Differential Inspiratory Muscle Pressure Contributions to Breathing during Dynamic Hyperinflation

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1 Differential Inspiratory Muscle Pressure Contributions to Breathing during Dynamic Hyperinflation SHENG YAN and BENGT KAYSER Montréal Chest Institute, Royal Victoria Hospital, Meakins-Christie Laboratories, McGill University, Montréal, Québec, Canada During dynamic hyperinflation, the ventilatory pump is facing increased demand because it must overcome the intrinsic positive end-expiratory pressure (PEEPi) and decreased capacity since it must operate at a dynamically increased end-expiratory lung volume (EELV). The aim of this study was to evaluate the relative pressure contribution by the diaphragm and inspiratory rib cage muscles (RCMs) during dynamic hyperinflation. In six healthy subjects, dynamic hyperinflation was induced by limiting expiratory flow. The global inspiratory muscle pressure ( Pmus,i) and transdiaphragmatic pressure ( Pdi) were partitioned into the portion used to overcome PEEPi and the portion used to inflate the respiratory system. The Pdi/ Pmus,i ratio was used to estimate the pressure contribution of RCMs relative to that of the diaphragm. Our results suggest that (1) with increasing severity of dynamic hyperinflation, there is a significant increase in the inspiratory pressure contribution of RCMs relative to that of the diaphragm for inflating the respiratory system; (2) during dynamic hyperinflation, especially at high EELV, the major pressure contribution of the diaphragm is to overcome the PEEPi-imposed inspiratory threshold load, whereas the inspiratory pressure needed for the subsequent task of inflating the respiratory system is largely contributed by RCMs. This arrangement is consistent with the change in mechanical advantages of RCMs and the diaphragm during the development of dynamic hyperinflation. Yan S, Kayser B. Differential inspiratory muscle pressure contributions to breathing during dynamic hyperinflation. AM J RESPIR CRIT CARE MED 1997;156: (Received in original form November 19, 1996 and in revised form April 3, 1997) Supported by the Montréal Chest Institute, the Association Pulmonaire du Québec, and the T. J. Costello Memorial Research Fund. Dr. Kayser is the recipient of post-doctoral fellowship from Merck-Frosst. Correspondence and requests for reprints should be addressed to Dr. S. Yan, Montréal Chest Institute Research Center, 3650 St. Urbain Street, Room 526, Montréal, PQ, H2X 2P4 Canada. sheng@meakins.lan.mcgill.ca Am J Respir Crit Care Med Vol pp , 1997 Dynamic hyperinflation is common in patients with chronic obstructive pulmonary disease (COPD) during acute exacerbations requiring mechanical ventilation (1, 2), but it has also been reported in patients with stable COPD during resting breathing (3, 4). During dynamic hyperinflation, end-expiratory lung volume (EELV) is above the relaxation volume, resulting in a positive end-expiratory pressure (PEEPi) that has to be overcome by the inspiratory muscles before inspiratory flow can start (5). Dynamic hyperinflation thus decreases the capacity of and increases the demand to the inspiratory muscles. Most of the previous studies of dynamic hyperinflation reported methods to measure PEEPi and/or discussed various factors likely affecting the reliability of these measurements (2, 6 8). How the different inspiratory muscles contribute to breathing during dynamic hyperinflation has not been investigated in detail. In particular, how the diaphragm, the major inspiratory muscle, contributes to overcoming the PEEPiimposed inspiratory threshold load and subsequently to inflating the respiratory system has not been reported before. Because with increasing EELV, the diaphragm progressively shortens and its ability to generate pressure is gradually impaired (9, 10), we hypothesized that during dynamic hyperinflation, although the diaphragm may still play an important part in generating pressure to overcome the PEEPi-induced inspiratory threshold load, there is a need for a proportionately greater increase in pressure contribution of the inspiratory rib cage muscles (RCMs) over that of the diaphragm to overcome PEEPi and to inflate the respiratory system. Accordingly, the major purposes of the present study were to measure the pressure contribution of the diaphragm during dynamic hyperinflation and to estimate the pressure contribution of RCMs relative to that of the diaphragm to overcome the PEEPi-induced inspiratory threshold load and to inflate the respiratory system. For these purposes, we induced dynamic hyperinflation in healthy subjects by limiting expiratory flow by a Starling resistor (8, 11, 12) and measured inspiratory muscle pressure responses. We interpreted our experimental findings on the basis of different changes in mechanical advantages of the RCMs and diaphragm during the development of dynamic hyperinflation. METHODS Subjects Six healthy subjects, all belonging to our laboratory staff and therefore familiar with respiratory maneuvers such as respiratory muscle relaxation, volunteered. Only one knew the precise purpose of the study. The study was approved by our institutional ethics committee, and informed consent was obtained from all the subjects.

2 498 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL Experimental Setup The experimental setup was similar to that in a previous study (8). The experiment was performed with the subject seated in a high-back armchair, breathing through a mouthpiece, and wearing a noseclip. The mouthpiece was connected via a pneumotachograph to a two-way nonrebreathing valve (Type 2600; Hans-Rudolph, St. Louis, MO). The latter was connected to a bag-in-box plethysmograph in a closed circuit. Respiratory flow was measured by the pneumotachograph (Fleisch No. 2; Fleisch, Lausanne, Switzerland) attached to a differential pressure transducer (Validyne Corp., Northridge, CA). Changes in EELV were measured by the bag-in-box system. Respiratory timing signals, including breathing frequency (f), inspiratory and expiratory time (TI and TE), were calculated from the flow signal. Esophageal and gastric pressures (Pes and Pga) were measured by balloon-tipped catheters positioned in the lower esophagus and stomach and connected to differential pressure transducers (Validyne). Transdiaphragmatic pressure (Pdi) was obtained by subtraction of Pes from Pga. End-expiratory carbon dioxide partial pressure (PET CO ) was measured at the 2 mouthpiece by a CO 2 analyzer (Ametek CD-3A; Sunnyvale, CA). In order to limit expiratory flow and induce dynamic hyperinflation, a Starling resistor (8, 11, 12) was connected to the expiratory line of the breathing circuit by a three-way stopcock type valve (Hans Rudolph 2120C). The Starling resistor consisted of a compressible rubber tube contained in a Plexiglas chamber. The chamber was pressurized by connecting it to the expiratory side of the valve system near the mouthpiece by a side tube. Expiratory mouth pressure was thus relayed to the chamber, which compressed the rubber tube, rendering flow independent of expiratory efforts at 0.6 L/s. Protocol An individual static chest wall pressure-volume relationship was obtained by repeated respiratory muscle relaxation maneuvers during passive deflation from TLC to FRC against a high nonlinear resistance. Three successful relaxations were performed by each subject. A relaxation was judged successful by the reproducibility of the chest wall relaxation pressure-volume curves, a smooth decline of Pes and Pga from TLC to FRC, and a zero Pdi (13). Static pressure-volume relationships of the chest wall were constructed by plotting lung volume (VL) against Pes with the VL at the equilibrium volume (FRC) scaled to zero. After a brief period of adjusting to breathing on the non-flow-limited breathing circuit, quiet breathing data were obtained for 5 min. Then, with the subjects remaining on the mouthpiece, the expiratory route was opened to the Starling resistor. To induce dynamic hyperinflation, the subjects were subsequently instructed to increase breathing frequency from their natural frequency to 20, 25, 30, 35, and 40 breaths/min using a metronome. No other instructions were given. Specifically, the subjects were left free to choose their tidal volume (VT), respiratory timing, and the preference of their respiratory muscle use. At each frequency, 6 to 10 breaths were recorded for data analysis. Figure 1. Illustration of the measurement of global inspiratory muscle pressure ( Pmus,i) during dynamic hyperinflation. The thick line represents the static pressure-volume relationship of the chest wall. The thin line is a dynamic esophageal pressure (Pes)- lung volume (VL) breathing loop. The arrows show the clockwise direction of the loop formation. VL is set to zero at the equilibrium volume. End-expiratory lung volume is increased to the level of AC because of dynamic hyperinflation. Points A and B represent the Pes-VL relationships at the beginning and end of inspiratory flow. See text for further explanations. Data Recording and Analysis Respiratory flow, VL, Pes, Pga, and PET CO were preamplified by an 2 eight-channel strip-chart recorder (HP 7758B; Hewlett-Packard, Waltham, MA) passed through a 12-bit analog-to-digital converter and recorded by a computer. Data analysis was performed on averaged breaths (five to eight breaths). With dynamic hyperinflation, inspiratory muscle effort must start prior to the start of inspiratory flow to overcome PEEPi. A sudden decrease in Pes just before inspiratory flow has been used to measure dynamic PEEPi (2 4). However, since end-expiratory Pes baseline is subject to influences from activities of various respiratory muscles (2, 6 8), we used the individual chest wall pressure-volume curve as the reference for measuring global inspiratory muscle pressure contribution ( Pmus,i) for a given lung volume. The schema for Pmus,i measurement is shown in Figure 1. A clockwise dynamic VL-Pes loop (thin line) during breathing is superimposed on the static pressure-volume curve of the chest wall (thick line). Points A and B represent the beginning and end of inspiratory flow, respectively. EELV is increased because of dynamic hyperinflation as indicated by the level of AC. The Pmus,i required to initiate the inspiratory flow (thus to overcome the PEEPi-imposed inspiratory threshold load) and to accomplish the whole inspiration was measured as the Pes value at the beginning and the end of inspiratory flow, respectively, relative to the Pes value on the chest wall pressure-volume curve for a given endexpiratory and end-inspiratory VL (the pressure differences given by AC and BD). The sign of Pmus,i measured this way is always negative. The Pmus,i to overcome the respiratory system elastance during inspiratory flow was calculated as BD-AC. The pressure contribution of the diaphragm to initiate inspiratory flow and to accomplish the whole inspiration was measured as the Pdi value at the beginning and end of inspiratory flow, respectively, relative to the Pdi baseline during resting breathing, which was assumed to be zero when the subject sits relaxed in an upright position (13). The ratio Pdi/ Pmus,i was used to evaluate the pressure contribution of RCMs relative to that of the diaphragm for a given condition. TABLE 1 BREATHING PATTERN* Quiet Unloaded Breathing Starling Resistor Breathing VT, L f, breaths/min V E L/min TI, s TE, s * Breathing pattern parameters during quiet breathing and during Starling resistor breathing at the highest end-expiratory lung volume. VT tidal volume; f breathing frequency; TI inspiratory time; TE expiratory time; V E minute ventilation. Significantly different from quiet unloaded breathing (p 0.05).

3 Yan and Kayser: Inspiratory Muscle Contributions during Dynamic Hyperinflation 499 Figure 2. Individual results of the global inspiratory muscle pressure ( Pmus,i) and transdiaphragmatic pressure ( Pdi) to overcome the PEEPi-imposed inspiratory threshold load (before beginning of inspiratory flow) with increasing end-expiratory lung volume ( EELV) during dynamic hyperinflation. The data are presented as individual values or mean SD. Paired t tests and least-squares linear regressions were used for statistical analysis when appropriate. A p value less than 0.05 was considered to be statistically significant. RESULTS All the subjects developed dynamic hyperinflation during expiratory Starling resistor breathing. The individual maximal increases in EELV ranged from 0.87 to 2.32 L. The breathing pattern parameters are given in Table 1 for quiet unloaded breathing and for Starling resistor breathing at the highest EELV. All subjects responded similarly to the Starling resistor breathing: VT remained relatively constant; TI and TE were significantly shortened; minute ventilation ( V E) was significantly increased (because of the imposed increase in f). PET CO 2 significantly decreased (because of increased V E), from 38 5 mm Hg during quiet unloaded breathing to 28 4 mm Hg during Starling resistor breathing at the highest EELV. Pmus,i and Pdi to overcome the PEEPi-imposed inspiratory threshold load and to initiate the inspiratory flow during dynamic hyperinflation are shown in Figure 2. The negativity of Pmus,i linearly increased with increasing EELV in each Figure 3. Individual results of the global inspiratory muscle pressure ( Pmus,i) and transdiaphragmatic pressure ( Pdi) to inflate the respiratory system (between beginning and end of inspiratory flow) with increasing end-expiratory lung volume ( EELV) during dynamic hyperinflation.

4 500 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL Figure 4. Individual results of the transdiaphragmatic pressure to global inspiratory muscle pressure ratio ( Pdi/ Pmus,i) with increasing end-expiratory lung volume ( EELV) during dynamic hyperinflation. The upper panels show the results for overcoming the PEEPi-imposed inspiratory threshold load (before the beginning of inspiratory flow); the lower panels show the results for inflating the respiratory system (between the beginning and end of inspiratory flow). Subject No. TABLE 2 SLOPES OF Pdi/ Pmus,i RATIO AGAINST EELV* Before Inspiratory Flow During Inspiratory Flow Mean SD * Individual slopes of Pdi/Pmus,i ratio as a function of EELV during dynamic hyperinflation. Pmus,i global inspiratory muscle pressure; Pdi transdiaphragmatic pressure; EELV end-expiratory lung volume. Significantly different from before inspiratory flow (p 0.05). subject; Pdi also increased, but with considerable variability (see Subjects 3, 4, and 5). Pmus,i and Pdi to inflate the respiratory system (between the beginning and end of inspiratory flow) during dynamic hyperinflation are shown in Figure 3. The magnitude of Pmus,i increased with increasing EELV in four subjects (Subjects 2, 3, 5, and 6) and was relatively constant in the remaining two subjects. The Pdi showed a tendency to decrease with increasing EELV in all but one subject (Subject 5). The Pdi/ Pmus,i ratio is shown in Figure 4 before the start of inspiratory flow (upper panels) and between the beginning and end of inspiratory flow (lower panels) during dynamic hyperinflation. With increasing EELV, the negativity of Pdi/ Pmus,i before the start of inspiratory flow significantly decreased in four subjects (Subjects 1 to 4) (p 0.05), remained unchanged in one subject (Subject 5), and significantly increased in one subject (Subject 6) (p 0.05); the negativity of the same ratio between the beginning and end of inspiratory flow significantly decreased in all the subjects (p 0.05). The individual slopes of Pdi/ Pmus,i ratio against EELV relationships before inspiratory flow as well as between the beginning and end of inspiratory flow are shown in Table 2. The average slope before inspiratory flow was , which was not significantly different from zero, whereas the slope during inspiratory flow ( ) was not only significantly greater than zero but also significantly greater than the former (p 0.05). In Figure 5, averaged Pmus,i and Pdi before the start of inspiratory flow are expressed as a percentage of Pmus,i and Pdi as developed for the whole inspiration (from the beginning of inspiratory effort to the end of inspiratory flow). With increasing EELV, about half of the total Pmus,i was developed before inspiratory flow to overcome the PEEPi-imposed inspiratory threshold load, whereas 75% of the total Pdi was developed for the same purpose (p 0.01). DISCUSSION In the present study, we induced dynamic hyperinflation in healthy subjects by expiration through a Starling resistor and measured Pdi and Pmus,i to assess the pressure contributions of the diaphragm and the overall inspiratory muscles during breathing. We partitioned Pdi and Pmus,i into the contributions to overcome the PEEPi-imposed inspiratory threshold load and to subsequently inflate the respiratory system. We further used the Pdi/ Pmus,i ratio to evaluate the pressure contribution of RCMs relative to that of the diaphragm. We found that before the start of inspiratory flow, the magnitude of both Pmus,i and Pdi increased with increasing EELV with no consistent change in the Pdi/ Pmus,i ratio as a function of EELV, whereas between the beginning and the end of the inspiratory flow, there was a significant decrease in the negativity of the Pdi/ Pmus,i ratio with increasing EELV. We interpret these results as follows: (1) with increasing magnitude of dynamic hyperinflation, there is a greater increase in the in-

5 Yan and Kayser: Inspiratory Muscle Contributions during Dynamic Hyperinflation 501 Figure 5. Global inspiratory muscle pressure ( Pmus,i) (open circles) and transdiaphragmatic pressure ( Pdi) (closed circles) before the beginning of inspiratory flow expressed as a percentage of Pmus,i and Pdi for the whole inspiratory effort during dynamic hyperinflation. Group mean results are shown. EELV end-expiratory lung volume. spiratory pressure contribution of RCMs relative to that of the diaphragm for inflating the respiratory system than for overcoming PEEPi; (2) during dynamic hyperinflation, especially at high EELV, the major pressure contribution of the diaphragm is to overcome the PEEPi-imposed inspiratory threshold load, whereas the inspiratory pressure needed for the subsequent task of inflating the respiratory system is largely contributed by RCMs. Technical Considerations In this study, we used Pmus,i to assess the global inspiratory muscle pressure contribution before the start of and between the beginning and end of inspiratory flow. The former is similar to, but more accurate than, dynamic PEEPi. Dynamic PEEPi is determined as an abrupt decrease in Pes relative to its immediate preceding baseline before inspiratory flow starts (3, 4). However, expiratory muscle (2, 6 8) or tonic inspiratory muscle activities (8) during dynamic hyperinflation elevate or lower the expiratory Pes baseline, respectively, and therefore dynamic PEEPi may overestimate or underestimate the true inspiratory muscle pressure contributions. Our recent work (8) using the Campbell diagram to evaluate PEEPi demonstrated that it is difficult to reliably estimate the inspiratory muscle effort to overcome PEEPi without information of the relaxation pressure-volume relationship of the chest wall. This is because the static pressure-volume curve of the chest wall describes the relationship between lung volume and pleural pressure when all respiratory muscles are relaxed and any departure from this curve requires respiratory muscle activity (13). In the present study, we found that in all subjects, the end-expiratory Pes fell to the right of the static pressure-volume relationship of the chest wall under most or all of the occasions during Starling resistor breathing, indicating expiratory muscle recruitment. The average maximal deviation was cm H 2 O. Hence, using the individual static pressure-volume curve of the chest wall as reference, our measurement of Pmus,i for a given end-expiratory or end-inspiratory lung volume presumably gives a reliable measurement of the global inspiratory muscle pressure contribution under each condition. As a modification of the original concept of Macklem and coworkers (14), more recent investigators have employed the Pga/ Pes ratio to partition the relative inspiratory muscle pressure contributions (15 17). We did not use this method in the present study. Instead, we chose to use the Pdi/ Pmus,i ratio for the same purpose because a change in Pdi/ Pmus,i can be interpreted similarly to that in Pga/ Pes, but Pmus,i can be directly linked to PEEPi. On the basis of our definition, inspiratory Pmus,i, reflecting global inspiratory muscle pressure contribution, is negative, leading to a negative Pdi/ Pmus,i ratio when Pdi 0. Decreasing the negativity of Pdi/ Pmus,i ratio requires a decreasing Pdi for a given Pmus,i or an increasing negativity of Pmus,i for a given Pdi, and therefore indicates an increase in pressure contribution from RCMs relative to that of the diaphragm. When Pdi is zero, Pdi/ Pmus,i ratio becomes maximal (zero). Under such a condition, all the Pmus,i must be generated by RCMs. In fact, if the diaphragm is the only muscle contracting such as during phrenic nerve stimulation (RCMs are relaxed), the calculated Pdi/ Pmus,i ratio based on previous data (18, 19) was around 2.5 at FRC, significantly more negative than the same ratio shown in Figure 4 where both RCMs and diaphragm presumably contributed their pressures to a variable extent. Effect of Dynamic Hyperinflation on Inspiratory Muscle Use Earlier investigators (20 22) have studied the effect of continuous positive airway pressure (CPAP) on inspiratory muscle responses. Although CPAP induces acute hyperinflation, it moves the inspiratory volume-pressure relationship to the right along the pressure axis, so that inspiration is assisted and PEEPi is not present (23). During dynamic hyperinflation, generation of inspiratory pressure is required not only for inflating the respiratory system but also for counteracting the inspiratory threshold pressure brought about by PEEPi. This task has to be accomplished when inspiratory muscles are in a mechanical disadvantage secondary to the shortening of the inspiratory muscles with an operating lung volume above the relaxation volume (24). Hence, dynamic hyperinflation loads the inspiratory pump by reducing the capacity of, as well as by increasing the demand to, the inspiratory muscles. This feature is unique and probably differs from all other types of inspiratory loads. As shown previously, even though both muscle groups shorten with increasing lung volume, major differences exist between RCMs and the diaphragm. First, at FRC, the resting length of the diaphragm is close to its optimal length, whereas that of the parasternal intercostals is 15% longer than its optimal length (25). Thus, increasing EELV from FRC would initially move the parasternal intercostals towards their optimal length. Second, from FRC to TLC, the diaphragm shortens by 30 to 40% (10), whereas the scalenes and parasternal intercostals shorten by only 6 and 10%, respectively (26, 27). Third, with increasing lung volume, the two muscular parts of the diaphragm (crural and costal) change from a parallel to an in series configuration, which impairs the function of the diaphragm as a pressure generator (28). Consequently, at TLC, the ability of the diaphragm to generate pressure is dra-

6 502 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL matically impaired (18, 19), but that of the parasternal intercostals is well preserved (29). On this basis, one can expect that during dynamic hyperinflation, an increased pressure contribution from RCMs will take over the task of generating pressure to maintain breathing. This reasoning is consistent with our observations for the inspiratory pressure contributions to inflate the respiratory system (between the beginning and end of inspiratory flow) during dynamic hyperinflation. Indeed, the amplitude of Pmus,i increased with increasing EELV in most subjects, presumably reflecting a greater respiratory system elastance at high volumes, whereas Pdi remained relatively constant or decreased (Figure 3), leading to a significant decrease in the negativity of Pdi/ Pmus,i ratio with increasing EELV in all subjects (Figure 4, lower panels, and Table 2). By contrast, we did not find a consistent change in Pdi/ Pmus,i ratio as a function of EELV before the beginning of inspiratory flow (Figure 4, upper panels, and Table 2). To overcome the PEEPi-imposed inspiratory threshold load, Pdi increased with increasing Pmus,i nearly proportionately despite a progressive increase in EELV (Figure 2). This suggests that relative pressure contributions of RCMs and diaphragm to overcome the PEEPi-imposed inspiratory threshold load remain relatively constant over different levels of dynamic hyperinflation. Further, the diaphragm spent as much as 75% of the total Pdi generated within one breathing cycle to overcome the PEEPi-imposed inspiratory threshold load. This was significantly more than that from Pmus,i, which amounted to 50% (Figure 5). We therefore conclude that during dynamic hyperinflation, the major pressure contribution of the diaphragm is to overcome PEEPi, whereas the inspiratory pressure required to inflate the respiratory system is largely generated by RCMs. The maintenance of a relatively constant Pdi/ Pmus,i ratio before the beginning of inspiratory flow may at first appear surprising because the diaphragm, compared with RCMs, is more significantly deprived of its mechanical advantage by contracting at high lung volumes, as stated above. Our results would suggest that to overcome the PEEPi-imposed inspiratory threshold load, the activation of the diaphragm must be progressively increased beyond that of RCMs in order to keep the Pdi/ Pmus,i ratio relatively constant or to be less affected by the increasing degree of dynamic hyperinflation. If this were the case, the question arises why the subjects had a greater decrease in the negativity of this ratio during inspiratory flow as EELV increased. The answer may be found in the characteristic features of a PEEPi-induced inspiratory threshold load. During inspiratory resistive and elastic loading, inspiratory flow starts instantaneously with inspiratory muscle contraction so that the processes to overcome the load and to inflate the respiratory system occur simultaneously. During inspiratory threshold loading, the situation is different. The total inspiratory effort can be divided clearly into two phases by the beginning of inspiratory flow, with the inspiratory muscle velocity of shortening much slower in the first phase before flow starts (determined by chest wall distortion and gas compression) than in the second phase during flow. According to the forcevelocity relationship, both RCMs and the diaphragm should be better at generating inspiratory pressure in the first phase than in the second phase. However, if the amount of shortening of the diaphragm is greater than that of RCMs between FRC and TLC (10, 26, 27), the velocity of shortening of the diaphragm must be greater than that of RCMs during flow. In other words, the capacity of the diaphragm as an inspiratory pressure generator will be more affected during flow. This then results in most of the pressure contribution of the diaphragm being developed to overcome the PEEPi-imposed inspiratory threshold load, leaving RCMs as the major inspiratory pressure generator to inflate the respiratory system. Alternatively, these results may be explained by failure to maintain the increased diaphragmatic drive throughout the whole inspiration (30) as dynamic hyperinflation develops. Finally, it needs to be pointed out that the current results were obtained from healthy subjects. Their inspiratory muscles presumably had sufficient reserve for extra demands. 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