Monitoring Pulmonary Function

Monitoring Pulmonary Function

Symposium on Pulmonary Problems in Surgery Monitoring Pulmonary Function William A. Cook, M.D.* Advances in the technology of pulmonary function te...

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Symposium on Pulmonary Problems in Surgery

Monitoring Pulmonary Function

William A. Cook, M.D.*

Advances in the technology of pulmonary function testing equipment, and a growing awareness among surgeons of pulmonary problems in their patients have combined to move the study of ventilation and respiration to the bedside of surgical patients. Although thoracic surgeons have long sought the counsel of their physician counterparts, it has now been recognized that no surgical patient is safe from disastrous pulmonary compromise and its contribution to morbidity and mortality. Because of this, surgical patients of all types are now tested preoperatively and carefully followed for the earliest signs of pulmonary failure. Preoperative testing of virtually all aspects of gas exchange and transport are widely available, but special problems arise when this same information is sought in the patient unable to cooperate, on a ventilator, or breathing gas mixtures other than room air. The respiratory functions of the lung are determined by five factors reflecting all the respiratory functions of the lung. Under laboratory conditions these parameters are easily obtained with equipment which is often linked to analog computers that give an immediate readout of the desired test. Alternately, the information may be fed in digital form to a large digital computer for performance of computations and storage as a physiologic data bank. We utilize the Vertek 6000 in our ward laboratory for some of these data. This yields a digital readout of lung volumes and gas flow rates based on a nitrogen washout curve and a timed pneumotachographic spirometer. Figure 1 shows the curves generated by this machine as its basis of computation. This provides a check on the computer functions. An example of the larger computer utilization is shown in Figure 2. This is a computer generated printout sheet for a patient studied in our central pulmonary function testing laboratory.1s The raw data are entered on punch cards from a remote terminal in the laboratory. This laboratory provides the additional parameters of breathing mechanics from a body plethysmograph, gas diffusion by bag and box exchange of carbon monoxide, and gas distribution by a closed system helium equilibration time. Perfusion is obtained either by the Fick method or cardiogreen dye dihi*Associate Professor of Surgery and Acting Director of Division of Cardiothoracic Surgery, Albert Einstein College of Medicine, Bronx, New York

Surgical Clinics of North America- Vol. 54, No.5, October 1974

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Figure 1. Nitrogen washout (left) and timed vital capacity (right) curves generated by Vertek 6000. Ahatomic deadspace, aggregate alveolar ventilation volume, functional residual capacity, and residual volume are computed from the washout curve. Vital capacity, timed vital capacity and maximum midexpiratory flow rate are computed from the spirogram.

tion method of cardiac ou tpu t determination. 9 , 11 Usually arterial blood oxygen and carbon dioxide tensions and pH are obtained at rest and exercise at the time of these pulmonary function tests. Another influence on the gas transport system is the uptake and dissociation of gas by the red cell. Studies of these influences are quite complex, require skilled technicians and carefully adjusted equipment, and are affected by many factors besides lung function. These include temperature, pH, Pco z , and the concentration of diphosphoglyceric acid. The importance of these values to thorough understanding of oxygenation at the tissue level cannot be overemphasized. One method which can be used to obtain a relative value for this parameter is to take a sample of venous blood and determine its pH, Po z and Oz saturation. Using the Severinghouse Slide Rule, the pH and Po z can be used to calculate the predicted O 2 saturation. Z3 Comparison of the measured with the predicted saturation will show whether there is a right shift with increased unloading of oxygen at the tissue level or a left shift with decreased oxygen unloading. Obviously most of this information has been available in good laboratories for many years. Now evidence exists which prompts us to make the difficult shift to bedside study.

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BRONX MUNICIPAL HOSPITAL CENTER-CHEST SERVICE REPORT OF PULMONARY FUNCTION STUDIES DATE-02.15.68

NAME-DOE, JOHN AGE-36 SEX-M HT-162 CMS WT-48 KGS

"*

ARTERIAL BLOOD AT REST 02 SAT 92 PCT P02 66 MMHG 46 PCT HCT PAC02 45 MMHG PH 7.38

NO-442702 WD-OPD *', DIFFUSION-DCO-SB

1. 2. 3.

19.2 23.9 26.8

MEAN 23.3 NORM 25.0

D/V

4.79 5.95 6.66

CC/MIN/MM HG HDR 0.36 0.48 0.51

5.80 5.42

0.45 0.48

':'" ARTERIAL BLOOD AT EXERCISE 92 PCT 02 SAT P02 66 MMHG PAC02 52 MMHG PH 7.26

':":' DIFFUSION -DCO SS CC/MIN/MM HG DCO SS 18.4 (N = 16 ) CO EXT RAT 0.31 (N = 0.50)

,,,:' LUNG VOLUME BTPS (N = 5.45) TLC 4.93 L (N = 3.91) VC 2.35 L (N = 1.54) RV 2.58 L (N = 0.28) 0.52 RV/TLC 3.43 L FRC ERV 0.85 L HE MIX 3.5 MIN (N=2.5 )

*" VENTILATION AT REST MIN VENT (N = 5.74) 7.11 L/MIN/M2 RESP RATE 22 TIDAL VOL 480 CC BTPS VD/VT 0.48 02 CONS 168 CC/MIN/M2 (N = 130) RQ 0.86 VENTEQUIV 34 LlL 02 eN = 25. )

':,', FLOW RATES FVC 2.35 FEV 1 0.69 FEV l/VC 29 43 FEV 2/VC FEV 3/VC 53 MMF 0.18

':,* EXERCISE DIFFUSION AND VENTILATION NOT DONE

BTPS L L PCT PCT PCT LlSEC

(N = 3.91) (N = 3.38) (N= 75) (N= 85) (N= 95) (N = 2.0)

BSA

1.49 M2

" AFTER BRONCHODILATOR NOT DONE

",:, EXERCISE TEST MAX TOLERANCE-3MPH 10PCT GR DURATION -14.0 MIN HEART RATESTART = gO MAX = 110 COMPLETED TEST - DYSPNEA

Figure 2, Computer printout sheet generated by central pulmonary function laboratory computer in form submitted to the patient chart.

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Fifteen years ago the cardiac catheterization laboratory was adapted to bedside use in the study of the severely ill patient. The ensuing period has seen a rapid growth in description and understanding of the complex, often unexpected, hemodynamic changes in these patients, as well as a correlation of the hemodynamic changes with blood gas alterations and a few ventilatory parameters. As a bonus, the instrumentation itself has become more reliable, mobile, and sophisticated. Our objective for the past 6 years has been to begin the same process for the study of lung function. Fundamentally, the concept was to create a mobile pulmonary function laboratory for use at the bedside or in the operating room, and to modify the equipment and study methods in such a way that the functions could be measured in the unconscious or anesthetized patient on artificial ventilation and when breathing oxygen-enriched gas mixtures when necessary. This system allows monitoring of pulmonary functions and correlation of them with blood gas and hemodynamic studies. I also feel that within the data obtainable from such complete monitoring must lie the means for earlier detection and subsequent reversal of developing pulmonary pathology. That pulmonary failure is the most common cause of death in all groups of severely ill patients is the powerful impetus for the effort. As previously stated, five pulmonary functions are mandatory for the depth of study we sought in our basic concept, and our unit was designed to achieve them. They are: (1) ventilational mechanics, (2) ventilation, (3) distribution, (4) diffusion, and (5) perfusion. Our desire to study patients in non-steady, uncooperative, and unconscious states, on a high O 2 inspired gas mixture, dictated the selection of some study methods. These methods were: 1. Mechanics of ventilation by biaxial loop display of esophageal minus mouth pressure against pneumotachographic measurement of rate of gas flow or, by integration, volume of gas flow. 2. Ventilation of O 2 and CO 2 by continuous measurement of gas levels during phasic ventilation. This also provides breath-by-breath respiratory quotient. 3. Distribution of inspired gas by open circuit He++ washout curve. 4. Diffusion of inspired gas by an open circuit CO diffusion technique. 5. Perfusion of pulmonary capillaries by an open circuit N 2 0 washin-steady state-washout curve. This approximates cardiac output.

The unit, except for foreign gases used in small concentrations in the studies, is a noninvasive method of study with no chance for bacterial contamination of the patient. As such it provides noninvasive data on both pulmonary and cardiac function, simply on the basis of the subject's breathing. To accomplish these ends, certain compromises in methodology have been made which will be pointed out. The errors introduced by these compromises are of small magnitude and constant for any given patient so that trends of change can be reliably detected. Alternate methods for studies will also be pointed out so that interested investigators will be aware of the possibilities. Otherwise our current model will be used as a framework for discussion of equipment and methodology (Fig.3A).

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EQUIPMENT Gas Supply All of our determinations are made with open system techniques. Mobility of equipment and the large ventilatory volumes of some sick patients made closed bag and box systems impractical. To effect this we use carefully assayed inspired gas mixtures from portable cylinders. To control gas delivery in the cooperative patient a demand type valve is used, similar to those used in scuba diving (Fig. 3B). No attempt to monitor delivered volume is made. In unconscious or anesthetized patients, the same cylinders are used with volume-cycled ventilators to supply the inspired gas mixture. In pressure-cycled ventilators, they supply the gas and also the pressure to drive the ventilator. Depending on the gas detection systems used, it may be necessary to have each foreign gas in its own cylinder mixed with air or oxygen, or to use a mixing valve. This will depend on the ability of the detection system to discriminate the gas under study. For instance, if two gases are detected by infrared absorption, each will be additive to the other. If one is known the other can be subtracted. An alternate method for providing the inspired gas is to make the desired mixtures with a gas pump and to store them in a large weather balloon equipped with a two-way valve. This loses the advantages of pressurized gas cylinders previously noted. It is desirable, however, to have appropriate concentrations of all the foreign gases mixed in a single cylinder for the sake of convenience and portability.

Mouthpiece A variety of arrangements is available for this purpose. We have chosen the Rudolph one-way valve because of its small volume, ease of cleaning, and rapid response to small gas flows. It has been modified by tapping it at three points for inspired, mouth, and end-tidal gas sampling (Fig. 3, C and D). A Fleisch pneumotachograph was ground to precisely fit the mouth side of the valve. By fitting this inside the valve the dead space of the whole assembly is 10 cc. The ports on either side of the pneumotachograph screen are attached by short tubes to a Statham PM-5 differential pressure transducer. This gives the gas flow or volume during ventilation. The esophageal pressure is measured by a second Statham PM-131 TC differential pressure transducer with the pressure drop across the valve and pneumotachograph screen subtracted by using mouth pressure as a reference. The pressure in the esophagus is measured with a special thin-walled balloon. The pneumotachograph screen is heated electrically from connections to the central module. Recently Spitzer et al. have described a rotating valve assembly used in study of trauma patients. 25 Using this apparatus they determined minute ventilation, O 2 consumption, pulmonary mechanics, nitrogen washout, and carbon monoxide diffusing capacity by the rebreathing method.

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Figure 3. A, A, Bedside Bedside pulmonary pulmonaryfunction function unit. left is is cylinder cylinder of of gas gas with with demand demand unit. At At left valve, and in front of of it it the the strain strain gauges gauges and and mouthpiece. At center center is is meter meter console console with with gas meters and switching switching valve valve assembly. assembly. Note Douglas bag attached to expired gas port at bottom. At right is recorder-amplifier unit with rapid-writer attachment. B, Gas cylinder with reduction valve and demand breathing valve (lower left) for delivery of foreign gases. C, Mouthpiece disassembled to show ported Rudolph valve (left), support arm (center), and Fleisch pneumotachograph (right). D, Mouthpiece assembled. Note cord to electrical supply for heating pneumotachograph screen.

Switching Valve One of the essential technical features in our unit is an automatic switching valve. This unit contains five solenoid valves, activated by turning a knob, that sample room air, calibrating inhaled gas, mouth gas, end-tidal gas, and mixed expired gas (Fig. 3E). The samples are pulled through the various gas meters by a vacuum pump and can either be dumped into the atmosphere or returned to the expired gas sampling port by a switch. The end-tidal sample is obtained just distal to the exhalation valve. Sampling is triggered by a pressure-sensitive switch connected to the solenoid. This opens the solenoid just at the beginning of negative pressure during voluntary ventilation or positive pressure during mechanical ventilation, and sucks in the sample of gas last expired from the lung. Inside the unit there is a 3 liter chamber with a rotor through which the expired gas passes. This provides the mixed expired gas samples.

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Gas Meters Following the solenoid switch for the appropriate sample, the vacuum pump pulls the gas through one or more of five gas meters.':' They are: (a) paramagnetic O2 meter, (b) infrared absorption CO2 meter, (c)katapherometric He++ meter, (d) infrared absorption CO meter, and (e) infrared absorption N 2 0 meter. The meters are mounted together in a single console along with the switching valve. This console is equipped with large diameter wheels for easy movement (Fig. 3F). These meters have proved linear and stable and, in the case of the oxygen and carbon dioxide meters, rapid enough in response for phasic breath-by-breath analyses. These two meters are set to respond on a synchronized time base so that each breath can be analyzed for exchange of both gases and an instantaneous respiratory quotient is available. After passage through the meters, the sampled gases are returned to the expired gas line. The gas meters of this unit are one part of the unit that could benefit from newer technology. There are now mass spectrometers available of a ':'Supplied by Instrumentation Associates of New York and made by Godart, N.V., Bilthoven, Holland.

Figure 3.3. Continued. Continued. Figure E, Switching Switching valve valve showing showing E, portsfor for entry entryof ofmouth mouth,, inhaled, inhaled, ports end-tidal, and and expired expired gas gas samsamend-tidal, ples. Knob Knob controlling controlling solenoids solenoids ples. is seen seen at at center. center. is F, Gas meter console with (top to-bottom) CO" He++, 0" N,O, switching valve, and CO meters. Along each side is a bracket to support the mouthpiece-differential pressure transducer assembly. This unit is equipped with a central fuse panel, a retractable power cord, and large wheels. G, Recorder-Amplifier unit with transducers attached to two upper channels and the flow channel patch cord connected to gated integration channel for volume. Protractor is attached to face of small oscilloscope for direct reading of resistance and compliance. Gas meters are attached to D.C. amplifiers at bottom center.

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size and price to make them suitable for use in such a unit. The advantages of spectrometric analysis are several. Calibration is much simpler and more easily maintained. Size of the gas sample for testing is very small. Pressure effects on the meters are negligible. Total water content of inspired gas can be monitored, and this has recently been reported as an important factor in ventilation therapy.5 The drawbacks of spectrometric analysis will lie in the resolution of gases with approximate molecular weights. This problem can be solved by utilization of other foreign gases where necessary, such as acetylene, for determination of pulmonary capillary perfusion instead of nitrous oxide. These are minor considerations weighed against the practical efficiency of the method and the stability of the equipment. Volume Measurement At the base of the console there is a port from which all expired gas exits. To this port a respirometer or a Douglas bag is connected, depending on whether the gas is desired for further study or a simple measure of volume of ventilation is sought. Minute volume is also available by integration of the flow obtained with the pneumotachograph. Signal Amplification, Modification, and Recording We use the Electronics for Medicine DR 12 as a recording system." The two differential pressure transducers used in determination of mechanics of breathing are attached to Model SGM amplifier channels. The flow signal is further passed to a Modell.R.D. gated integration channel which, when desired, brings back the volume slope to zero each time flow changes direction. Esophageal pressure is plotted against either flow or volume on the small oscilloscope as a loop vector display. A protractor fitted over the face of this oscilloscope allows instantaneous computation of dynamic resistance or compliance by simply aligning its movable portion with the long axis of the loop. Either the linear data or the loop can be recorded for calculation. The gas meters are connected to the recorder by a common cable with a junction box on each end and thence to Model DCT direct current amplifiers. In addition there are available two SGM channels for vascular pf¢-ssure monitoring, a Model TMD temperature channel, and a Model EEP channel for electrocardiogram or electroencephalogram recording. The output of these channels is presented on the large oscilloscope and, for calculation or permanent records, is photographically printed by a Model RWR rapid writer automatic developing attachment (Fig. 3G).

METHODS OF CLINICAL UTILIZATION Ventilational Mechanics The basic assumptions in the study of dynamic pulmonary compliance and resistance were delineated by Rahn, Otis, Mead and others. 20 - 22 Ambiavagar and Roberts, and Shimizu and Lewis have described *Supplied by Electronics for Medicine, White Plains, New York.

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methods similar to those we use in the clinical setting. 1 • 24 The specific method used with the compliance and resistance protractor of the Electronics for Medicine recorder was described by Burdick. 8 The pressure differential across the pneumotachograph is calibrated with known gas flows. In use the flow is set on the vertical axis and the pressure difference between the mouth and esophagus on the horizontal axis of the oscilloscope. By aligning the protractor with the long (flow) axis of the loop, resistance can be read directly off the scale on the protractor. If the flow signal is passed through the gate mode and integrated against time, a signal is generated which returns to zero as flow reverses in either direction. Display of this volume on the vertical axis against the esophageal pressure on the horizontal axis creates a loop of dynamic compliance which, again, can be computed directly with the protractor. These loops can be recorded by the camera on the DR 12 and the individual linear components can also be recorded for calculation if desired (Fig. 4). From these values the work of breathing can also be computed. Increased resistance was largely due to large airway obstruction with mucus. Decreased compliance was more often seen with atelectasis, small airway plugging, stiff lungs due to a variety of causes as varied as mitral valve disease and "shock lung," and stiff chests after injury or thoracotomy. As compliance decreases and the work of breathing increases, mechanical ventilation may be indicated. This is specially true when the cardiac output is fixed by myocardial disease or injury. Often the compliance can be seen to improve remarkably when more adequate ventilation is established along with continuous positive pressure breathing which tends to open atelectatic pulmonary units. Definite compromises with the most advanced techniques for pulmonary mechanics are present in our unit; for example, the addition of a shutter in the mouthpiece for static compliance as described by Spitzer and his co-workers. 25 Despite this we feel the errors seen with our method

Pressure 0 ----~;:::.:;:ft'~c~:..._--------Esophageal _ _ _ Pressure

Volume---

Flow -

o--~--~--~--~~---+--~'----r-

Figure 4. Linear record of values for calculation of ventilational mechanics. Values required for compliance or resistance are given simultaneously. At top is the esophageal pressure, at bottom is the gas flow rate, in the center is the gated integration or volume curve. Patient was on voluntary ventilation.

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C02 Vols.%

V~;'% ~~ 210 20 19

~~--~~~----~~----~~~--~~~

18

•.~~l~O C02

Vol~%

20 . 19 18

Figure 5. Phasic 02-C02 ventilation record. At bottom is normal ventilation with CO2 curve above 0 per cent line and O 2 curve below 0 per cent line. At top is same subject hyperventilating. Note decrease in end-tidal CO2 level and decrease in O2 uptake with each breath. Subject was breathing room air.

approximate 5 per cent, and we are able to study the patient under any circumstance. Additional information on mechanics is available when the patient is on mechanical ventilation, as the tidal volume can be varied and a pressure-volume curve generated. In the anesthetized patient, chest wall resistance is reduced and quite accurate values for the compliance of the lung itself can be obtained. Ventilation Timed volume of ventilation is available from three sources with this unit. The pneumotachographic volume can be made additive rather than gated to return to zero and plotted against a time base. At the exhalation port of the meter console we have attached a Wright Respirometer which can take a timed reading of ventilation, or a Douglas bag can be attached to this same port and a timed sample passed from it through a dry gas meter. As previously mentioned, the gas used for sampling is returned to the line before it reaches this port so there is no volume loss due to sampling volumes. With the switching valve on the "mouth" setting in our unit, the portions of this ventilation represented by oxygen (0 2 ) and carbon dioxide (C0 2 ) are seen for each breath as phasic curves which are continuously displayed on a volume per cent scale (Fig. 5). For CO 2 this will always increase from a baseline of zero volumes per cent to an end-tidal high dependent on ale volar ventilation. The baseline for oxygen can be set at any given F\ O 2 and will always decrease to an end-tidal low dependent on oxygen uptake in the lung. The information available in these parameters includes the volume of ventilation of O 2 , the volume of ventilation of CO 2 , and the respiratory quotient for each breath. From these curves extrapolation will yield the arterial O2 and CO 2 content in volumes per cent, since the end-tidal concentration will equal the arterial level if there is no diffusion block. This

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is especially true of CO 2 , which has a greater diffusibility than O 2 , Conversely, if direct arterial readings of these volumes are available, a comparison of the arterial and alveolar values will reveal a diffusion block for either gas. With arterial and venous values of either gas available, the cardiac output can be calculated by the Fick principle since volumes per cent of O 2 and CO 2 consumed and expired are available. The curve configuration of the capnogram is an indirect indication of the homogeneity of alveolar ventilation. In the healthy lung the shape of the wave is nearly square with a flat plateau top. When there is unequal ventilation, this plateau rises from the end of the sharp deflection representing anatomic dead space to the end-tidal value as progressively less ventilated alveoli empty.14. 16 Analysis of this curve and the end-titdal value can be used to control mechanical ventilation both as to volume of ventilation and the design of the ventilator's gas flow pattern. With the switching valve set on "end-tidal" a continuous end-tidal value can be displayed if desired. This can be useful for long-term follow-up of mechanical ventilation by less skilled personnel, as deviations in the level of end-tidal CO 2 are easily detected.

Distribution Even though the minute volume of ventilation may be adequate in a given patient, the P a c02 and/or P AC0 2 may remain elevated due to an abnormal relationship in the ratio of ventilation to perfusion (V/Q).4 Reduction of ventilation to portions of the normal lung results in local vascular hypoxia and concomitant decreases in blood flow, thereby normalizing the V/Q. In certain situations, however, there may be circumstances that defeat this adjustive mechanism. In chronic obstructive lung disease a portion of the lung, called the "slow space," ventilates oxygen and CO 2 much more slowly than normal. 13 This portion, which may comprise as much as three-fourths of the lung volume, may receive as little as onetenth of the ventilation but be perfused by half the blood flow. Hypoxia will then result because the well ventilated or hyperventilated areas can only saturate the blood passing them while the other half remains unsaturated. 15 Other causes of unequal V/Q ratio are obstruction of small airways by mucus, plasma, or blood, collapse of the lung, flail chest with decreased aeration of the underlying alveoli, pneumonitis, and the type of rapid shallow breathing often seen after surgery on chest and abdomen. 2 Nitrogen washout studies as a way to determine the distribution of gas in the lungs have already been alluded to as a preoperative study. The gas distribution characteristics of the phasic CO 2 curve have also been discussed. Nitrogen washout coupled with spirometry can give a very accurate picture of the slow space contribution. A high percentage of the patients we wished to study were not breathing room air and therefore could not be studied by N2 washout. A foreign gas was needed which could be washed in and out of the lung, which dissolved negligibly in pulmonary tissue, and which was not readily absorbed by the blood. For our equipment He++ was chosen. In a unit designed for mass spectrometric gas analysis, argon might be more suitable as a test gas. An additional consideration related to the usual range of the gas meters and the physi-

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% He'" Concentration

-5

Figure 6. Helium washout curve made with end-tidal sampling. Flow and volume from pneumotachograph at bottom. Note stepwise decrease of He++ curve with each respiration.

cal behavior of helium vs. nitrogen is that the nitrogen washout technique may underestimate the "slow space" and give a false functional residual capacity. 13 The reader is referred to the detailed article by Hickam and his coworkers on the characteristics of, and computations related to, functional residual capacity derived from the open circuit helium wash-in wash-out curve. Based on some of the assumptions put forward in this article we have chosen the wash-out curve as most representative of "slow space" contributions. We have chosen to work at a helium concentration of 5 per cent. This gas is breathed from the gas cylinder-demand valve arrangement as previously described. Then with the switching valve set for either the end-tidal or mixed expired sample, the patient is turned back to room air or whatever F , 0 2 he was being given. A washout curve is then created which is smooth in the mixed expired curve or stepped in the end-tidal curve (Fig. 6). In either case this is related to the volume of ventilation obtained by pneumotachograph, spirometer, or Douglas bag collection, depending on what further analysis is to be made. As described by Hickam et al., the functional residual capacity, the contributions of fast and slow spaces, and the corrected functional residual capacity can be computed. '3 Alternately, or more simply, the volume of ventilation and/or the time required to wash-out to 0 per cent He++ can be used to obtain an approximation of the improvement or worsening of gas distribution patterns in a given patient with serial studies performed during the course of treatment.

Diffusion The diffusion of O 2 and CO 2 across the alveolar-capillary membrane, plasma, and erythrocyte is essential to the proper respiration of the patient's tissues. The efficiency of this movement of gas can be found if the difference in partial pressure in blood and alveolus is known and if the rate of transfer can be determined. A number of extraneous factors will influence such studies in the clinical patient including: concentrations of

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O 2 and CO 2 in the alveoli, a thick alveolar wall, a thick capillary membrane, separation of these membranes by fluid or fibrosis, intra-alveolar fluid, dilation of capillaries, a decreased number of functioning capillaries or alveoli, exercise or other causes of increased cardiac output, the number of erythrocytes and their Hgb content in the capillaries, and the rate of transfer and association across the membrane and interior of the erythrocyte. 6 As used in our unit those deviations due to airway distribution patterns will be detected by the helium wash-out studies just described. Those related to perfusion will be dealt with in the section which follows. Thus we are seeking the true pulmonary diffusing capacity which includes the movement of gas across the membranes and into the erythro~\ cyte. Although high degrees of alveolar-capillary block may produce a slight barrier to CO 2 exchange, clinical problems are usually related to O2 transfer because it is much less diffusible than CO 2 , Although all of the values necessary to a direct calculation of the diffusion capacity of O2 are available with our equipment, we have again selected a foreign gas that can be introduced into the system irrespective of the oxygen concentrations the sick patient may be breathing. The only gas other than O2 with a hemoglobin affinity is carbon monoxide (CO). It in fact has such an incredible affinity for hemoglobin that maximum saturation could be attained with a Pco of less than 1 mm Hg. Selection of the best method to determine CO-diffusing capacity for our clinical setting was difficult and again required a compromise. Because we were able by other studies to identify perfusion and ventilation abnormalities we selected the end-tidal method. 3 This was particularly suited to our switching valve which can give inspired, end-tidal, and mixed expired values at the turn of a knob. The volume of ventilation is also available as described. Breath holding techniques are not feasible in many of the patients to be studied, and if we wish to remain noninvasive we must substitute the end-tidal value of CO for the P aC02 of the Filley method which requires arterial puncture.1O When the discrepancies of ventilation and perfusion can be identified, there is good correlation of the two techniques. 19 In practice the CO-containing gas mixture is introduced through the demand valve at known concentrations with the switching valve set to the "inspired" position and the FICO recorded. Then the valve is switched to "end-tidal" position and the patient allowed to breathe the gas until the level of end-tidal F ACO is stable. Then for 1 or 2 minutes the volume of ventilation (V) is recorded and the valve switched to "mixed expired" and FEco recorded. The computation is then: DLCO =

(FICO - FEco) x V F ACO X (barometric pressure - 47)

This study can be repeated with ease when following the course of such alveolar-capillary block problems as acute pulmonary edema, shock lung, or the transplant rejection syndrome. 7 In a unit set up for mass spectrometric gas analysis, CO diffusion studies are complicated by the similarity in molecular weight of nitrogen

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and CO. Wagner et al. have described a solution to this problem using C1SO isotope to obtain a discernible difference in mass. 27

Perfusion In order for gas exchange to occur between the tissues and the alveoli, blood must flow through the lung and, more particularly, past ventilated alveoli. Nitrous oxide (N 2 0) was the first gas used to define this pulmonary capillary blood flow.17 This was based on the equal solubility of N 20 in the alveolar capillary membranes and the blood, and on the fact that the plasma saturates rapidly so that any uptake of N 2 0 from the alveoli must be produced by the flow of fresh plasma past the alveoli. The method was abandoned because a stable alveolar concentration could not be achieved before recirculation appeared in patients with uneven gas distribution. Lee and DuBois developed a method for instantaneous measurement using a body plethysmograph, and Wasserman and Comroe modified the technique using the fixed thorax as the plethysmograph. 193, 28 U sing this technique and computer subtraction of the spirographic curves described while breathing air from the curves described while breathing N 2 0, Greenberg et al. have clinically analyzed both the instantaneous pulmonary capillary blood flow and the characteristics of the capillary pulse wave in a group of patients undergoing cardiac surgery. 12 We have chosen to use a method in which either a steady-state N 2 0 absorption slope or direct measurement of F]N 2 0, F EN 2 0, and F AN 20 is the basis of computation of pulmonary capillary flow (Qc). These methods have shown a high degree of correlation with Qc derived from the Fick equation for oxygen, and good internal correlation of multiple determinations in individual patients at rest and exercise. 26 An open system is used. The patient inspires a known concentration (4 to 5 vols. per cent) of N 2 0 checked with the switching valve in "inspired" position to get F 1N20, then allowed to breathe the gas mixture with the switching valve in "expired" position until the wash-in is complete and the level plateaus at F EN20. The switching valve is turned to "end-tidal" and a reading taken for F AN 2 0. From this the calculations are:

(Where V is the volume of ventilation recorded from either the pneumotachograph or respirometer, 0.91 the factor to correct ventilation volume to S.T.P.D., 0.42 the Bunsen absorption coefficient for solubility in blood, and P B the barometric pressure.) When used in conjunction with the helium wash-in curve, a very accurate point of complete mixing can be obtained for the value of F E N2 0 and F AN 2 0. In patients with a marked obstructive component, a steadystate technique is used similar to that used in the Filley technique of CO diffusion. Again the patient is allowed to breathe a 4 to 5 vol. per cent mixture of N 2 0 and the "mixed expired" sample curve recorded. The wash-in curve rises to a "steady-state," after 3 minutes the patient is switched to an inspired gas with no N 2 0, and a wash-out curve is

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described. The time required to wash-out to 20 per cent of F]N 2 0 is read (KT) and this time is divided by 2 (K2~' This half time is marked off from the start of NzO breathing on the curve. The point of intersection of this line (~T) with the slope of the steady-state plateau level is used to determine F E N2 0 (Fig. 7). These methods give very reliable Qc values based on a foreign gas and free of the limitations in the Fick method for O2 due to high F]o2 levels or abnormalities in the oxygen-carrying capacity of the blood in sick patients. Alterations in capillary perfusion occur due to conditions other than change in cardiac output. These include anatomic shunting in the heart or lungs, blockade of pulmonary vessels by fat or thrombotic emboli, and destruction of pulmonary vessels by emphysema.

SUMMARY A unit for monitoring ventilation, ventilational mechanics, gas distribution, gas diffusion, and pulmonary capillary perfusion of the lungs has been described suitable to bedside investigation of these functions in very ill patients. Where pertinent some alternate methods of investigation have been suggested. This unit has been devised in the hope that bedside study of pulmonary functions in these sick people will have the same impact on descriptive clinical pathophysiology and treatment of pulmonary disease as bedside measurement of hemodynamics has had in the decade just past.

F'N,O

FEN20

..=t---------------_

3

I---,'-rdj-ng-'-tea-d-y,-ta-te-"'"

1 ---: I

6. FEN 2 0

l~,,~~ N2 0

I

- - = CO'lstant

I

6t

I I I I I

tlme=t(min) respiration

end

Figure 7. Nitrous oxide wash-inisteady-stateiwash-out curve. Note gradually riSing plateau as progressively more N 2 0 recirculates, and also intersection of line drawn along it to intersection with Kti2line where F EN,O is read. Explanation of curve is given in text along with calculations for Qc.

1042

WILLIAM

A.

COOK

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