Measurement of the work of ventilation during passive inflation was obtained using a previously described and validated method , as briefly summarized below.
The mechanical work performed by the ventilator to inflate the respiratory system (Wtot,rs), excluding the endotracheal tube, was computed integrating the area of PaO2 (corrected for the resistive components of the endotracheal tube) during inspiration over the inflation volume. The mechanical work performed by the ventilator to inflate the chest wall (Wtot,w) was computed, integrating the area subtended by Pes and volume. Subtracting Wtot,w from the corresponding work of the total respiratory system, we obtained the total work of the lung (Wtot,L).
Values are expressed as mean +/- SD. The mean value of three breaths was used for each variable and for each experimental condition. To perform different fittings, we used GraphPad Prism[trade mark sign] version 2.0 software (GraphPad Software, Inc, San Diego, CA). Different equations were used: linear regression, hyperbola, one-phase exponential decay, one-phase exponential association. Analysis between groups was performed by using analysis of variance.
The general characteristics of the patients are presented in Table 1. Patients in all three groups were comparable in gender distribution, age, and height (P = not significant) and significantly differed in weight (P < 0.01) and BMI (P < 0.01). The average tidal volume and inspiratory flow were 0.619 +/- 0.062 L and 0.470 +/- 0.090 L/s, 0.702 +/- 0.100 L and 0.490 +/- 0.070 L/s, and 0.681 +/- 0.069 L and 0.470 +/- 0.090 L/s for normal patients, moderately obese patients, and morbidly obese patients, respectively.
The FRC decreased with BMI (Figure 1). There was a major decrease in FRC with a moderate increase in body mass (FRC = 11.97 x exp[-0.096 x BMI] + 0.46; r = 0.86; P < 0.01).
As shown in Figure 2, respiratory compliance decreased with BMI, and decreases were evident with small increases in body mass (Cst,rs = 233.3 x exp[-0.086 x BMI] + 40; r = 0.86; P < 0.01). The reduction in respiratory compliance with BMI was caused by a reduction in both lung compliance (Cst,L = 7198 x exp[-0.230 x BMI] + 71.5; r = 0.81; P < 0.01) and chest wall compliance (Cst,w = 257.7 -2.078 x Cst,w; r= 0.45; P < 0.05).
As shown in Figure 3, total respiratory resistance markedly increased with BMI (Rmax,rs = 2.55 x exp[0.03 x BMI]; r = 0.81, P < 0.01), and this increase was caused mainly by an increase in the resistance of the lung (Rmax,L = 1.78 x exp[0.03 x BMI]; r = 0.84, P < 0.01). Chest wall resistance was not significantly correlated with BMI (r = 0.06). The increase in the resistance of the lung with BMI was caused mainly by the increase in airway resistance (Rmin,L = -3.6 + 0.23 x BMI; r = 0.84) because the relationships of both DR,rs and DR,L with BMI were extremely weak (r = 0.44; P < 0.05 and r = 0.46; P < 0.05, respectively).
As shown in Figure 4, oxygenation (PaO2/PAO2) exponentially decreased with increasing BMI (PaO2/PAO2 = 1.23 x exp[-0.037 x BMI] + 0.196; r = 0.81; P < 0.01). Consequently, D(A-a)O2 was linearly correlated with BMI (D[A-a]O2 = -7.15 + 3.37 x BMI; r = 0.84; P < 0.01). PaCO2 was not significantly related to BMI (r = 0.06).
As shown in Figure 5, the work of breathing performed by the ventilator on the respiratory system linearly increased with increasing BMI (Wtot,rs = 0.10 + 0.02 x BMI; r = 0.88; P < 0.01), and it was related both to the lung component (Wtot,L = 0.23 x exp[0.026 x BMI]; r = 0.81; P < 0.01) and to the chest wall component (Wtot,w = 0.58 x BMI/[51.0 + BMI]; r = 0.47; P < 0.01).
During general anesthesia with patients in the supine position, 1) body mass is an important determinant of lung volumes, oxygenation and respiratory mechanics, mainly affecting the lung component; 2) alterations in respiratory mechanics are present not only in patients with severe obesity, but also in patients with moderate obesity; 3) the work of breathing increases with body mass and was quite near or even greater than the commonly reported limits of muscle fatigue in most of the overweight patients .
We found a linear relationship between the increase in BMI and the reduction in FRC. The FRC is reduced in recumbent adult humans after the induction of anesthesia, and the magnitude of its reduction-with consequent atelectasis formation-has been related to age, weight, and height . However, the mechanisms of FRC reduction and atelectasis formation during anesthesia are not completely understood.
The formation of atelectasis has been ascribed to a decreased distribution of ventilation in the dependent lung zones during anesthesia and mechanical ventilation. The loss of the diaphragmatic tone induced by anesthetics makes the movement of the diaphragm passively dependent on the relative pressures present at its thoracic and abdominal slices . Because there is a gravitational pressure gradient in the abdomen due to the presence of abdominal viscera, the distribution of ventilation is preferentially directed toward the nondependent lung regions. With increasing BMI, an increase in abdominal mass and intraabdominal pressure is expected . Consequently, the gravitational intraabdominal pressure gradient is likely increased, with an increased load particularly on the most dependent lung regions and a consequent, and more important, cephalad displacement and reduction in the passive movements of the dependent part of the diaphragm. This preferential alteration of the diaphragm likely favors the development of more atelectasis in the dependent lung regions [17,18]. However, studies performed in normal subjects using a three-dimensional fast computed tomography scan questioned the role of the diaphragm alone in determining atelectasis formation and reducing FRC [4,5]. It is likely that the interaction of several potentially significant factors, such as the thoracic spine, rib cage, and diaphragm, leads to a reduction in FRC and atelectasis formation.
We found that the reduction in respiratory compliance with increasing BMI was caused mainly by the lung component, with chest wall compliance only weakly dependent on the BMI. Similar results were obtained by Hedenstierna and Santesson  and Van Lith et al. , who found approximately normal values of chest wall compliance in anesthetized and paralyzed obese subjects. The most likely cause of the reduction in lung compliance with BMI is simply the reduction in FRC, with the intrinsic mechanical characteristics of the lung being approximately normal.
From our data, it is quite clear that chest wall compliance is only weakly influenced by the increase in BMI. Several factors may, however, explain the slight influence of BMI on chest wall compliance: the presence of the pressure-volume curve of the chest wall on a flatter section of the elastic recoil of the chest wall, due to a greater reduction in the total thoracic volume in overweight patients; or the presence of a progressively increased mass added to the chest wall and/or abdomen in patients with an increased BMI. Both of these factors explain the reduction in chest wall compliance in obese subjects .
We found that respiratory system resistance increased with increasing BMI, mainly because of an increase in lung resistance, whereas chest wall resistance seemed unaffected. The increase in lung resistance was caused mainly by the airway resistance component, whereas the viscoelastic component was only weakly dependent on BMI.
Using body plethysmography, Zerah et al.  found airway resistance values comparable to ours in awake seated patients with different severity of obesity. Moreover, they also observed that airway resistance was approximately twice as high in patients with severe obesity compared with those with minimal obesity. One hypothesis to explain the increase in airway resistance with BMI is that the large decrease in FRC and/or an intrinsic narrowing of the airways in obesity are responsible for these abnormalities. Indeed, Briscoe and Dubois  showed that airway conductance, i.e., the reciprocal of airway resistance, was linearly related to lung volume, in normal awake subjects. We found that DR,rs and DR,L were only weakly associated with BMI. This is in line with the results of Zerah et al. , who found that the difference between the resistance of the total respiratory system and airway resistance (equivalent to DR,rs in our study) was little affected by increasing BMI.
We found that oxygenation, expressed as PaO2/PAO2 ratio, decreased with increasing BMI. The major cause of this decrease is likely related to the reduction in FRC. Moderate to severe hypoxemia has been reported in supine obese subjects during both spontaneous breathing and anesthesia and paralysis [8,17,13]. Moreover ventilation-perfusion mismatch has been reported even in awake, seated, obese subjects . The lung bases are well perfused, but they are underventilated because of airway closure and alveolar collapse. This effect is likely more pronounced and enhanced in obese subjects in the supine position during anesthesia and paralysis.
In contrast, PCO2 was not correlated to BMI, as previously reported in awake and anesthetized obese subjects without obesity hypoventilation syndrome .
We found that the work of breathing of the total respiratory system increased with BMI. The increase was due to both the lung and chest wall components, but the former was more significant.
Measurements of the work performed by the ventilator during passive inflation may be an index of the actual work performed by the respiratory muscles during spontaneous breathing . Our results are in line with those of Suratt et al. , who hypothesized a predominant effect of the lung, not the chest wall, in determining the work of breathing in awake, obese, upright subjects. On the contrary, other authors found a prevalent increase in the respiratory work of breathing due to the chest wall component , and others did not find any increase in the work of breathing with increasing BMI . However, in these latter studies, no attempt was made to assure complete relaxation of the respiratory muscles. Thus, the role of the chest wall in determining the work of breathing may have been overestimated.
In conclusion, we found that the BMI is an important determinant of lung volumes, respiratory mechanics, and oxygenation in anesthetized patients in the supine position.
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