key: cord-0861618-0o37mn94 authors: Mols, G; Kessler, V; Benzing, A; Lichtwarck-Aschoff, M; Geiger, K; Guttmann, J title: Is pulmonary resistance constant, within the range of tidal volume ventilation, in patients with ARDS? date: 2017-12-13 journal: Br J Anaesth DOI: 10.1093/bja/86.2.176 sha: 2993d62ce25a506bc9ab63d3653a6ffb23600e2c doc_id: 861618 cord_uid: 0o37mn94 When managing patients with acute respiratory distress syndrome (ARDS), respiratory system compliance is usually considered first and changes in resistance, although recognized, are neglected. Resistance can change considerably between minimum and maximum lung volume, but is generally assumed to be constant in the tidal volume range (V(T)). We measured resistance during tidal ventilation in 16 patients with ARDS or acute lung injury by the slice method and multiple linear regression analysis. Resistance was constant within V(T) in only six of 16 patients. In the remaining patients, resistance decreased, increased or showed complex changes. We conclude that resistance within V(T) varies considerably from patient to patient and that constant resistance within V(T) is not always likely. Acute respiratory distress syndrome (ARDS) is associated with considerable changes in respiratory system mechanics. 1 Clinicians are most interested in the elastic properties of the respiratory system; resistance to gas¯ow is of less interest. Although resistance is volume dependent when large volume ranges are studied, it is often assumed to be constant within the tidal volume range (V T ). This neglect of resistance in ARDS patients may be because resistance is rarely treated, unlike in obstructive pulmonary diseases. We did not consider resistance when we studied volumedependent changes in compliance within V T in 16 patients suffering from ARDS or acute lung injury (ALI). 2 We determined resistance data but did not evaluate them, considering them irrelevant to the effect of the ventilator settings. However, volume-dependent resistance could be of interest, so we have now considered changes in resistance within V T on the basis of the same measurements. We studied 16 consecutive adult patients with ARDS or ALI (de®ned according to Bernard and colleagues 3 ). Compliance measurements from these patients have been reported. 2 We obtained approval from the institutional ethical committee and written informed consent of the patients' relatives. Patients' lungs were ventilated 4 using a Servo 900C ventilator (Siemens-Elema, Solna, Sweden) in the pressure-controlled mode. We used consensus guidelines that have been previously reported in detail. 2 Since the effects of the given ventilator settings were of greatest interest, the settings were not changed and recruitment manoeuvres were not used. Determination of resistance: volume-dependent R slice and R MLR In two patients, gas¯ow rate was measured with a heated pneumotachograph (Fleisch no. 2; Metabo, Epalinges, Switzerland) connected to the endotracheal tube, which was calibrated with a syringe of 1000 (SD 1) ml (calibration syringe 54500460; Jaeger, Wu Èrzburg, Germany). A differential pressure transducer (SPS1, Hoffrichter, Schwerin, Germany) was used to determine the¯ow proportional pressure difference across the pneumotachograph. Airway pressure was measured by a transducer (1210A; ICSensors, Milpitas, CA, USA) previously tested for linearity between P80 and +80 mbar and calibrated using a Revue Thommen calibrator (Waldenburg, Switzerland). Signals were digitized at 100 Hz with 12-bit resolution (SDM863; Burr Brown, Tucson, AZ, USA). In 14 patients a CP-100 pulmonary monitor (Bicore Monitoring Systems, Irvine, CA, USA), calibrated according to the manufacturer's instructions, was used for measurements. The raw data were sampled with 50 Hz and passed to a laptop computer. Thereafter, the raw data from both systems were transmitted to a SparcStation 4 workstation (Sun Microsystems, Palo Alto, CA, USA) to calculate volume-dependent respiratory system resistance (and compliance) using the slice method. 5 6 The slice method uses multiple linear regression (MLR). 7 Rather than using data derived from end-inspiratory and end-expiratory airway occlusion manoeuvres, MLR uses ow, pressure and volume data of the whole breath. If resistance and compliance are assumed to be constant within the tidal volume range, a simple linear model is usually used for this calculation to give average values of resistance and compliance by analysing inspiration and expiration signals obtained during mechanical ventilation without¯ow interruption. Consequently, the resulting`dynamic' resistance and compliance values include pressure components associated with stored viscoelastic energy and the effects of inhomogeneous gas distribution. The slice method enhances standard MLR because changes in respiratory variables over the volume of interest (usually the V T ) can be determined. For this purpose, the V T is ®rst divided into six volume slices of equal size and MLR is done separately for each slice. The resulting plot of R slice (or C slice ) over the volume slices give volume-dependent resistance (or compliance) within V T . There are other differences between the slice method and standard MLR. With standard MLR, resistance data are affected by the¯ow-dependent drop in pressure across the endotracheal tube. With the slice method, this effect is eliminated by continuously calculating tracheal pressure (P trach ) before the actual slice calcutions. 8 9 To ensure the accuracy of the P trach calculation in this study, obstruction of the endotracheal tube by secretions or kinking was excluded by suctioning of the airways immediately before the measurements and then monitoring the time constant of passive expiration (t). 10 The uppermost and lowermost 5% of the pressure±volume loop were excluded from the analysis because of distortions caused by operation of the ventilator valves. Another difference is that the slice method automatically Step 1: the outer loop is based on measured airway pressure (P aw ) and volume. Continuous calculation of the¯ow-dependent pressure drop across the endotracheal tube yields the inner loop, representing tracheal pressure (P trach ). Step 2: the loop is divided into six slices of equal volume excluding the uppermost and lowermost 5% of the loop. In each slice, one value of resistance and compliance is calculated based on the simple linear RC model. The resulting R slice and C slice data drawn over volume give the course of these parameters within tidal volume (compare with Figure 2 ). Two additional steps may be used to verify the quality of the ®t. Step 3: the P trach ±volume loop (thin line) is reconstructed using calculated respiratory parameters and measured¯ow and volume. The match of the measured and reconstructed P trach ±volume loop give an estimate of the appropriateness of the ®t and the model in describing the raw data. Step 4: The absolute difference (mean and SD) between measured and reconstructed P trach ±volume-loop (DP) is given for each slice. considers intrinsic positive end-expiratory pressure (PEEP). 11 The principle of the slice method is shown in an example of a pressure±volume loop ( Figure 1 ). Step 1 involves calculation of P trach . The tidal volume is then divided into six slices (step 2) and resistance and compliance are calculated for each slice separately. To assess goodness of ®t, the P trach ±volume loop is reconstructed using calculated respiratory parameters for each slice and measured¯ow and volume data. The match of the measured and the reconstructed P trach ±volume loop is shown in part 3 of Figure 1 . The absolute deviation (mean plus one SD) of the two loops (DP) is shown in part 4 ( Figure 1 ). The quality of the ®t and the appropriateness of the model are demonstrated by the small DP; the ®t is best in the middle of V T . Since the uppermost (and lowermost) 5% of the loop are not adequately described by a model not including inertance, these parts of the loop were excluded from the analysis. In principle, the course of resistance and compliance within V T would be better described with a higher (ideally in®nite) number of slices, thus increasing the volume resolution of the method. However, for stability of a leastsquares ®t, a suf®cient amount of sampling points per slice is required. Cardiac oscillations transmitted to the measured pressure signal cause considerable noise. Use of six slices gives a good compromise between volume resolution and noise. 5 To reduce noise further, R slice data for 15 breaths were averaged. As well as R slice , we calculated resistance over the entire pressure volume loop (R MLR ). 7 12 . We modi®ed the original slice method 5 and did not calculate volume-equidistant data sets from time-equidistant raw data. This computation is time-consuming and requires user intervention, which prevents online calculations of mechanical parameters and hinders clinical application. We therefore no longer use this transformation. 2 6 13 All data are given as mean (SD). Patient characteristics are presented in Table 1 . Patients had both pulmonary and extrapulmonary ARDS/ALI. There was no relationship between resistance (or compliance) data and diagnosis. The course of R slice within V T in each patient is shown in Figure 2 (mean (SD) mbar litre ±1 s). R MLR is drawn as a horizontal line within each plot and its absolute value and SD are given. R slice was constant or almost constant within V T in patients A, B, E, H, L and P, and it increased in patients D, G, J, K, M and N. A concave pattern of R slice was observed in patients C and I and a convex pattern in patient O. In patient F, R slice decreased within V T . The C MLR data are given above each graph. The change in C slice within V T , which has been reported previously, 2 is indicated by the symbol above each graph. To be sure that the resistance±volume pattern did not merely re¯ect the¯ow pattern, the absolute gas¯ow rate in each slice (mean (SD)) in one representative breath in each patient is shown in Figure 3 . As a quality control for the ®t, the mean absolute deviation between measured and reconstructed pressure±volume loop is given in Table 2 . The mean number of sample points in each slice is given. Resistance often changed within the relatively small tidal volume in ARDS or ALI patients. The course of resistance within V T varied markedly from patient to patient, with different patterns of R slice . Volume-dependence of resistance in ARDS patients occurs over relatively large volume ranges, 14 but the course of resistance within V T has not been described before. To determine the course of resistance (and compliance) within V T , data from the whole breath, i.e. from inspiration and expiration, were used. The resulting mechanical measurements thus represent both phases of the respiratory cycle. Inspiratory and expiratory resistance can be separated by standard (whole-breath) MLR. 7 However, the stability of the ®t procedure would have been overstrained by calculation of volume-dependent resistance separately for inspiration and expiration. The slice method determines resistance as the sum of airway and tissue resistance. The two can be separated with the interrupter technique using sophisticated technical equipment. 15±18 However, airway resistance data obtained by the interrupter technique inevitably contain the resistance of the endotracheal tube. By contrast, resistance data obtained by the slice method are based on calculated P trach after elimination of the resistance of the endotracheal tube. 8 9 In the slice method, the pressure±volume loop is divided into six slices of equal volume. Potential effects of the gas ow rate on the mechanical parameters are assumed to be negligible. However, the characteristic decelerating¯ow pattern of pressure-controlled ventilation used here calls this assumption into question. Therefore, we plotted the absolute mean¯ow rate in each slice for every patient (Figure 3 ). While slightly differing from patient to patient, the¯ow rate was distributed over the slices (i.e. the V T ) with a convex pattern. If resistance were to increase with¯ow rate, a similar pattern would be expected. This pattern was present in patient O and, to a lesser extent, in patients A and H. In all other patients, the course of R slice within V T was not related to¯ow values. Consequently,¯ow has only a minor effect on the course of R slice within V T . This conclusion supports the ®ndings of Eissa and colleagues, 14 who reported resistance to be grossly independent from the gas¯ow rate in ARDS patients, although their data were obtained by using the interrupter technique. Fig 2 R slice data within V T (mean and SD, mbar litres ±1 s; markers for SD often not visible). Note the different scaling on the y-axis. The numbers (R1±6) refer to slices; volume increases from left to right. R MLR of the same breaths are plotted as a straight horizontal line, mean values (with SD) are given. The letters mark the patients studied. C MLR (ml mbar ±1 ) is given above each plot. A symbol showing the course of C slice over volume as previously described 2 is also shown. Resistance within the tidal volume in ARDS Resistance increased considerably in most patients, as often reported in ALI and ARDS patients. 19±21 Classically, resistance should decrease during lung in¯ation, 22 so a decrease in R slice should also be expected even within the small V T . Such a pattern of R slice occurred only in patient F, whereas in patient O R slice decreased only at greater lung volume within the tidal volume range. In most of the patients, other patterns of R slice were found. The constant R slice (found in six of 16 patients) is relatively easy to interpret. The studied volume range, i.e. the V T , may have been too small for a change of resistance to occur. Other patterns of R slice are more interesting. Several investigators reported an increase of resistance with lung in¯ation in ALI patients. 20 21 23 24 In these reports, however, the studied volume range was larger. Eissa and colleagues 14 investigated the volume dependence of airway resistance in ARDS patients at different PEEP levels, and hence different lung volumes. Although they studied a volume range that was greater than the tidal volumes studied here, they reported an increase of resistance with lung in¯ation starting from high PEEP levels (10 or 15 cm H 2 O). At lower PEEP levels (0 and 5 cm H 2 O) they observed a concave pattern. These data are not directly comparable because they were obtained with the interrupter technique during constant inspiratory¯ow. How can we interpret an (unexpected) increase in resistance? Longitudinal stretching of airways at high lung volumes could perhaps decrease their cross sectional area, and thus increase resistance. 14 The mean (with SD)¯ow rate (ml s ±1 ) is shown for each slice in one breath of each patient. The numbers (F1±6) refer to slices; volume increases from left to right. The letters mark the patients studied. Note the different scaling on the y-axis in patient I. The distribution of¯ow rate over volume (slices) should not be confused with a plot of¯ow rate over time, which decreases during pressure-controlled ventilation. Table 2 Quality control of the ®t procedure. DP=mean absolute difference between original and reconstructed pressure±volume loops (using calculated respiratory parameters for each slice and measured¯ow and volume data). The number of sample points in each slice was obtained from the ®rst breath, which was recorded in each patient. Data are mean (SD) Our data show no apparent association of PEEP with the course of R slice . This may be because the PEEP was high throughout. Moreover, since larger interindividual differences in lung mechanics exist in ARDS patients, pulmonary overdistension could not be expected at a distinct PEEP level, especially when V T also differs. However, it may be helpful to consider the C slice data reported previously. 2 A decrease in C slice is interpreted as overdistension. A decreasing C slice coincided with an increasing R slice , at least in the upper slices, in eight of 16 patients (C, D, G, I, J, K, M and N). These data may support the interpretation by Eissa and colleagues 14 of longitudinal airway stretching at high lung volume. As an alternative explanation for the volume-dependent increase in resistance, Pesenti and colleagues 21 suggested an increased tissue resistance caused by inhomogeneity of ventilation at high PEEP levels. This study has two limitations. First, it is an incidental observation. The data were obtained with another end in view, i.e. the analysis of volume-dependent compliance within V T . 2 The resistance data reported here were not sampled with an a priori hypothesis and no plan was followed to investigate the volume dependency of resistance after changes in ventilator settings. Secondly, the resistance data presented here represent the behaviour of the whole respiratory system, containing the lungs and chest wall. While the chest wall's resistance to air¯ow can be neglected, 20 viscoelastic properties of the chest wall may contribute to the`dynamic' resistance of the respiratory system. It would only have been possible to separate the resistance of the lung resistance from that of the chest wall by measurement of pleural pressure. It is dif®cult to measure pleural pressure, so oesophageal pressure is often used as a surrogate. In principle, determination of the lungs' inherent resistance based on measurements of oesophageal pressure would be desirable and this could easily be added to the slice method. However, our purpose in measurement of respiratory mechanics with the slice method in this and other studies 2 6 13 is to develop a concept that will help clinicians to set the ventilator. A non-invasive approach that could be used in standard ventilator equipment is therefore preferable. Measurement of oesophageal pressure is not suited for routine care, because its application is invasive and requires careful adjustment of the catheter's position. Furthermore, oesophageal pressure may not exactly represent pleural pressure, because it is affected by the weight of the mediastinum in the supine position. 25 Resistance changes considerably, not only in large volume ranges, but also within the relatively small V T . The method used allows non-invasive and continuous recording of volume-dependent resistance. Clinical bene®ts for ARDS patients will come only if a thorough explanation of volume-dependent resistance can be derived. Respiratory compliance and resistance in mechanically ventilated patients with acute respiratory failure Volume-dependent compliance in ARDS: proposal of a new diagnostic concept Report of the American±European consensus conference on ARDS: de®nitions, mechanisms, relevant outcomes and clinical trial coordination Consensus conference on mechanical ventilationÐ Determination of volumedependent respiratory system mechanics in mechanically ventilated patients using the new slice method Static versus dynamic respiratory mechanics for setting the ventilator Digital computer calculation of human pulmonary mechanics using a least squares ®t technique Continuous calculation of intratracheal pressure in tracheally intubated patients Calculation of intratracheal pressure in the presence of pediatric endotracheal tubes Detection of endotracheal tube obstruction by analysis of the expiratory¯ow signal Intrinsic PEEP monitored in the ventilated ARDS patient with a mathematical method Respiratory mechanics by least square ®tting in mechanically ventilated patients: applications during paralysis and during pressure support ventilation Delayed derecruitment after removal of PEEP in patients with acute lung injury Effects of positive end-expiratory pressure, lung volume, and inspiratory¯ow on interrupter resistance in patients with adult respiratory distress syndrome A theoretical analysis of the interrupter technique for measuring respiratory mechanics Effect of valve closure time on the determination of respiratory resistance by¯ow interruption Interrupter airway and tissue resistance: errors caused by valve properties and respiratory system compliance The traveling shutter wave analyses non-linear compliance during mechanical ventilation Analysis of behavior of the respiratory system in ARDS patients: effects of¯ow, volume, and time Alterations of lung and chest wall mechanics in patients with acute lung injury: effects of positive end-expiratory pressure The effects of positive end-expiratory pressure on respiratory resistance in patients with the adult respiratory distress syndrome and in normal anesthetized subjects Nunn's Applied Respiratory Physiology, 4th Edn Flow and volume dependence of respiratory system¯ow resistance in patients with adult respiratory distress syndrome Flow and volume dependence of respiratory system mechanics during constant ow ventilation in normal subjects and in adult respiratory distress syndrome Impairment of lung and chest wall mechanics in patients with acute respiratory distress syndrome: role of abdominal distension An expanded de®nition of the adult respiratory distress syndrome The authors are indebted to Professors Heike Pahl and Ru Èdiger Bittner for critical revision of the manuscript and to Christoph Steinke (Eng.) for technical assistance.