Clinical Science and Molecular Medicine (1978), 55,125-128 SHORT COMMUNICATION Revised standards for normal resting dead-space volume and venous admixture in men and women E. A . H A R R I S , E V E R . S E E L Y E A N D R . M . L. W H I T L O C K Clinical Physiology Department, Green Lane Hospital, Auckland, New Zealand (Received 19 October 1977; accepted 18 April 1978) Summary 1. Data have been combined from three previous series to provide revised standards for the prediction of physiological dead-space volume (V,), arterial oxygen tension (Pa,o,), alveolar-toarterial oxygen-tension difference (FA,O; - Pa,oJ and venous admixture fraction (Qva/Qt) in the sitting position. 2. These standards, based on measurements in 96 healthy men and women aged from 20 to 74 years, largely confirm conclusions drawn from the first series of 48 subjects. 3. V, is best predicted on age, height, tidal volume and the reciprocal of respiratory frequency. Pa,o, PA,^, - Pa,oJ and Qva/Qt are adequately predicted on age alone. Key words: alveolar oxygen, dead space, oxygen, venous admixture. Introduction Equations for the prediction of normal dead-space volume and venous admixture in the sitting position, based on data for 24 men and 24 women aged 20-73 years, were presented by Harris, Hunter, Seelye, Vedder & Whitlock (1973) and Harris, Kenyon, Nisbet, Seelye & Whitlock (1974). Since then, similar studies have been made on 24 healthy subjects at rest and on exercise (Bradley, Harris, Seelye & Whitlock, 1976; Harris, Seelye & Whitlock, 1976) and on 24 subjects in the sitting and supine positions (Rae, Withy, Seelye & Harris, 1977), so that values are now available in 96 healthy men and women in the sitting position. We have analysed this material and now present revised standards for the prediction of physiological dead-space volume ( V,), arterial oxygen tension (Pa,oJ, alveolar-to-arterial oxygen-tension difference (PA,o, Pa,o,) and the venousadmixture fraction (Qva/&) when air or oxygen is breathed. Methods These were described in detail in the papers cited above. Sixteen men and 16 women in each of the age groups 20-30, 39-51 and 60-74 years were studied, seated comfortably, breathing air or 0, in the steady state. Inspired and expired gas concentrations of 0,, N, and CO,, expired gas volumes and respiratory frequency were measured during two consecutive 3 min periods; during the second minute of each, 5 ml of arterial blood was drawn evenly into a heparinized glass syringe from a radial artery catheter. Complete calculations were made for each 3 min period, and since no systematic difference was found between these duplicates all results were expressed as their mean value. Dead-space volume was calculated from the modified Bohr equation: V , = VT (Pa,co, - PE,coJ/Pa,coz where V, is dead-space volume (ml), V, tidal volume (ml) and Pa,coz and PE,coZare respectively arterial and expired-gas CO, tensions (kPa). In each case, two values for V , were calculated, one from Pago, expressed at the patient’s oral temperature and one at 0.8OC higher than this, as an estimate of pulmonary capillary temperature (Edwards, Velasquez & Farhi, 1963), which has been shown to be relevant to V , measurement, especially during exercise (Bradley et al., 1976). Correspondence: Dr E. A. Harris, Clinical Physiology Department, Green Lane Hospital, Auckland, 3, New Zealand. 125 126 E. A . Harris, Eve R . SeeIye aHd R . M. L . Whitlock Alveolar 0, tension (PA,o,) was calculated for air-breathing from the alveolar gas equation: PA,o,= P,,o, - Pa,co, [F,,o, + (1 - FI,o,)lRl where P,,o, and FI,02are respectively inspired 0, tension and concentration and R is the gasexchange ratio. When 0, was breathed, Pa,o, Was taken as 0.9973 (P, - 6.27) - Pa,co, kPa [O.9973(PB47) - Pa,co, mmHg1 where P, is barometric pressure and 0.9973 the mean inspired 0, concentration. If during 0,breathing, expired N, concentration ( F E , ~ , )was greater than 0.0050, P1,o2 was taken as (1 FE,NZ)(PB - 6.27) kPa [I - FE,N2)(PB - 47) mmHg]. Venous admixture was calculated from the kquation: (jva/Qt = (C’C,O~- ca,oj/[(C’c,o, - ca,o21 + (Ca,o, - CV,o,)l where C ‘ C , ~ ,and Ca,o, are respectively endpulmonary-capillary and arterial 0, content [determined from PA,o, and Pa,o, by Kelman’s (1966) subrodtinel and CC,o, is the mixed-venous 0, content; (Ca,o, - CT,oJ was assumed to be 50 mill. These experiments yielded, for V,, 96 mean values when Greathing air and 96 on 0,,and, for Pa,Oj, (PA,O, - Pa,oJ and Q v a l b , 96 values on air and 95 ori 0, (one set of data on 0, was rejected because of gross contamination of the inspired 0, with air). Since there was no systematic air - 0, difference in V,, all 192 values were combined for analysis. Statistical analysis Pa,o,, ( P A , 0 2 - Payo,) and Qva/Qt are adequately predicted by age alone for both sexes combined (Harris et al., 1974). Only air-brehhing Pa,o, is distributed homoscedastically on age; limits were calculated from the standard deviation about regression. Clinically only a low Pa,o, is of interest, and single-sided limits are therefore used. Analysis of VD was by multiple regression (Daniel 8c Woods, 1971)on various combinations and transformations, as independent variables, of age, height, CO, output, ventilation and respiratory frequency, a PDP8-E computer being used. Goodness of fit and the relevance of each predictor were judged from the multiple correlation, residual standard deviation, partial regression coefficients and the effect on V Dof changing eaeh predictor by four times its standard deviation. Confidence limits are given as 95, 99 and 99.9% intervals above the regression plane. Results Gas tensions are given in kPa (with mmHg in parentheses), age in years, height in cm and volumes in ml. Dend-space volume The most satisfactory of 1 1 regressions tested was that on age, height, tidal volume and reciprocal of frequency. Four of the 192 measured values of Vd fell persistently beyond 3 SD from regression; these four were excluded as probable errors and the regression was recalculated. Detailed results have been deposited as Clinical Science and hfolecular Mkdicine Table nos. 7817 and 8 with the Librarian, Royal Society of Medicine, Wimpole Street, Londan W J M SAE, from whom copies can be obtained on request. The recommended equations are: Referred to oral temperature VD = 0.859 (age) + 1-32(height) + 0.264 V , 905lf - 179, n 188, Ry,l,34 0-8640,sy1,23426-01 ml, confidence intervals 43, 61 and 82 ml above regression. Referred to ‘pulmonary-capillary’ temperature VD = 6.834 (age) + 1.26 (height) + 0.296 8791f - 174, n 188,Ry,12340.8926, sy,,234 24.86 ml, confidence intervals 41, 58 and 78 ml above regression. vT These equations are valid for both sexes aged 20-74 years, V, up to 900 ml and f up to 25 breathslmin. n is the number of data sets, Ry1,234 the multiple correlation and syl1234 the residual SD about regression. All regression coefficients are highly significant (2P < 0.001). Venous admixture The individual data have been deposited as described above. Table 1 shows mean values and SD Of Pa,02,(PA,02 - Pa,O,) and &a/@ in each of the three age-groups, breathing air and breathing oxygen. Apart from Pa,o, breathing air, the variance increases significantly ( P < 0.01 by Ptest) with age; in other words the distribution with age is heteroscedastic. Since some of the individual values - Normal dead-space and venous admixture 127 TAELE1. Arterial oxygen pressure ,(Pa@,), alveolar to arterial oxygenpressure di~erence(PA@, - Pa,o,) and venous-admixture fraction (QvafQt) in 96 healthy men and women, seated, breathing air and breathing oxygen Pa@, and PA,o~ - Pa,o, are expressed in kPa (values in parentheses are mmHg); QvalQt values are percentages. Breathing 0, Breathing air Pa,o, Age 2&30 years No. of subjects Mean SD Age 39-5 1 years No. of subjects Mean SD Age 59-74 years No. of subjects Mean SD PA,o,- Pa,o, QvaIQt pa,o, PA,O, - ~ a j o , QvaIQt 32 86.11 (645 * 88) 2.512 (18.84) 32 3.25 (24.3 8) 2.094 (15.7 1) 32 1.48 31 82.95 (622.18) 3.781 (28.36) 31 6.22 (46.65) 3.943 (29.57) 31 2.76 32 80.78 (605.90) 5.416 (40.62) 32 8.29 (62.18) 5.393 (40.45) 32 3.65 32 13.22 (99.16) 1.028 (7.71) 32 0.756 (5.67) 0.673 (5.05) 32 1.28 32 12.36 (92.7) 1.031 (7.73) 32 1.47 (11.03) 0.797 (5.98) 32 2.96 32 11.55 (86.63) 1.144 (8.58) 32 2.45 (18.38) 1.107 (8.30) 32 4.98 1.095 1.915 of (PA,o, - Pa,oJ and Qva/Qt were negative, a logarithmic transformation (which might have achieved homoscedasticity) was impossible. A straightforward regression analysis *as possible, therefore, only in the case of Pa,o, breathing air. This gave: Pa,o, = 14.1 - 0.390 (age) kPa [Pao, = 105.8 - 2.925 (age) mmHg1, n = 96, r = -0.5352, sy.x = 1.07 kPa (8.03),confidence limits 1-78, 2.53 and 3.41 kPa (13.35, 18-98 and 25-58 mmHg) below regression. Qva/Qt alters little when gas tensions are expressed at ‘pulmohary capillary’ temperature (Harris et al., 1976). For predictive purposes the oral reference temperature is adequate. Discussion We explored many more combinations of independent variables for predicting VD than previously (Harris et al., 1973), yet the present andysis confirms our original choice. The regression parameters have changed a little but the confidence intervals are practically the same. All regressions examined showed marginally better fits when VD was referred to ‘pulmonary capillary’ temperature. This may mean that it is the truer estimate, but it seems to offer little predictive advantage for resting 2.641 0.939 1.736 2.272 For prediction they recommended a multiple regression equation on age and PA,o?The present results show, for a subject of 45 years, a 95% interval of 1.78 kPa (13.35 mmHg) for Pa,o, and of 1.46 kPa (10.95 mmHg) for (PA,o, Pa,o j, bearihg out the results of Gillies et al. (1977). It probably matters little whether predictioll is made of (PA,o, - P a , o j on age, we have dofib, or of Pa,o, on age and PA,o,. However, in practice, the data needed to calculate PA,o, are usually not available and a prediction on age alone is helpful. It is emphasized that the data when breathing 0, are for normal, not deep, breaths after at ieast 15 min of 0,-breathing, with expired N, concentration below 1%. While this is a fairly common procedure for which a prediction is useful, it does not measure anatomical venous shunt (Harris et al., 1976). Acknowledgments We thank our subjects, the staff of the Clinical Physiology Department over several years and Mrs Joan Findlay for indispensable support. The work was supported by a grant to E.A.H. from the Medical Research Council of New Zealand. References VD. Gillies, Petrie, Morgan & Sykes (1977) showed that the residual variance of Pa,o, on age is reduced when PA,o,is taken into account as well. BRADLEY,C.A., HARRIS,E.A., SEELYE,E.R. & WHITLOCK, R.M.L. (1976) Gas exchange during exercise in healthy people. I. The physiological dead-space volume. CZinicaZ Science and Molecular Medicine, 5 1,323-333. 128 E. A . Harris, Eve R . Seelyle and R . M . L. Whitlock DANIEL,C. & WOODS,F.S. (1971) Fitting Equations to Data. Wiley-Interscience, New York. EDWARDS,A.W.T., VELASQUEZ, T. & FARHI,L.E. (1963) Determination of alveolar capillary temperature. Journal of Applied Physiology, 18,107-1 13. GILLIES,I.D.S., PETRIE, A., MORGAN,M. & SYKES,M.K. (1977) Analysis of possible factors iduencing Pa,o, and (PA,o, - Pa,oJ in patients awaiting operation. British Journal of Anaesthesia, 49,427-438. HARRIS,E.A., HUNTER,M.E., SEELYE,E.R., VEDDER,M. & WHITLOCK,R.M.L. (1973) Prediction of the physiological dead-space volume in resting normal subjects. Clinical Science and Molecular Medicine, 45,375-386. HARRIS,E.A., KENYON,A.M., NISBET,H.D., SEELYE,E.R. & WHITLOCK,R.M.L. (1974) The normal alveolar-arterial oxygen-tension gradient in man. Clinical Science and Molecular Medicine, 46,89-104. HARRIS,E.A., SEELYE,E.R. & WHITLOCK,R.M.L. (1976) Gas exchange during exercise in healthy people. 11. Venous admixture. Clinical Science and Molecular Medicine, 5 1, 335-344. KELMAN,G.R. (1966) Digital computer subroutine for the conversion of oxygen tension into saturation. Journal of AppliedPhysiology, 21,1375-1376. REA,H.H., WITHY,S.J.,SEELYE,E.R. & HARRIS,E.A. (1977) The effects of posture on venous admixture and respiratory dead space in health. American Review of Respiratory Disease, 115,571-580.
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