Respiratory restriction and elevated pleural and esophageal pressures in morbid obesity

Abstract

To explore mechanisms of restrictive respiratory physiology and high pleural pressure (P_Pl) in severe obesity, we studied 51 obese subjects (body mass index = 38–80.7 kg/m²) and 10 nonobese subjects, both groups without lung disease, anesthetized, and paralyzed for surgery. We measured esophageal and gastric pressures (P_Es, P_Ga) using a balloon-catheter, airway pressure (P_AO), flow, and volume. We compared P_Es to another estimate of P_Pl based on P_AO and flow. Reasoning that the lungs would not inflate until P_AO exceeded alveolar and pleural pressures (P_AO > P_Alv > P_Pl), we disconnected subjects from the ventilator for 10–15 s to allow them to reach relaxation volume (V_Rel) and then slowly raised P_AO until lung volume increased by 10 ml, indicating the “threshold P_AO” (P_AO-Thr) for inflation, which we took to be an estimate of the lowest P_Alv or P_Pl to be found in the chest at V_Rel. P_AO-Thr ranged from 0.6 to 14.0 cmH₂O in obese and 0.2 to 0.9 cmH₂O in control subjects. P_Es at V_Rel was higher in obese than control subjects (12.5 ± 3.9 vs. 6.9 ± 3.1 cmH₂O, means ± SD; P = 0.0002) and correlated with P_AO-Thr (R² = 0.16, P = 0.0015). Respiratory system compliance (C_RS) was lower in obese than control (0.032 ± 0.008 vs. 0.053 ± 0.007 l/cmH₂O) due principally to lower lung compliance (0.043 ± 0.016 vs. 0.084 ± 0.029 l/cmH₂O) rather than chest wall compliance (obese 0.195 ± 0.109, control 0.223 ± 0.132 l/cmH₂O). We conclude that many severely obese supine subjects at relaxation volume have positive P_pl throughout the chest. High P_Es suggests high P_Pl in such individuals. Lung and respiratory system compliances are low because of breathing at abnormally low lung volumes.

obesity is a known cause of restrictive respiratory physiology and low lung volumes. Morbidly obese individuals [body mass index (BMI) ≥ 40 kg/m²] have reduced total lung capacity (TLC), functional residual capacity (FRC), and vital capacity (VC) (6, 26). These subjects often have FRC reduced to near residual volume (RV); the reduction of FRC is even greater in the supine position (26). Such reductions in lung volume suggest elevation of pleural pressure (P_Pl) in morbid obesity.

To date, the studies of respiratory restriction in the obese have focused on changes in P_Pl that determine chest wall and lung compliance (C_CW, C_L) rather than estimating P_Pl itself. Naimark and Cherniack (11) and later Sharp et al. (16) reported that chest wall compliance was significantly reduced in obesity while lung compliance was normal. Subsequent studies by Hedenstierna and Santesson (5) and Suratt et al. (20) reported contrary findings of normal C_Cw and decreased C_L in the obese. More recently, Pelosi et al. (13) found both C_CW and C_L to be reduced in morbidly obese subjects.

All the aforementioned studies reported changes in esophageal pressures (P_Es); none reported actual values of P_Es, presumably due to concern about the validity of esophageal manometry in estimating P_Pl in the obese. Although esophageal balloon catheters have been used to estimate P_Pl in normal subjects (3), their use in the obese has not been validated.

In this study we report values of P_Pl as estimated independently by esophageal balloon and by using the relation between the airway pressure (P_AO) and lung volume (V_L) during passive inflation of the lungs. We studied severely obese subjects and normal-weight controls, anesthetized and paralyzed, and tested the hypotheses that our severely obese subjects had higher P_Pl than normal subjects and that P_Es is a useful indicator of P_Pl in obese subjects. We also related P_Es to estimated P_Pl, gastric pressure (P_Ga), and BMI and studied the compliance of the respiratory system (C_RS), C_CW. and C_L.

SUBJECTS AND METHODS

Subjects.

Fifty morbidly obese subjects and one moderately obese subject, which we will collectively call “severely obese subjects,” and 10 nonobese subjects (BMI < 30), all with healthy lungs, were studied immediately after induction of general anesthesia for elective surgery at Beth Israel Deaconess Medical Center. The severely obese subjects had BMI ranging from 38.0 to 80.7 kg/m² (48.5 ± 8.9, mean ± SD) and were aged 20 to 69 yr (43.8 ± 11.9 yr), and 33 were female (see Supplement available with the online version of this article). Ten control subjects had BMI ranging from 19.2 to 29 kg/m² (25.2 ± 2.8 kg/m²) and were aged 21–61 yr (44.7 ± 11.4), and 8 were female. Two additional subjects originally recruited as controls were found to have mild obesity, BMI slightly above 30 kg/m²; they were not included in the analysis but are shown in the figures with distinct symbols. The research was approved by the Committee on Clinical Investigations, and subjects gave informed written consent before study.

Measurements.

Subjects were studied before surgical incision and immediately after induction of general anesthesia including complete muscle relaxation using vecuronium with or without succinylcholine. Subjects were supine and mechanically ventilated with 100% O₂ with tidal volumes of 0.64 ± 0.11 liters (Supplemental Table S-1, available with the online version of this article) and no preset positive end-expiratory pressure (PEEP), although a small PEEP was present in all subjects due to ventilator characteristics. P_Ga and P_Es were measured using an adult esophageal balloon catheter (Ackrad Laboratories), passed by mouth or nose to position the balloon's tip at 60 cm from the incisors to measure P_Ga and then withdrawn to 40 cm to measure P_Es. (In 25 subjects in whom it was not possible to advance the balloon into the stomach, P_Ga was not measured.) The 10-cm-long balloon was inflated with 0.5–1.0 ml of air. P_AO was measured at the endotracheal tube, and airflow was measured with a pneumotachometer (Fleisch pneumotachograph type 1, Metabo SA). Signals were digitized, displayed, and recorded using Windaq software and hardware (Dataq Instruments, Akron, OH).

Threshold inflation airway pressure, P_AO-Thr.

A major aim of this study was to estimate the distribution of pleural pressure surrounding the lungs. To do this, we inferred P_Pl from the airway pressure needed to cause lung inflation. We reasoned that in a relaxed intubated subject with open airways, if the highest P_Pl to be found in the chest is subatmospheric, then inflation should begin immediately as the airway pressure (P_AO) is raised above atmospheric pressure. By contrast, if the lowest P_Pl to be found in the chest is above atmospheric pressure, the lungs would not begin to inflate until P_AO is raised above that lowest P_Pl (where the local transpulmonary pressure would first become positive). Therefore_, the P_AO at which the lung volume first begins to increase is an approximate indicator of the lowest P_Pl to be found in the chest at relaxation volume (V_Rel).

We determined the “threshold P_AO” (P_AO-Thr), the P_AO required to initiate lung inflation during the slow increase in P_AO from relaxation volume. To prevent noise in the flow signal from being interpreted as the start of inspiratory flow we needed to use a 10-ml increase in lung volume as our criterion for the start of inflation (Fig. 1). If there were no pulmonary resistive or elastic pressures to be overcome during a 10-ml inflation, P_AO-Thr would be zero when the lowest P_Pl to be found in the chest at V_Rel was negative, and P_AO-Thr would be equal to the lowest P_Pl to be found in the chest at V_Rel when the lowest P_Pl was positive. Under these theoretical conditions, P_AO-Thr would be an upper bound of the lowest P_Pl to be found in the chest at V_Rel.

Fig. 1.

A: typical data from one experiment, illustrating the protocol (see text for explanation), showing airway pressure (P_AO), gastric pressure (P_Ga), and esophageal pressure (P_Es). Note the pressure rise when the balloon is withdrawn from stomach into the lower esophagus. B: third quasi-static inflation in A with expanded time scale and volume channel added. The gradual rise in P_AO above the threshold airway pressure (P_AO-Thr) causes lung inflation. P_AO-Thr is 7.3 cmH₂O in this example. (The threshold volume change of 10 ml is not visible at this scale.)

In reality, pulmonary resistance and lung elastance would raise the measured P_AO-Thr above atmospheric pressure even with all the intrapulmonary airways open and P_Pl subatmospheric everywhere in the chest at V_Rel. To estimate how much P_AO-Thr would be increased in such circumstances, we used a computational model to calculate the volume-time course of inflation, assuming that P_AO increased at a constant rate, alveolar pressure (P_Alv) = ΔV/C_RS, and inspiratory flow rate = (P_AO − P_Alv)/R_RS, where ΔV is the volume increment above V_Rel and R_RS is respiratory resistance. We assumed a relatively high rate of increase in P_AO = 4 cmH₂O/s, a high R_RS = 15 cmH₂O · l⁻¹ · s, and a low C_RS = 0.02 l/cmH₂O to conservatively estimate a high value of P_AO-Thr due to resistance and elastance, namely 1.3 cmH₂O (See Supplement, Fig S-1, available with the online version of this article). With these assumptions, P_AO-Thr would be <1.3 cmH₂O if most of the airways in the lung were open and P_Pl surrounding most of the lung at V_Rel was at atmospheric pressure or below. Conversely, P_AO-Thr would be >1.3 cmH₂O if most of the airways in the lung were closed (presumably due to positive pleural pressures at V_Rel) and/or if P_Pl surrounding most of the lung was above atmospheric pressure. Higher P_AO-Thr values, by inference, would indicate commensurately higher P_Pl surrounding most of the lung at V_Rel.

Protocol.

The protocol is illustrated in Fig. 1A. We measured P_Ga and P_Es during five or more tidal mechanical breaths. Then we disconnected the subject from the ventilator for 10–15 s to allow deflation to V_Rel, connected an Ambu bag to the endotracheal tube, and squeezed it to increase P_AO gradually at 1- 3 cmH₂O/s (mean = 1.5 cmH₂O/s) until the bag was nearly empty. The deflation to V_Rel and subsequent quasi-static inflation for determination of P_AO-Thr were repeated three times with at least one intervening minute of mechanical ventilation (Fig. 1A).

Analysis.

We measured P_AO and P_Es and P_Ga at end expiration (P_Es-EE, P_Ga-EE) and at end inspiration (P_Es-EI, P_Ga-EI) averaged over five consecutive tidal breaths. We also measured the P_Es at V_Rel (P_Es-Rel). Dynamic compliance of the respiratory system (C_RS) was defined as average tidal volume change (ΔV_L, found by integration of flow) divided by the average difference in P_AO from end inspiration to end expiration at instants of zero flow: C_RS = ΔV_L/ΔP_AO. Similarly, the dynamic compliance of the lung (C_L) was defined as C_L= ΔV_L/ΔP_L, where P_L = transpulmonary pressure = P_AO − P_Es, and dynamic compliance of the chest wall (C_CW) as C_CW = ΔV_L/ΔP_Es.

To explore the mechanism of obesity-related restriction, we compared the elastance of the respiratory system (E_RS = 1/C_RS) with its additive components, lung and chest wall elastance (E_L = 1/C_L and E_CW = 1/C_CW; E_RS = E_L + E_CW).

Statistics.

We used linear regression with correlation analysis to test the associations between P_AO-Thr, P_Es-Rel, BMI, and P_Ga, and Student's t-test to compare the compliance and elastance values between obese and control groups. Statistical significance was assumed for P < 0.05. Results are reported as means ± SD.

RESULTS

P_AO-Thr ranged from 0.6 to 14.0 cmH₂O (3.1 ± 3.0 cmH₂O) in the obese group and from 0.2 to 0.9 cmH₂O (0.4 ± 0.2 cmH₂O) in the control group (P < 0.0001). In most of our obese subjects (22 female and 15 male), P_AO-Thr was above 1.3 cmH₂O indicating that most of the airways were closed and/or P_Pl surrounding most of the lung was above atmospheric pressure at V_Rel. By contrast, all control subjects had P_AO-Thr below 1.3 cmH₂O, indicating that most of the airways were open and P_Pl was subatmospheric surrounding most of the lung at V_Rel.

P_Es-Rel ranged from 3.0 to 25.7 cmH₂O (12.5 ± 3.9 cmH₂O) in the severely obese group and from 0.7 to 12.2 cmH₂O (6.9 ± 3.1 cmH₂O) in the control group (P < 0.0001). In all subjects, there was a significant correlation between P_Es-Rel and P_AO-Thr (R² = 0.16, P = 0.0015, Fig. 2) and a weak correlation in the obese group analyzed separately (R² = 0.086, P = 0.0363).

Fig. 2.

P_Es at relaxation volume (P_Es-Rel) plotted against P_AO-Thr, with line of regression (R² = 0.16, P = 0.0015).

In the 30 obese subjects in whom it was possible to pass the balloon into the stomach, P_Ga-EE ranged from 6.7 to 17.0 cmH₂O (11.5 ± 2.8 cmH₂O). P_Ga and P_Es were well correlated in all subjects at end expiration and end inspiration (R² = 0.44, P < 0.0001 and R² = 0.39, P < 0.0001 respectively, Fig. 3) and in the obese group analyzed separately (R² = 0.17, P = 0.0225 and R² = 0.13, P = 0.0470).

Fig. 3.

P_Ga at end expiration and end inspiration plotted against the corresponding P_Es, with regression lines showing correlations (R² = 0.44, P < 0.0001, and R² = 0.39, P < 0.0001, respectively). The majority of subjects have above-normal intra-abdominal pressure (IAP) (P_Ga at end expiration ≥ 10 cmH₂O).

C_RS in the severely obese group was lower than in the controls (P < 0.0001, Table 1). C_CW in the obese group was not statistically different from values in the control group (Table 1), whereas C_L was substantially lower in obese than in controls (P = 0.0016, Table 1). Respiratory system elastance (E_RS), which is the sum of E_L and E_CW, was strongly correlated with E_L in all subjects (R² = 0.91, P < 0.0001, Fig. 4) and in the obese group (R² = 0.90, P < 0.0001), whereas E_RS was not significantly correlated with E_CW. In all subjects, neither P_Es-Rel nor P_Ga-EE was correlated with E_CW. However, both P_Es-Rel and P_Ga-EE were positively correlated with both E_L and E_RS (R² ≥ 0.17, P ≤ 0.0092).

Table 1.

Range and mean values of C_RS, C_CW, and C_L in severely obese and control subjects

	CRS, l/cmH2O	CCW, l/cmH2O	CL, l/cmH2O
Control group (BMI < 30 kg/m2)	0.041–0.063 (0.053 ± 0.007)	0.086–0.539 (0.223 ± 0.132)	0.044–0.142 (0.0.084 ± 0.029)
Severely obese group	0.017–0.054 (0.032 ± 0.008)	0.072–0.554 (0.195 ± 0.109)	0.018–0.090 (0.043 ± 0.016)
P value (unpaired t-test)	P < 0.00001	P = 0.5284	P < 0.0016

Values are ranges (means ± SD). C_RS, respiratory system compliance; C_CW, chest wall compliance; C_L, lung compliance; BMI, body mass index.

Fig. 4.

Dynamic respiratory system elastance (E_RS) plotted against dynamic lung elastance (E_L). E_RS was principally determined by E_L in our severely obese subjects (P < 0.0001).

In all subjects, BMI was positively correlated with E_RS (R² = 0.23, P < 0.0001) and E_L (R² = 0.20, P < 0.0003) but not with E_CW. In the obese subjects, neither P_AO-Thr (Fig. 5) nor P_Es-Rel was correlated with BMI. When the BMI range was expanded to include the controls, a weak correlation was found for P_AO-Thr (R² = 0.068, P = 0.0425) and a stronger correlation for P_Es-Rel (R² = 0.26, P < 0.0001).

Fig. 5.

P_AO-Thr plotted against body mass index (BMI). P_AO-Thr was not correlated with BMI in our obese subjects (R² = 0.0002) but was weakly correlated when the control group was included in the regression (R² = 0.068). (There are superimposed symbols in the control group.)

To explore the mechanism leading to high P_AO-Thr, we analyzed data obtained during inflation of the lung with the Ambu bag. We reasoned that in subjects with low P_AO-Thr, the inflation would begin with open airways, and the quasi-static inflation P_AO-V_L curve would be relatively linear, whereas in those obese subjects with high P_AO-Thr, inflation would begin with many airways closed, and the quasi-static inflation P_AO-V_L curve would exhibit the effects of recruitment after prior airway closure. Comparing the quasi-static inflation P_AO-V_L curves from the obese subjects with the five highest and five lowest P_AO-Thr values, we found that in the lowest P_AO-Thr group (Fig. 6A), the inflation P_AO-V_L curves appear almost linear above V_Rel, consistent with open airways in a lung at a positive transpulmonary pressure (P_AO − P_Pl) at end exhalation. By contrast, in the highest P_AO-Thr group (Fig. 6B), the pressure rises before inflation begins, and the curves have a downward convexity or “knee” characteristic of air space recruitment, beyond which volume increases in a nearly linear fashion.

Fig. 6.

Quasi-static inflation P_AO-lung volume (V_L) curves of the lungs in morbidly obese subjects with the 5 lowest (A) and 5 highest (B) P_AO-Thr. Curves of the subjects with the highest P_AO-Thr exhibited a downward convexity (“knee”) early in inflation. FRC, functional residual capacity.

DISCUSSION

The major finding of this study is that pleural pressure in obese subjects at V_Rel, whether estimated using P_Es or inferred from airway pressure and flow measurements, is greater than normal, often substantially above atmospheric pressure. This is the first report of resting values of P_Es in anesthetized, paralyzed obese subjects. Steier et al. (18) reported elevated baseline P_Es in conscious obese subjects, but most previous studies of P_Es in supine subjects have ignored the resting “baseline” values of P_Es, reporting only changes in P_Es.

This is also the first study to estimate P_Pl in obese subjects by a method independent of P_Es. The correlation between P_Es-Rel and P_AO-Thr suggests that both measurements can be used to estimate the likelihood of high effective P_Pl in obese supine subjects. However, although P_Es and P_AO-Thr are correlated, they differ substantially and variably. What could explain this difference? First, P_Es is thought to be higher than P_Pl in the supine posture (7, 25). The esophagus is roughly midway between the ventral and dorsal boundaries of the thoracic cavity, and in the supine posture, there is a hydrostatic increase in pressure within the mediastinum due to the weight of the heart and mediastinal tissues above. Therefore, P_Es is probably higher than P_Pl surrounding the lung at the same height in thorax, a discrepancy estimated to be ∼5 cmH₂O (25). Second, the hydrostatic pressure gradient in the pleural space could cause P_AO-Thr (i.e., the lowest pleural pressure surrounding a large part of the lung) to be lower than P_Pl at mid-lung height. Even when P_Pl at mid-lung height is positive (presumably causing airway closure and positive pressures in the dependent alveoli), P_Pl may be negative in nondependent lung regions, where open airways and atmospheric alveolar pressures at V_Rel enable P_AO-Thr values to be low. Third, when widespread positive P_Pl at V_Rel causes closure of most of the small airways, P_AO-Thr will be higher than P_Pl by the opening pressure required to open small airways closed by a meniscus (2). The opening pressure of healthy human airways is unknown, but opening pressure has been estimated to be in the range of 3 cmH₂O in excised rat lungs (2), and it may not be much higher in healthy lungs that have not developed widespread atelectasis. In this study, when P_AO-Thr is >1.3 cmH₂O, P_AO-Thr is an estimate of the minimum pleural pressure surrounding a substantial portion of the lung at V_Rel plus any opening pressure. In summary, P_AO-Thr and P_Es-Rel are correlated, although hydrostatic pressure gradients in the mediastinum and pleural space and the opening pressure of the collapsed airways weaken the correlation.

The second major finding is that, compared with control subjects, our severely obese subjects are characterized by lower C_RS and C_L, whereas C_CW is usually normal. This finding differs from those of Naimark and Cherniak (11) and Sharp et al. (16), who measured compliance while subjects breathed spontaneously or relaxed respiratory muscles voluntarily. Both studies had reported normal C_L with low C_CW in obesity. However, more recent studies during muscle paralysis (5) or with confirmed diaphragm relaxation (20) reported normal C_CW in obesity, suggesting that differences in C_CW were due to the experimental method. Van Lith et al. (23) investigated this possibility by comparing elastance in six healthy obese subjects both during voluntary muscle relaxation and during anesthesia with paralysis. They found higher E_RS and E_CW during voluntary relaxation than during paralysis, suggesting that incomplete relaxation in early studies could have contributed to lower C_CW in the obese (23). By exception, Pelosi et al.(13) found both C_CW and C_L to be significantly lower in anesthetized, paralyzed, morbidly obese subjects studied after major abdominal surgery.

It is possible that ventilation with 100% oxygen in our study could have contributed to development of atelectasis that reduced C_L in the obese group (4). C_L was not reduced in the control group, suggesting high P_Pl and consequent small airway closure would be required for the formation of atelectasis in obese subjects. Furthermore, the short duration of ventilation on 100% oxygen (∼10 min) argues against the primary role of atelectasis in reducing C_L in the obese.

Another possibility is that C_L is lower in obese subjects because the positional artifact that increases P_Es in supine subjects is volume dependent (7). The importance of this artifact is said to decrease during inflation because upward movement of the ventral thorax lifts the heart and mediastinal contents, which no longer rest as heavily on the esophagus and balloon (7). However, the artifactual reduction in P_Es during inflation would cause the apparent elastance of the lung to increase and that of the chest wall to decrease by the same amount, so the sum of these elastances, which is E_RS, would not be altered. Therefore, the strong correlation of respiratory system elastance, which is independent of P_Es, with lung elastance (R² = 0.8962) argues against this explanation and suggests that the increase in E_RS is caused by a real increase in E_L. In addition, the above artifact could cause a downward concavity of the P_Es-V_L curve as the positive pressure artifact in P_Es decreased during inflation (see rationale and depiction in Ref. 7). We examined the quasi-static inflation curves of chest wall (P_Es-V_L curves) in those subjects pictured in Fig. 6B and found no hint of the decreasing compliance that might be predicted by this mechanism (7).

The fact that C_Cw is normal in obese subjects is consistent with “mass loading” of the chest wall rather than “stiffening of the chest” by elastic loading, as demonstrated experimentally by Sharp et al. (15).

Model of P-V curves in obesity.

Another mechanism whereby high P_Pl could cause low compliance of the lung and respiratory system is shown schematically in Fig. 7. In Fig. 7A, pressure-volume (P-V) curves are drawn for a normal lung and chest wall, and the respiratory system P-V curve was constructed by adding the pressures across lung and chest wall. FRC (taken as equal to V_Rel) is the volume at which lung and chest wall recoil pressures are equal and opposite. In this depiction, the normal lung is shown as having a region of low compliance and stiffening at low volumes where airway closure occurs at negative transpulmonary pressures. This region of the inflation P-V curve of normal lungs is seldom observed in vivo, because normally transpulmonary pressures are not statically negative, especially in upright subjects (14). However, this behavior is observed routinely in experimental preparations, for example when excised lungs are exposed to sustained negative P_AO (24). Stiffening of the lungs at very low volumes has also been demonstrated in healthy breath-hold divers after they empty their lungs below residual volume by employing glossopharyngeal exsufflation (8).

Fig. 7.

Hypothetical pressure-volume curves in normal (A) and obese (B) subjects, showing effects of increased pleural pressure (P_Pl) on lung behavior above FRC. In the normal respiratory system (RS; A), FRC is above closing volume, and the P_AO-V_L curve is relatively linear. In some obese subjects (B), the high P_Pl lowers FRC to closing volume. The normal lung appears noncompliant, and the inflation P_AO-V_L curve has a “knee.”

Figure 7B illustrates the possible effects of an increase in extrapulmonary volume, for example fat, within the chest wall or “mass loading” (15). The chest wall P-V curve as drawn exhibits higher pressures at any lung volume without being stiffer (i.e., without a decrease in slope), consistent with our observations of normal C_CW and high P_Es in many obese subjects. The volumes of intra-abdominal and mediastinal fat increase in obesity (9), which could cause the chest wall to contain more volume and the lung to be smaller than normal at V_Rel, making the pleural pressure more positive. Since the normal chest wall curve stiffens at low volumes, largely due to developing tension in the diaphragm (17), the chest wall curve becomes more compliant as chest wall volume increases. Thus increasing the volume of fat within the chest wall could actually increase its compliance over much of the vital capacity.

In the resulting respiratory system P-V curve in Fig. 7B, FRC has decreased to a lung volume near the former RV, where the lung's P-V curve is stiffened by small airway closure, a phenomenon that causes the respiratory P-V curve to exhibit a downward convexity (24) similar to that observed by Pelosi et al. (13) in anesthetized obese subjects.

This theoretical analysis is consistent with the quasi-static inflation P_AO-V_L curves of the obese subjects with the five highest and five lowest P_AO-Thr values (Fig. 6). In the lowest P_AO-Thr group, the inflation P_AO-V_L curves were nearly linear above V_Rel, consistent with most of the airways being open and P_Pl surrounding most of the lung being at or below atmospheric pressure (Fig. 6A). Increasing airway pressure caused inflation. By contrast, in the group with highest P_AO-Thr, the P_AO-V_L curves have a “knee” or region of downward convexity above V_Rel, consistent with pleural pressure surrounding most of the lung being above atmospheric pressure, causing closure of most small airways at V_Rel. As P_AO increased, initially there was little inflation until the airways opened and positive pleural pressure was exceeded, enabling progressive recruitment of lung regions until the P_AO-V_L curve followed a linear trajectory similar to those in the low P_AO-Thr group.

During spontaneous breathing, positive end-expiratory alveolar pressure, known as intrinsic PEEP (PEEP_i), is greater in obese subjects and is increased by the supine posture (12). PEEP_i constitutes a threshold load for inspiration, increasing the work of breathing and increasing the dynamic elastance of the lung during tidal ventilation. Our findings that dynamic E_L and E_RS were positively correlated with P_Es-Rel and P_Ga-EE suggest that high pleural pressures in the obese reduce the FRC, lowering expiratory flow rates, increasing PEEP_i, and reducing the measured dynamic lung compliance.

As expected, P_Ga was elevated in most of our obese subjects. Assuming the equivalence of P_Ga and bladder pressure in assessing intra-abdominal pressure (IAP) (1), and using reference values of the World Congress on Abdominal Compartment Syndrome (10), we found 23 of 30 obese subjects (76%) had IAP greater than normal (P_Ga ≥ 10 cmH₂O), and three of them (all female) had IAP in the range of abdominal hypertension (P_Ga ≥ 16.3 cmH₂O).

P_Ga and P_Es were correlated at end expiration and end inspiration in all subjects (Fig. 3) and in the obese group, as was reported in ventilated patients by Talmor et al. (21). However, the correlation is not very strong for several reasons. The distal esophagus is lower than the gastric fundus in supine subjects, causing a gravitational pressure gradient that raises P_Es relative to P_Ga to differing degrees among subjects. In addition, there may be passive tension in the diaphragm in some subjects reducing P_Es relative to P_Ga. Finally, the aforementioned effects of the mediastinal contents pressing on the esophagus contribute variability and weaken the correlation between P_Es and P_Ga.

In obese and control subjects combined, there was a weak correlation of P_AO-Thr with BMI and a stronger correlation of P_Es with BMI. However, contrary to expectation, we found no correlation between BMI and P_AO-Thr (Fig. 5) or P_Es in our severely obese subjects, suggesting that obesity, per se, is not predictive of high pleural pressure. The question whether the pattern of obesity (abdominal vs. peripheral) might affect the elevation of P_Pl was tested in the final 13 obese subjects in whom we measured waist circumference (WC) and sagittal abdominal diameter (SAD), the anthropometric correlates of intra-abdominal fat volume and the intra-abdominal pressure (19, 22). Neither WC nor SAD was correlated with P_AO-Thr or P_Es-Rel in this cohort, nor was there any sex-based difference in the levels of P_AO-Thr and/or P_Es-Rel in obese subjects.

In conclusion many morbidly obese supine subjects appear to have high, often positive pleural pressure surrounding most of the lung while relaxed at V_Rel. High pleural pressure would cause tidal breathing to be initiated from low end-expiratory volumes where the lungs are less compliant and airways are prone to close on exhalation. This finding is variable and not predictable from BMI, WC, or SAD. High esophageal pressure is a useful, if imperfect, indicator of the likelihood of high pleural pressure in these subjects.

GRANTS

This work was supported by grant HL-52586 from the National Institutes of Health.

DISCLOSURES

None of the authors has any financial interest that could be affected by the subject of this report. No conflicts of interest are declared by the authors.