- Email: [email protected]
A new method for noninvasive measurement of pulmonary gas exchange using expired gas
Accepted Manuscript Title: A new method for noninvasive measurement of pulmonary gas exchange using expired gas Authors: John B. West, G. Kim Prisk PII: DOI: Reference:
S1569-9048(17)30321-X https://doi.org/10.1016/j.resp.2017.09.014 RESPNB 2871
To appear in:
Respiratory Physiology & Neurobiology
Received date: Revised date: Accepted date:
28-7-2017 11-9-2017 26-9-2017
Please cite this article as: West, John B., Prisk, G.Kim, A new method for noninvasive measurement of pulmonary gas exchange using expired gas.Respiratory Physiology and Neurobiology https://doi.org/10.1016/j.resp.2017.09.014 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
A new method for noninvasive measurement of pulmonary gas exchange using expired gas Running head: noninvasive measurement of gas exchange status John B. West and G. Kim Prisk Department of Medicine University of California, San Diego La Jolla, CA 92093-0623 Correspondence to:
John B. West, M.D., Ph.D.
UCSD Department of Medicine 0623A 9500 Gilman Drive La Jolla, CA 92093-0623 Telephone:
858-534-4192
Fax:
858-534-4812
E-mail:
[email protected]
Highlights .
We describe a new method of measuring the efficiency of
pulmonary gas exchange using expired gas .
This avoids arterial puncture which is invasive, requires
technical expertise, and is expensive .
The result is a more comprehensive assessment of gas exchange
than that using ideal alveolar gas
1
Abstract Measurement of the gas exchange efficiency of the lung is often required in the practice of pulmonary medicine and in other settings. The traditional standard is the values of the PO2, PCO2, and pH of arterial blood. However arterial puncture requires technical expertise, is invasive, uncomfortable for the patient, and expensive. Here we describe how the composition of expired gas can be used in conjunction with pulse oximetry to obtain useful measures of gas exchange efficiency. The new procedure is noninvasive, well tolerated by the patient, and takes only a few
minutes.
It
could
be
particularly
useful
when
repeated
measurements of pulmonary gas exchange are required. One product of the procedure is the difference between the PO2 of end-tidal alveolar gas and the calculated PO2 of arterial blood. This measurement is related to the classical alveolar-arterial PO2 difference based on ideal alveolar gas. However that traditional index is heavily influenced by lung units with low ventilation-perfusion ratios, whereas the new index has a broader physiological basis because it includes contributions from the whole lung. Key Words: alveolar gas; alveolar-arterial oxygen difference; alveolar PO2; alveolar PCO2; oxygen dissociation curve 1. Introduction It is frequently necessary to measure the efficiency of gas exchange of the lung, and this is often essential in many patients with pulmonary disease.
2
In these instances, it is common to make a measurement at the time of diagnosis, and then do subsequent measurements in order to follow the progress of the disease. The traditional method of measuring gas exchange is that using arterial blood gases. This typically gives the arterial PO2, PCO2, and pH. However this measurement
has some
disadvantages. The procedure is invasive, may be uncomfortable for the patient,
requires
a
technically
skilled
person,
has
occasional
complications, and is expensive. Therefore it would be valuable to have a noninvasive method of measuring gas exchange efficiency that was well tolerated by the patient and could be easily repeated. This would not necessarily obviate the use of an arterial blood gas measurement, especially in the early stage of management, but could be useful in following the progress of the disease. Another population of people in which this method could be useful is normal subjects, or patients with lung disease, who are living at high altitude. All these people have hypoxemia, and therefore the limitations discussed later requiring a reduced arterial PO2 would not apply. In this report, the potential of using the composition of expired gas to determine gas exchange efficiency is explored. The analysis of expired gas goes back over 100 years to the early days of respiratory physiology. At that time, the analysis of the gas was carried out by collecting individual samples, and using chemical methods such as the Haldane gas analyzer (Haldane 1920). However about 60 years ago, rapidly responding gas analyzers were introduced, and, for example, a mass
3
spectrometer could provide a rapid, accurate analysis of all the respiratory gases (West 1957). This equipment was generally large and cumbersome. In the last few years miniaturized, rapidly responding, accurate gas analyzers have become available, and these have been exploited here to make a device that can be hand-carried to the patient to give immediate results. When used in conjunction with a pulse oximeter, valuable information about the efficiency of pulmonary gas exchange can be derived. Pulse oximetry by itself also has a role in obtaining information about pulmonary gas exchange. It has the great advantage of being noninvasive. However it is a blunt instrument. Because of the shape of the oxygen dissociation curve, it is possible for the arterial PO2 to fall from about 100 to 60 mm Hg, that is by 40%, while the SpO2 changes from 97 to 90%, that is by only 7%. Therefore although the arterial oxygen saturation can be useful in following the progress of a patient with lung disease, the signal from the oximeter changes relatively little. Nevertheless the device is extensively used in a hospital setting to determine treatment, for example, in the mechanical ventilation of patients. 2. Hardware The device consists of a small portable box containing the rapidly
4
responding oxygen and carbon dioxide sensors, a pump to draw in the gas sample, the appropriate software, and a screen to display the data. For oxygen, fast-responding electrochemical cells such as those available from Teledyne are available. For carbon dioxide, thermal conductivity or infrared sensor cells are suitable. For the measurement, the patient wears a nose clip, and breathes through a disposable cardboard tube about 8 cm long and 1.5 cm diameter. A capillary sampling tube is inserted into the side of this tube, and a small volume of the inspired and expired gas is continually transported to the analyzers by a small pump. The result is a continuous display of the inspired and expired PO2 and PCO2 as shown in Figure 1. In practice the patient breathes through the tube for only 2 or 3 minutes until a steady state has been achieved. 3. Software As can be seen from figure 1, the instantaneous values of the inspired and expired PO2 and PCO2 are continually displayed. In addition, the software reads off the end-tidal values for both the PO2 and PCO2 using a procedure that averages small variations in the values near the end of the expiration. These end-tidal values are also displayed over a period of about a minute on another tracing to determine whether a steady state of gas exchange has been achieved. The software also calculates the respiratory exchange ratio from the end-tidal and inspired values for PO2 and PCO2.
Steady state can also be ascertained by monitoring the
stability of the respiratory exchange ratio, RQ in Figure 1. As indicated in figure 1, the display also reads out the barometric pressure (from a
5
miniature barometer), inspired PO2, and respiration rate. The SpO2 and heart rate are also displayed from the pulse oximeter. A software package calculates the arterial PO2 from the arterial oxygen saturation given by the SpO2.
Modern oximeters measure the oxygen
saturation with considerable accuracy. The derivation of arterial PO2 is done using the Hill equation: PO2^n = P50^n x [SO2 / (1-SO2)] where the symbol ^ means raised to the power of, P50 is the PO2 for 50% oxygen saturation, n is 2.7, and SO2 is the arterial oxygen saturation given by the SpO2.
In order to invert the Hill equation, that is to
calculate the PO2 from the SO2, the software takes the logarithm of the equation. This allows it to be solved algebraically. Severinghaus (1979) and others have shown that this equation given above fits the oxygen dissociation curve closely. For example, between the saturations of 94 and 30%, the error in the calculated PO2 is less than 5 mm Hg. The software also takes account of the effects of changes in the PCO2 on the pH of the blood, because changes in the pH alter the oxygen affinity of hemoglobin. This is done using the Kelman subroutines (Kelman 1966, 1968) which allow the P50 to be calculated from the arterial PCO2 assuming that the base excess is zero, that is that the blood is on the normal buffer line. The equation is: P50 = 0.221 x PCO2 + 17.9. The end-tidal PCO2 is used for the arterial value. The effects of changes in the PCO2 on the P50 are relatively small. For example, an increase in
6
PCO2 from 40 to 50 mm Hg results in a change in P50 of only about 2 mm Hg. In patients with severe COPD, the end-tidal PCO2 will be appreciably lower than the arterial value because of the contribution of alveolar dead space. 4. Analysis As indicated above, the device gives the difference between the end-tidal PO2 and the calculated arterial PO2 (as derived from the pulse oximeter reading). Figure 2 shows a graphic display of this value, and how it compares with the traditional alveolar-arterial oxygen difference using the calculated PO2 of ideal alveolar gas. This classical oxygen- carbon dioxide diagram shows the gas composition of lung units for all ventilation-perfusion ratios from zero, the value for mixed venous blood, to infinity, the value of inspired gas (Rahn and Fenn 1955). For simplification, the diagram shows the inspired PO2 and PCO2 to be those of air at sea level, and the mixed venous point is that for the normal lung with a PO2 of 40 and PCO2 of 45 mm Hg. The VA/Q line shows all possible values for the PO2 and PCO2 and lung units throughout the lung. First look at the derivation of number 1. This uses the measured arterial PO2 and PCO2 from an arterial blood gas sample (labeled “a”). However the alveolar values are not known in this classical analysis. Instead the so-called ideal alveolar PO2 is calculated. The ideal alveolar gas
7
composition is that which the lung would have if there were no ventilation-perfusion inequality and the respiratory exchange ratio was the same as the actual lung (labeled “i”). This calculation is done by taking the PCO2 of the arterial sample, and assuming that the PCO2 of ideal alveolar gas is the same. This is a reasonable assumption because the line joining the alveolar ideal point and the arterial point is almost horizontal as shown in the figure. The alveolar gas equation is then used to calculate the ideal alveolar PO2 using the inspired PO2 and the measured or assumed respiratory exchange ratio. Now turn to the derivation of number 2. Again we have the arterial PO2 on the left, although this is calculated as described above from the SpO2. On the right we have the alveolar PO2, which is given by the end-tidal value (labeled “A”). It can be seen that the difference between alveolar and arterial PO2 measured by the new device is larger than the traditional PO2 difference between arterial blood and ideal alveolar gas. It could be argued that this new value shown in number 2 is more informative than the traditional value shown in number 1. The traditional value depends heavily on the contribution of lung units with low ventilation-perfusion ratios. By contrast, the new value shown in number 2 includes both the contributions of lung units with low ventilationperfusion ratios, and those with abnormally high ratios. It is therefore a more comprehensive metric for the distribution of ventilation-perfusion ratios in the lung.
8
5. Limitations The device described here has limitations. One is that it is only accurate when the arterial oxygen saturation is abnormally low, that is in patients with hypoxemia, or subjects at high altitude. The reason is that the oxygen dissociation curve has such a shallow slope above a saturation of about 93% that the calculation of arterial PO2 from the SpO2 is inaccurate. Many patients with lung disease, and millions of people who live at high altitude have an arterial oxygen saturation below 93%. Therefore the population for which the new device will be valuable is large. Another limitation is that the device does not take account of any changes in the oxygen affinity of hemoglobin caused by alterations in base excess, body temperature, or 2,3 diphosphoglycerate (DPG). In practice the last two limitations will not apply to many patients. However some patients such as those with long-standing COPD are likely to have changes in their base excess. The same is true of people who are acclimatized to high altitude Ideally the patient should be in a steady state of gas exchange. Some patients hyperventilate when asked to breathe through a mouthpiece, although if they are asked to close their eyes and relax this often helps. This is frequently a problem when an arterial blood gas sample is taken because of the apprehension associated with the procedure. In practice, if
9
an arterial blood sample shows an unexpectedly low PCO2 associated with an unexpectedly high pH, we commonly attribute this to hyperventilation caused by the anxiety of the procedure.
6. Preliminary results The main purpose of this report is to describe a new potential method of measuring abnormal pulmonary gas exchange. However a number of measurements have been made on outpatients with lung disease at UCSD after appropriate IRB approval. These have shown that in 22 patients who had an arterial oxygen saturation of 93% or less (average 91, SD 1.83), the differences between the end-tidal and calculated arterial PO2 was generally in the range of 30 to 70 mm Hg (average 47, SD 19). By contrast, the corresponding differences in people with normal lungs are very small, approaching zero. These results show that, as expected, the index shown as # 2 in Figure 2 has a substantial value in patients whose lung disease is severe enough to result in appreciable desaturation. More extensive measurements, including arterial blood gas values, have been made in 5 inpatients all of whom had severe chronic obstructive pulmonary disease. These studies were made in the Stevenson Memorial Hospital, Alliston, ON, Canada after IRB approval.
The difference
between the end-tidal and calculated arterial PO2 ranged from 54 to 98 mmHg, and the difference between these values and the classical ideal alveolar- arterial oxygen difference averaged 24 mmHg. These results
10
confirm that, as expected, the difference between index 1 and 2 in figure 2 is substantial, and are consistent with the assertion that the new technique is a more comprehensive index of abnormal gas exchange that the traditional one based on ideal alveolar gas. Disclosures The University of California San Diego has licensed MediPines Corp., Newport Beach CA to develop the device. John B West and G Kim Prisk state a financial interest. Acknowledgments We thank Peter D Wagner for help with deriving the arterial PO2 from the arterial oxygen saturation, and Dipen Makadia, Pranav Agarwal and Oswaldo Ramirez for some of the data.
11
References 1. Haldane, JS. 1920. Methods of air analysis. 3rd edition, Griffin, London.
2. Kelman, G. R. 1966. Calculation of certain indices of cardiopulmonary function using a digital computer Respir Physiol 1:335-343.
3. Kelman, G. R. 1968. Computer program for the production of O2-CO2 diagrams Respir Physiol 4: 260-269
4. Rahn, H., Fenn, W. O. 1955. A graphical analysis of the respiratory gas exchange. American Physiological Society, Washington DC.
5. Severinghaus, J. W. 1979. Simple, accurate equations for human blood O2 dissociation computations. J Appl Physiol Respir Environ Exerc Physiol 46:599-602.
6. West, J. B.,
1957. Measurement of the ventilation-perfusion ratio
inequality in the lung by the analysis of a single expirate. Clin. Sci. 16: 529-5
12
Figure captions Figure 1. Typical screenshot of the output of the device. Note the continuous records of inspired and expired PO2 (red) and PCO2 (blue). Nine breaths are shown. Below these are plots of the end-tidal PO2 and PCO2 for 18 breaths to show whether the patient is in a steady state. Other information in the output includes the end-tidal PO2 and PCO2 values, respiratory exchange ratio (RQ), respiratory rate, calculated arterial PO2, difference between the end-tidal and calculated PO2 here called the Oxygen Deficit, heart rate, SpO2, barometric pressure, and inspired PO2.
Figure 2.
Classical oxygen-carbon dioxide diagram showing the
ventilation-perfusion ratio line connecting the mixed venous point v with the inspired gas point I (here shown for sea level conditions and with a typical mixed venous point). The ideal alveolar point, i is shown at the intersection of the blood and gas R lines where R stands for respiratory exchange ratio. The traditional alveolar-ideal alveolar difference is shown as number 1. The alveolar-arterial oxygen difference given by the new 13
device is shown as number 2. Note that number 1 is mainly determined by lung units with low ventilation-perfusion ratios. By contrast, 2 has contributions from these lung units, and also lung units with abnormally high ventilation-perfusion ratios.
Figure 3. Graphical representations of some preliminary clinical results for
outpatients
(Figure
A)
and 14
inpatients
(Figure
B).
3A
15
3B
16
S1569-9048(17)30321-X https://doi.org/10.1016/j.resp.2017.09.014 RESPNB 2871
To appear in:
Respiratory Physiology & Neurobiology
Received date: Revised date: Accepted date:
28-7-2017 11-9-2017 26-9-2017
Please cite this article as: West, John B., Prisk, G.Kim, A new method for noninvasive measurement of pulmonary gas exchange using expired gas.Respiratory Physiology and Neurobiology https://doi.org/10.1016/j.resp.2017.09.014 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
A new method for noninvasive measurement of pulmonary gas exchange using expired gas Running head: noninvasive measurement of gas exchange status John B. West and G. Kim Prisk Department of Medicine University of California, San Diego La Jolla, CA 92093-0623 Correspondence to:
John B. West, M.D., Ph.D.
UCSD Department of Medicine 0623A 9500 Gilman Drive La Jolla, CA 92093-0623 Telephone:
858-534-4192
Fax:
858-534-4812
E-mail:
[email protected]
Highlights .
We describe a new method of measuring the efficiency of
pulmonary gas exchange using expired gas .
This avoids arterial puncture which is invasive, requires
technical expertise, and is expensive .
The result is a more comprehensive assessment of gas exchange
than that using ideal alveolar gas
1
Abstract Measurement of the gas exchange efficiency of the lung is often required in the practice of pulmonary medicine and in other settings. The traditional standard is the values of the PO2, PCO2, and pH of arterial blood. However arterial puncture requires technical expertise, is invasive, uncomfortable for the patient, and expensive. Here we describe how the composition of expired gas can be used in conjunction with pulse oximetry to obtain useful measures of gas exchange efficiency. The new procedure is noninvasive, well tolerated by the patient, and takes only a few
minutes.
It
could
be
particularly
useful
when
repeated
measurements of pulmonary gas exchange are required. One product of the procedure is the difference between the PO2 of end-tidal alveolar gas and the calculated PO2 of arterial blood. This measurement is related to the classical alveolar-arterial PO2 difference based on ideal alveolar gas. However that traditional index is heavily influenced by lung units with low ventilation-perfusion ratios, whereas the new index has a broader physiological basis because it includes contributions from the whole lung. Key Words: alveolar gas; alveolar-arterial oxygen difference; alveolar PO2; alveolar PCO2; oxygen dissociation curve 1. Introduction It is frequently necessary to measure the efficiency of gas exchange of the lung, and this is often essential in many patients with pulmonary disease.
2
In these instances, it is common to make a measurement at the time of diagnosis, and then do subsequent measurements in order to follow the progress of the disease. The traditional method of measuring gas exchange is that using arterial blood gases. This typically gives the arterial PO2, PCO2, and pH. However this measurement
has some
disadvantages. The procedure is invasive, may be uncomfortable for the patient,
requires
a
technically
skilled
person,
has
occasional
complications, and is expensive. Therefore it would be valuable to have a noninvasive method of measuring gas exchange efficiency that was well tolerated by the patient and could be easily repeated. This would not necessarily obviate the use of an arterial blood gas measurement, especially in the early stage of management, but could be useful in following the progress of the disease. Another population of people in which this method could be useful is normal subjects, or patients with lung disease, who are living at high altitude. All these people have hypoxemia, and therefore the limitations discussed later requiring a reduced arterial PO2 would not apply. In this report, the potential of using the composition of expired gas to determine gas exchange efficiency is explored. The analysis of expired gas goes back over 100 years to the early days of respiratory physiology. At that time, the analysis of the gas was carried out by collecting individual samples, and using chemical methods such as the Haldane gas analyzer (Haldane 1920). However about 60 years ago, rapidly responding gas analyzers were introduced, and, for example, a mass
3
spectrometer could provide a rapid, accurate analysis of all the respiratory gases (West 1957). This equipment was generally large and cumbersome. In the last few years miniaturized, rapidly responding, accurate gas analyzers have become available, and these have been exploited here to make a device that can be hand-carried to the patient to give immediate results. When used in conjunction with a pulse oximeter, valuable information about the efficiency of pulmonary gas exchange can be derived. Pulse oximetry by itself also has a role in obtaining information about pulmonary gas exchange. It has the great advantage of being noninvasive. However it is a blunt instrument. Because of the shape of the oxygen dissociation curve, it is possible for the arterial PO2 to fall from about 100 to 60 mm Hg, that is by 40%, while the SpO2 changes from 97 to 90%, that is by only 7%. Therefore although the arterial oxygen saturation can be useful in following the progress of a patient with lung disease, the signal from the oximeter changes relatively little. Nevertheless the device is extensively used in a hospital setting to determine treatment, for example, in the mechanical ventilation of patients. 2. Hardware The device consists of a small portable box containing the rapidly
4
responding oxygen and carbon dioxide sensors, a pump to draw in the gas sample, the appropriate software, and a screen to display the data. For oxygen, fast-responding electrochemical cells such as those available from Teledyne are available. For carbon dioxide, thermal conductivity or infrared sensor cells are suitable. For the measurement, the patient wears a nose clip, and breathes through a disposable cardboard tube about 8 cm long and 1.5 cm diameter. A capillary sampling tube is inserted into the side of this tube, and a small volume of the inspired and expired gas is continually transported to the analyzers by a small pump. The result is a continuous display of the inspired and expired PO2 and PCO2 as shown in Figure 1. In practice the patient breathes through the tube for only 2 or 3 minutes until a steady state has been achieved. 3. Software As can be seen from figure 1, the instantaneous values of the inspired and expired PO2 and PCO2 are continually displayed. In addition, the software reads off the end-tidal values for both the PO2 and PCO2 using a procedure that averages small variations in the values near the end of the expiration. These end-tidal values are also displayed over a period of about a minute on another tracing to determine whether a steady state of gas exchange has been achieved. The software also calculates the respiratory exchange ratio from the end-tidal and inspired values for PO2 and PCO2.
Steady state can also be ascertained by monitoring the
stability of the respiratory exchange ratio, RQ in Figure 1. As indicated in figure 1, the display also reads out the barometric pressure (from a
5
miniature barometer), inspired PO2, and respiration rate. The SpO2 and heart rate are also displayed from the pulse oximeter. A software package calculates the arterial PO2 from the arterial oxygen saturation given by the SpO2.
Modern oximeters measure the oxygen
saturation with considerable accuracy. The derivation of arterial PO2 is done using the Hill equation: PO2^n = P50^n x [SO2 / (1-SO2)] where the symbol ^ means raised to the power of, P50 is the PO2 for 50% oxygen saturation, n is 2.7, and SO2 is the arterial oxygen saturation given by the SpO2.
In order to invert the Hill equation, that is to
calculate the PO2 from the SO2, the software takes the logarithm of the equation. This allows it to be solved algebraically. Severinghaus (1979) and others have shown that this equation given above fits the oxygen dissociation curve closely. For example, between the saturations of 94 and 30%, the error in the calculated PO2 is less than 5 mm Hg. The software also takes account of the effects of changes in the PCO2 on the pH of the blood, because changes in the pH alter the oxygen affinity of hemoglobin. This is done using the Kelman subroutines (Kelman 1966, 1968) which allow the P50 to be calculated from the arterial PCO2 assuming that the base excess is zero, that is that the blood is on the normal buffer line. The equation is: P50 = 0.221 x PCO2 + 17.9. The end-tidal PCO2 is used for the arterial value. The effects of changes in the PCO2 on the P50 are relatively small. For example, an increase in
6
PCO2 from 40 to 50 mm Hg results in a change in P50 of only about 2 mm Hg. In patients with severe COPD, the end-tidal PCO2 will be appreciably lower than the arterial value because of the contribution of alveolar dead space. 4. Analysis As indicated above, the device gives the difference between the end-tidal PO2 and the calculated arterial PO2 (as derived from the pulse oximeter reading). Figure 2 shows a graphic display of this value, and how it compares with the traditional alveolar-arterial oxygen difference using the calculated PO2 of ideal alveolar gas. This classical oxygen- carbon dioxide diagram shows the gas composition of lung units for all ventilation-perfusion ratios from zero, the value for mixed venous blood, to infinity, the value of inspired gas (Rahn and Fenn 1955). For simplification, the diagram shows the inspired PO2 and PCO2 to be those of air at sea level, and the mixed venous point is that for the normal lung with a PO2 of 40 and PCO2 of 45 mm Hg. The VA/Q line shows all possible values for the PO2 and PCO2 and lung units throughout the lung. First look at the derivation of number 1. This uses the measured arterial PO2 and PCO2 from an arterial blood gas sample (labeled “a”). However the alveolar values are not known in this classical analysis. Instead the so-called ideal alveolar PO2 is calculated. The ideal alveolar gas
7
composition is that which the lung would have if there were no ventilation-perfusion inequality and the respiratory exchange ratio was the same as the actual lung (labeled “i”). This calculation is done by taking the PCO2 of the arterial sample, and assuming that the PCO2 of ideal alveolar gas is the same. This is a reasonable assumption because the line joining the alveolar ideal point and the arterial point is almost horizontal as shown in the figure. The alveolar gas equation is then used to calculate the ideal alveolar PO2 using the inspired PO2 and the measured or assumed respiratory exchange ratio. Now turn to the derivation of number 2. Again we have the arterial PO2 on the left, although this is calculated as described above from the SpO2. On the right we have the alveolar PO2, which is given by the end-tidal value (labeled “A”). It can be seen that the difference between alveolar and arterial PO2 measured by the new device is larger than the traditional PO2 difference between arterial blood and ideal alveolar gas. It could be argued that this new value shown in number 2 is more informative than the traditional value shown in number 1. The traditional value depends heavily on the contribution of lung units with low ventilation-perfusion ratios. By contrast, the new value shown in number 2 includes both the contributions of lung units with low ventilationperfusion ratios, and those with abnormally high ratios. It is therefore a more comprehensive metric for the distribution of ventilation-perfusion ratios in the lung.
8
5. Limitations The device described here has limitations. One is that it is only accurate when the arterial oxygen saturation is abnormally low, that is in patients with hypoxemia, or subjects at high altitude. The reason is that the oxygen dissociation curve has such a shallow slope above a saturation of about 93% that the calculation of arterial PO2 from the SpO2 is inaccurate. Many patients with lung disease, and millions of people who live at high altitude have an arterial oxygen saturation below 93%. Therefore the population for which the new device will be valuable is large. Another limitation is that the device does not take account of any changes in the oxygen affinity of hemoglobin caused by alterations in base excess, body temperature, or 2,3 diphosphoglycerate (DPG). In practice the last two limitations will not apply to many patients. However some patients such as those with long-standing COPD are likely to have changes in their base excess. The same is true of people who are acclimatized to high altitude Ideally the patient should be in a steady state of gas exchange. Some patients hyperventilate when asked to breathe through a mouthpiece, although if they are asked to close their eyes and relax this often helps. This is frequently a problem when an arterial blood gas sample is taken because of the apprehension associated with the procedure. In practice, if
9
an arterial blood sample shows an unexpectedly low PCO2 associated with an unexpectedly high pH, we commonly attribute this to hyperventilation caused by the anxiety of the procedure.
6. Preliminary results The main purpose of this report is to describe a new potential method of measuring abnormal pulmonary gas exchange. However a number of measurements have been made on outpatients with lung disease at UCSD after appropriate IRB approval. These have shown that in 22 patients who had an arterial oxygen saturation of 93% or less (average 91, SD 1.83), the differences between the end-tidal and calculated arterial PO2 was generally in the range of 30 to 70 mm Hg (average 47, SD 19). By contrast, the corresponding differences in people with normal lungs are very small, approaching zero. These results show that, as expected, the index shown as # 2 in Figure 2 has a substantial value in patients whose lung disease is severe enough to result in appreciable desaturation. More extensive measurements, including arterial blood gas values, have been made in 5 inpatients all of whom had severe chronic obstructive pulmonary disease. These studies were made in the Stevenson Memorial Hospital, Alliston, ON, Canada after IRB approval.
The difference
between the end-tidal and calculated arterial PO2 ranged from 54 to 98 mmHg, and the difference between these values and the classical ideal alveolar- arterial oxygen difference averaged 24 mmHg. These results
10
confirm that, as expected, the difference between index 1 and 2 in figure 2 is substantial, and are consistent with the assertion that the new technique is a more comprehensive index of abnormal gas exchange that the traditional one based on ideal alveolar gas. Disclosures The University of California San Diego has licensed MediPines Corp., Newport Beach CA to develop the device. John B West and G Kim Prisk state a financial interest. Acknowledgments We thank Peter D Wagner for help with deriving the arterial PO2 from the arterial oxygen saturation, and Dipen Makadia, Pranav Agarwal and Oswaldo Ramirez for some of the data.
11
References 1. Haldane, JS. 1920. Methods of air analysis. 3rd edition, Griffin, London.
2. Kelman, G. R. 1966. Calculation of certain indices of cardiopulmonary function using a digital computer Respir Physiol 1:335-343.
3. Kelman, G. R. 1968. Computer program for the production of O2-CO2 diagrams Respir Physiol 4: 260-269
4. Rahn, H., Fenn, W. O. 1955. A graphical analysis of the respiratory gas exchange. American Physiological Society, Washington DC.
5. Severinghaus, J. W. 1979. Simple, accurate equations for human blood O2 dissociation computations. J Appl Physiol Respir Environ Exerc Physiol 46:599-602.
6. West, J. B.,
1957. Measurement of the ventilation-perfusion ratio
inequality in the lung by the analysis of a single expirate. Clin. Sci. 16: 529-5
12
Figure captions Figure 1. Typical screenshot of the output of the device. Note the continuous records of inspired and expired PO2 (red) and PCO2 (blue). Nine breaths are shown. Below these are plots of the end-tidal PO2 and PCO2 for 18 breaths to show whether the patient is in a steady state. Other information in the output includes the end-tidal PO2 and PCO2 values, respiratory exchange ratio (RQ), respiratory rate, calculated arterial PO2, difference between the end-tidal and calculated PO2 here called the Oxygen Deficit, heart rate, SpO2, barometric pressure, and inspired PO2.
Figure 2.
Classical oxygen-carbon dioxide diagram showing the
ventilation-perfusion ratio line connecting the mixed venous point v with the inspired gas point I (here shown for sea level conditions and with a typical mixed venous point). The ideal alveolar point, i is shown at the intersection of the blood and gas R lines where R stands for respiratory exchange ratio. The traditional alveolar-ideal alveolar difference is shown as number 1. The alveolar-arterial oxygen difference given by the new 13
device is shown as number 2. Note that number 1 is mainly determined by lung units with low ventilation-perfusion ratios. By contrast, 2 has contributions from these lung units, and also lung units with abnormally high ventilation-perfusion ratios.
Figure 3. Graphical representations of some preliminary clinical results for
outpatients
(Figure
A)
and 14
inpatients
(Figure
B).
3A
15
3B
16