A method for estimating respiratory muscle efficiency using an automated metabolic cart

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Respiration Physiology 106 ( 19961 17 I. 177

A method for estimating respiratory muscle efficiency using an automated metabolic cart Michael Sherman *, Amir Matityahu, Dave Campbell I)ivi.siml ~/ Puhnona O" and Critical ('are Medicine, Department ~)f Medicine. AIh'gheny University Howitals ('Olter ('itv. M('t~Oltallnenlann SHiool 01 Medicine, Broad and Vim' Streets. Mail Stop 107. Phihldelphia. PA 191¢12-1 It~2. l/.%1 Accepted I 9 August 1996

Abstract

We measured respiratory muscle efficiency (RME) in twelve healthy human subjects by dividing the added energy cost of breathing against a threshold resistance load by the associated increase in caloric expenditure. Caloric expenditure v,,as calculated using steady-state measurements of oxygen consumption and carbon dioxide production during loaded and unloaded breathing. Calculated RME ranged from 1.7% to 5.5c~ (mean 3.5%). The coefficient of variation in six subjects averaged 13~. We compared these calculations with a previously described oxygen consumption-based method that did not incorporate carbon dioxide production measurements. We found that changes in the respiratory quotient during resistive breathing could cause significant errors in oxygen consumption-based calculations of RME. Limits of agreement of 95G suggest that thc oxygen-consumption-based calculations could potentially overestimate efficiency by as much as 5.0c7¢ or underestimate by up to 3.4%. We recommend that carbon dioxide prcxtuction be measured when this technique for estimation of RME is used. This can be easily accomplished through the use of an automated metabolic cart. Kevwor, ls: Mammals, humans: Metabolism, cost of breathing: Muscle, respiratory, efficiency: Work of hreathing, respira-

tory

nluscle

1. Introduction

Mechanical efficiency of respiratory muscles is the ratio of mechanical work of breathing to the energy equivalent of the metabolism of the respiratory musclcs (Roussos, 1985) and has proved useful in evaluating muscle function in emphysema, asthma, and exercisc (Campbell et al., 1957; Cherniack. 1959: Margaria et al., 1960; Milic-Emili and

*Corresponding author. "l'cl.: +1 215 762-7013" Fax: ~-1 215 762-8728.

Petit, 1960; Weiner et al., 1989, 1990: Hsia et al., 1993). While measurements of mechanical work of breathing frequently require invasive measurements with an esophageal balloon (Margaria el al.. 1960: Milic-Emili and Petit, 1960: Hsia et al.. 1993). several studies have demonstrated that a reasonable estimate of efficiency can be obtained non-invasively by measuring oxygen consurnption at rest, adding a known external resistance, and dividing the added respiratory muscle work by the increase in the energy equivalent of oxygen consumption (Campbell et al., 1957: Cherniack, 1959: Wether et al., 1989. 1990).

(1034-5687/96/SI5.0() Copyright (,:3 1996 Elsevier Science B.V. All rights reser,,ed. PII S O I ) 3 4 - 5 6 8 7 ( t ) B ) t ) O 0 7 1 - O

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M. S h e r m a n ('t a l . / R c . v ) i r a t i , m I'hv.~u,h,~v IO(> ~ lt)gt), 171

The method described by Campbell et al. (1957) and Cherniack (1959) measured oxygen consumption with a closed-circuit spirometer. Subjects were required to breathe 100% oxygen and the metabolism of the respiratory muscles was calculated fi'om the difference in oxygen consumption between resting state and breathing against a mechanical load. Mechanical work was added by having the patient inspire through tubing under a water seal. Weiner et al. (1989, 1990) simplified the technique. Subjects breathed into a mixing chamber for 15 rain. Added mechanical work was applied using two successive threshold resistors, and subjects breathed through these resistors for 3 rain periods. Oxygen consumption (%'o,) was measured over the last 30 sec of each resistance breathing period using an open circuit method. In all of these studies, the energy equivalent of the metabolism of the respiratory muscles is calculated using measurements of oxygen consumption and assuming that subjects had a constant respiratory quotient (RQ) of 0.82 which did not change when the subject was breathing through the resistive load. This assumption could result in errors if the actual respiratory quotient varied during or between tests. These methods also use specialized equipment not available in most clinical laboratories. The purpose of this paper is to describe a convenient and more accurate method of estimating respiratory muscle efficiency using an automated metabolic cart. Since the metabolic cart measures both oxygen consumption and carbon dioxide production, R (the respiratory exchange ratio) can be calculated and RQ therefore estimated. We demonstrafe that a significant error may be inm)duced when a constant RQ is assumed when calculating respiratory muscle efficiency. 2. Method Twelve trained normal subjects were studied. Subjects were asked to breathe normally while wearing a face mask sealed tightly around the nose and mouth. The face mask included inspiratory and expiratory valves which were connected using low resistance tubing to an automated portable system of indirect calorimetry (Cybermedic MetaScope metabolic cart, Louisville, Colorado, USA).

/72

"['he MetaScope measures the concentrations of inspired and expired oxygen using a paramagneIic 02 cell. Expired tlow is measured with a heated Fleisch #1.5 pneumotachograph and the meast, red tlow is it|tegrated over time to calculate tidal volunm and minute ventilation. Carbon dioxide is measured using an infrared sensor cell. CO_, production (9c,~,) is calculated by multiplying the expired minute ventilation by the difference between expired and inspired CO: concentrations. Vo, is calculated using the Haldane transformation (Wagner et al., 1973~. A mixing chamber is built into the expiratory limb of the metabolic cart to collect the expired gas prior to analysis. (}as exchange variables were calculated over 20 sec time intervals and reported at one rain intervals. The system was validated using a methanol burn. and tv,.'o point oxygen and carbon dioxide ~,,,as. calibration was perfomled at the beginning of each study and at 20 rain intervals if a study lasted hmger than 20 rain. After a 3 rain calibration period, subjects were asked tO breathe normally for a 20 rain period while seated in a reclining chair in a darkened, quiet room. Alter a live rain period of observation to insure that a stable respiratory rate was present, a continuous equilibration interval of 5 to 15 rain was used for analysis to approximate steady state conditions. Equilibration was defined by less than a 5 ~ change in R, and less than a 10% change in Vo. and V¢.o over the period used for analysis, as per protocols of Feurer and colleagues (Feurer et al., 1984: Feurer and Mullen, 1986) and Makk et al. (1990). A threshold resistor of 15 to 20 cm H,O was then placed along the inspiratory limb of the face mask {the exact magnitude of the load was previously selected based on individual subject tolerance). The magnitude of the inspiratory resistance pressm'e was verified using a water manometer. Subjects were asked to continue to breathe in a steady rhythm for an additional 20 rain period. Again, a continuous 5 to 15 rain steady state interval was used for analysis. Subjects were withdrawn I"rom the study if they were unable to produce steady state values. Added mechanical work per minute was calct.lated by' multiplying the minute ventilation during resistive breathing by the added threshold inspiratory pressure and converting to joules min I. Caloric expenditure per minute was calculated using Weir's

M. Sherman et al./ Respiration Physiology 1(~5 ~19967 171- / 77

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equation (Wcir, 1949):

2.1. S t a t i s t i c a l analvsi,s"

Energy expenditure = 3.9(Vo, ) + I. 1(~/co:)

Results are expressed as means + standard de,Aations. Reproducibility was assessed in six subjects. Four subjects repeated efficiency measurements on threc separate days: two completed the measurement on two separate days. The cocfticicnt of variation was calculated. Agreement between V~, and caloric based calculations of efficiency was determined by the method of Bland and Airman (1986). Absolute differences bctwecn the ~/o, and caloric methods were calculated and compared to absolute diffcrenccs bctween corrected Vo, and caloric methods using a paired Student t test. Differences werc considered signilicant at p < 0.05.

where %'o, and Vco: are measured in ml gas rain- i. Metabolism of respiratory muscles was calculated by determining the difference in energy expenditure between the resting state and when breathing against the threshold resistor. The difference in caloric expenditure was converted to joules r a i n - i using Joule's equivalent. Efficiency was then calculated by dividing the added mechanical work by the added energy expenditure: Respiratory muscle efficiency = V H x P x 0.0980-4 (EEr-

EEb) x 4.184

(I)

where VEr is ventilation during resistance breathing, P is threshold pressure in cm H~O, 0.09804 is a factor to convert cm H 2 0 to kilopascals, EEr is energy expenditure during resistance breathing in kilocalories per minute, EEb is baseline energy expenditure in kiloca[ories per minute, and 4.184 is Joule's equivalent. This will be referred to as the 'caloric" or "calorimetric" method. A "Vo," or 'oxygen consumption' based method of measuring respiratory muscle efficiency assumes a constant RQ of 0.82 and was calculated using an equation modilied from Campbell et al. (1957) and C h e m i a c k (1959): Respiratory muscle efficiency = Vt-r x P x (/.09804 (V~,~ - Vo:h) x 4.825 x 4.184

12)

where Vo:r is the oxygen consumption measured during resistive breathing, ~'o:b is the oxygen consumption at baseline, and 4.825 is the caloric value of I liter of oxygen when RQ is 0.82 (Lusk, 1924). For the purpose of comparison, the 'Vo: method' was corrected by substituting the caloric values of oxygen appropriate to the observed R at baseline and during resistance breathing. Caloric equivalents of oxygen of Weir (1949) were also substituted tot values derived by Lusk (1924). The result will be referred to as the "corrected '~'o:' method.

3. Results Subject characteristics are listed in Table I. All subjects were without known medical problems except for subject 2, who had a past history of asthma which was quiescent, requiring no medications at the time of the study. Table 1 also shows respiratory muscle efliciency measured with the caloric method, which ranged from a low of 1.7% to a high of 5.5c27. intra-subject variability is shown in Table 2. The coefficient of variation averaged 13% (range 3.3-18.8c/c I.

Table 1 Sul2iect characteristics and respirator', muscle efficiency Subject

Age

Sex

FVC ,',;. pred. i

RI-cal i'.>}I

I 2 3 4 5 6 7 8 9 In II 12 Mean SD

31) 38 30 27 39 32 3(1 39 33 32 35 29 34 4.3

Female Male Male Male IZemale Male Female Male Male Male Male Male

121 9~, I01) 93 t)o 97

4.78 ~.35 2.3 I 1.72 2.65 548 2.78 4 211 4.16 407 2.8~ 233 ),.39 I. 14

11)7

1(17 05 105 I(10 87 10(1.6 8.7

REcal = respirator.,,,muscle et'ficienc~ measured by increase in caloric expenditure with re,;istance breathing. SD = standard de~ iation.

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M. Sherman el al. / R c w i r a t i ( m I'h.~siolo.~,v 1Or) t /9q6 ~ 171 / 77

"Fable 2 Reproducibility of respiratory muscle efficiency measurements, in six subjects Subject

Trial 1

Trial 2

Trial 3

Mean

C.V.

4 5 8 1[I 11 Mean SD

1.72 2.65 4.2{) 4.(17 2.g6 3.29 0.94

1.25 2.65 4.22 3.16 3.74 3.01 1.(.)2

1.4g 3.59 4.45

1.49 2.96 4.29 3.62 3.30 3.14 0.93

15.65 18.33 3.29 17.69 18.83 13.13 7.07

3.19 1.25

A scattergram comparing the two methods is shown in Fig. I A. Based on 22 observations in 12 subjects, 95e~• limits of agreement would suggest that the oxygen consumption measurements could potentially overestimate efficiency by 5.0% or underestimate by 3.4%. This wide range is due to a large standard deviation in the mean difference between measurements and is demonstrated by the wide scatter shown in Fig. I A. Fig. I B is a scattergram comparing the corrected Vo: to the caloric method. Limits of agreement of 95% suggest that the corrected Vo: method could overestimate the caloric method by 1.44% or underestimate by 1.48%. The mean absolute difference between the caloric and ~'o: methods was 1.23 + 1.88%. This difference decreased significantly to 0.30 + 0.67% when the ~'o: method was ton'coted for changes in R (p < 0.03 ). 4. Discussion Our measurements of respiratory muscle efficiency are similar to those previously reported by investigators using similar techniques (Campbell et al., 1957; Cherniack, 1959; Weincr et al., 1989; Wciner et al., 1990), but are lower than others (Margaria et al., 1960, Milic-Emili and Petit, 1960; Hsia et al., 1993). Measurements by Margaria et al. (1960) and Hsia et al. (1993) were obtained during exercise. Respiratory muscle efficiency during excrcisc could difl'cr from rcst measurements because of changes in diaphragmatic blood flow during exercise (Robertson et al., 1977) and because efficiency is higher at more rapid respiratory rates (Mommaerts, 1969). Higher

resting respiratory muscle efficiency measurements were repolled by Milic-Emili and Petit (1960); hmvever, these studies were done in the supine position using an esophageal balloon to measure pressure. In this position, nleasured efficiency would be expected to be higher because of improved length-tension relationships of the diaphragm and decreased use of postural muscles to stabilize the diaphragm Work of breathing is also likely to be overestimated in this position, due in part to the increased effect of cardiac artifact on esophageal balloon pressures (Baydur ct al.. 1982). All of these studies are also subject to the cn'or introduced by using the ~/o: measurements to determine the energy equivalent of the metabolism of the respiratory musclcs without measurement of R. The major problem we have observed using this technique lies in the ability of subjects to maintain a steady state. While no subjects had to be dropped from the stud)', some required several training trials betbre they were able to maintain the required five to fifteen min of steady state. Once trained, subjects were able to reproduce measurements of respiratory muscle efficiency reasonably well over several days. The coefficient of variation of 13% is similar to thal described for oxygen cost of breathing, a measurement that is also a measure of respiratory muscle function (Dodd el al., 1988). This variation is small and may bc due to slight variations in breathing pattern, body position, or changes in relative contributions of inspiratory muscles that may occur from one day to the next. There is a potential error in measuring the amount of added mechanical work performed during resistance breathing. The product of minute ventilation and mouth pressure does not measure the work performed by respiratory muscles to compress alveolar gas or the work associated with changes in abdominal and thoracic partitioning. However, Jaeger and Otis (1964) note that the increase in the rate of work due to compressibility was not measurable in free breathing normal subjects, and only became measurable if a resistance of 38 cm H20 is added m the circuit. Similarly, Goldman et al. (1976) reported that little or no chest wall distortion occurs at resting minute ventilation, although increasing minute ventilation (either through exercise or carbon dioxide rebreathing) may be associated with up to a 25~>~

liB1

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M, Sherman et a l . / R e s p i r a t i o n Phv,~iology 106 ¢ 1996) 171 •177

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Fig. I. Comparison of methods of measuring respiratory muscle efficiency. (A) Scattergram comparing simultaneous oxygen consumption and caloric mcthods of measuring respiratory muscle efficiency. 95c~ limits of agrecment suggest REVO2 could potentially overestimate REcal by 5.0% or underestimate by 3.4c~. (B) Scattergram correcting the oxygen consumption method for changes in R and comparing with the caloric method of measuring respiratory muscle efficiency. 95~ limits of agrcemcnt suggest that REVO2c couht polentially overestimate REcal by 1.44% or underestimate by 1.48%. REVO2-respiratory musclc efficiency measured using increase in ox~rgen consumption during resistive breathing. REVO2c-oxygen consumption method corrected for respiratory quotient and for differences m calculations of caloric value of oxygen (see text). REcal-respiratory musclc efficiency measured using increase in caloric expenditure during rcsisti',e breathing. The solid line is the line of identity. underestimate of the work of breathing. We added a relativcly low threshold resistance of 15-20 cm H 2 0 and the minute ventilation of our subjects did not increase during resistance breathing. It is therefore unlikely that these errors would significantly affect our measurements. However, this method should not bc used with a threshold resistor > 3 8 cm H_,O, or with an added work load that significantly increases minute ventilation (such as adding dead space or carbon dioxide rebreathing). While most of our estimates of respiratory muscle efficiency using the calorimetric and Vo: based methods agreed closely, we found seven measurements in four outlier subjects where a large difference (> 1% difference in efficiency) was found. Variability in the respiratory exchange ratio was re-

sponsible for most of this difference in all four of these outliers (the other eight subjects had minimal change in their respiratory exchange ratios). This can be illustrated with subject 11, who had the largest difference in efficiency measurements (2.86% vs 10.080~). Subject 11 had a minute ventilation of 8.3 while breathing through a 15 cm H~0 threshold resistor. His oxygen consumption at baseline was 301 ml min The ~'o, with resistance breathing was 307 ml rain i Using the oxygen consumption based measurement of eMciency, we calculated his efficiency to be: 8.3 x 15 x 0.09804 (307 - 301) x 4.825 x 4.184 × l(X) = 10.08%

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M. S h e r m a n et al. / Re.v~iratton I'h.~ ~iolo.~,v l o b ~ l (lqh ) 1 7 1 - 1 7 7

This subject had a significant change in his respiratory exchange ratio, however. His steady state R at baseline was 0.77: R during resistance breathing was 0.98. The caloric equivalent fi)r oxygen at an R of 0.77 is 4.764: the caloric equivalent for oxygen at an R of 0.98 is 5.022. The corrected measure of efficiency should then be: 8.3 x 15 x 0.09804 (307 x 5.022 x 4.184) - (301 x 4.764 × 4.184) x 100 = 2.71% which is reasonably close to the measure we obtained using the calorimetric method of 2.86%. This correction for R essentially duplicates Eq. 1 above, as multiplying oxygen consumption by the caloric equivalent of oxygen at the appropriate R value gives energy in calorics. There remains a small difference between this calculation and the calculation of caloric expenditure performed by the metabolic cart. This is due to the difference in calculations of the caloric value of oxygen. Standard tables of calories per liter oxygen consumed are derived from Lusk (1924) using the equation R - 0.707 K --- 4.686 + x 0.361 0.293 where K is the caloric value of 1 L of oxygen. Most computerized metabolic carts (including the Cybermedic cart used in this study) calculate calorics using Weir's equation (Weir, 1949), which was derived from the equation: K=3.9+

1.1 x R

Using Weir's caloric values for oxygen, patient 11 has an efficiency of 2.94¢/~ ,, somewhat closer to the actual number we obtained using the caloric measurements. These differences are obviously small and arc not a significant factor in explaining the difference between the two calculations of respiratory muscle efficiency. Similar calculations correcting the Vo,-based method for changes in R, and using Wcir's equation for calculating the oxygen equivalent tbr oxygen, were performed on the other 21 measurements (Fig. I B). The differences between the two methods were significantly decreased after these corrections were perfi~rmed as shown by the decrease in 'scatter', and as evidenced by the decrease in the mean

absolute differences + standard deviations between the two methods and the improvement in 95'~ limits of agreement. We believe that the observed change in respiratory exchange ratios reflects a change in underlying respiratory quotient. While most of our subjects had an initial change in minute ventilation when resistance breathing was initiated, this invariably returned to baseline values after two or three minutes. The live minute waiting period before analysis of gas exchange data was adequate to enable subjects to stabilize their oxygen consumption, carbon dioxide production and minute ventilation. We believe that this period of equilibration reflects a condition near enough to steady state fi)r R to closely approximate RQ. While an initial change in R may reflect a change in ventilation associated with the initiation of resistance. R measured during the period of equilibrium should reflect the metabolic effects associated with resistance breathing. Wasserman et al. (1987) demonstrated a similar, subject dependent, variable rise in R with skeletal muscle exercise and ascribed this elevation to increased utilization of carbohydrate during muscular work as compared to rest. This increase has been shown to "level off" 5 rain after the initiation of work. Similarly, we found that the rise in RQ from added respiratory muscle work was subject-dependent, with some subjects having a greater response than others. As with skeletal muscle work, we also observed a qevcl-off" of the rise in R after 5 rain of loaded breathing. We conclude that changes in the respiratory quotient during resistive breathing can cause significant discrepancies in the calculation of respiratory muscle efficiency. We therefore recommend that carbon dioxide production be measured when this technique for estimation of respiratory muscle efficiency is used. Using an automated metabolic cart provides a convenient means of obtaining this measurement.

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M. Sherman et al. / Respiration Physiology 106 ~19961 171 177

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