Partitioning of Lung and Chest-wall Mechanics Before and After Lung-volume-reduction Surgery

Brief Communications Partitioning of Lung and Chest-wall Mechanics Before and After Lung-volume-reduction Surgery AMAL JUBRAN, FRANCO LAGHI, MALINDA MAZUR, SAIRAM PARTHASARATHY, EDWARD R. GARRITY, Jr., PATRICK J. FAHEY, and MARTIN J. TOBIN Division of Pulmonary and Critical Care Medicine, Edward Hines Jr. Veterans Administration Hospital, Hines; and Loyola University of Chicago Stritch School of Medicine, Chicago, Illinois In the study reported here, we partitioned the mechanics of the respiratory system into lung and chest-wall components, using the rapid occlusion technique in seven patients with severe emphysema before lung-volume-reduction surgery and 3 mo later. Patients showed improvements in 6-min walk (p 0.01) and dyspnea (p 0.05). The resistances of the respiratory system and chest wall were not altered by surgery. Ohmic airway resistance did not change, but the component of lung resistance ( RL) due to viscoelastic behavior (stress relaxation) and time-constant inhomogeneities (pendelluft) decreased in six patients (p 0.03). Dynamic elastance of the lung (E dyn,l ) decreased after surgery (p 0.02), whereas dynamic elastance of the chest wall did not change. The ratio of dynamic intrinsic positive end-expiratory pressure (PEEP i ) to static PEEP i, which also reflects viscoelastic properties and time-constant inhomogeneities, increased after surgery (p 0.05). The decrease in dyspnea was related to the decrease in E dyn,l (r 0.81, p 0.03), and tended to be related to the decrease in RL (r 0.71, p 0.07). In conclusion, lung-volume-reduction surgery decreased dynamic pressure dissipations caused by stress relaxation and time-constant inhomogeneities within lung tissue, and it had no effect on the static mechanical properties of the chest wall. Jubran A, Laghi F, Mazur M, Parthasarathy S, Garrity ER, Jr, Fahey PJ, Tobin MJ. Partitioning of lung and chestwall mechanics before and after lung-volume-reduction surgery. AM J RESPIR CRIT CARE MED 1998;158:306 310. Following lung-volume-reduction surgery, patients with emphysema show improvement in dyspnea, exercise tolerance, and airflow obstruction (1 4). Although the mechanism of benefit is largely unknown, recent reports suggest that improvements in lung elastic recoil (2), airway conductance (4), and diaphragmatic function (5) may play a role. Hyperinflation, a hallmark of emphysema, causes breathing to occur at an unfavorable position on the pressure volume curve of both the lung and the chest wall, leading to an increase in the work of breathing (6). Other factors contributing to the increase in respiratory work include increases in airway resistance, lung-tissue resistance, time-constant inequality within the lung (pendelluft), pressure losses in the viscoelastic units of the lung (stress relaxation), and intrinsic positive endexpiratory pressure (PEEP i ) (7). It is conceivable that the benefit of lung-volume-reduction surgery is due to alterations (Received in original form June 23, 1997 and in revised form January 20, 1998) Supported by grants from the Veterans Administration Research Service and from the American Lung Association of Metropolitan Chicago. Correspondence and requests for reprints should be addressed to Amal Jubran, M.D., Division of Pulmonary and Critical Care Medicine, Edward Hines Jr. VA Hospital, Hines, IL 60141. Am J Respir Crit Care Med Vol 158. pp 306 310, 1998 Internet address: www.atsjournals.org in one or more of these factors. In a group of patients with emphysema undergoing lungvolume-reduction surgery, we partitioned the mechanics of the total respiratory system into the lung and chest-wall components. Partitioning was achieved by passive ventilation and the rapid airway occlusion technique, which also allowed us to differentiate between the contributions to total respiratory system resistance of ohmic airway resistance and viscoelastic behavior/time-constant inhomogeneities, and to fractionate total dynamic elastance into the components derived from static elastance and additional elastic pressure stored in viscoelastic units (8). To the best of our knowledge, this is the first detailed breakdown of respiratory-system mechanics with an examination of the effect of lung-volume-reduction surgery on each individual component. METHODS Patients We studied six men and one woman (age 62 4 yr [mean SE]) with severe airflow limitation and roentgenographic evidence of emphysema. These patients were the same patients in whom we concurrently measured respiratory-muscle performance before and after surgery (5). The study was approved by the Human Studies Subcommittee of the Edward Hines Jr. Veterans Administration Hospital, and informed consent was obtained from each patient. Approximately 25%

Brief Communication 307 TABLE 1 PASSIVE MECHANICS OF RESPIRATORY SYSTEM, LUNG, AND CHEST WALL IN PATIENTS BEFORE AND AFTER SURGERY Before Surgery After Surgery p Value R max,rs, cm H 2 O/L/s 8.5 0.6 8.5 1.1 0.97 R max,l, cm H 2 O/L/s 6.5 0.5 7.1 1.1 0.55 R max,w, cm H 2 O/L/s 2.1 0.4 1.4 0.3 0.11 R min,rs, cm H 2 O/L/s 6.2 0.5 6.7 1.0 0.61 R min,l, cm H 2 O/L/s 5.2 0.6 5.9 1.0 0.48 R min,w, cm H 2 O/L/s 1.0 0.2 1.1 0.3 0.88 R rs, cm H 2 O/L/s 2.3 0.5 1.2 0.3 0.10 RL, cm H 2 O/L/s 1.3 0.3 0.7 0.2 0.20 RW, cm H 2 O/L/s 1.0 0.3 0.6 0.1 0.11 E dyn,rs, cm H 2 O/L 13.2 1.8 10.7 1.1 0.07 E dyn,l, cm H 2 O/L 4.6 0.5 3.5 0.4 0.02 E dyn,w, cm H 2 O/L 8.6 1.8 7.3 1.1 0.23 E st,rs, cm H 2 O/L 9.8 1.9 9.4 1.1 0.69 E st,l, cm H 2 O/L 2.8 0.2 2.6 0.6 0.66 E st,w, cm H 2 O/L 7.2 1.8 6.9 1.1 0.76 PEEP i,dyn,rs, cm H 2 O 2.5 0.6 2.3 0.5 0.64 PEEP i,dyn,l, cm H 2 O 2.3 0.5 2.3 0.5 0.99 PEEP i,dyn,w, cm H 2 O 0.2 0.1 0.1 0.1 0.01 PEEP i,stat,rs, cm H 2 O 8.7 1.8 6.7 1.5 0.07 PEEP i,stat,l, cm H 2 O 7.3 1.7 5.3 1.5 0.02 PEEP i,stat,w, cm H 2 O 1.3 0.3 1.4 0.3 0.86 R max,rs, R max,l, and R max,w represent the maximum resistance of the respiratory system, lung, and chest wall, respectively; R min,rs, R min,l, and R min,w represent the minimum resistance of the respiratory system, lung, and chest wall, respectively; R rs, RL, and RW represent the additional resistance of the respiratory system, lung, and chest wall, respectively; E dyn,rs, E dyn,l, and E dyn,w represent the dynamic elastance of the total respiratory system, lung, and chest wall, respectively; E st,rs, E st,l, and E st,w represent the static elastance of the total respiratory system, lung, and chest wall, respectively; PEEP i,dyn,rs, PEEP i,dyn,l, and PEEP i,dyn,w represent the dynamic intrinsic positive end-expiratory pressure of the total respiratory system, lung, and chest wall, respectively; PEEP i,stat,rs, PEEP i,stat,l, and PEEP i,stat,w represent the static intrinsic positive end-expiratory pressure of the total respiratory system, lung, and chest wall, respectively. of each lung was resected via a median sternotomy (1). All patients were enrolled in a structured, supervised exercise rehabilitation program for a minimum of 6 wk before and 12 wk after surgery. Apparatus Flow was measured with a heated Fleisch pneumotachograph (Hans Rudolph, Kansas City, MO) placed between the mouthpiece and the Y-piece of the external ventilator circuit. Esophageal pressure (Pes) and gastric pressure (Pga) were measured separately with two thinwalled, latex-balloon-tipped catheters (Erich Jaeger, Wurzberg, Germany) coupled to pressure transducers (MP-45; Validyne, Northridge, CA). Airway pressure (Paw) was measured at the mouthpiece with a tap connected to another transducer. Transpulmonary pressure (PL) was obtained by subtracting Pes from Paw. Electromyographic (EMG) activity of the diaphragm was monitored with surface EMG electrodes. Functional Assessment Lung volumes were measured by body plethysmography and timed spirometry. The magnitude of dyspnea was quantified with a visual analog scale, on which patients marked their response to the question How uncomfortable is your breathing? Six-minute walking distance was performed according to the standard procedure. Protocol Data were recorded 1 to 2 wk before and 3 mo after surgery. Each patient was studied in the sitting position while breathing through a mouthpiece, which in turn was connected to a ventilator (7200a; Puritan Bennett, Carlsbad, CA). Passive ventilation was achieved by gradually increasing the backup rate on the ventilator until the patient s inspiratory muscle activity was completely suppressed. Cessation of patient effort was confirmed by the absence of inspiratory phasic EMG activity and negative deflections of Pes and Paw, and by the uniformity of pressure contour and breath-cycle duration (9, 10); cessation of expiratory muscle recruitment was confirmed by the absence of deviations in the Pga tracings. Because of the flow and volume dependency of resistance and elastance, we maintained identical flow and tidal volume (VT) settings in each patient before and after surgery. For the group, a VT of 0.729 0.06 L and a flow of 1.07 0.05 L/s were used. Lung volume, 6-min walking distance, and dyspnea score at rest were also recorded. Figure 1. Minimum resistance (R min,l, left panel) and additional resistance ( RL, right panel) of the lung in the seven study patients before and after surgery. RL, which represents the additional resistance due to time-constant inequality and viscoelastic pressure dissipations within the lung, decreased in all but one patient (p 0.03). R min,l, which represents ohmic airway resistance, displayed a variable response among the patients. Circles and bars represent group mean SE.

308 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 158 1998 Figure 2. Dynamic elastance of the lung (E dyn,l, left panel) and additional elastance of the lung ( EL, right panel) in the seven study patients before and after surgery. E dyn,l decreased after surgery in the overall group (p 0.02). EL, which represents the additional elastic pressure stored in the viscoelastic units of lung tissues, decreased in all but one patient (p 0.05). Circles and bars represent group mean SE. Physiologic Measurements The mechanics of the respiratory system were partitioned into the lung and chest-wall components using Pes and the constant-flow, rapid-occlusion method (10, 11). The airway opening was occluded at the end of a passive inflation for a duration sufficient to achieve a pressure plateau. After the occlusion, there was an immediate decrease in both Paw and PL from a peak value (P peak ) to a lower initial value (P init ), followed by a gradual decrease until a plateau (P plat ) was achieved; the second decrement is termed P. P init was measured by back-extrapolation of the slope of the latter part of the pressure tracing to the time of airway occlusion (8). The maximum and minimum resistances of the total respiratory system (R max,rs and R min,rs, respectively), lung (R max,l and R min,l, respectively), and chest wall (R max,w and R min,w, respectively) were computed by dividing P peak P plat and P peak P init from the Paw, PL, and Pes tracings, respectively, by the flow immediately preceding the occlusion (8). The additional resistances of the respiratory system ( R rs ), lung ( RL), and chest wall ( RW) were calculated as R max,rs R min,rs, R max,l R min,l, and R max,w R min,w, respectively. R min is considered to reflect ohmic airway resistance (i.e., true airflow resistance in the absence of unequal time constants within the lung) (8). R reflects the viscoelastic properties (stress relaxation) of respiratory tissue when the lung is normal, and also includes a significant contribution from gas redistribution between alveoli with high- and low-pressure units (i.e., pendelluft) when the lungs are abnormal and inhomogenous (8). Dynamic PEEP i values of the respiratory system (PEEP i,dyn,rs ), lung (PEEP i,dyn,l ), and chest wall (PEEP i,dyn,w ) were computed as the change in Paw, PL, and Pes, respectively, generated by the ventilator to initiate airflow (12). Static PEEP i values of the total respiratory system (PEEP i,stat,rs ), lung (PEEP i,stat,l ), and chest wall (PEEP i,stat,w ) were measured as the change in Paw, PL, and Pes, respectively, after the airway was occluded at end-expiration (11). Dynamic elastances of the respiratory system (E dyn,rs ), lung (E dyn,l ), and chest wall (E dyn,cw ) were measured by dividing P init PEEP istat on the Paw, PL, and Pes tracings, respectively, by VT. Static elastances of the total respiratory system (E st,rs ), lung (E st,l ), and chest wall (E st,w ) were measured by dividing P plat PEEP istat on the Paw, PL, and Pes tracings, respectively, by VT. Data Analysis Mechanics of the respiratory system, lung, and chest wall before and after surgery were compared through paired t tests. Regression analysis was used to calculate the correlation coefficient between different variables. RESULTS Surgery produced improvements in lung function. FVC increased from 2.02 0.12 to 2.46 0.15 L (p 0.01); FRC decreased from 6.93 0.46 L to 6.28 0.47 L (p 0.01); and RV decreased from 5.97 0.45 L to 5.23 0.48 L (p 0.01). Dyspnea at rest, assessed by a visual analog scale, decreased from 57 11 mm to 22 6 mm (p 0.05), and the distance covered during a 6-min walk increased from 808 115 feet to 1,198 99 feet (p 0.01). Mechanical characteristics of the respiratory system, lung, and chest wall in patients before and after surgery are shown in Table 1. RL decreased by 59% in six of seven patients (p 0.03), whereas R min,l remained unchanged after surgery (Figure 1). E dyn,l decreased by 24% after surgery (p 0.02) (Figure 2), and E dyn,rs tended to decrease (p 0.07). PEEP i,stat,l decreased by 28% after surgery (p 0.02), and PEEP i,stat,rs tended to decrease (p 0.07). The ratio of PEEP i,dyn,l to PEEP i,stat,l reflecting time-constant inequalities and/or viscoelastic pressure losses increased by almost 60% after surgery (p 0.05) (Figure 3). Resistance, elastance, and PEEP i of the chest wall were not altered by surgery. The change in dyspnea was positively correlated with the change in E dyn,l (r

Brief Communication 309 0.81), and tended to correlate with the change in RL (r 0.71) (Figure 4). Figure 3. The ratio of dynamic PEEP i to static PEEP i of the lung in the seven study patients before and after surgery. This ratio increased after surgery in the overall group (p 0.05), suggesting an improvement in viscoelastic behavior and/or a reduction in time-constant inhomogeneities. Circles and bars represent group mean SE. DISCUSSION Lung-volume-reduction surgery decreased the dynamic pressure dissipations resulting from stress relaxation and timeconstant inhomogeneities within lung tissue. The mechanical properties of the chest wall were not altered by the surgery. R max,rs originated almost completely within the lungs, with minimal contribution from the chest wall (Table 1). The pulmonary flow resistance (R max,l ) was largely due to airway resistance (R min,l ), with a smaller additional resistance ( RL) due to time-constant inequality and viscoelastic pressure dissipations within the lungs. The resistance values in our patients were considerably lower than those reported in ventilator-dependent patients with chronic obstructive pulmonary disease (COPD) (11), presumably because our patients were in a stable condition, without evidence of acute decompensation, and were breathing through a mouthpiece without an artificial airway. The ohmic resistance of the airway (R min,l ) was unaffected by surgery, whereas RL decreased in six of the seven patients (p 0.03) (Figure 1). Moreover, the decrease in RL was associated with a reduction in dyspnea after surgery (Figure 4). This suggests that the beneficial action of surgery is mediated in part through a decrease in time-constant inhomogeneity (pendelluft) and/or pressure losses in viscoelastic units. The decrease in RL may be a consequence of the decrease in lung volume effected by surgery, since RL has been shown to decrease as a function of lung volume (7). The tendency toward a decrease in E dyn,rs after surgery was due to a decrease in E dyn,l (Table 1). This decrease in E dyn,l is in agreement with our parallel study (5), in which an increase Figure 4. The relationship between the change in dyspnea, measured with a visual analog scale (VAS), and the change in dynamic elastance of the lung (E dyn,l ) (left) and the change in additional resistance of the lung ( RL) (right) before and after surgery in the seven study patients. The change in dyspnea was positively correlated with the change in E dyn,l (r 0.81, p 0.03), and tended to correlate with the change in RL (r 0.71, p 0.07).

310 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 158 1998 in dynamic lung compliance (C dyn ) was observed after surgery. The different values for E dyn,l and C dyn in the two studies can be explained by the different methodologies employed. Since the present paper focuses on respiratory mechanics during passive conditions, E dyn,l was measured with the constantflow, rapid occlusion technique (8). In contrast, the measurement of C dyn in our parallel study was obtained during spontaneous breathing (13). Because E stat,l did not change after surgery, the decrease in E dyn,l is likely to have resulted from a decrease in the additional elastic pressure stored in viscoelastic units of the pulmonary tissues, and/or from time-constant inhomogeneities within the lung, (i.e., EL) (7). Indeed, EL (E dyn,l E stat,l ) decreased in six of the seven patients (p 0.05) (Figure 2). In contrast to our observations, Gelb and colleagues (4) noted an increase in E stat,l after surgery. The discrepancy between the reports is probably because they (4) studied patients in the operating room immediately after surgery, whereas our study was performed 3 mo after surgery; accordingly, the increase in E stat,l in their patients could have been due to the effects of anesthesia and/or surgical trauma to lung tissue. Moreover, the distending pressures were different in the two studies: Gelb and colleagues (4) measured elastance at end-expiratory lung volume (EELV), EELV 0.60 L, and EELV 1.0 L, whereas we measured it at EELV 0.73 L. Of note, the elastance of the chest wall did not change with surgery in either study. Surgery produced a decrease in PEEP i,stat,l without a change in PEEP i,dyn,l (Table 1). Static PEEP i represents the average level of PEEP i in nonhomogeneous lung after equilibration of alveolar pressure among lung units with varying time constants, whereas dynamic PEEP i represents the lowest regional value of PEEP i that needs to be overcome to initiate lung inflation. The ratio of PEEP i,dyn,l to PEEP i,stat,l increased after surgery (Figure 3), and the increase in this ratio tended to correlate negatively (r 0.61) with P, which is the secondary decrease in pressure between the initial drop to the final plateau during an end-inspiratory occlusion (7, 8). This supports the notion that the ratio of PEEP i,dyn,l to PEEP i,stat,l reflects time-constant inequalities within the lung and/or increased viscoelastic pressure losses, as has been suggested by Maltais and coworkers (12). The combined changes in the ratio of PEEP i,dyn,l to PEEP i,stat,l, RL, and EL suggest that characteristic responses to lung-volume-reduction surgery include a decrease in time-constant inhomogeneity and viscoelastic pressure losses in lung tissue. The amelioration of dyspnea was correlated with improvements in RL and E dyn,l (Figure 4). The decrease in E dyn,l suggests that breathing took place on a more compliant portion of the pulmonary pressure-volume curve after surgery; this decrease in operating lung volume could be partly responsible for the symptomatic improvement following surgery (14). The second factor associated with the decrease in dyspnea, RL, may also be explained by a decrease in lung volume (7). Specifically, the decrease in RL implies that lung emptying is more efficient and that flow limitation is somewhat lessened. As a result, patients need no longer increase their lung volume to increase expiratory flow. Indeed, EELV probably decreases in these patients, as suggested by a decrease in PEEP i,stat (Table 1, Figure 3). This decrease in EELV will cause the inspiratory muscles to operate at a more favorable position on the length tension curve, with an improvement of pressure-generating capacity, as shown in our parallel study (5). Moreover, lessening of dynamic collapse may also have contributed to symptomatic improvement, since compression of the airways has been shown to contribute to dyspnea, probably through activation of the upper-airway mechanoreceptors (15). In conclusion, we found that the decrease in dyspnea achieved by lung-volume-reduction surgery is related to decreases in time-constant inhomogeneities (pendelluft) and in the storage of additional resistive and elastic pressure in the viscoelastic units of the pulmonary tissues. References 1. Cooper, J. D., E. P. Trulock, A. N. Triantafillou, G. A. Patterson, M. S. Pohl, P. A. Deloney, R. S. Sundaresan, and C. L. Roper. 1995. Bilateral pneumectomy (volume reduction) for chronic obstructive pulmonary disease. J. Thorac. Cardiovasc. Surg. 109:106 119. 2. Sciurba, F. C., R. M. Rogers, R. J. Keenan, W. A. Slivka, J. Gorcsan, P. F. Ferson, J. M. Holbert, M. L. Brown, and R. J. Landreneau. 1996. Improvement in pulmonary function and elastic recoil after lung reduction surgery for diffuse emphysema. N. Engl. J. Med. 334:1095 1096. 3. Benditt, J. O., D. E. Wood, F. D. McCool, S. Lewis, and K. Albert. 1997. Changes in breathing and ventilatory muscle recruitment patterns induced by lung volume reduction surgery. Am. J. Respir. Crit. Care Med. 155:279 284. 4. Gelb, A. F., R. J. McKenna, Jr., M. Brenner, R. Fischel, A. Baydur, and N. Zamel. 1996. Contribution of lung and chest wall mechanics following emphysema resection. Chest 110:11 17. 5. Laghi, F., A. Jubran, A. Topeli, P. J. Fahey, E. R. Garrity, Jr., J. M. Arcidi, D. J. De Pinto, L. C. Edwards, and M. J. Tobin. 1998. Effect of lung volume reduction surgery on neuromechanical coupling of the diaphragm. Am. J. Respir. Crit. Care Med. 157:475 483. 6. Gibson, J. 1995. Respiratory muscles. In P. M. A. Calverley and N. Pride, editors. Chronic Obstructive Pulmonary Disease. Chapman & Hall, London. 185 203. 7. Guerin, C., M. L. Coussa, N. T. Eissa, C. Corbeil, M. Chasse, J. Braidy, N. Matar, and J. Milic-Emili. 1993. Lung and chest wall mechanics in mechanically ventilated COPD patients. J. Appl. Physiol. 74:1570 1580. 8. Bates, J. H. T., A. Rossi, and J. Milic-Emili. 1985. Analysis of the behavior of the respiratory system with constant inspiratory flow. J. Appl. Physiol. 58:1840 1848. 9. Jubran, A., W. B. Van de Graaff, and M. J. Tobin. 1995. Variability of patient-ventilator interaction with pressure support ventilation in patients with COPD. Am. J. Respir. Crit. Care Med. 152:129 136. 10. Jubran, A., and M. J. Tobin. 1997. Passive mechanics of lung and chest wall in patients who failed or succeeded in trials of weaning. Am. J. Respir. Crit. Care Med. 155:916 921. 11. Polese, G., A. Rossi, L. Appendini, G. Brandi, J. H. T. Bates, and R. Brandolese. 1991. Partitioning of respiratory mechanics in mechanically ventilated patients. J. Appl. Physiol. 71:2425 2433. 12. Maltais, F., H. Reissman, P. Navalesi, P. Hernandez, A. Gursahaney, V. M. Ranieri, M. Sovilj, and S. B. Gottfried. 1994. Comparison of static and dynamic measurements of intrinsic PEEP in mechanically ventilated patients. Am. J. Respir. Crit. Care Med. 150:1318 1324. 13. Frank, N. R., J. Mead, and B. G. Ferris, Jr. 1957. The mechanical behavior of the lungs in healthy elderly persons. J. Clin. Invest. 36:1680 1687. 14. O Donnell, D. E., and K. A. Webb. 1993. Exertional breathlessness in patients with chronic airflow limitation: the role of hyperinflation. Am. Rev. Respir. Dis. 148:1351 1357. 15. O Donnell, D. E., R. Sanii, N. R. Anthonisen, and M. Younes. 1987. Effect of dynamic airway compression on breathing pattern and respiratory sensation in severe chronic obstructive pulmonary disease. Am. Rev. Respir. Dis. 135:912 918.