STUDIES ON THE INTRAPULMONARYMIXTURE OF GASES.III. AN OPEN CIRCUIT METHODFOR

MEASURINGRESIDUAL AIR

By ROBERTC. DARLING, ANDRECOURNAND,AND DICKINSON W. RICHARDS, JR.

(From the Research Service, First Division, Welfare Hospital, Department of Hospitals, New YorkCity,' and the Department of Medicine, College of Physicians and Surgeons,

Columbia University, New York City)

(Received for publication March 12, 1940)

In the preceding paper, the use of the closedrebreathing circuit for measuring residual air wasdiscussed and tested to determine the possibleerror due to imperfect gas mixture within thelungs. It was found that such an error wasprobably present not only in all cases of severepulmonary emphysema, but also in some normalsubjects with large residual air. Some of thereasons for the inadequacy of the closed circuitmeasurements are apparent from analysis of theessential features of such a circuit. In the firstplace, the inspiratory gas mixture is alwayschanging. Thus there would appear to be nosustained equilibrium between spirometer andlungs. As soon as equilibrium is approached forone concentration of the breathing mixture, theinspiratory gas has already changed. Thischange is most marked when the spirometervolume is allowed to diminish as oxygen isabsorbed. McMichael's technique of replacingthe oxygen, as tested by us, did not remove thediscrepancies due to poor mixing within thelungs. Furthermore, such a procedure intro-duces further technical difficulty and fails tochange the fact that the inspiratory gas is stillvarying, at the start, until approximate equi-librium is reached. In our experience, the ad-justment of a proper flow of oxygen for replace-ment was difficult even in normal subjects. Insubjects with arterial oxygen unsaturation, themaintenance of a constant volume in the closedcircuit was practically impossible due to theoxygen deficit and resultant changing rate ofoxygen replacement necessary.

The second difficult feature of closed circuitmeasurements is the exact calculation of theoxygen absorbed. The tracings in abnormal and

1 Formerly Research Division, Metropolitan Hospital,Department of Hospitals, New York City.

even in some normal subjects are often so irregu-lar that an exact base line cannot be drawn, yetthe calculation demands accuracy in this detail.

Thirdly, with the usual closed circuit tech-nique the net change in lung nitrogen concen-tration is rarely more than three-tenths of anatmosphere. With such a figure, any error inalveolar measurement (or in the assumed values)is magnified at least three-fold in the final resi-dual air value.

To avoid these three points of difficulty, anopen circuit method has been devised, with pureoxygen as the breathing mixture. In such aprocedure, the subject is allowed to breatheoxygen for a period of time sufficient to washpractically all the nitrogen out of the lungs. Forthis period all the expired gases are collected andfinally measured and analyzed for nitrogen. Itwill be seen that the inspiratory gas is absolutelyuniform throughout and that there is no needto obtain a smooth breathing curve once theoxygen breathing has been started at a definitepoint in the breathing cycle. As in the closedcircuit, the concentrations of gases in the pul-monary spaces at start and end are estimated byalveolar specimens, yet here the simpler featuresof the procedure make these measurements lesssubject to error. Furthermore, since the netchange in alveolar nitrogen is approximatelyeight-tenths of an atmosphere, the effect of errorsin these measurements will not be greatly mag-nified in the course of calculation.

Thus the only errors that are to be anticipatedin this method are those due to failure of thealveolar measurements to represent the meanvalue of residual air nitrogen. It is possible topredict the probable direction of such error.Except in unusual circumstances, the alveolarspecimens in cases of poor distribution will tend

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ROBERTC. DARLING, ANDRECOURNAND,ANDDICKINSON W. RICHARDS, JR.

to represent the well aerated portions of thelungs, and to neglect the relatively poorly aeratedregions. Thus, in estimating the lung nitrogenconcentration on room air breathing at the start,the alveolar specimen obtained may be lower innitrogen than the average in the lung. Similarly,the alveolar specimen after a period of oxygenbreathing may fail to tap some nitrogen stillpresent in the poorly aerated regions and so besomewhat too low as measured. If breathing iscontinued long enough, the latter error shouldbe gradually reduced, since it is obvious thateventually all the nitrogen will be washed out.The expression used in the calculation is thedifference of the two alveolar values, "alv. a- alv. p." The likely error in each is a negativeone. If the errors are equal, they will canceleach other. However, since that in "alv. p" isprobably very slight, the expression "alv. a- alv. p" may be too small. Since this expres-sion is the denominator of a fraction in the cal-culation, the final value for functional residualair by this method could be somewhat too large.

To take an example, an alveolar specimen in acase of emphysema might give a value of 82 percent of nitrogen, when the average of all residualair nitrogen is actually 84 per cent. At the endof the period of oxygen breathing, let us say thatthe mean nitrogen of the residual air is 6 per cent.If the alveolar specimen as measured gives 4 percent of nitrogen, then the alveolar difference(0.82 - 0.04) will be the same as the true dif-ference of nitrogen concentrations in the residualair (0.84 - 0.06), the two errors thus cancelling.It is difficult to see how an error of method largerthan 5 per cent would be likely from this source.

An attempt has been made to test for thepresence of such an error. This test, analogousto that used for the Christie method in a pre-vious paper, consists of a similar type of experi-ment in which the expired gases are collectedduring a period of breathing room air immedi-ately following prolonged oxygen breathing. Inother words, first all the nitrogen is washed outof the lungs; then, during a subsequent period ofroom air breathing, the amount of retainednitrogen in the lungs is measured.

Such a procedure is really a reversal of theoxygen breathing experiment, in so far as thedirection of the nitrogen shift is concerned. In

this case, errors in alveolar measurement willcause an effect of opposite sign in the value ob-tained, as can be seen from analysis of the factorsinvolved. Here the expression " alv. p - alv. a "is the denominator of a fraction in the calcula-tion. Alv. d, measuring the small nitrogen con-centration after oxygen breathing, may possiblyneglect nitrogen still trapped in the poorlyaerated regions. Thus it is too low, if at allwrong. Similarly, alv. p, taken after a subse-quent period of room air breathing, may be toohigh in nitrogen, since there may be some higheroxygen mixture still in the poorly aerated lungspaces. Thus the difference, "alv. p - alv. a,"may be definitely too high, and from this, theresidual air value too low. In contrast to theoxygen breathing experiment, from predictions inthis case a cancellation of errors in alveolarmeasurements will be unlikely. Therefore itmay be expected that this second open circuitmethod will be more likely to give erroneousresults than the first method.

The test of the open circuit procedures will bea comparison of residual air values obtained bythe two methods. If they differ, it will be evi-dence that the factor of poor mixing, as it in-fluences alveolar samples, is still a possible sourceof error in the measurements. If they agree,one may consider the value obtained probablynot significantly affected by erroneous alveolarmeasurements. It will be of special interest tocompare this evidence with that obtained in thesame subjects by the analogous test procedurein the closed circuit, reported in a previous paper.

PROCEDURE2

The apparatus for the open circuit methods was thesame as that used for nitrogen excretion measurements inthe first paper of this series. The diagram is reproducedhere. The arrangement consists essentially of two openbreathing circuits fitted with flutter valves (F1, F2, F3, F4)connected adjacent to the mouthpiece (M) at the valve(V1), which can be used to shift the breathing from onecircuit to the other. One circuit, the main circuit, isattached on its inspiratory side to a rubber anesthesia bag(B1), this in turn to an oxygen tank. The expiratory side

2 In collaboration with Dr. Eleanor D. Baldwin, we haverecently devised a simplification of this open circuitmethod, based on results in 200 cases studied. In thenew technique, alveolar sampling is eliminated, the onlygas analysis necessary being that from the spirometer.This will be reported in a subsequent paper.

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INTRAPULMONARYMIXTURE OF GASES

Main circuit

'==Z Side circuit

F.

V4Vs

T --,%

e

7

F

T:

Z.

a.Z.

1-1-

FIG. 1. OPEN CIRCUIT APPARATUSFOR MEASUREMENTOF RESIDUAL AIRM, mouthpiece. Alv., group of three evacuated gas sampling tubes. VI, V2, V3, V4, three-way

respiratory valves. F1, F2, F3, F4, one-way rubber flutter valves. B1, B2, small rubber anesthesia bags.T, one-hundred liter (Tissot) gasometer. S, valve and attachment for obtaining gasometer samples.For further explanation, see text.

leads to a Tissot gasometer of 100-liter capacity. On theside circuit there is an additional valve (V2) with which theinspiratory gas flow can be cut off during alveolar sampling.The inspiratory arm of this circuit leads to an anesthesiabag (B2) and oxygen tank, which were replaced by a tubeleading from outside air when atmospheric air was thedesired breathing mixture. On the expiratory arm evacu-

ated sampling tubes labelled "alv." are inserted close tothe valve (V2). The dead space from mouthpiece to thesetubes is about 100 cc.

The procedure for a determination of functional residualair by the open circuit method was started with VI turnedto the side circuit. The main circuit and gasometer were

thoroughly washed out with oxygen. Six successive wash-ings of 10 to 20 liters each were found adequate. Afterthe washing, V, was opened to connect the main circuitto the open room and a flow of 4 to 5 liters per minute ofoxygen maintained in this circuit. The bag (B2) in theside circuit was replaced by a room inlet tube. Then withV1 unchanged, the subject, under basal conditions, was

attached to the mouthpiece. When breathing quietly, hewas instructed to exhale maximally for an alveolar sample.At the same time, the valve (V2) was turned to close the

inspiratory side of the circuit. The alveolar sample was

taken at the end of approximately five seconds of expira-tion and V2 then reopened. This sample, designated"alv. a," was thus a Haldane-Priestley alveolar sampleand represented an attempted measure of average lunggas concentration on room air breathing.

Following this sampling, at least two minutes of room

air breathing were allowed in order to restore quiet breath-ing. Then V3 was turned to direct the oxygen flow of themain circuit into the gasometer and V1 was turned to themain circuit at exactly the end of a normal expiration.By watching carefully the respiratory rhythm for thefew previous breaths, this latter valve turn could be madeaccurately at the desired moment.

For the next seven minutes of oxygen breathing theexpired gases were collected in the gasometer. Duringthis time, the oxygen flow was maintained to keep thebag (B1) about one-half full. The period of seven minuteswas the standard one used. Results of trials with longerperiods will be presented to show that seven minutes isprobably adequate.

At the conclusion of the seven minutes, the valve (V1)was again turned to the side circuit, this time at any point

AIv

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ROBERTC. DARLING, ANDRECOURNAND,ANDDICKINSON W. RICHARDS, JR.

during expiration, preferably near the beginning. At thesame time, the subject was instructed to expire fully foran alveolar sample. For this, as for all alveolar sampling,the valve (V2) had been turned to close the inspiratoryarm of the side circuit. This alveolar sample, designated"alv. p," was taken at approximately five seconds ofexpiration as before.

Following this, the patient was disconnected and themain circuit flushed out with 5 to 10 liters of oxygen, thewash gas being allowed to mix in the gasometer with thecollected expired gases. The valve (V,s) was next turnedto close the entire gasometer contents, whose volume andthe temperature were then recorded. A sample was takenfrom the gasometer for analysis within one to two minutes,after first flushing out the inlet and outlet pipes of thegasometer proper with the collected gases. This samplewill be designated as " Tissot" sample in future references.

An approximation of the dead space of the gasometerwas necessary for the final calculation. It will becomeapparent from the calculation to be discussed that thisneed only be an approximation. With the procedure asoutlined, the effective dead space consisted only of thegas space under the bell when fully lowered. The dimen-sions of this space were measured and its volume calculatedgeometrically. The volume of the tubing did not need tobe considered, since it was filled with oxygen at both thestart and the end of the experiment.

Each experiment required the analysis of three gassamples, two "alveolar" and one "Tissot." In addition,the contents of each new oxygen tank required analysisfor the small amount of inert gases. All gases wereanalyzed with a Haldane gas analysis apparatus. In thecase of the samples of very high oxygen content, the dilu-tion method was employed, as described in the first paperof this series. (The Van Slyke-Neill manometric appa-ratus can also be used for gas analysis.) Analysis of thealveolar specimens required an accuracy of only 0.1 to0.2 per cent, so that possibly a simpler method might beemployed. However, a high degree of accuracy was neces-sary in the analysis of the Tissot sample. In all cases theanalyses were done in duplicate to check within 0.05 percent. All analyses were reported as decimal fractions ofan atmosphere of nitrogen, as dry gas.

CALCULATION

The first step in the calculation requires an expressionfor the total nitrogen in the expired gas in excess over thatinspired. The volume of expired gas is known, but thatinspired unknown. However, the nitrogen content of theinspired gas is so low that no significant error is involvedby assuming that the inspired volume equals the expiredvolume. The gasometer volume obtained and correctedto dry gas at standard temperature and barometric pres-sure will be designated as V0. To this the measured deadspace volume (D.S.) has been added for the calculation.Then (1) Total excess N2 in gasometer

= ( Vo+D.S.)(" Tissot" N2- "02 tank " N2).Of this, a part has come from nitrogen originally in thelung spaces, a further part from excreted nitrogen from

the blood.(2) N2 from functional residual air (F.R.A.)

= (Vo+D.S.) (" Tissot " N2- "02 tank" N2)-N2 excreted.Also (3) N2 from functional residual air

=F.R.A. Vol. (alv. d-alv. p).(4) F.R.A. Vol.

(Vo+D.S.) (" Tissot" N2-" 02 tank " N2)- N2 excreted

alv. a-alv. pFrom the first paper of this series:

(5) N2excreted = 220 Xalv. d-alv. pN2excreed 220X 0.80

(For seven minutes; 10 cc. added to 220 cc. for eachminute after seven, if longer period.)

Substituting:

(6) F.R.A.(Vo+D.S.)(' Tissot" Nj-" 02tank" N2) 275

alv. d-alv. p

The F.R.A. value here obtained was then corrected totemperature 370 C. and saturation with water vapor toobtain the values reported in our results.

The reversed procedure used to test these results wassomewhat more complicated in practice but similar inprinciple. In this case the bag (B1) was replaced with aninlet tube from outside air. The bag (B2) was in placeand connected with an oxygen tank. In preparation themain circuit and gasometer were thoroughly washed withroom air. The subject was attached to the mouthpiecewith valve V1 open to the side circuit and an oxygenflow of 4 to 5 liters per minute in that circuit. Quietbreathing of oxygen was maintained for ten minutes. Atthe end of that time, an alveolar specimen was taken inthe usual manner and quiet oxygen breathing was resumedin the same circuit for two further minutes. This alveolarspecimen was designated as "alv. a" and considered as ameasure of lung gas concentrations two minutes later, sinceit had been found by a series of tests that the alveolarnitrogen value during oxygen breathing reached a plateauvalue after ten minutes or less in both normal subjectsand patients with emphysema, the maximum change inalveolar nitrogen from tenth to twelfth minute being lessthan 1 per cent.

At the end of the complete twelve minutes of oxygenbreathing, the valve (VI) was turned to the main circuitexactly at the end of a normal expiration. The expiredgases were then collected for a seven-minute period (orlonger) of room air breathing, after which an alveolarspecimen was taken in the side circuit as before. Thetubing of the main circuit was then flushed into the gasom-eter with 5 to 10 liters of room air, the valve (V,) closed,and the gasometer voltime and temperature read. Agasometer sample was taken promptly as before, afterfirst flushing out the tubing of the gasometer itself withthe first part of the collected gas.

As in the previous procedure, there were three gassamples and one volume measurement. In this case, how-ever, the inspiratory volume, as well as the expiratory

612

INTRAPULMONARYMIXTURE OF GASES

volume, needed to be known for the calculation. Sincethe respiratory quotient was normally less than unityunder basal conditions, the inspiratory volume was greaterthan the expiratory volume by an amount of some 200 to400 cc. for the seven minutes. Direct measurement ofthe inspiratory volume with sufficient accuracy was foundto be technically cumbersome. In our experience it was

simpler to decide upon a correction factor (AV) to beadded to the expiratory volume in order to determine theinspiratory volume. To do this the carbon dioxide excre-

tion and the oxygen consumption per minute were deter-mined from a six-minute collection of expired air on room

air breathing, usually done just before the other tests on

the same day. From this, (02 absorbed per minute- CO2excreted per minute) X7=&AV for seven minutes of room

air breathing. This would seem to be an accurate correc-

tion in subjects with normal arterial oxygen saturation.In cases with arterial oxygen unsaturation, however,

there is an excess oxygen absorption during the first fewminutes of oxygen breathing. Following resumption ofroom air breathing after oxygen, there is a diminishedoxygen intake until the arterial unsaturation is reestab-lished. It may be assumed with sufficient accuracy forthe present purpose that the excess oxygen intake in one

instance equals the diminution in the other. Accordingly,in such cases the oxygen deficit of the subject was esti-mated from respiratory tracings taken with a recordingspirometer. This oxygen deficit was subtracted from theAV value obtained above, giving a corrected AV.

The calculation proceeded in an analogous manner tothat in the first method. In this instance there was

nitrogen retained in the lungs instead of washed out.

(1) N2 retained in lung= (Vo+D.S. +A&V)0.791 (Vo+D.S.) Tissot N2-N2 absorbed into blood.

Also (2) N2 retained in lung=F.R.A.(alv. p-alv. a) and

(3) N2 absorbed into blood =220Xalv p-alv. a0.80

(4) F.R.A.(Vo+D.S.) (0.791 -" Tissot " N2) +0.791 XAV 275.

alv. p-alv. d-

RESULTS

The subjects for this study were selected bythe same criteria as those in the preceding paper.

There were four normal subjects, including thetwo in whom the closed circuit method gave

doubtful results. In all there were ten patientswith severe pulmonary emphysema, of whomsixwere included in the series of the previous paper.

These six were studied by both of the new

methods described. The remaining four were

tested only by the first of the two new methods,which is the one proposed as a practical test.

It will be apparent, from the two precedingpapers of this series as well as this present one,

that this new method for residual air has beendevised primarily for the study of cases of ab-normal, unequal, or ineffective pulmonary ven-tilation, in which previous methods, such as thatof Christie, have been found inaccurate. It ison the basis of such unusual or extreme casesthat any new method must be judged. If inthese cases, or at least in a fair proportion ofthem, the method can provide a reasonablyaccurate and consistent measure of residual air,then the method can perhaps be consideredworthy of further trial.

The results should be examined, therefore, caseby case, rather than by any attempt at statisticalanalysis.

The results of tests on these subjects may becompared in several ways.

(1) Comparison of results by each of the twoopen circuit techniques (Table I). This willdemonstrate whether the slowness or poornessof distribution of respiratory gases, in any givencase, is sufficient to invalidate the techniqueused.

TABLE I

Functional residual air determinations by open circuit methods

NORMALSUBJECTS

Decesng Increaing Ratio of aver-Nmbe lung Ns lung N2 agP valuee

Subject Lnth of A _ A _ __ G GilGUittts a-Aver- R Aver-

aOe Cloned

tions -Lg agr cut

minuta.J.L ... . . 5 1220 (1140-1300) 1060 (1005-1090) 0.87 0.98

A.C ... 2 2055 (2015-2095) 1930 (1880-1980) 0.94 1.02

R.C.D. 3 2890 (2695-3000) 2770 (2410-0) 0.96 0.83

D.W.R..I 2 3450 (3250-3650) 3355 (3310-3400) 0.97 0.72

SUBJECTS WITH PULMONARYEMPHYSEMA

M.K.... 2 4065 (4030-4100) 3845 (3760-3930) 0.95 0.72

Ant.C... 2 3225 (3080-3370) 3245 (3760-3250) 1.01 0.88

F.H.... 1 2670 2540 0.95 0.64

J.C ... 7 3 5980 (5940-050) 5450 (5250-5740) 0.91 0.8310 1 6250 5765 0.92 0.87

D.HE... 7 4 3325 (3050-3590) 2855 (2805-2910) 0.86 0.8110 1 3395 3290 0.97

H.K 7 4 2960 (2895-3140) 2095 (1700-2560) 0.71 0.5910 3 3080 (2855-3285) 2490 (2445-2520) 0.81 0.52

* Ratio= average value by increasing lung nitrogenmethod .average value by decreasing lung nitrogenmethod.

t Figures computed from Paper II of this series.

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ROBERTC. DARLING, ANDRECOURNAND,ANDDICKINSON W. RICHARDS, JR.

(2) Comparison of the relative agreement be-tween the two open circuit techniques, with therelative agreement between the two closed circuittechniques. This is given by the two ratios, inthe last two columns of Table I.

(3) Average values by the open circuit methodcan be compared with average values in the samesubject by the closed circuit method of Christie(Table III). This will provide, for any givencase, a criterion as to whether the various sourcesof error in the Christie method do actually cancelout, leaving a residual air value comparable withthat of the open circuit method. In this com-parison it will be important to note not only thedifference of average results, but also to comparethe range or reproducibility of results by the twomethods.

Table I presents the first type of comparison,listing the average open circuit results, the range,and number of determinations. In the twocolumns on the right are listed also the ratio ofthe two values by the open circuit methodsparallel with the ratio of the two closed circuitresults in the same subjects.

Among the four normal subjects, it will be seenthat all agree within 200 cc. These include thetwo subjects, D. W. R. and R. C. D., whoshowed 500 and 900 cc. difference, respectively,with the two closed circuit methods. Thus itmay be seen that in this group of normal subjectsthere is no evidence of serious error due to maldis-tribution in the open circuit methods.

It may be noted that the open circuit methodsin the case of J. L. give somewhat poorer agree-ment than the closed circuit. The reason forthis is not entirely clear. It seems probable,however, that the error lies in the increasinglung nitrogen method. In the case of small sub-jects, the assumed AV factor in this method hasa much larger relative influence on the resultthan in larger subjects.

Considering now the six abnormal subjects, itwill be seen that the first four show satisfactoryagreement between the two methods. Agree-ment within 10 per cent may be considered satis-factory. The fifth subject, D. H., showed a 13per cent difference by the standard seven-minutetest. Using a twelve-minute period, however,there was good agreement. It should be noted

that the only significant change by the twelve-minute test was an increase in the result by thesecond method. This is a part of the evidencewhich leads to the tentative conclusion that aseven-minute period is adequate for the decreas-ing lung nitrogen method.

The sixth subject is the only one in whomagreement could not be reached. This case willbe discussed in detail later.

The striking difference between the open andclosed circuit methods, tested by analogous pro-cedures, is shown in the last two columns, whichmay be considered as comparative indices of theinfluence of poor mixing on the results. It willbe seen that, in every instance among the abnor-mal subjects, the index shows much better agree-ment by the two open circuit techniques.

Table II presents in detail the results on thesubject H. K., the sixth one in Table I, in whom

TABLE II

Functional residual air by open circuit methodsSubject-H. K.

Date Decreasing lung Increasing lungNit method N2 method

December 15, 1938 ..... 2895 2385December 16, 1938 ..... 3095 1700December 20, 1938 ..... 3140 2560December 24, 1938 ... . 3110* 2510*December 27, 1938 .. . 3285t 2520tJanuary 17, 1939. 2700 1735

2855t 2445t

S.D. S.E. S.D. S.E.m

Mean 7-minute value ........ 2960 130 65 2095 510 255Mean 11-minute-12-minute

value .................... 3080 275 160 2490 50 29

* 11 minutes. f 12 minutes.

agreement could not be reached. This subjectwas a man of sixty-five with a history of increas-ing cough and dyspnea for twelve years. Theetiology of his condition was unknown. Therewas no evidence of tuberculosis. There were dif-fuse asthmatic rales, but no improvement withthe use of adrenalin. Roentgenogram of thechest showed increased hilar markings and darkareas at the periphery suggesting emphysematousbullae. His arterial oxygen saturation was 85per cent. At- the time of testing, he was practi-cally bedridden because of dyspnea, though thissymptom varied considerably from day to day.

As shown in Table II, there was a considerablevariation in values obtained for functional re-

614

INTRAPULMONARYMIXTURE OF GASES

sidual air in this subject in experiments continuedover a month's time. It will be noted, however,that the figures by the decreasing lung nitrogentechnique are rather consistent, considering thatthe subject's clinical state varied considerablyfrom one day to the next. It was the increasinglung nitrogen technique which gave the widervariations, and these figures generally are lowerthan the other group. This is the type of errorwhich is to be expected (see above) with the in-creasing nitrogen technique, when intrapulmon-ary mixture is extremely poor. Furthermore, byprolonging the period of breathing such an errorshould become less, and Table II, in the secondcolumn, shows a clear tendency for the figures inthe eleven- and twelve-minute period to be higherthan the seven-minute period. In the first col-umn, little difference is noted with prolongationof the breathing period.

Table III presents the data for comparison ofopen and closed circuit techniques in the same

TABLE III

Comparison of functional residual air values by Christie,modified Christie, and new open circuit methods

NORMALSUBJECTS

Closed circuit Open circuitRatio

Sub- Modified Christie method Decreasing lung N2 ofject M___ __ e~an

Num- Mean Range Num- Mean Range uesber ber

J.L ... 12 1320 (1170-1485) 5 1220 (1140-1300) 1.08A.C.... 2 2235 (2155-2315) 2 2180 (2100-2265) 1.02D.W.R. 3 3540 (3200-3770) 2 3450 (3250-3650) 1.02R.C.D. 5 3250 (2890-3545) 3 2890 (2695-3000) 1.13

SUBJECTS WITH PULMONARYEMPIYSEMA

Ant.C.. 2 3240 (3140-3340) 2 3225 (3080-3370) 1.00A.M. .. 6 2750 (2290-3435) 4 2570 (2550-2600) 1.07K.H... 2 3255 (3240-3270) 2 3590 (3580-3600) 0.91D.H... 2 3140 (3070-3210) 5 3355 (3050-3590) 0.94J.C.... 4 6570 (5980-7760) 4 6050 (5940-6250) 1.08J.S... 2 3630 (3615-3645) 1 3515 1.03F.H.... 1 3020 1 2670 1.13H.K... 3 3835 (3560-4060) 7 3010 (2855-3285) 1.27M.S.... 6 (2230-3750) 8 (2420-3570)M.K... 10 (2245-5260) 12 (2130-4100)

subjects, listing the results by the standardChristie procedure, calculated with alveolar spec-

imens, and by the open circuit method, using thedecreasing lung nitrogen technique.

Among the normal subjects, the first twogave results in close agreement by the modifiedChristie and the new methods, as expected fromthe fact that previous analysis indicated both

methods were reliable. In the case of the thirdsubject, D. W. R., with whom the closed circuitcould not be proved reliable, still the two circuitsgave practically the same results. It is apparenthere that in the standard closed circuit methodthere must have been a fair balance of the variouserrors which were mentioned.

In the case of the fourth subject, R. C. D., inwhom also the closed circuit gave doubtful re-sults, the open circuit gave significantly lower re-sults with less variability on successive tests, andwith a good agreement with both open circuittechniques. Thus it would seem here that thestandard closed circuit method gave an errone-ously high value.

The group of abnormal subjects includes tenpatients. The last two of these were unusualcases, however, and will be presented in detailin a later tabulation.

Considering for the moment the first eight sub-jects only as far as a comparison of the averageresults, it will be seen that the first six show in-significant differences between average open andclosed circuit results. As before, a difference ofless than 10 per cent is considered insignificant.In the seventh case, F. H., and more markedlyin the eighth case, H. K., the closed circuit valuesare significantly higher.

It is probably important that these two sub-jects had the greatest pulmonary disability of thegroup.

Let us next note the reproducibility of resultsby the two methods in these same eight patients.In two of them, A. M., and J. C., the open cir-cuit shows much less difference in successive tests.The other subjects either showed a similar rangeor else the data are insufficient to determine therange. It should be mentioned that the rangeof values in many of the subjects probably re-flects not only the accuracy of the method, butalso the actual volume variation from day to day.

Table IV presents the detailed results on thetwo remaining subjects, M. S., and M. K. Theyare considered together because of their similarclinical pictures and comparable results on re-sidual air determinations. They were both menof slightly under forty years of age, with pro-longed histories of nearly constant asthma andbronchitis. Each had marked arterial anoxemiaand secondary polycythemia. M.K. had had

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ROBERTC. DARLING, ANDRECOURNAND,ANDDICKINSON W. RICHARDS, JR.

Date

TABLE IV

Functional residual airClosed circuit

Modified Christiemethod

Subject-M. S.October 19................

October 24................

October 30 ...... -

November 8...............

November 18*.............

December 26*.............

Subject-M. K.May 7, 1938...............May 13, 1938..............May 17, 1938..............

September 21, 1938.September 22, 1938.October 19, 1939...........

October 21, 1939...........

October 26, 1939...........

October 28, 1939...........

November 15, 1939*........

December 28, 1939*........

22853295

259022303750331024502805

3890355027103125

.42505260

2530224532202955

in each case. Whether either method is alsoin error cannot be deduced from such variable

Open circuit data.Decreasng I re ocniinlung Nn In order to obtain a more stable condition, eachof these subjects was tested in duplicate by bothmethods, following the use of " Vaponefrin "

2420 spray inhalation, or adrenalin by hypodermic in-3110 jection. The results of these tests are listed on

3220 the last two days in each subject. Very little2815 more can be said from these results except that

the variability from test to test on the same day

3140 seems to be reduced. It is obvious that average3210 values in these two subjects have no meaning.2850 One can only conclude that these subjects are un-

suitable for residual air measurements by eitherthe closed or open circuits. Certainly a part ofthis difficulty is due to actual change in the func-tional residual air volume itself. It may be that

4030 poor intrapulmonary gas mixture is a factor, pro-4100 ducing significant errors of measurement. Their

3230 extremely slow mixture is shown by their values2780 for alv. p nitrogen, which were frequently as high2240 as 10 per cent after seven minutes of oxygen21303050 breathing.3605405034502920276029752660

* Tests on these dates performed after the use of "Vapo-nefrin" bronchodilator spray.

several bouts of right-sided cardiac decompensa-tion with massive edema, but was compensatedat the time of these measurements. M. S. hadslight cardiac weakness only, and had had one

episode of mild edema. Each of these patientshad a large element of bronchial spasm in hisdisability, as shown by partial relief with adren-alin; However, free of asthma with adrenalin,they still had arterial anoxemia.

A striking feature in both these subjects was

the extreme variability of their respiratory dis-ability, and likewise their extremely irregular re-

spiratory curves. In the case of M. K., on one

occasion following a cough, a sudden shift of 1000cc. was noted in the base line of a respiratorytracing. This variability of actual residual airvolume would seem to be indicated in the meas-

urements taken up to the last two days of tests

DISCUSSION

It is apparent from the results that the newmethod does not entirely solve the problem ofaccurate residual air measurement. It has beenshown and should be again emphasized that, inseverely diseased lungs and probably also in somenormal individuals, there is an imperfect mixtureof gases within the lungs during breathing. Thisfactor may be an important one in any methodinvolving the estimation of average gas con-centrations within the lungs. Since no methodwithout such estimations was found, the aim ofthe new method was to minimize the effect ofthese potentially erroneous measurements.

The theoretical advantages of the new methodwere clear cut. By keeping the inspiratory gasmixture of constant composition, it offered a bet-ter chance of adequate intrapulmonary mixing.The "mixing" approached by the procedure isactually a simple process of emptying the lung ofall, or nearly all, its contained nitrogen. By in-creasing the net alveolar nitrogen change, thenew method reduced the relative error due toerroneous " alveolar" samples. Furthermore, it

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INTRAPULMONARYMIXTURE OF GASES

avoided the necessity of measuring oxygen con-sumption from a respiratory tracing. Accuracyin this is necessary in the Christie method, yetoften difficult in patients with emphysema orother pulmonary conditions.

The new method, tested on a small group ofpicked subjects, has shown definite improvementover the closed circuit method, in so far as theprobable effect of poor mixing is concerned. Themethod of testing this effect has been the sameas that used for the closed circuit; namely, therepetition of the test with a reversal in the direc-tion of the nitrogen shift, by which the probableerror due to poor mixing was also reversed in di-rection. On the basis of such a test, the newmethod showed no evidence of error in any nor-mal subjects nor in any but one of the patientswith pulmonary disease. Even in this one sub-ject, the trend of repeated tests increasing thebreathing time indicated the probable accuratefigure. This was a contrast to similar evidenceby the closed circuit method where two normalsubjects and all subjects with emphysema showedconsiderable discrepancies due to poor mixing.

With this evidence in its favor, the results bythe open circuit method have been comparedwith the results obtained in the same subjects bythe closed circuit. Three normal subjects andsix patients with emphysema gave nearly iden-tical values by open and closed circuit methodsrespectively. One normal subject and two pa-tients with severe emphysema gave significantlyhigher results by the closed circuit technique.This is in accordance with the prediction offeredin the analysis of possible errors of method in thesecond paper of this series. In addition, twoother patients with emphysema showed a con-siderably wider range of variation in residual airvalues on successive tests by the closed as com-pared with the open circuit method.

It is thus apparent that the new method canbe used with some assurance of reliability in alarger group of abnormal subjects in whomsuchmeasurements are notoriously difficult. It wouldseem that this point is its chief practical justifica-tion, in addition to the theoretical advantagesmentioned.

Even in our small group of subjects, however,there were two unusual cases in whom both

methods gave variable results. A part of thiswas undoubtedly due to actual change in the vol-ume, but still it leaves two exceptions in whomthe reliability of the method could not be proved.In such cases it would be desirable to havea method in which no problem of mixing isinvolved.

Our primary interest has been the identifica-tion and quantitation of disturbances in mixing.Both an increase in the residual air and a dis-turbance in mixing may add to the pulmonarydisability in cases of emphysema. In cases wherethe maldistribution factor is large, the closed cir-cuit method may give a value which representsthe true functional residual volume plus an in-crement that is actually an error of method dueto poor mixing of intrapulmonary gases. Thisfactor of disturbed distribution is probably alarge one in contributing to the pulmonary dis-ability in emphysema. Therefore, it is impor-tant to differentiate it from the effect of a mereincrease in the residual lung volume. The opencircuit method should give a better measure ofthe latter without serious error from the former.With an accurate measure of the volume, itshould be possible to quantitate disturbances indistribution separately.

SUMMARY

1. A new open circuit method of measuringresidual air is described.

2. A test for this method is also described, con-sisting of a reversal of the nitrogen shift in theoriginal procedure.

3. Results of the use of these two proce-dures are presented on a group of four normalsubjects and six patients with severe pulmonaryemphysema.

4. A comparison is made between results bythe new method and by the modified Christiemethod on a series of four normal subjects andten patients with severe pulmonary emphysema.

5. The probable significance of the results isdiscussed.

CONCLUSIONS

1. The open circuit method for residual airdetermination offers a better means of avoiding

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ROBERTC. DARLING, ANDRECOURNAND,ANDDICKINSON W. RICHARDS, JR.

error due to maldistribution of pulmonary gases

than the closed circuit method. This is shownby the test procedure as well as theoreticalconsiderations.

2. The modified Christie method gives errone-

ously high values for residual air in some cases ofsevere pulmonary emphysema.

3. It is possible with the new method to dis-tinguish more surely the factor of imperfect gas

distribution from that of excessive residual lungvolume in the evaluation of the disturbancesassociated with pulmonary emphysema.

BIBLIOGRAPHY1. Cournand, A., Darling, R. C., Mansfield, J. S., and

Richards, D. W., Jr., Studies on the intrapulmonarymixture of gases. II. Analysis of the rebreathingmethod (closed circuit) for measuring residual air.J. Clin. Invest., 1940, 19, 599.

2. Herrald, F. J. C., and McMichael, J., Determination oflung volume: simple constant volume modificationof Christie's method. Proc. Roy. Soc., London,Series B, 1939, 126, 491.

3. Darling, R. C., Cournand, A., Mansfield, J. S., andRichards, D. W., Jr., Studies on the intrapulmonarymixture of gases. I. Nitrogen elimination fromblood and body tissues during high oxygen breath-ing. J. Clin. Invest., 1940, 19, 591.

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