International Journal of Clinical Monitoring and Computing 4: 11-20, 1987 �9 Martinus Nijhoff Publishers, Boston - Printed in the Netherlands

Non-invasive measurement of respiratory mechanics in ICU patients

J. Milic-Emili, S.B. Gottfried & A.Rossi McGill University, Montreal, Canada

Keywords: compliance and resistance of total respiratory system, frequency-dependence of resistance; intrinsic PEEP, long volumes

1. Introduction

Routine measurements of respiratory mechanics in mechanically ventilated patients for acute respira- tory failure are seldom performed. This probably reflects the general notion that in the intensive care setting (ICU), results of respiratory function tests are quite difficult to obtain (20). As a matter of fact, however, in mechanically ventilated patients a detailed analysis of respiratory mechanics can readily be performed with simple and commonly available equipment, namely a penumotachograph system to measure flow (V), an integrator to obtain volume changes (A V) from the flow signal, and a pressure transducer to measure the pressure at the airway opening (Pao). Here it should be noted that same commercial ventilators allow direct measure- ment of these variables (e.g. Siemens 900C, Pu- ritan-Bennett 7200). With the above equipment it is possible to determine non-invasively the static and dynamic compliance of the total respiratory system (4, 5, 17, 18), the frequency-dependence of the total respiratory flow resistance (17), and to establish if expiration is limited by dynamic com- pression of the intrathoracic airways (5). By adding an esophageal balloon-catheter system (13), the data of total respiratory system mechanics can be partitioned into lung and chest wall components.

In this article we will first review some of the basic respiratory mechanics tests, and next we will describe a battery of non-invasive methods for measurement of respiratory mechanics which have been adapted to mechanically ventilated patients.

2. General considerations on testing of respiratory mechanics

Table i lists some of the basic respiratory mechan- ics variables and their measurement methods.

Because most individuals can not relax volun- tarily their respiratory muscles, the compliance and flow resistance of the total respiratory system and of the chest wall are seldom measured in ambula- tory patients (1). Accordingly, in such patients me- chanics measurements are necessarily confined to pulmonary compliance and flow resistance (which are invasive as esophageal balloons need to be swallowed), or to measurement of airway flow re- sistance. By contrast, in mechanically ventilated patients relaxation of the respiratory muscles can more readily be achieved, and hence non-invasive measurement of total respiratory system's com- pliance and flow resistance can easily be obtained.

While for practical reasons body plethysmogra- phy is not feasible in mechanically ventilated pa- tients, the functional residual capacity can be mea- sured using other methods (see below). Measurements of vital capacity and its subdivi- sions, and of forced vital capacity can be obtained in ICU patients provided that they are capable to perform such voluntary maneuvers. Such measure- ments, however, are beyond the scope of the pres- ent review which is limited to mechanical ventila- tion.

In short, from the above considerations it ap- pears that in mechanically ventilated patients a

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detailed analysis of respiratory mechanics can be achieved more readily than in ambulatory pas- tients. Furthermore, mechanics data pertaining to the total respiratory system can be obtained non- invasively. By use of the esophageal balloon tech- nique, the total respiratory system's mechanics can be partitioned into lung and chest wall compo- nents, as the esophageal balloon technique can readily be applied to patients in the ICU (13). However, for most intents and purposes, non-in- vasive measurement of respiratory mechanics should suffice to assess the status and progress of ICU patients.

3. Methods for assessing respiratory mechanics in mechanically ventilated patients

3.1. Lung volumes

The functional residual capacity can be measured using gas dilution and nitrogen washout methods adapted to allow investigation during mechanical ventilation (6, 22). These techniques do not mea- sure the total thoracic gas volume, but rather the gas contained in air spaces with open airways. Changes in total thoracic volume (including gas, liquid and solids) can be estimated by non-invasive methods such as radiography, strain gauges, mag- netometers, bellows pneumographs and inductive plethysmograpy. The latter technique (19) is par- ticularly promising for studies in ICU patients, as it

also allows partitioning of the respiratory move- ments into motion of the rib cage and of the abdo- men-diaphragm. Such studies are bound to provide useful clinical information.

3.2. End-inspiratory occlusion technique

The static compliance of the total respiratory sys- tem (Cst,rs) is conventionally obtained by dividing the inflation volume (AV) by the difference be- tween the 'plateau' pressure measured at the air- way opening (tracheal pressure) during end-in- spiratory airway occlusion (breathhold for 1 to 2 s) and the PEEP set by the ventilator (Fig. 1) (21). Such measurements are correct provided that at end-expiration the elastic recoil pressure (Pel,rs) is zero, i.e. that no further pressure is available to produce expiratory flow (18). This was the case for the ARDS patient in Fig. 1, in whom the expiratory flow prior to lung inflation became nil (expiratory pause), indicating that during expiration the respi- ratory system had time to reach its elastic equilibrium point (Pel,rs = 0). In most ICU pa- tients, however, Pel,rs does not become zero dur- ing expiration (18), the end-expiratory Pel,rs being termed auto-PEEP (16) or intrinsic PEEP (PEEPi) (18). When present, PEEPi needs to be subtracted from the end-inspiratory 'plateau' pressure to ob- tain the correct value of Cst,rs (18):

Cst,rs = AV/(end-inspiratory 'plateau' Pel,rs-PEEP-PEEPi). (1)

Table 1. Methods used for measurement of some basic respiratory mechanics variables.

Variables Measurement method

Vital capacity and its subdivisions Total lung capacity and its subdivision

Forced expired vital capacity (FEV~, MMFR, etc.) Static and dynamic compliance of total respiratory system Static and dynamic compliance of lungs Static and dynamic compliance of chest wall Flow resistance of total respiratory system

Pulmonary flow resistance Airway flow resistance

Spirometry Body plethysmography Gas dilution and N2-washout techniques Spirometry For methods used in spontaneously breathing subjects Esophageal balloon technique Esophageal balloon technique For methods used in spontaneously breathing subjects see ref. 12 Esophageal balloon technique Body plethysmography

13

F L O W o.s olf \., f

. .

VOLUME (I)

111

OCCLUSION RELI[AS[

"-!t AT AIRWAY ~ OPENn~

~'Pmax

PEEP

Fig. 1. Tracings of flow, volume, and pressure at the airway opening in a mechanically ventilated (Bennett MA-2) patient with ARDS with PEEP of 8.5 cm H_,O. Airway occlusion at end-inspiration was performed at point indicated by the first arrow. This results in an immediate drop of pressure from a peak value (Pmax) to P1, therafter decreasing gradually to a 'plateau' value representing the end- inspiratory elastic recoil pressure of the total respiratory system (Pel,rs). In this subject expiratory flow became nil before the end of expiration, and inspiratory flow started synchronously with the onset of positive pressure inflation, indicating that the end-expiratory Pel,rs relative to PEEP is zero. Accordingly, static compliance of the total respiratory system (Cst,rs) is given by the inflation volume divided by the end-inspiratory 'plateau' pressure minus PEEP (A V/Pel, rs). Modified from Rossi et af. (18).

In this connection it should be noted that most ventilators do not return to zero end-expiratory pressure when set on ZEEP (18). Accordingly, when ZEEP is used, the positive pressure of the ventilator (which can amount up to 1.4cmH20 ) needs also to be subtracted from the end-inspira- tory 'plateau' Pel,rs (17, 18).

PEEPi can readily be measured with ventilators (e.g. Siemens 900C) provided with an occlusion hold at end-expiration, which allows measurement of the end-expiratory 'plateau' pressure (i.e. PEEPi). Most ventilators, however, do not have this option, and hence assessment of PEEPi is more problematic. A full discussion of the different ways to assess PEEPi and of the factors determing its magnitude can be found elsewhere (18).

From records such as shown in Fig. 1, the 'effec- tive dynamic compliance' is commonly determined by dividing AV by the peak airway opening pres- sure (Pmax) prior to end-inspiratory airway occlu- sion minus PEEP. This variable clearly does not represent the dynamic compliance of the total res- piratory system as Pmax includes the resistive com- ponent of the applied pressure. Pmax can never- theless be used in assessment of abnormalities of

respiratory mechanics. In fact, (Pmax-PEEP)/AV is a useful index of the effective inspiratory imped- ance of the total respiratory system.

The true dynamic compliance, however, can be readily computed by dividing AV by the Pao im- mediately after end-inspiratory oclusion (P1 in Fig. 1) minus PEEP. If PEEPi is present, the dynamic compliance of the total respiratory system (Cdyn,rs) is given by

Cdyn,rs = A V / P 1 - PEEP - P2) (2)

where P~ is Pao at the point of zero flow prior to lung inflation and may differ somewhat from PEEPi (18).

During constant-flow inflation it is also possible to determine the frequency-dependence of resis- tance, as recently described by Rossi et al. (17). Although ventilators such as used on the patient in Fig. 1 (Bennett MA-2) do not provide a constant flow from the very onset of inspiration, most of the inspiration usually occurs with a constant flow, allowing determination of frequency-dependence of resistance, as described below.

From records such as shown in Fig. 1, the total flow resistance of the respiratory system (endo-

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tracheal tube and equipment included) is con- ventionally obtained by dividing the difference be- tween Pmax and the end-inspiratory 'plateau' pressure by the constant flow prior to the airway occlusion (21). This resistance value, however, rep- resents the resistance corresponding to a respira- tory frequency of zero, and has been defined Rrs,max (2, 17):

Rrs,max = Pmax - end-inspiratory 'plateau' Pel,rs

constant V (3)

By contrast, the resistance corresponding to in- finite respiratory frequency (Rrs,min) is given by:

Rrs,min = Pmax - P1 constant V (4)

With normal lungs (i.e., in the absence of time constant inhomogeneities), Rrs,max should ap- proximate Rrs,min, apart from a small difference which is due to stress relaxation. That is, during breathhold at end-inspiration Pao decreases slightly with time, reflecting the viscoelastic prop- erties of the respiratory system (7). As a result, Rrs,max is slightly greater than Rrs,min even in subjects with normal lungs. By contrast, in patients with severe time constant inhomogeneities within the lungs (e.g., chronic obstructive pulmonary dis- ease, COPD), the difference between P~ and the end-inspiratory 'plateau' pressure is more pro- nounced (reflecting 'pendelluft') (15) and accord- ingly the difference between Rrs,max and Rrs,min becomes very large, reflecting frequency-depen- dence of resistance (2, 15, 17). In this connection it should be noted that Rrs,min reflects the flow resis- tance that would obtain in the absence of time constant inhomogeneities within the respiratory system, while the difference between Rrs,max and Rrs,min reflects the maximal contribution of the time constant inequalities to the resistive be- haviour of the respiratory system (apart from the small stress relaxation component noted above) during constant-flow inflation (Fig. 2). In short, analysis according to Eqs.3 and 4 allows definition of the frequency-dependence of resistance, while analysis according to Eqs.1 and 2 enables to establish the extent by which Crs,dyn and Crs,st differ.

Such analysis has been performed on the ARDS patient of Fig. 1, whose average values of intrinsic Rrs,max and Rrs,min (equipment and tube resis- tance excluded) amounted to 4.5 and 1.8cm H20. l-l .s, respectively (17). Rrs,min in this pa- tient was similar to the values obtained on mechan- ically ventilated normal subjects (3). The substan- tially greater values of Rrs,max than Rrs,min, however, indicate the presence of substantial time constant inequalities within the lungs which were probably caused by inhomogeneities in elastic properties. In fact, in this ARDS patient Cst,rs was lower (50ml. cm H2 O-l) than normal, and his Cdyn,rs was 10% lower than Cst,rs. Although anectodal, the results on this patient suggest that ARDS may be characterized as peripheral lung disease, as reflected by no change in central airway resistance (normal Rrs,min), substantial fre- quency-dependence of resistance (Rrs,max/ Rrs,min = 2.5), decreased Cst,rs, and frequency- dependence of compliance.

In patients with COPD mechanically ventilated for management of acute respiratory failure, Rrs,min is in general considerably increased (Fig. 3) and the difference between Rrs,max and Rrs,min becomes very pronounced. This is associ- ated with low Cst,rs values probably reflecting pul- monary hyperinflation (5, 17, 18) and lower Cdyn,rs than Cst,rs reflecting frequency-depen- dence of compliance. Thus, COPD patients exhibit both central airways disease (markedly increased Rrs,min) and peripheral lung disease (frequency- dependence of both Rrs and Crs). By contrast in ICU patients with etiologies different from COPD, the changes in Rrs,min and Rrs,max are in general less pronounced (Fig. 3).

Apart from the variables defined by Eqs. 1-4, from records such as shown in Fig. 1, it is also possible to derive Cst,rs and Rrs,max by analysis of the relationship between Pao and volume during lung inflation (3,17). In this connection it should be noted that simple inspection of the time-course of Pao during constant-flow inflation, provides useful information about Cst,rs. If Pao during constant "Q increases linearly with time, as is the case in Fig. 1, Cst,rs is likely to be constant over the volume range considered. A decrease in Cst,rs with increasing

15

10

8

v_" 6 6 3: E 4 r

v

U~ "- 2

NORMAL LUNG

A

�9 i

R rs, min

INCLUDING TUBE �9 8

EXCLUDING

PERIPHERAL LUNG DISEASE

R~, min I

B I I

~"R ' rs, max

~ Rrs,max

t N r s , ~ at I = ~

!

PERIPHERAL LUNG DISEASE + INCREASED

CENTRAL AIRWAY RESISTANCE !

C

R rs, min at f = q>~

0 I I I I

0 50 100 0 50 100 0 50 100

RESPIRATORY FREQUENCY (rain -1)

Fig. 2. Schematic diagrams illustrating frequency-dependence of total respiratory system's flow resistance (Rrs). A: In the absence of time-constant inequalities within the lungs (normal lungs), Rrs should be independent of respiratory frequency (f), as shown by solid lines which reflect intrinsic Rrs (lower line) and total Rrs (including the resistance of an endotracheal tube size #8 cut to a length of 24 cm at a flow of 11- s-~). In practice, due to stress relaxation there is an apparent increase of Rrs at low frequencies even in lungs with homogeneous time-constants (broken lines). In the presence of increased central airway resistance (e.g. stenosis of the bronchi), the relationship between Rrs and f should be shifted upwards, while with a larger tube it should be shifted downwards. B: In the absence of changes in airway resistance but in the presence of unequal elastic properties of the air spaces (and hence unequal time-constants), intrinsic Rrs,min remains normal while Rrs,max at f = 0 increases, i.e., frequency-dependence of resistance is exhibited. C: In the presence of increased central airway resistance and peripheral lung disease (e.g. COPD) both intrinsic Rrs,max and Rrs,min increase.

lung volume is in general associated with a pres- sure-time profile characterized by an upward con- cavity, while the opposite should be true when compliance increase with lung volume (Fig. 4). Such measurements, however, can best be made with ventilators which provide constant-flow from the onset of inspiration.

The constant-flow inflation method described above is appealing both for its simplicity and be- cause it provides a comprehensive on-line assess- ment of respiratory mechanics. It can not only be applied on patients with relaxed respiratory mus- cles, but also on patients who trigger the ventilator (assist inspiration) provided that most of the in- spiration is passive (relaxed).

3.3. Interrupter method

This technique, which was originally proposed by yon Neergaard and Wirz (14), has been recently adapted by Gottfried et al. (4, 5) to determine respiratory system mechanics during anesthesia and in patients mechanically ventilated for man- agement of acute respiratory failure. Use of this method in a patient with myasthenia gravis requir- ing mechanical ventilation is shown in Fig. 5. Fol- lowing end-inspiratory airway occlusion, a series of brief (about 0.2 s) interruptions of expiratory flow were performed throughout the subsequent re- laxed expiration. (This can be accomplished using a rapidly responding pneumatic valve or by manual

16

25

2o

Z

U) mmm

U) W 10

0 m

r Z -- 5 n- p-

Z

- ~ o COPD

S

N

0 I I R r s (max) R r s (rain)

Fig. 3. Values of maximum (Rrs,max) and minimum (Rrs,min) intrinsic flow resistance of the total respiratory system (equipment and tube resistance subtracted) in 11 mechanically ventilated patients (5 with COPD and 6 with different etiologies). From Rossi et al. (17).

occlusion of the airway opening). An immediate 'plateau' in post-interruption airway pressure con- sistently occurred during each interruption throughout the course of expiration, indicating the continued presence of respiratory muscle relaxa- tion. Under these conditions, the plateau in airway pressure represents the total pressure available to overcome the expiratory flow resistance of the res- piratory system (Pres,rs). By plotting the plateau in airway pressure during interruption against the im- mediately preceding flow for each interruption throughout expiration, the passive flow resistive properties of the respiratory system can be deter-

mined (4, 5). Furthermore, since the plateau in post-interruption airway pressure also represents the elastic recoil of the total respiratory system (Pel,rs), the passive elastic properties of the respi- ratory system can be obtained from plots of the plateau in post-interruption airway pressure and the corresponding volume above the end-expira- tory position for each interruption throughout ex- piration (4, 5). Thus, measurement of the 'plateau' in the airway pressure during interruption, the im- mediately preceding flow, and the coresponding volume above the end-expiratory position permit simultaneous determination of the flow resistive

17

Z A B C

==

TIME Fig. 4. Schematic diagrams illustrating time-course of pressure applied at the airway opening by a constant-flow ventilator in a patient with total compliance of the respiratory system constant (A), decreasing (B), and increasing (C) during lung inflation. Case C should occur when a distinct 'knee' is present on the inflation static volume-pressure curve of the respiratory system (11), while case B usually reflects pulmonary hyperinflation. In the presence of severe time constant inequalities within the lungs, pattern C can be present even if compliance is constant over the change in volume produced by the ventilator (2).

and elastic characteristics of the total respiratory system during expiration.

An immediate post-interruption 'plateau' in air- way pressure such as exhibited in Fig. 5, is found in humans with normal lungs (4, 5). By contrast, in patients with severe lung disease characterized by time-constant inhomogeneities (e.g., COPD), the post-interruption 'plateau' is not reached immedi- ately, as shown in Fig. 6. As for occlusion at end- inspiration (Fig. 1), the difference between the pressure rise immediately succeeding the occlusion and the subsequent 'plateau' pressure indicates fre- quency-dependence of resistance (and com- pliance). Values of Rrs,min and Rrs,max (Eqs.3 and 4) can again be determined by dividing, respec- tively, the immediate rise in Pao following the in- terruption and the 'plateau' Pao by the flow pre- ceding the interruption. As for occlusion at end- inspiration, Rmin in this case represents the total flow resistance at infinite frequency (3, 16). By contrast, Rmax measured during expiratory inter- ruptions of flow does not correspond to the resis- tance at zero frequency since flow during expira- tion is not constant. Nevertheless, Rmax measured during relaxed expiration can provide useful clini-

cal information (5). More importantly, the inter- rupter method allows to detect whether expiratory flow during mechanical ventilation is limited by dynamic compression of the intrathoracic airways. The occurrence of expiratory flow limitation is in- dicated by the characteristic pattern of flow tran- sients observed with the re-establishment of flow following expiratory interruptions (Fig. 6), similar to that observed by Knudson and co-workers (10) during 'partial' maximal forced expiratory maneu- vers. This phenomenon has been attributed to high peak flows generated in the conducting airways undergoing compression just prior to the develop- ment of expiratory flow limitation (5, 10).

While flow limitation usually occurs only during forced expiratory maneuvers in normal subjects, Hyatt (8) and others have demonstrated the pre- sence of expiratory flow limitation during tidal breathing in stable patients with severe COPD. The occurrence of expiratory flow limitation in passively mechanically ventilated patients may be related in part to excessive hyperinflation associ- ated with inward recoil of the chest wall throughout expiration, the resulting positive pleural pressure being sufficiently in excess of intraluminal pressure

18

(, s")

V ~ E (l iters)

J

~ SELEAM

~ ~ _

I I I I lu Im

~ E A L n. ~ § T PRESSURE ~ . . , . , o j o - ~ # " -

Fig,. 5. Use of the interrupter technique to determine the passive mechanical properties of the respiratory system in a patient mechanically ventilated for management of respiratory failure caused by myasthenia gravis. The airway was occluded at endiinflation (first arrow) and maintained until a plateau in tracheal pressure occurred. The occlusion was then rapidly released and a series of interruptions performed throughout the subsequent passive expiration. During the period of interruption, flow fell promptly to zero and expired volume remained unchanged. Following initial oscillations due to inertial properties, a plateau in tracheal pressure promptly occurred and was observed consistently throughout expiratory interruptions. This indicated the continued presence of respiratory muscle relaxation as well as rapid equilibration between alveolar and tracheal pressure. Similarly, the flows immediately preceding and following interruptions were not different. Note the change in paper speed indicated by the lower arrow. From Gottfried et al. (5).

FLOW m~f C~S I ~ _ . ~ ~ _ 0..") �9

(me,s) O.S

P I

71 - ,

! I m

Fig. 6. As Fig. 5, in a COPD patient. Note that, unlike the patient in Fig. 5, (a) the 'plateau' in post-interruption pressure is not reached immediately following each occlusion; and (b) the flow after release of the occlusions is not similar to that prior to the occlusion but exhibits a characteristic high flow transient. For further explanations see text.

to promote dynamic airway compression. Kimball et al. (9) have emphyasized the likelihood of ven- tilator dependence in the presence of expiratory flow limitation and extreme hyperinflation. The recognition of dynamic airway compression and expiratory flow limitation therefore has definite clinical importance and may be easily detected by the characteristic flow trafisients following expira- tory interruptions.

3.4. Static volume-pressure relationship of the total respiratory system

Gottfried et al. (4, 5) have described the measure- ment of the expiratory static V-P curve of the respi- ratory system using the interrupter technique. This approach can also be applied during lung inflation, and extended to larger lung volumes than the AV delivered by the ventilator. In fact, both Suter (20) and Matamis et al. (11) have stressed the import- ance for measuring static V-P curves during lung inflation in ICU patients.

3.5. Conclusions

Despite the number of adult patients requiring pro- longed mechanical ventilation for varied clinical conditions, quantitative determination of respira- tory mechanics are not routinely performed. The ability and use of such measurements would be expected to aid in clinical decision making and in the management of such critically ill patients. The constant-flow inflation method and the interrupter technique have been demonstrated to be valid in the intubated, mechanically ventilated patients, and appear to be especially suited to this purpose. These approaches enable on-line quantitative de- termination of static and dynamic compliance, and of frequency-dependence of flow resistance of the total respiratory system. The static volume-pres- sure relationship throughout the observed tidal volume range can be rapidly examined, avoiding erroneous determinations of Crs from single mea- surements of volume and pressure at end-inspira- tion alone. The presence and amount of intrinsic PEEP can also be readily assessed. Similarly, the presence of dynamic airway compression and ex-

19

piratory flow limitation may be recognized by the characteristic flow transients present following ex- piratory interruptions. Direct determination of res- piratory system resistance should also enable prompt, quantitative assessment of the clinical efficacy of various therapeutic interventions in the mechanically ventilated patient, such as bron- chodilator administration, which has not been pre- viously available. Lastly, the quantitative changes in respiratory system mechanics which may occur in mechanically ventilated patients and the influ- ence of this on the ability to discontinue ventilatory support or ultimate patient outcome are largely unknown. Serial evaluation of respiratory system mechanics may aid in the investigation of these and other important clinical issues in the management of patients receiving mechanical ventilation.

4. Summary

Recent methods developed for non-invasive deter- mination of the mechanical properties of the respi- ratory system have been reviewed. These methods can provide valuable on-line information in pa- tients mechanically ventilated in the intensive care unit setting. More extensive use of such methods should help to provide a better understanding of the physiopathologic processes and adaptive mech- anisms present in patients who require mechanical ventilation.

References

1. Agostoni E, Mead J: Statics of the respiratory system. In: Handbook of Physiology. Respiration. Washington, D.C. Am Physiol Soc 1964, Sect. 3, Vol. I, Chapt. 13, pp. 387- 409.

2. Bates JTM, Rossi A, Milic-Emili J: Analysis of the be- havior of the respiratory system with constant inspiratory flow. J Appl Physiol 59: 1840-1848, 1985.

3. Behrakis PK, Higgs BD, Baydur A, et al.: Respiratory mechanics during halothane anesthesia and anesthesia-par- aylsis in humans. J Appl Physiol 55: 1085-1092, 1983.

4. Gottfried S, Higgs B, Rossi A, et al.: Interrupter technique for measurement of total respiratory system elastance and resistance in anesthetized humans. J Appl Physiol 59: 647- 652, 1985.

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5. Gottfried SB, Rossi A, Higgs BD, et al.: Non-invasive determination of respiratory system mechanics during me- chanical ventilation for acute respiratory failure. Am Rev Respir Dis 131: 672-677, 1985.

6. Hedenstierna G, McCarthy G: Mechanics of breathing, gas distribution and functional residual capacity at different frequencies of respiration during spontaneous and artifical ventilation. Br J Anaesth 47: 706-712, 1975.

7. Hughes R, May AJ, Widdicombe JG: Stress relaxation in rabbit's lungs. J Physiol (London) 146: 85-97, 1959.

8. Hyatt RE: The interrelationships of pressure, flow and volume during respiratory maneuvers in normal and em- physematous subjects. Am Rev Respir Dis 83: 676-683, 1961.

9. Kimball WR, Leith DE, Robins AG: Dynamic hyperinfla- tion and ventilator dependence in chronic obstructive pul- monary disease. Am Rev Respir Dis 126: 991-995, 1982.

10. Knudson RJ, Mead J, Knudson DE: Contribution of air- way collapse to supramaximal expiratory flows. J Appl Physiol 36: 653-667, 1974.

11. Matamis D, Lemaire F, Haft A, et al.: Total respiratory pressure volume curves in the adult respiratory distress syndrome. Chest 86: 54-57, 1984.

12. Mead J, Agostoni E: Dynamics of breathing. In: Handbook of Physiology. Respiration. Washington, D.C. Am Physiol Soc 1964, Sect. 3, Vol I, Chapt. 14, pp 411-427.

13. Milic-Emili J: Measurement of pressures in respiratory physiology. In: Otis AB (ed) Techniques in the life sci- ences, P4/II, 1-22, Elsevier Scientific Publishers, Ireland, Ltd., 1984.

14. Neergaard J von, Wirz K: Die Messung der Str6mungswiderst~inde in den Atemwegen des Menschens,

insbesondere bei asthma und emphysem. Z Kiln Med 105: 51-82, 1927.

15. Otis AB, McKerrow CB, Bartlett A, et al.: Mechanical factors in distribution of pulmonary ventilation. J Appl Physiol 8: 427-443, 1956.

16. Pepe PE, Marini JJ: Occult positive end-expiratory pres- sure in mechanically ventilated patients with airflow ob- struction. Am Rev Respir Dis 126: 166-170, 1982.

17. Rossi A, Gotffried SB, Higgs BD, et al.: Respiratory me- chanics in mechanically ventilated patients with respiratory failure. J Appl Physiol 59: 1849-1858, 1985.

18. Rossi A, Gottfried SB, Zocchi L, et al.: Measurement of static compliance of the total respiratory system in patients with acute respiratory failure during mechanical ventila- tion: the effect of 'intrinsic PEEP'. Am Rev Respir Dis 131: 672-677, 1985.

19. Sackner MA: Monitoring of ventilation without physical connection to the airway: a review. In: Scott FD, Raflery EB, Goulding L (eds) ISAM Proceedings of the Third International Symposium on Ambulatory Monitoring. Ac- ademic Press, London, 1980, pp 299-319.

20. Surer PM: Assessment of respiratory mechanics in ARDS. In: Zapal WM, Falke KJ (eds) Acute respiratory failure. Lung Biology in Health and Disease, Vol. 24, Marcel De- kker, Inc., New York, pp 507-519, 1985.

21. Suter PM, Fairley HB, Isenberg MD: Optimum end-ex- piratory airway pressure in patients with acute pulmonary failure. N Engl J Med 292: 284-289, 1975.

22. Suter PM, Schlobohm RM: Determination of functional residual capacity during mechanical ventilation. Anesthe- siology 41: 605-607, 1974.