorporated to display the results of the four different samples and the gaps between them.

(60) STEP 1. MEASURE COHb from two blood samples drawn from any arterial or venous site (usually elbow or wrist of non-dominant arm; venous is recommended since less painful). The first (air-tight) blood gas sample tube is filled while the subject is breathing normally without holding their breath (BHt=0) and labeled “A” or “V” as the case may be. A second tube is left in while the subject is asked to hold their breath for 35-40 seconds, at which time this now full tube is discarded and replaced with another empty one that is labeled “T”.

(61) STEP 2. CALCULATE GAP in % COHb between either arteries and tissues [=A−T=ΔAT] or tissues and veins [=T−V=ΔTV], as appropriate for the blood sample drawn. Gaps can be calculated manually by the user from the measured CO-oximeter results or by firmware or software in the device or an associated application. To track results, manual users of the method (or the device automatically) should record the date and time of all measurements.

(62) STEP 3. INTERPRET RESULTS

(63) 3A. Regarding Absolute Values of A, V and T:

(64) In non-smokers, the typical healthy range of % COHb is 0-2% in A, V and T. If the CO level in any one of these compartment is significantly higher than all the others at any time, the others will either gradually rise to meet it (if the endogenous and/or exogenous CO exposure continues unabated for hours), or if the exposure stops, the highest level will fall quickly along with all the others to some new level of dynamic equilibrium that is lower than all of them.

(65) In smokers, even several hours after smoking, each of A, V and T typically are in the range of 5-10% COHb. During smoking and other acute CO exposures, the % COHb in A is higher than in T and V (A>T>V), but post-poisoning this is reversed, with T>V>A.

(66) Levels of A, V and/or T above 10% in smokers and 5% in non-smokers are considered acute CO poisoning and should be treated immediately. If chronic, any level over 2% or more in non-smokers is unhealthy.

(67) When A=T or V=T, this indicates the subject is in equilibrium with CO.

(68) 3B. Regarding the Absolute Values of the ΔAT and ΔTV Gaps:

(69) In non-smokers and smokers when not smoking, the healthy stable range for both ΔAT and ΔTV is positive from zero to +1. This is due to continuous production of endogenous CO in healthy lungs that enters tissues via arterial blood but does not all come out via venous blood as some is bound to heme proteins in tissues and some is metabolized to carbon dioxide.

(70) It is considered unhealthy if either gap is >1.

(71) When ΔAT>1%, this disequilibrium indicates very recent or current exogenous CO exposure that is still being absorbed into tissues from A faster than it can be excreted from T.

(72) When ΔTV is >1%, this disequilibrium indicates an unhealthy high level of CO coming out of tissues due to prior exogenous and/or endogenous CO exposures that have not yet been fully metabolized to CO.sub.2 and/or excreted.

(73) 3C. Regarding the Relative Magnitude of the ΔAT and ΔTV Gaps:

(74) While clinically useful information can be obtained by comparing the size of the AT and TV gaps, to do so requires both arterial and venous punctures, which this method seeks to avoid in order to reduce pain, risk and expense. That said, the method can be validated by drawing both arterial and venous samples at BHt=0 and BHt=35-40 and showing that the results for T are the same. Thus one need only compare the % COHb in A and V. When A=V, the subject is in dynamic equilibrium but they are net inhaling CO when A>V and net exhaling CO when V>A.

(75) Part 4—Applications of Method Apart From Carbon Monoxide Testing.

(76) The method described in parts 1, 2 and 3, to measure the relative levels of CO in L, A, V and T via breath, skin or fingernails, and blood can be adapted straightforwardly to measure the levels of other biologically active and medically significant gases for which suitable instruments exist.

(77) The method could be used, for example, with instruments that measure O.sub.2, CO.sub.2, and alcohol via breath, blood and skin or nails, and with exhaled breath analyzers that already exist for H.sub.2, H.sub.2S and NO. These devices generally measure only one gas in only one compartment (such as artery or vein, lung or tissue) and only after one specified breath holding time interval, if any, usually BHt=0. No changes to the hardware of these devices are required. They need only changes to their firmware and/or software to enable measuring, recording, and displaying values associated with specific breath holding times L, A, V and T.

(78) Even technologically advanced devices that continuously measure both arterial and venous levels of % O.sub.2Hb and % COHb, such as Masimo's line of “pulse CO-oximeters” with signal extraction technology (SET®) only display the arterial results. If they also were to also display the venous values of what Masimo calls SpO2 and SpCO® (which are equivalent to the % O.sub.2Hb and % COHb), the breath holding techniques of the present invention would not be needed to estimate the difference between venous and arterial; and then the devices could also calculate and continuously display the even more clinically significant A−V gaps in O.sub.2 and CO. This type of information would also allow users to continuously monitor whether SpCO® was in equilibrium (when A=V), was being net absorbed from arterial blood into tissues (when A−V>0), or was being net excreted (when A−V<0).

(79) Such modified devices could also calculate and display the delivery of oxygen from arterial blood into tissues by the A−V difference or gap in SpO.sub.2, which would be far more clinically useful than the arterial saturation level alone,

(80) The breath holding methods described in Part 2, above, would still be needed to estimate the relative average % SpCO® level in all tissues, but if the device displayed both A and V results together, users could see how far apart they were at BHt=0 and then watch them converge towards equilibrium during breath holding.

(81) For those gases such as oxygen which are always higher in lungs and arteries than in tissues and veins (or vice versa, like carbon dioxide), comparing measurements made while breathing normally (BHt=0) with those made after some fixed time of breath holding such as from BHt=20 and/or BHt=35 provides a way to compare rates of oxygen uptake and carbon dioxide output per unit time among individuals and even within the same individual if retested later. As above, all measurements should be made either seated or supine for consistency, and they should only start after the initial transient anomalies seen in O.sub.2 (going up) and CO.sub.2 (going down) associated with the deep inhalation just before breathholding have passed. Hence the recommendation to compare measurements made at BHt=20 and 35.