Flow and Volume Dependence of Respiratory System Flow Resistance in Patients with Adult Respiratory Distress Syndrome 1- 3
C. TANTUCCI, C. CORBEIL, M. CHASSE, F. M. ROBATTO, S. NAVA, J. BRAIDY, N. MATAR, and J. MILlC-EMILI
Introduction
Several studies have shown that ARDS is characterized not only by decreased pulmonary and total respiratory system compliance but also by increased airway, pulmonary, and thoracic (lung plus chest wall) tissue flow resistance (1-3). These measurements were carried out during constant-flow inflation at inspiratory flows and volumes that varied among patients and between studies. Recent reports, however, have shown that in normal anesthetized-paralyzed humans (4), dogs (5), and cats (6, 7), the pulmonary, chest wall, and total respiratory flow resistance (Rrs) vary markedly with both inflation flow and volume. Using the technique of rapid airway occlusion durring constant flow inflation, Eissa and coworkers (8, 9) have recently studied the flow and volume dependence of Rrs in patients with ARDS. Rrs was partitioned into the interrupter resistance (Rint), which in humans reflects airway resistance (10, 11), and the effective additional resistance (L\Rrs) that results from (1) time-related pressure dissipations caused by the viscoelastic properties of the thoracic tissues, i.e., the so-called thoracic tissue flow resistance (4-7), and (2) timeconstant inequalities within the lung (pendelluft) (4, 9). They found that in patients with ARDS Rint was about two times higher than normal and varied relatively little with both inflation flow and volume (8). In contrast, L\Rrs was markedly increased, especially at low inflation flows, and was markedly flow and volume dependent (9). However, the method used by Eissa and coworkers (8, 9) involves long experiments (about 15 min to establish the relationships of Rrs, Rint, and L\Rrs to flow at a single inflation volume) and time-consuming data analysis. Furthermore, such measurements require a ventilator with which it is possible to change from one breath to
SUMMARY Using a simple and rapid technique, we studied the flow and volume dependence of the total resistance of the respiratory system (Rrs) In six patients with ARDS. At any given Inflation volume, Rrs decreased progressively with Increasing flow (V) according to the following hyperbolic function: Rrs = a/V + b, where a and b are constants. At any fixed Inflation flow, Rrs Increased progressively with Increasing Inflation volume. The observed flow and volume dependence of Rrs Is probably mainly due to the viscoelastic properties of the pUlmonary and chest wall tissues. The flow and volume dependence of Rrs found In the patients with ARDS Is qualitatively similar to that previously observed In normal anesthetized paralyzed SUbJects. In ARDS, however, Rrs was considerably greater than In the normal subjects, Indicating that besides a low respiratory compliance ARDS Is characterized by a high flow resistance. This mainly reflects Increased effective flow resistance of the pUlmonary and chest wall tissues, although airway resistance Is also higher than normal. AM REV RESPIR DIS 1992; 145:355-360
another, either the inflation flow while keeping the inflation volume fixed or the inflation volume while keeping the flow fixed (8, 9). These stringent requirements are met by some ventilators (e.g., Servo 900C; Siemens, Berlin, Germany) (8, 9) but not all (e.g., Model 7200; PuritanBennett, Carlsbad, CA). In the present report, we have used a simple and rapid method for determining the flow and volume dependence of Rrs in patients with ARDS who were ventilated with 7200 Puritan-Bennett ventilators. The measurements could be completed in less than 8 min, and they provided Rrs versus flow relationships at different inflation volumes. In addition, our method allows (1) determination of the static inflation volume-pressure relationship of the respiratory system, and (2) partitioning of Rrs into Rint and L\Rrs at baseline inflation flow and volume. Methods Six patients with ARDS who were admitted to the intensive care unit of Saint-Luc Hospital were studied. In five patients ARDS was caused by sepsis, and in one it was associated with hypovolemic shock requiring multiple blood transfusions (table 1). Patients 1 to 3 had never smoked, Patients 4 and 5 were smokers (both 30 pack-years), and the last was an ex-smoker (7.5 pack-years untillOyr ago).
All patients were studied within the first 2 days from the moment they met the following criteria for ARDS (12): (1) the presence of bilateral diffuse infiltrates on chest radiography; (2) a known predisposing illness for at least 18h before the radiographic changes; (3) a pulmonary capillary wedge pressure less than 15 mm Hg; (4) an arterial Po, ~ 50 mm Hg with a fractional inspired 0, concentration of 0.5 during positive end-expiratory pressure (PEEP). The study was approved by the institutional ethics committee, and informed consent was obtained from each patient or next of kin. Patients were supine, intubated (Sheridan's cuffed endotracheal tube with internal diameter of 8 mm in Patients 2 to 6 and 9 mm in Patient 1)and mechanically ventilated with
(Received in original form July 5, 1990 and in revised form August 8, 1991) 1 From the Respiratory Division, Hopital SaintLuc, Universite de Montreal, and the MeakinsChristie Laboratories, McGill University,Montreal, Quebec, Canada. 2 Supported by the Medical Research Council of Canada, the J. T. Costello Memorial ResearchFund, the Fondation de l'Hopital Saint-Luc, and the Respiratory Health - Network of Centres of Excellence, Canada. 3 Requests for reprints should be addressed to Dr. N. Matar, Respiratory Division, Hopital SaintLuc, 1058 St. Denis Street, Montreal, Quebec, Canada H2X 3J4.
355
356
TANTUCCI, CORBEll, CHASSE, ROBATTO, MAYA, BRAIDY, MATAR, AND MILlC-EMILI
TABLE 1 CLINICAL DATA OF SUBJECTS WITH ARDS
Patient Age No. Sex (yr)
1 2 3 4 5 6
F F F M M F
Mean ± SO
37 88 67 48 49 35 54.0 20.2
Baseline Baseline Baseline PEEP Height Weight Pao. Paco. Baseline Baseline (em H2O) (mmHg) (mm Hg) pH (kg) (em) FlO.
160 163 157 172 175 152 163.2 8.8
71 62 58 67 60 48 61.0 7.9
72 80 76 72 95 87 80.3 9.1
7.50 7.35 7.36 7.34 7.41 7.47 7.40 0.07
30 36 50 44 35 37 38.7 7.1
5.0 12.5 15.0 5.0 12.0 8.0 9.6 4.2
0.55 0.90 0.90 0.80 0.80 0.55 0.75 0.16
Etiology Sepsis Hypovolemic shock Sepsis Sepsis Sepsis Sepsis
TABLE 2 BASELINE VALUES OF VARIOUS VENTILATORY VARIABLES IN PATIENTS WITH ARDS
1 2 3 4 5 6 Mean ± SO
V
6V (L)
6V (mllkg)
(Lis)
0.825 0.880 0.680 1.085 0.875 0.880 0.871 0.130
11.6 14.2 11.7 16.2 14.6 18.3 14.4 2.6
0.82 1.30 0.99 1.20 0.91 0.90 1.02 0.19
TI (s)
TE (s)
1.04 3.24 0.84 3.44 0.86 3.42 1.03 3.25 1.08 3.20 1.08 3.20 0.99 3.29 0.11 0.11
TllTtot
PEEPi (em H2O)
6FRC (L)
Cst,rs (Llem H2O)
0.24 0.20 0.20 0.24 0.25 0.25 0.23 0.02
0.0 16.5 0.0 4.0 4.5 3.0 4.6 6.1
0
0.030 0.023 0.021 0.059 0.034 0.068 0.039 0.020
0 0.050 0.085 0.090 0.045 0.044
Definition of abbreviations: t. V = inflationvolume; V = constant inspiratory flow; TI = inspiratory time; TE = expiratorytime; Tifftot = duty cycle;PEEPi = intrinsic positiveend-expiratory prassure; t.FRC = volumeabovethe relaxation point of the respiratory system; Cst,rs = static compliance of the respiratory system.
constant inflation flow using the control ventilation mode of the 7200 Puritan-Bennett ventilator. Upon decision of the primary physicians, all patients weresedated intravenously with diazepam, 0.1 to 0.2 mg/kg, and paralyzed with pancuronium bromide, 0.1 to 0.2 mg/kg. The baseline ventilatory settings are listed in table 2. Prior to the measurements of respiratory mechanics they all received PEEP, as indicated in table I. Respiratory mechanics were measured after PEEP wastemporarily removed. The baseline ventilatory settings (table 2) were kept constant throughout the study, except for the single-breath tests described in Procedure below. Tracheal pressure (Ptr) was measured via an end-sealed noncompliant 160 catheter (I. 7 mm ID) connected to a pressure transducer (Validyne MP45, ± 100 em H.O; Validyne Inc., Northridge, CA). The catheter tip, provided with six lateral holes, was positioned such that it protruded 2 to 3 cm into the trachea. With the system used to measure Ptr there was no appreciable shift or alteration in amplitude up to 20 Hz. Flow (V) was measured with a heated pneumotachograph (Fleisch no. 3; Fleisch, Lausanne, Switzerland), which was inserted via cones between the proximal end of the endotracheal tube and the Y-connecter of the ventilator. The pneu-
Procedure and Data Analysis The following measurements are carried out in each patient, 10min after removalof PEEP. During this period the subjects reached a steady state, as judged by stability of the Ptr, expired Pco., and pulse-oxymeter records.
Staticinflation volume-pressure (V-P) relationship 0/ the respiratory system. While
Definition of abbreviations: FlO, = fraction of inspired 0,; PEEP = positiveend-expiratory pressure.
Patient No.
cutaneous O. saturation and to adjust FlO. while PEEP was removed from the patients in order to avoid excessive desaturations. During the study a physician not involved in the experiment was always present to provide for patient care.
motachograph, which was connected to a differential pressure transducer (ValidyneMP 45, ± 2.5 em H.O), was linear over the experimental flow range. The equipment dead space (not including the endotracheal tube) was 169 ml. Special care was taken to avoid air leaks around the tracheal cuff and from the breathing circuit. For monitoring, changes in volume were obtained by electrical integration of the flow signal (Model 8815A;HewlettPackard Inc., Andover, MA). All signals were recorded on an eight-channel pen recorder (7758A; Hewlett-Packard, Palo Alto, CA) with a paper speed of 10 mm/s and on magnetic tape (Hewlett-Packard 3968A). The Ptr and V signals were played back at a sample frequency of 200 Hz by a 12-bit analog-todigital converter on an IBM compatible personal computer for subsequent data analysis. In this analysis, volume was obtained by digital integration of the flow signal. Arterial blood gases were measured with an ABL 330 blood gas analyzer (Radiometer, Copenhagen, Denmark), and the end-tidal CO. fraction was monitored with a CO. analyzer (CO. Monitor; Datex, Helsinki, Finland). The values of Flo. and blood gases at the time of the investigation are listed in table 1. A pulse-oxymeter (Nellcor, Hayward, CA) was used to monitor the arterial trans-
keeping the inflation flow at the baseline setting value, single-breath end-inspiratory airway occlusions were performed at different inflation volumes (AV) ranging from 0.1 to 1 L. Inflation volume was changed with the appropriate button on the ventilator. In each test breath occlusions were maintained until an apparent plateau in tracheal pressure was achieved. Because the 7200 Puritan-Bennett ventilator is programmed for a maximal endinspiratory pause of only 2 s, which may not suffice to achieve a plateau in Ptr during the 2-send-inspiratory hold, wealso occluded the inspiratory and expiratory lines of the ventilator by clamping the ventilator tubings. In this way, longer end-inspiratory occlusion holds could be achieved. The inspiratory and expiratory lines were similarly occluded at end-expiration until a plateau in Ptr was achieved, representingintrinsic PEEP (PEEPi) (1, 2, 13). Because PEEPi implies dynamic pulmonary hyperinflation, i.e., that the endexpiratory lung volume (ELV) during mechanical ventilation exceeds the relaxation volume of the respiratory system (Vr), we also measured the difference between ELV and Vr (hereintermed AFRC) by removingthe Y-piece of the ventilator from the pneumotachograph during expiration, allowing the patient to exhale until expiratory flow ceased, indicating that the subject had reached Vr (2). After each test breath, baseline ventilation was resumed until the tracheal pressure records returned to baseline values (usually in a few breaths). Tests were performed in random order. Because the plateau values of Ptr represent the static elastic recoil pressure of the respiratory system (Pst), plots of AV versus Pst allowed to construct the static inflation V-P curve of the respiratory system. The static compliance of the respiratory system .(Cst.rs) was measured by dividing the baseline AV (table 2) by the corresponding valueof end-inspiratory Pst minus PEEPi, if present (2). This compliance will henceforth be termed standard compliance.
Total resistance ofrespiratorysystem(Rrs). While keeping the inflation volume at baseline setting, a series of single-breath lung inflations at different inspiratory flows (up to 2 L/s) wereperformed in random order. Flow was changed with the appropriate button on the ventilator. After each test breath, baseline ventilation was resumed until the trache-
357
FLOW RESISTANCE IN ARDS
1.0
20 Pst
12
34
5
0.8
2 :3~
15 0.6
5' N
o >
z
o
...~ 1!;
::l:
E
0.4
2
10
;;
..."-
0.2
D:
+--------r---,-------r------,
00
o
20
10
30
40
Plr(cmH20)
10
0.8
06
04
02
OO+--_ _-t-r-_ _ 0.0
05
-r-_-_-~_,
1.0
15
2
a
INSPIRATORY FlOW (lis)
Fig. 1. Toppanel. Relationship between inflation volume (~V) and tracheal pressure (Ptr) under static conditions (Pst) and during a series of five inflations made with differing inflation flows. Bottom panel. Inspiratory volume-flow (~v-iJ) relationships corresponding to top panel. Numbers on curves identify ~ V-Ptrand ~ V-Vrelationship obtained during the same inflation. Patient 4.
al pressure records returned to the pretest values. Dynamic inflation !::N versus Ptr relationships were plotted as shown in figure 1 (top panel) together with the corresponding static curve. The concurrent AV versus V relationships were also displayed, as shown in figure 1 (bottom panel). Isovolume pressure-flow relationships for the total respiratory system were computed by plotting the resistive pressure (Ptr-Pst) derived from figure 1 (top panel) against the corresponding flow from figure 1 (bottom panel). As shown by the AV- V relationships in figure 1 (bottom panel), with the 7200 Puritan-Bennett ventilator about 0.2 s were required to achieve the preset constant inflation flows. Partitioning of respiratory system resistance. The records obtained during endinspiratory airway occlusion at baseline inflation volume and flow (table 2) were used to partition Rrs into the interrupter resistance (Rint) and ARrs, as previously described in detail (4).Briefly, Riot was obtained by dividing the immediate drop in Ptr after endinspiratory airway occlusion by the immediately preceding flow, whereas ARrs was derived by dividing the slow postocclusion pressure change in Ptr up to its plateau value by the flow preceding the end-inspiratory flow interruption. The immediate and slowchanges in Ptr wereobtained by computer-fitted curves
Fig. 2. Top panel. Relationships between resistive inflation pressure (PtrPst) and inspiratory flow obtained at different inflation volumes (~V) from Figure 1 in Patient 4. Values of constants of equation 1 together with regression coefficients are indicated. Bottom panel. Isovolume relationships between total respiratory resistance (Rrs) and inspiratory flow computed according to equation 2 using values of constants in top panel. Closed triangle = y = 3.08 + 8.22x, R = 0.99; open square = y = 2.71 + 8.28x, R = 0.99; closed square = y = 1.79 + 8.37x,R = 0.99; open circles = y = 0.52 + 8.23x, R = 0.99; closed circles = y = 0.49 + 7.41x, R = 0.99.
5
o -t--~-'---~-'----'---'---~-T o 05 1.5 2 INSPIRATORY FLOW (Lis)
30 tN
ILl
0.8 0.6
"
20
::J
0.4
0N
::l:
E
2
'"
eX:
0.2 0.1
10
o-t-----.----~--.-~-___,_-~-__r
o
2 INSPIRATORY FLOW (Lis)
as previously described (4, 14). In calculation of Rint and Rrs, the errors caused by the closing time of the ventilator valve were corrected according to Kochi and coworkers (6). The whole experimental protocol could be completed in less than 8 min. Regressionanalysis was made with the leastsquares method. Comparison with normal anesthetized paralyzed subjects (4) was made using the unpaired t test. Values are mean ± SE unless otherwise specified.
Results Intrinsic PEEP, ranging from 3 to 16.5 em H 2 0 , was present in four of the six patients (table 2). PEEPi was associated with a modest degree of dynamic pulmonary hyperinflation, as evidenced by the small values of AFRC, which ranged from zero to 90 ml. For technical reasons AFRC could not be measured in the patient with the highest PEEPi (Patient 2). Standard static respiratory compliance amounted to 39 ± 8 mllcm H 2 0 (table 2). The relationships between resistive pressure (Ptr-Pst) and flow obtained at different inflation volumes in Patient 4 are depicted in figure 2 (top panel). At
all inflation volumes, the relationships were linear functions of the type: Ptr-Pst
=a +
bV
(1)
where a is intercept at V = 0 and b is slope. The value of a increased significantly with inflation volume (p < 0.005), whereas the volume-related changes of slope b were not significant. Similar results were found in all patients, the correlation coefficients of the regressions (equation 1) ranging between 0.96 and 0.99 (p < 0.001). The average values of the constants a and b for different inflation volumes of the six patients are given in table 3. Because Rrs = (Ptr-Pst)/V, equation 1 implies that the total respiratory resistance decreases hyperbolically with increasing V: Rrs
=
a/V
+ b
(2)
The isovolume relationships between Rrs and V for patient 4, computed according to equation 2, are depicted in figure 2 (bottom panel). The average isovolume relationships between Rrs and V of the six patients with ARDS are shown in figure 3. At all inflation volumes, Rrs
358
lANlUCCI, CORBEIL, CHASSE, ROSATTO, NAVA, BRAIDY, MAlAR, AND Mille-EMILI
TABLE 3
TABLE 4
RELATIONSHIPS OF RESISTIVE PRESSURE WITH flOW OBTAINED AT DIFFERENT INFLATION VOLUMES IN PATIENTS WITH ARDS·
BASELINE VALUES OF RESPIRATORY SYSTEM RESISTANCE AND ITS COMPONENTS IN PATIENTS WITH AROS·
Ptr-Pst = a + bV !1V (L)
a
b
(em H2O)
(em H2O/LIs)
2.56 2.88 3.07 3.22 3.28
0.1 0.2 0.4 0.6 0.8
± ± ± ± ±
2.28 1.92 2.16 2.39 2.98
5.52 5.67 6.05 6.57 6.89
± ± ± ± ±
3.30 3.19 2.71 2.34 2.22
Definition of abbreviations: Ii V = intlation volume: Plr = dynamic tracheal pressure at different inflation volumes; Pst = static pressure at corresponding inflation volumes; II = inspiratory flow; a, b = constants of equation t. • Values are mean ± SO.
30
Patient No.
1 2 3 4 5 6 Mean ± SO
Rrs Rint (em H2 0 /LIs) (em H20/LIs)
11.0 9.5 10.3 12.6 15.2 8.9 11.2 2.3
1.9 4.8 4.7 7.2 4.4 2.2 4.2 1.9
t>Rrs (em H2 0 /LIs)
9.1 4.7 5.6 5.4 10.8 6.7 7.0 2.4
Definition of abbreviations: Ars = respiratory system resistance; Aint = interrupter resistance; liArs = additional resistance. • Measurements were obtained at ventilator settings lndlcated in Table 2.
1 'J,V IL)
25
~
20
I£
15
e
II:
10
0.8
0 .s
v.. 0.5
1.5
25
INSPIRATORY FLOW (U,)
Fig. 3. Averageisovolume relationship between total respiratory resistance (Rrs) and inspiratory flow of six patients.
decreased progressively with increasing flow, approaching an asymptote corresponding to b (equation 2) at high V. At any given flow Rrs increased with increasing liV, At baseline inflation flow and volume we partitioned Rrs into the interrupter resistance (Rint) and .liRrs (table 4). Rrs amounted to 11.2 ± 1 ern H 20/LIs, whereas Rint was 4.2 ± 0.8 cm H 20/LIs, indicating that under these conditions Rint represented 38070 of Rrs, whereas a greater proportion (62%) was due to liRrs. Because in patients with ARDS Rint does not change significantly with flow (8), whereas Rrs increases progressively with decreasing flow (figure 3), the percent fraction of Rint to Rrs should be less at low inspiratory flows than at baseline flow. Indeed, at V of 0.25 Lis, Rint at baseline inflation volume should represent only 21% of Rrs. Discussion
Before the results of the present study can be discussed, some methodologic
considerations are required. The technique of rapid airway occlusion during constant flow inflation allows partitioning of Rrs into Rint and liRrs at different inflation flows and volumes. In practice, however, such measurements are limited to a fixed inflation flow or a fixed inflation volume because the experimental time required is rather long (4, 9, 11). Furthermore, such measurements can be obtained only with special ventilators (e.g., Siemens servo 9ooC). The approach used in the present study is rapid and feasible with virtually all ventilators that provide constant inflation flow. Furthermore, the present method allows a full characterization of flow and volume dependence of Rrs. In addition, at baseline inflation flow and volume, Rrs can be partitioned into Rint and liRrs. Thus, the present approach appears to be particularly suitable for clinical assessment of respiratory mechanics.
Static Inflation V-P Curves In line with previous studies (1, 2), we found that patients with ARDS often exhibit a substantial PEEPi. It should be noted, however, that the four patients with ARDS who exhibited PEEPi included two smokers (Patients 4 and 5), an exsmoker (Patient 6), and a very old (88 yr) nonsmoker. PEEPi has to be taken into account for correct measurement of Cst,rs (15). Indeed, in Patient 2 the uncorrected value of standard Cst.rs was 30% lower than the corrected one. The values of standard Cst,rs (39 ± 8 mllcm H 20) were significantly lower (p < 0.005) than in normal anesthetized paralyzed subjects (4) but were close to those found by Broseghini and coworkers (2) in eight
patients with ARDS studied during the first day of mechanical ventilation (35 ± 2 mllcm H 20). In agreement with Broseghini and coworkers (2), we found that in patients with ARDS the values of liFRC are small (up to 90 ml).
Flow and Volume Dependence of Respiratory System Resistance The conventional equation for describing the relationship between Rrs and flow at a fixed lung volume is given by (16): Rrs
=
Rti + K 1 + K2 V
(3)
where Rti is flow resistance of thoracic tissues, which is assumed to be independent of flow, and K 1 and K 2 are empirical constants (Rohrer's constants), which describe the relationship between airway resistance (Raw) and flow (16): Raw
=
K 1 + K2 V
(4)
Equation 3 is the basis of one of the tenets of respiratory mechanics, namely, that at a fixed lung volume, Rrs should increase with increasing Vbecause of the term K 2V. Another tenet is that at a fixed flow, Rrs should decrease with increasing inflation volume because of a decrease in both Raw (17) and Rti (18), the former reflecting airway dilatation, whereas the latter should result because the linear velocity of thoracic tissues decreases with increasing lung volume, and hence the flow-dependent pressure losses within the thoracic tissues should be reduced. Equation 3 assumes that the thoracic tissues exhibit pure (Newtonian) resistive behavior. However, recent studies on animals (5-7) and humans (4, 11) have shown that this is not the case: the thoracic tissues exhibit characteristic viscoelastic behavior that is adequately explained by a spring-and-dashpot model (4, 5). This model predicts that at fixed lung volume, Rti (and hence Rrs) should decrease with increasing inflation flow. A useful empirical function relating isovolume Rti with Vis given by (4, 7): Rti
=
a/V + b'
(5)
where a and b' are constants. Replacing Rti in equation 3 with this function, the following is obtained:
= a/V + b' + K 1 + K2 V (6) b' + K 1 = b, equation 6 becomes: Rrs = a/V + b + K2 V (7)
Rrs For
If K2 is negligible, equation 7 is simplified into equation 2.
359
FLOW RESISTANce IN ARDS
flow of our patients with ARDS together with the corresponding relationship 25 tN:O.5L obtained by D'Angelo and coworkers (4) in 16 normal anesthetized paralyzed sub, -, jects. In both cases a marked decrease ARDS (n;::6) of Rrs occurred at flow rates between 0.2 and 1 Lis. At inspiratory flow of 0.4 Lis, which is close to the mean inspiratory flow rate during spontaneous breathing +-~--,-~-.-~--,-----.-----,at rest, Rrs amounted to 14.3 ± 3.3 em 1 1.5 05 2.5 H 2 0 / L/ s in the patients with ARDS INSPIRATORY FLOW (lis) compared with 5.6 ± 0.7 em H 20/L/s Fig. 4. Average (:t SEM) relationships between respiin the normal anesthetized paralyzed ratory system resistance (Rrs)and inflationflow at fixed inflation volume (~ V) of 0.5 L in six patients withARDS (p < 0.001) subjects. At inspiratory flow of present study and inthe 16normalanesthetized paraof 1 Lis, corresponding to the baseline lyzed sUbjects of D'Angelo and coworkers (4). inflation flow of our patients during mechanical ventilation, Rrs amounted to 9.4 ± 1.9 cm H 2 0 / L / s in the patients compared with 4.2 ± 0.5 em H 2 0 l L i s in the In cats in which K 2 is relatively high normal subjects (p < 0.01). Thus, the (6, 7), the experimental isovolume rela- difference in Rrs between patients and tionships between Rrs and V closely fit normal subjects decreased from 8.7 em equation 7. By contrast, in dogs (5) and H 2 0 / L/ s at V of 0.4 Lis to 5.2 em in normal humans (4, 11) K 2 is negligi- H 2 0 / L/ s at V of 1 Lis. Broseghini and ble, at least at low flow rates, and hence coworkers (2) have previously shown that their experimental isovolume Rrs- V rela- Rrs is increased in ARDS. In their study, tionships closely fit equation 2. Because which was carried out at fixed inflation in patients with ARDS K 2 is also negligi- flow of 0.77 Lis and volume of 0.82 L, ble (8), their data also closely fit equa- Rrs amounted to 15.5 ± 1.6em H 2 0 I Lis. tion 2 (figure 2, bottom panel). Thus, At comparable inflation flow and volcontrary to the predictions in equation ume, the values of Rrs in our patients 3, in patients with ARDS, as in normal were 11.6 ± 2.3 em H 2 0 / L/ s. In seven humans (4, 11) and animals (5, 7), Rrs patients with ARDS, Eissa and coworkdecreases with increasing flow because ers (9) determined the relationship beof the peculiar behavior of Rti (figure tween Rrs and Vat a fixed inflation vol3). It should be noted, however, that alume of 0.7 L. Their results were virtually though in normal humans time-constant . identical to those found in the present inequalities within the lung contribute study at comparable inflation volume. little to Rrs (19), this effect may be great- The present results, however, provide Rrs er in ARDS (9). It should be stressed, versus V relationships at different inflahowever, that time-constant inequalities tion volumes, providing a more compreshould have qualitatively the same effect hensive picture of flow and volume deon Rrs as viscoelastic behavior, i.e., Rrs pendence of Rrs, In our patients, Rint averaged 4.2 ± should decrease with increasing V and 0.8 em H 2 0 / L / s. Similar values were increase with increasing s:V (9, 19). Studies on experimental animals (5, 7), found by Eissa and coworkers (8) at comnormal humans (4, 11), and patients with parable inflation flow and volume, ARDS (9) have shown that, at fixed in- whereas Broseghini and coworkers (2) flation flow, Rrs increases with increas- found higher values (8 ± 1.6 ern H 201 ing inflation volume because of the pe- Lis). In all studies, the values of Rint were culiar behavior of RtL The same was true greater than in normal anesthetized parain our patients with ARDS, as shown in lyzed subjects in whom, under comparafigures 3 and 4. This phenomenon reflects ble conditions, Rint amounts to 2.5 em the fact that whereas Raw decreases with H 2 0 / L/ s. In our patients Rint was 68070 increasing ~V, there is a concomitant in- higher than normal. According to figure crease of ~Rrs, which is more pro- 4, at the same inflation volume and at a comparable flow rate of 1 Lis, Rrs in nounced (4, 5, 7-9, 11). In our patients the values of Rrs were our patients was 124% greater than norconsiderably higher than in normal per- mal. Thus, in line with previous results sons, as shown in figure 4, which depicts (1,2,9), it appears that ARDS more prothe average isovolumefzs.V = O.5L)rela- foundly affects ~Rrs than Rint. In this tionship between Rrs and inspiratory connection it should be noted that in nor30
, ,, ,
\
\
\
\
\
mal humans Rint probably closely reflects airway resistance (to). Indeed in normal humans the chest wall does not appear to contribute to Rint (11). Whether this is also true in patients with ARDS remains to be ascertained. The increase in Rint in patients with ARDS is probably caused by airway flooding (20, 21), reduced lung volume (22), vagal reflexes (23), etc. The increase in ~Rrs may be due to a reduction in aerated lung volume (24), to effects of diffuse lung inflammation on the viscoelastic properties of the lung (3), etc. Although the nature of the changes in ~Rrs and Rint is poorly understood, the present results imply that in ARDS there is a marked increase in both elastic and resistive work of breathing. At low flows the increase in resistive work is due mainly to increased ~Rrs. The present results also indicate that, for comparative purposes, measurements of Rrs have to be standardized for fixed inflation volume and flow. Further studies are needed to elucidate the nature of the changes in airway resistance and ~Rrs in patients with ARDS. Acknowledgment The writers wish to thank the medical and nursing staff of the Respiratory Division, Hopital Saint-Luc, for valuable assistance.
References 1. Bernasconi M, Ploysongsang Y, Gottfried SB, Milic-Emili J, Rossi A. Respiratory compliance and resistance in mechanically ventilated patients with acute respiratory failure. Intensive Care Med 1988; 14:547-53. 2. Broseghini C, Brandolese R, Poggi R, et al. Respiratory mechanics during the first day of mechanical ventilation in patients with pulmonary edema and chronic airway obstruction. Am Rev Respir Dis 1988; 138:355-61. 3. Wright PE, Bernard GR. The role of airflow resistance in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 1989; 139: 1169-74. 4. D'Angelo E, Calderini E, Torri G, Robatto FM, Bono D, Milic-Ernili J. Respiratory mechanics in anesthetized paralyzed humans: effects of flow, volume, and time. J Appl Physiol 1989; 67:2556-64. 5. Similowski T, Levy P, Corbeil C, et al. Viscoelastic behavior of lung and chest wall in dogs determined by flow interruption. J Appl Physiol1989; 67:2219-29. 6. Kochi T, Okubo S, Zin WA, Milic-Emili J. Flow and volume dependence of pulmonary mechanics in anesthetized cats. J Appl Physiol 1988;64:441-50. 7. Kochi T, Okubo S, Zin WA, Milic-Emili J. Chest wall and respiratory system mechanics in cats: effects of flow and volume. J Appl Physiol 1988; 64:2636-46. 8. Eissa N, Ranieri VM, Corbeil C, et al. The ef-
360 fects of inspiratory flow rate on the resistive properties of the total respiratory system in ARDS patients (abstract). Am RevRespir Dis 1990;141:A582. 9. Eissa N, Ranieri VM, Corbeil C, et al. Analysis of behavior of the respiratory system in ARDS patients: effects of flow, volume, and time. J Appl Physiol 1991; 70:2719-2729. 10. Liistro G, Stanescu D, Rodenstein D, Veriter C. Reassessment of the interruption technique for measuring flow resistance in humans. J Appl Physiol 1989; 67:933-7. II. D'Angelo E, Robatto FM, Calderini E, et al. Pulmonary and chest wall mechanics in anesthetized paralyzed humans. J Appl Physiol 1991; 70:2602-10. 12. Danek SJ, Lynch P, Weg JG, Dantzker DR. The dependence of oxygen uptake on oxygen delivery in the ARDS. Am Rev Respir Dis 1980; 122: 387-95. 13. Pepe PE, Marini 11. Occult positive endexpiratory pressure in mechanically ventilated patients with airflow obstruction. Am Rev Respir Dis 1982; 126:166-70.
TANTUCCI, CORBEIL, CHASSE, ROBATTO, NAVA, BRAIDY, MATAR, AND MIlle-EMILI
14. Bates JHT, Hunter I, Sly PD, Okubo S, Filiatrault S, Milic-Emili J. The effect of valve closure time on the determination of the respiratory resistance by flow interruption. Med Bioi Eng Comput 1987; 25:136-40. 15. 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 ventilation. Am Rev Respir Dis 1985; 131:672-7. 16. Mead J, Agostoni E. Dynamics of breathing. In: Fenn WO, Rahn H, eds. Handbook of physiology. Section 3, vol I: Respiration. Washington, DC: American Physiological Society 1964; 411-27. 17. Briscoe WA, DuBois AB. The relationship between airway resistance, airway conductance and lung volume in subjects of different age and body size. J Clin Invest 1958; 37:1279-85. 18. Grimby G, Takishima T, Graham W, Macklem PT, Mead J. Frequency dependence of flow resistance in patients with obstructive lung disease. J Clin Invest 1968; 47:1455-65. 19. Otis AB, McKerrow CB, Bartlett RA, et al.
Mechanical factors in distribution of pulmonary ventilation. J Appl Physiol 1956; 8:427-43. 20. Cook CD, Mead J, Schreiner GL, Frank NR, Craig JM. Pulmonary mechanics during induced pulmonary edema in anesthetized dogs. J Appl Physiol 1959; 14:177-86. 21. Michel RP, Zocchi L, Rossi A, et al. Does interstitial lung edema compress airways and arteries? A morphometric study. J Appl Physiol 1987; 62:108-15. 22. Sharp JT, Griffith GT, Bunnell IL, Greene DG. Ventilatorymechanics in pulmonary edema in man. J Clin Invest 1958; 37:tlI-7. 23. Chung HF, KeyesSJ, Morgan BM, Jones PW, Snashall PD. Mechanisms of airway narrowing in acute pulmonary edema in dogs: influence of the vagus and lung volume. Clin Sci 1983; 65:289-96. 24. Gattinoni L, Pesenti A, Avalli L, Rossi F, Bomibino M. Pressure-volume curve of total respiratory system in acute respiratory failure. Am Rev Respir Dis 1987; 136:730-6.
C. TANTUCCI, C. CORBEIL, M. CHASSE, F. M. ROBATTO, S. NAVA, J. BRAIDY, N. MATAR, and J. MILlC-EMILI
Introduction
Several studies have shown that ARDS is characterized not only by decreased pulmonary and total respiratory system compliance but also by increased airway, pulmonary, and thoracic (lung plus chest wall) tissue flow resistance (1-3). These measurements were carried out during constant-flow inflation at inspiratory flows and volumes that varied among patients and between studies. Recent reports, however, have shown that in normal anesthetized-paralyzed humans (4), dogs (5), and cats (6, 7), the pulmonary, chest wall, and total respiratory flow resistance (Rrs) vary markedly with both inflation flow and volume. Using the technique of rapid airway occlusion durring constant flow inflation, Eissa and coworkers (8, 9) have recently studied the flow and volume dependence of Rrs in patients with ARDS. Rrs was partitioned into the interrupter resistance (Rint), which in humans reflects airway resistance (10, 11), and the effective additional resistance (L\Rrs) that results from (1) time-related pressure dissipations caused by the viscoelastic properties of the thoracic tissues, i.e., the so-called thoracic tissue flow resistance (4-7), and (2) timeconstant inequalities within the lung (pendelluft) (4, 9). They found that in patients with ARDS Rint was about two times higher than normal and varied relatively little with both inflation flow and volume (8). In contrast, L\Rrs was markedly increased, especially at low inflation flows, and was markedly flow and volume dependent (9). However, the method used by Eissa and coworkers (8, 9) involves long experiments (about 15 min to establish the relationships of Rrs, Rint, and L\Rrs to flow at a single inflation volume) and time-consuming data analysis. Furthermore, such measurements require a ventilator with which it is possible to change from one breath to
SUMMARY Using a simple and rapid technique, we studied the flow and volume dependence of the total resistance of the respiratory system (Rrs) In six patients with ARDS. At any given Inflation volume, Rrs decreased progressively with Increasing flow (V) according to the following hyperbolic function: Rrs = a/V + b, where a and b are constants. At any fixed Inflation flow, Rrs Increased progressively with Increasing Inflation volume. The observed flow and volume dependence of Rrs Is probably mainly due to the viscoelastic properties of the pUlmonary and chest wall tissues. The flow and volume dependence of Rrs found In the patients with ARDS Is qualitatively similar to that previously observed In normal anesthetized paralyzed SUbJects. In ARDS, however, Rrs was considerably greater than In the normal subjects, Indicating that besides a low respiratory compliance ARDS Is characterized by a high flow resistance. This mainly reflects Increased effective flow resistance of the pUlmonary and chest wall tissues, although airway resistance Is also higher than normal. AM REV RESPIR DIS 1992; 145:355-360
another, either the inflation flow while keeping the inflation volume fixed or the inflation volume while keeping the flow fixed (8, 9). These stringent requirements are met by some ventilators (e.g., Servo 900C; Siemens, Berlin, Germany) (8, 9) but not all (e.g., Model 7200; PuritanBennett, Carlsbad, CA). In the present report, we have used a simple and rapid method for determining the flow and volume dependence of Rrs in patients with ARDS who were ventilated with 7200 Puritan-Bennett ventilators. The measurements could be completed in less than 8 min, and they provided Rrs versus flow relationships at different inflation volumes. In addition, our method allows (1) determination of the static inflation volume-pressure relationship of the respiratory system, and (2) partitioning of Rrs into Rint and L\Rrs at baseline inflation flow and volume. Methods Six patients with ARDS who were admitted to the intensive care unit of Saint-Luc Hospital were studied. In five patients ARDS was caused by sepsis, and in one it was associated with hypovolemic shock requiring multiple blood transfusions (table 1). Patients 1 to 3 had never smoked, Patients 4 and 5 were smokers (both 30 pack-years), and the last was an ex-smoker (7.5 pack-years untillOyr ago).
All patients were studied within the first 2 days from the moment they met the following criteria for ARDS (12): (1) the presence of bilateral diffuse infiltrates on chest radiography; (2) a known predisposing illness for at least 18h before the radiographic changes; (3) a pulmonary capillary wedge pressure less than 15 mm Hg; (4) an arterial Po, ~ 50 mm Hg with a fractional inspired 0, concentration of 0.5 during positive end-expiratory pressure (PEEP). The study was approved by the institutional ethics committee, and informed consent was obtained from each patient or next of kin. Patients were supine, intubated (Sheridan's cuffed endotracheal tube with internal diameter of 8 mm in Patients 2 to 6 and 9 mm in Patient 1)and mechanically ventilated with
(Received in original form July 5, 1990 and in revised form August 8, 1991) 1 From the Respiratory Division, Hopital SaintLuc, Universite de Montreal, and the MeakinsChristie Laboratories, McGill University,Montreal, Quebec, Canada. 2 Supported by the Medical Research Council of Canada, the J. T. Costello Memorial ResearchFund, the Fondation de l'Hopital Saint-Luc, and the Respiratory Health - Network of Centres of Excellence, Canada. 3 Requests for reprints should be addressed to Dr. N. Matar, Respiratory Division, Hopital SaintLuc, 1058 St. Denis Street, Montreal, Quebec, Canada H2X 3J4.
355
356
TANTUCCI, CORBEll, CHASSE, ROBATTO, MAYA, BRAIDY, MATAR, AND MILlC-EMILI
TABLE 1 CLINICAL DATA OF SUBJECTS WITH ARDS
Patient Age No. Sex (yr)
1 2 3 4 5 6
F F F M M F
Mean ± SO
37 88 67 48 49 35 54.0 20.2
Baseline Baseline Baseline PEEP Height Weight Pao. Paco. Baseline Baseline (em H2O) (mmHg) (mm Hg) pH (kg) (em) FlO.
160 163 157 172 175 152 163.2 8.8
71 62 58 67 60 48 61.0 7.9
72 80 76 72 95 87 80.3 9.1
7.50 7.35 7.36 7.34 7.41 7.47 7.40 0.07
30 36 50 44 35 37 38.7 7.1
5.0 12.5 15.0 5.0 12.0 8.0 9.6 4.2
0.55 0.90 0.90 0.80 0.80 0.55 0.75 0.16
Etiology Sepsis Hypovolemic shock Sepsis Sepsis Sepsis Sepsis
TABLE 2 BASELINE VALUES OF VARIOUS VENTILATORY VARIABLES IN PATIENTS WITH ARDS
1 2 3 4 5 6 Mean ± SO
V
6V (L)
6V (mllkg)
(Lis)
0.825 0.880 0.680 1.085 0.875 0.880 0.871 0.130
11.6 14.2 11.7 16.2 14.6 18.3 14.4 2.6
0.82 1.30 0.99 1.20 0.91 0.90 1.02 0.19
TI (s)
TE (s)
1.04 3.24 0.84 3.44 0.86 3.42 1.03 3.25 1.08 3.20 1.08 3.20 0.99 3.29 0.11 0.11
TllTtot
PEEPi (em H2O)
6FRC (L)
Cst,rs (Llem H2O)
0.24 0.20 0.20 0.24 0.25 0.25 0.23 0.02
0.0 16.5 0.0 4.0 4.5 3.0 4.6 6.1
0
0.030 0.023 0.021 0.059 0.034 0.068 0.039 0.020
0 0.050 0.085 0.090 0.045 0.044
Definition of abbreviations: t. V = inflationvolume; V = constant inspiratory flow; TI = inspiratory time; TE = expiratorytime; Tifftot = duty cycle;PEEPi = intrinsic positiveend-expiratory prassure; t.FRC = volumeabovethe relaxation point of the respiratory system; Cst,rs = static compliance of the respiratory system.
constant inflation flow using the control ventilation mode of the 7200 Puritan-Bennett ventilator. Upon decision of the primary physicians, all patients weresedated intravenously with diazepam, 0.1 to 0.2 mg/kg, and paralyzed with pancuronium bromide, 0.1 to 0.2 mg/kg. The baseline ventilatory settings are listed in table 2. Prior to the measurements of respiratory mechanics they all received PEEP, as indicated in table I. Respiratory mechanics were measured after PEEP wastemporarily removed. The baseline ventilatory settings (table 2) were kept constant throughout the study, except for the single-breath tests described in Procedure below. Tracheal pressure (Ptr) was measured via an end-sealed noncompliant 160 catheter (I. 7 mm ID) connected to a pressure transducer (Validyne MP45, ± 100 em H.O; Validyne Inc., Northridge, CA). The catheter tip, provided with six lateral holes, was positioned such that it protruded 2 to 3 cm into the trachea. With the system used to measure Ptr there was no appreciable shift or alteration in amplitude up to 20 Hz. Flow (V) was measured with a heated pneumotachograph (Fleisch no. 3; Fleisch, Lausanne, Switzerland), which was inserted via cones between the proximal end of the endotracheal tube and the Y-connecter of the ventilator. The pneu-
Procedure and Data Analysis The following measurements are carried out in each patient, 10min after removalof PEEP. During this period the subjects reached a steady state, as judged by stability of the Ptr, expired Pco., and pulse-oxymeter records.
Staticinflation volume-pressure (V-P) relationship 0/ the respiratory system. While
Definition of abbreviations: FlO, = fraction of inspired 0,; PEEP = positiveend-expiratory pressure.
Patient No.
cutaneous O. saturation and to adjust FlO. while PEEP was removed from the patients in order to avoid excessive desaturations. During the study a physician not involved in the experiment was always present to provide for patient care.
motachograph, which was connected to a differential pressure transducer (ValidyneMP 45, ± 2.5 em H.O), was linear over the experimental flow range. The equipment dead space (not including the endotracheal tube) was 169 ml. Special care was taken to avoid air leaks around the tracheal cuff and from the breathing circuit. For monitoring, changes in volume were obtained by electrical integration of the flow signal (Model 8815A;HewlettPackard Inc., Andover, MA). All signals were recorded on an eight-channel pen recorder (7758A; Hewlett-Packard, Palo Alto, CA) with a paper speed of 10 mm/s and on magnetic tape (Hewlett-Packard 3968A). The Ptr and V signals were played back at a sample frequency of 200 Hz by a 12-bit analog-todigital converter on an IBM compatible personal computer for subsequent data analysis. In this analysis, volume was obtained by digital integration of the flow signal. Arterial blood gases were measured with an ABL 330 blood gas analyzer (Radiometer, Copenhagen, Denmark), and the end-tidal CO. fraction was monitored with a CO. analyzer (CO. Monitor; Datex, Helsinki, Finland). The values of Flo. and blood gases at the time of the investigation are listed in table 1. A pulse-oxymeter (Nellcor, Hayward, CA) was used to monitor the arterial trans-
keeping the inflation flow at the baseline setting value, single-breath end-inspiratory airway occlusions were performed at different inflation volumes (AV) ranging from 0.1 to 1 L. Inflation volume was changed with the appropriate button on the ventilator. In each test breath occlusions were maintained until an apparent plateau in tracheal pressure was achieved. Because the 7200 Puritan-Bennett ventilator is programmed for a maximal endinspiratory pause of only 2 s, which may not suffice to achieve a plateau in Ptr during the 2-send-inspiratory hold, wealso occluded the inspiratory and expiratory lines of the ventilator by clamping the ventilator tubings. In this way, longer end-inspiratory occlusion holds could be achieved. The inspiratory and expiratory lines were similarly occluded at end-expiration until a plateau in Ptr was achieved, representingintrinsic PEEP (PEEPi) (1, 2, 13). Because PEEPi implies dynamic pulmonary hyperinflation, i.e., that the endexpiratory lung volume (ELV) during mechanical ventilation exceeds the relaxation volume of the respiratory system (Vr), we also measured the difference between ELV and Vr (hereintermed AFRC) by removingthe Y-piece of the ventilator from the pneumotachograph during expiration, allowing the patient to exhale until expiratory flow ceased, indicating that the subject had reached Vr (2). After each test breath, baseline ventilation was resumed until the tracheal pressure records returned to baseline values (usually in a few breaths). Tests were performed in random order. Because the plateau values of Ptr represent the static elastic recoil pressure of the respiratory system (Pst), plots of AV versus Pst allowed to construct the static inflation V-P curve of the respiratory system. The static compliance of the respiratory system .(Cst.rs) was measured by dividing the baseline AV (table 2) by the corresponding valueof end-inspiratory Pst minus PEEPi, if present (2). This compliance will henceforth be termed standard compliance.
Total resistance ofrespiratorysystem(Rrs). While keeping the inflation volume at baseline setting, a series of single-breath lung inflations at different inspiratory flows (up to 2 L/s) wereperformed in random order. Flow was changed with the appropriate button on the ventilator. After each test breath, baseline ventilation was resumed until the trache-
357
FLOW RESISTANCE IN ARDS
1.0
20 Pst
12
34
5
0.8
2 :3~
15 0.6
5' N
o >
z
o
...~ 1!;
::l:
E
0.4
2
10
;;
..."-
0.2
D:
+--------r---,-------r------,
00
o
20
10
30
40
Plr(cmH20)
10
0.8
06
04
02
OO+--_ _-t-r-_ _ 0.0
05
-r-_-_-~_,
1.0
15
2
a
INSPIRATORY FlOW (lis)
Fig. 1. Toppanel. Relationship between inflation volume (~V) and tracheal pressure (Ptr) under static conditions (Pst) and during a series of five inflations made with differing inflation flows. Bottom panel. Inspiratory volume-flow (~v-iJ) relationships corresponding to top panel. Numbers on curves identify ~ V-Ptrand ~ V-Vrelationship obtained during the same inflation. Patient 4.
al pressure records returned to the pretest values. Dynamic inflation !::N versus Ptr relationships were plotted as shown in figure 1 (top panel) together with the corresponding static curve. The concurrent AV versus V relationships were also displayed, as shown in figure 1 (bottom panel). Isovolume pressure-flow relationships for the total respiratory system were computed by plotting the resistive pressure (Ptr-Pst) derived from figure 1 (top panel) against the corresponding flow from figure 1 (bottom panel). As shown by the AV- V relationships in figure 1 (bottom panel), with the 7200 Puritan-Bennett ventilator about 0.2 s were required to achieve the preset constant inflation flows. Partitioning of respiratory system resistance. The records obtained during endinspiratory airway occlusion at baseline inflation volume and flow (table 2) were used to partition Rrs into the interrupter resistance (Rint) and ARrs, as previously described in detail (4).Briefly, Riot was obtained by dividing the immediate drop in Ptr after endinspiratory airway occlusion by the immediately preceding flow, whereas ARrs was derived by dividing the slow postocclusion pressure change in Ptr up to its plateau value by the flow preceding the end-inspiratory flow interruption. The immediate and slowchanges in Ptr wereobtained by computer-fitted curves
Fig. 2. Top panel. Relationships between resistive inflation pressure (PtrPst) and inspiratory flow obtained at different inflation volumes (~V) from Figure 1 in Patient 4. Values of constants of equation 1 together with regression coefficients are indicated. Bottom panel. Isovolume relationships between total respiratory resistance (Rrs) and inspiratory flow computed according to equation 2 using values of constants in top panel. Closed triangle = y = 3.08 + 8.22x, R = 0.99; open square = y = 2.71 + 8.28x, R = 0.99; closed square = y = 1.79 + 8.37x,R = 0.99; open circles = y = 0.52 + 8.23x, R = 0.99; closed circles = y = 0.49 + 7.41x, R = 0.99.
5
o -t--~-'---~-'----'---'---~-T o 05 1.5 2 INSPIRATORY FLOW (Lis)
30 tN
ILl
0.8 0.6
"
20
::J
0.4
0N
::l:
E
2
'"
eX:
0.2 0.1
10
o-t-----.----~--.-~-___,_-~-__r
o
2 INSPIRATORY FLOW (Lis)
as previously described (4, 14). In calculation of Rint and Rrs, the errors caused by the closing time of the ventilator valve were corrected according to Kochi and coworkers (6). The whole experimental protocol could be completed in less than 8 min. Regressionanalysis was made with the leastsquares method. Comparison with normal anesthetized paralyzed subjects (4) was made using the unpaired t test. Values are mean ± SE unless otherwise specified.
Results Intrinsic PEEP, ranging from 3 to 16.5 em H 2 0 , was present in four of the six patients (table 2). PEEPi was associated with a modest degree of dynamic pulmonary hyperinflation, as evidenced by the small values of AFRC, which ranged from zero to 90 ml. For technical reasons AFRC could not be measured in the patient with the highest PEEPi (Patient 2). Standard static respiratory compliance amounted to 39 ± 8 mllcm H 2 0 (table 2). The relationships between resistive pressure (Ptr-Pst) and flow obtained at different inflation volumes in Patient 4 are depicted in figure 2 (top panel). At
all inflation volumes, the relationships were linear functions of the type: Ptr-Pst
=a +
bV
(1)
where a is intercept at V = 0 and b is slope. The value of a increased significantly with inflation volume (p < 0.005), whereas the volume-related changes of slope b were not significant. Similar results were found in all patients, the correlation coefficients of the regressions (equation 1) ranging between 0.96 and 0.99 (p < 0.001). The average values of the constants a and b for different inflation volumes of the six patients are given in table 3. Because Rrs = (Ptr-Pst)/V, equation 1 implies that the total respiratory resistance decreases hyperbolically with increasing V: Rrs
=
a/V
+ b
(2)
The isovolume relationships between Rrs and V for patient 4, computed according to equation 2, are depicted in figure 2 (bottom panel). The average isovolume relationships between Rrs and V of the six patients with ARDS are shown in figure 3. At all inflation volumes, Rrs
358
lANlUCCI, CORBEIL, CHASSE, ROSATTO, NAVA, BRAIDY, MAlAR, AND Mille-EMILI
TABLE 3
TABLE 4
RELATIONSHIPS OF RESISTIVE PRESSURE WITH flOW OBTAINED AT DIFFERENT INFLATION VOLUMES IN PATIENTS WITH ARDS·
BASELINE VALUES OF RESPIRATORY SYSTEM RESISTANCE AND ITS COMPONENTS IN PATIENTS WITH AROS·
Ptr-Pst = a + bV !1V (L)
a
b
(em H2O)
(em H2O/LIs)
2.56 2.88 3.07 3.22 3.28
0.1 0.2 0.4 0.6 0.8
± ± ± ± ±
2.28 1.92 2.16 2.39 2.98
5.52 5.67 6.05 6.57 6.89
± ± ± ± ±
3.30 3.19 2.71 2.34 2.22
Definition of abbreviations: Ii V = intlation volume: Plr = dynamic tracheal pressure at different inflation volumes; Pst = static pressure at corresponding inflation volumes; II = inspiratory flow; a, b = constants of equation t. • Values are mean ± SO.
30
Patient No.
1 2 3 4 5 6 Mean ± SO
Rrs Rint (em H2 0 /LIs) (em H20/LIs)
11.0 9.5 10.3 12.6 15.2 8.9 11.2 2.3
1.9 4.8 4.7 7.2 4.4 2.2 4.2 1.9
t>Rrs (em H2 0 /LIs)
9.1 4.7 5.6 5.4 10.8 6.7 7.0 2.4
Definition of abbreviations: Ars = respiratory system resistance; Aint = interrupter resistance; liArs = additional resistance. • Measurements were obtained at ventilator settings lndlcated in Table 2.
1 'J,V IL)
25
~
20
I£
15
e
II:
10
0.8
0 .s
v.. 0.5
1.5
25
INSPIRATORY FLOW (U,)
Fig. 3. Averageisovolume relationship between total respiratory resistance (Rrs) and inspiratory flow of six patients.
decreased progressively with increasing flow, approaching an asymptote corresponding to b (equation 2) at high V. At any given flow Rrs increased with increasing liV, At baseline inflation flow and volume we partitioned Rrs into the interrupter resistance (Rint) and .liRrs (table 4). Rrs amounted to 11.2 ± 1 ern H 20/LIs, whereas Rint was 4.2 ± 0.8 cm H 20/LIs, indicating that under these conditions Rint represented 38070 of Rrs, whereas a greater proportion (62%) was due to liRrs. Because in patients with ARDS Rint does not change significantly with flow (8), whereas Rrs increases progressively with decreasing flow (figure 3), the percent fraction of Rint to Rrs should be less at low inspiratory flows than at baseline flow. Indeed, at V of 0.25 Lis, Rint at baseline inflation volume should represent only 21% of Rrs. Discussion
Before the results of the present study can be discussed, some methodologic
considerations are required. The technique of rapid airway occlusion during constant flow inflation allows partitioning of Rrs into Rint and liRrs at different inflation flows and volumes. In practice, however, such measurements are limited to a fixed inflation flow or a fixed inflation volume because the experimental time required is rather long (4, 9, 11). Furthermore, such measurements can be obtained only with special ventilators (e.g., Siemens servo 9ooC). The approach used in the present study is rapid and feasible with virtually all ventilators that provide constant inflation flow. Furthermore, the present method allows a full characterization of flow and volume dependence of Rrs. In addition, at baseline inflation flow and volume, Rrs can be partitioned into Rint and liRrs. Thus, the present approach appears to be particularly suitable for clinical assessment of respiratory mechanics.
Static Inflation V-P Curves In line with previous studies (1, 2), we found that patients with ARDS often exhibit a substantial PEEPi. It should be noted, however, that the four patients with ARDS who exhibited PEEPi included two smokers (Patients 4 and 5), an exsmoker (Patient 6), and a very old (88 yr) nonsmoker. PEEPi has to be taken into account for correct measurement of Cst,rs (15). Indeed, in Patient 2 the uncorrected value of standard Cst.rs was 30% lower than the corrected one. The values of standard Cst,rs (39 ± 8 mllcm H 20) were significantly lower (p < 0.005) than in normal anesthetized paralyzed subjects (4) but were close to those found by Broseghini and coworkers (2) in eight
patients with ARDS studied during the first day of mechanical ventilation (35 ± 2 mllcm H 20). In agreement with Broseghini and coworkers (2), we found that in patients with ARDS the values of liFRC are small (up to 90 ml).
Flow and Volume Dependence of Respiratory System Resistance The conventional equation for describing the relationship between Rrs and flow at a fixed lung volume is given by (16): Rrs
=
Rti + K 1 + K2 V
(3)
where Rti is flow resistance of thoracic tissues, which is assumed to be independent of flow, and K 1 and K 2 are empirical constants (Rohrer's constants), which describe the relationship between airway resistance (Raw) and flow (16): Raw
=
K 1 + K2 V
(4)
Equation 3 is the basis of one of the tenets of respiratory mechanics, namely, that at a fixed lung volume, Rrs should increase with increasing Vbecause of the term K 2V. Another tenet is that at a fixed flow, Rrs should decrease with increasing inflation volume because of a decrease in both Raw (17) and Rti (18), the former reflecting airway dilatation, whereas the latter should result because the linear velocity of thoracic tissues decreases with increasing lung volume, and hence the flow-dependent pressure losses within the thoracic tissues should be reduced. Equation 3 assumes that the thoracic tissues exhibit pure (Newtonian) resistive behavior. However, recent studies on animals (5-7) and humans (4, 11) have shown that this is not the case: the thoracic tissues exhibit characteristic viscoelastic behavior that is adequately explained by a spring-and-dashpot model (4, 5). This model predicts that at fixed lung volume, Rti (and hence Rrs) should decrease with increasing inflation flow. A useful empirical function relating isovolume Rti with Vis given by (4, 7): Rti
=
a/V + b'
(5)
where a and b' are constants. Replacing Rti in equation 3 with this function, the following is obtained:
= a/V + b' + K 1 + K2 V (6) b' + K 1 = b, equation 6 becomes: Rrs = a/V + b + K2 V (7)
Rrs For
If K2 is negligible, equation 7 is simplified into equation 2.
359
FLOW RESISTANce IN ARDS
flow of our patients with ARDS together with the corresponding relationship 25 tN:O.5L obtained by D'Angelo and coworkers (4) in 16 normal anesthetized paralyzed sub, -, jects. In both cases a marked decrease ARDS (n;::6) of Rrs occurred at flow rates between 0.2 and 1 Lis. At inspiratory flow of 0.4 Lis, which is close to the mean inspiratory flow rate during spontaneous breathing +-~--,-~-.-~--,-----.-----,at rest, Rrs amounted to 14.3 ± 3.3 em 1 1.5 05 2.5 H 2 0 / L/ s in the patients with ARDS INSPIRATORY FLOW (lis) compared with 5.6 ± 0.7 em H 20/L/s Fig. 4. Average (:t SEM) relationships between respiin the normal anesthetized paralyzed ratory system resistance (Rrs)and inflationflow at fixed inflation volume (~ V) of 0.5 L in six patients withARDS (p < 0.001) subjects. At inspiratory flow of present study and inthe 16normalanesthetized paraof 1 Lis, corresponding to the baseline lyzed sUbjects of D'Angelo and coworkers (4). inflation flow of our patients during mechanical ventilation, Rrs amounted to 9.4 ± 1.9 cm H 2 0 / L / s in the patients compared with 4.2 ± 0.5 em H 2 0 l L i s in the In cats in which K 2 is relatively high normal subjects (p < 0.01). Thus, the (6, 7), the experimental isovolume rela- difference in Rrs between patients and tionships between Rrs and V closely fit normal subjects decreased from 8.7 em equation 7. By contrast, in dogs (5) and H 2 0 / L/ s at V of 0.4 Lis to 5.2 em in normal humans (4, 11) K 2 is negligi- H 2 0 / L/ s at V of 1 Lis. Broseghini and ble, at least at low flow rates, and hence coworkers (2) have previously shown that their experimental isovolume Rrs- V rela- Rrs is increased in ARDS. In their study, tionships closely fit equation 2. Because which was carried out at fixed inflation in patients with ARDS K 2 is also negligi- flow of 0.77 Lis and volume of 0.82 L, ble (8), their data also closely fit equa- Rrs amounted to 15.5 ± 1.6em H 2 0 I Lis. tion 2 (figure 2, bottom panel). Thus, At comparable inflation flow and volcontrary to the predictions in equation ume, the values of Rrs in our patients 3, in patients with ARDS, as in normal were 11.6 ± 2.3 em H 2 0 / L/ s. In seven humans (4, 11) and animals (5, 7), Rrs patients with ARDS, Eissa and coworkdecreases with increasing flow because ers (9) determined the relationship beof the peculiar behavior of Rti (figure tween Rrs and Vat a fixed inflation vol3). It should be noted, however, that alume of 0.7 L. Their results were virtually though in normal humans time-constant . identical to those found in the present inequalities within the lung contribute study at comparable inflation volume. little to Rrs (19), this effect may be great- The present results, however, provide Rrs er in ARDS (9). It should be stressed, versus V relationships at different inflahowever, that time-constant inequalities tion volumes, providing a more compreshould have qualitatively the same effect hensive picture of flow and volume deon Rrs as viscoelastic behavior, i.e., Rrs pendence of Rrs, In our patients, Rint averaged 4.2 ± should decrease with increasing V and 0.8 em H 2 0 / L / s. Similar values were increase with increasing s:V (9, 19). Studies on experimental animals (5, 7), found by Eissa and coworkers (8) at comnormal humans (4, 11), and patients with parable inflation flow and volume, ARDS (9) have shown that, at fixed in- whereas Broseghini and coworkers (2) flation flow, Rrs increases with increas- found higher values (8 ± 1.6 ern H 201 ing inflation volume because of the pe- Lis). In all studies, the values of Rint were culiar behavior of RtL The same was true greater than in normal anesthetized parain our patients with ARDS, as shown in lyzed subjects in whom, under comparafigures 3 and 4. This phenomenon reflects ble conditions, Rint amounts to 2.5 em the fact that whereas Raw decreases with H 2 0 / L/ s. In our patients Rint was 68070 increasing ~V, there is a concomitant in- higher than normal. According to figure crease of ~Rrs, which is more pro- 4, at the same inflation volume and at a comparable flow rate of 1 Lis, Rrs in nounced (4, 5, 7-9, 11). In our patients the values of Rrs were our patients was 124% greater than norconsiderably higher than in normal per- mal. Thus, in line with previous results sons, as shown in figure 4, which depicts (1,2,9), it appears that ARDS more prothe average isovolumefzs.V = O.5L)rela- foundly affects ~Rrs than Rint. In this tionship between Rrs and inspiratory connection it should be noted that in nor30
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mal humans Rint probably closely reflects airway resistance (to). Indeed in normal humans the chest wall does not appear to contribute to Rint (11). Whether this is also true in patients with ARDS remains to be ascertained. The increase in Rint in patients with ARDS is probably caused by airway flooding (20, 21), reduced lung volume (22), vagal reflexes (23), etc. The increase in ~Rrs may be due to a reduction in aerated lung volume (24), to effects of diffuse lung inflammation on the viscoelastic properties of the lung (3), etc. Although the nature of the changes in ~Rrs and Rint is poorly understood, the present results imply that in ARDS there is a marked increase in both elastic and resistive work of breathing. At low flows the increase in resistive work is due mainly to increased ~Rrs. The present results also indicate that, for comparative purposes, measurements of Rrs have to be standardized for fixed inflation volume and flow. Further studies are needed to elucidate the nature of the changes in airway resistance and ~Rrs in patients with ARDS. Acknowledgment The writers wish to thank the medical and nursing staff of the Respiratory Division, Hopital Saint-Luc, for valuable assistance.
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