Free
Education  |   September 2002
Can the Tomographic Aspect Characteristics of Patients Presenting with Acute Respiratory Distress Syndrome Predict Improvement in Oxygenation-related Response to the Prone Position?
Author Affiliations & Notes
  • Laurent Papazian, M.D., Ph.D.
    *
  • Marie-Héléne Paladini, M.D.
  • Fabienne Bregeon, M.D.
  • Xavier Thirion, M.D., Ph.D.
    §
  • Olivier Durieux, M.D.
  • Marc Gainnier, M.D.
    *
  • Laetitia Huiart, M.D.
    §
  • Serge Agostini, M.D.
  • Jean-Pierre Auffray, M.D.
  • * Professor, Service de Réanimation Médicale, † Staff Intensivist, Service de Réanimation Polyvalente, § Professor, Service d'Information Médicale, ∥ Professor, Service de Radiologie, Hôpitaux Sud, Marseille, France. ‡ Staff Intensivist, Laboratoire de Physiopathologie Respiratoire, UPRES EA 2201, Faculté de Médecine de Marseille, France.
  • Received from the Polyvalent Intensive Care Unit, Hôpital Sainte-Marguerite, Marseille, France.
Article Information
Education
Education   |   September 2002
Can the Tomographic Aspect Characteristics of Patients Presenting with Acute Respiratory Distress Syndrome Predict Improvement in Oxygenation-related Response to the Prone Position?
Anesthesiology 9 2002, Vol.97, 599-607. doi:
Anesthesiology 9 2002, Vol.97, 599-607. doi:
ACUTE respiratory distress syndrome (ARDS) has diverse causes and carries high morbidity and mortality rates. 1 It is characterized by profound hypoxemia, pulmonary hypertension, and poor lung compliance. In the absence of definitive therapy, management involves supportive care using mechanical ventilation with increased inspired oxygen concentration and positive end-expiratory pressure (PEEP). Prone positioning is one of the therapeutic strategies that has been recently proposed for ARDS patients, although the beneficial effects of prone positioning on arterial oxygenation were already described by Bryan 2 more than 20 yr ago. Other investigators have confirmed these findings. 3–9 Prone positioning is now more commonly used to improve oxygenation in ARDS patients.
Computed tomographic (CT) appearances of ARDS are variable. CT typically shows symmetric ground-glass opacification with gravity-dependent opacities when the patient is in the supine position. However, the literature contains many contradictory descriptions that range from ground-glass opacification to consolidation, from focal to generalized disease, and from homogeneous to patchy opacities. 10–17 These parenchymal opacities predominating in the dependent portions of the lung are thought to result from the collapse of the lowermost alveoli under the weight of the uppermost edematous lung, 6 the heart, 13 as well as pressure exerted by the abdominal contents. 7 It could therefore be hypothesized that the more opacities that are present in dependent regions of the lung when the patient is in the supine position, the better the improvement in oxygenation observed when the patients are turned prone.
The mechanisms by which the prone position induces an increase in arterial oxygen partial pressure (Pao2) are still controversial. Lamm et al.  18 showed that the prone position markedly improved dorsal lung ventilation and, accordingly, also improved dorsal lung ventilation-perfusion relations, with minimal if any compromise of ventral lung ventilation or ventral ventilation-perfusion relations. Therefore, as suggested by Albert and Hubmayr, 19 reversible airspace closure occurs in dorsal lung regions when patients with ARDS are supine, while turning them prone sufficiently alters dorsal lung transpulmonary pressures to reverse this closure without shifting the air-space closure to the ventral regions. A number of factors could contribute to this differential ability of the prone position to modify dorsal lung transpulmonary pressures. One of these factors is the direct transmission of the weight of the heart to the regions of the lung located beneath it. 19–22 Albert and Hubmayr, 19 studying CT scans of seven spontaneously ventilated patients, found that there was a dramatic decrease of the percent of both lungs located under the heart when the patients were turned prone. Moreover, Malbouisson et al.  13 showed, using a CT method, that the heart plays an important role in the loss of aeration of lung lobes in ARDS patients lying in the supine position.
Finally, in some ARDS patients, the prone position improves oxygenation, whereas in others it does not. The main objective of the current study was therefore to identify CT scan characteristics in the supine position that could accurately predict who will respond and who will not respond to prone positioning. A secondary objective was to evaluate characteristics of the lung regions that could be subjected to the weight of the heart in ARDS patients lying in the supine position. Our hypothesis was that the more dependent opacities present with the patient in the supine position, the better improvement in oxygenation will be related to the prone position.
Materials and Methods
Study Population
During a 2-yr period (from August 1998 to July 2000), 748 patients were admitted in the medical and surgical intensive care unit (15 beds) of Sainte-Marguerite University Hospital in Marseille, France. During this period, 95 patients met the American-European Consensus Conference criteria for ARDS. 23 The protocol was approved by the institutional review board (Comité Consultatif de Protection des Personnes dans la Recherche Biomédicale, Marseille, France). Correction of hypoxemia related to ARDS was based on the first-line use of inhaled nitric oxide or almitrine bismesylate before initiating prone positioning. The prone position was used in 71 patients when Pao2/fraction of inspired oxygen (Fio2) dur-ing nitric oxide (1–20 ppm) or almitrine bismesylate (2–16 μg · kg−1· min−1) was lower than 200 mmHg. CT scan was performed in 46 of the 71 potentially eligible patients. Therefore, 25 patients were not included in the current study. These 25 patients presented the following characteristics: age 50 ± 17 yr; SAPS II on admission: 39 ± 17; Logistic Organ Dysfunction System score: 5.5 ± 3.4; Lung Injury Score 24 : 3.3 ± 0.5; ARDS of pulmonary causes: 88%. Seven of these 25 patients were included in other studies. We excluded the remaining 18 patients because they had concurrent cerebral edema (n = 10), imminent death (n = 5), or major medical contraindications to being transported (n = 2). The remaining 46 patients (36 males, 10 females; age 50 ± 16 yr; SAPS II on admission: 39 ± 12) were prospectively investigated after written informed consent was obtained from each patient's next of kin. ARDS was related to pulmonary causes in 74% of the cases (pneumonia, n = 15; lung contusion, n = 12; aspiration, n = 6; miscellaneous, n = 1), and to extrapulmonary causes in 26% of the cases. On the day of ARDS diagnosis, Lung Injury Score was 3.1 ± 0.4, whereas Logistic Organ Dysfunction System was 4.8 ± 2.4. Prone positioning was initiated 3.1 ± 2.1 days after the beginning of ARDS. On inclusion into the study, respiratory parameters were as follows: tidal volume, 8.1 ± 1.9 ml/kg; Fio2, 0.78 ± 0.18; respiratory rate, 21.5 ± 4.5 breaths/min; and PEEP, 10.7 ± 2.3 cm H2O. The selection of appropriate PEEP level was performed by increasing PEEP in steps of 2 cm H2O. A blood gas analysis was performed after a 30-min period of stabilization of oxygen saturation. Finally, the lowest level of PEEP giving the greatest improvement of oxygenation was chosen. When no improvement was found while increasing PEEP, the level was set at 8 cm H2O. A recruitment maneuver was never performed. All patients were tracheostomized, sedated, and paralyzed with a continuous infusion of sufentanil, midazolam, and vecuronium bromide, and the lungs were ventilated using conventional volume-controlled mechanical ventilation (Puritan Bennett 7200 series; Mallinckrodt, Carlsbad, CA).
The Prone Position
All patients were positioned on special mattresses using a dynamic flotation system incorporating a sensor pad (Nimbus Prone Nursing®; Huntleigh Healthcare, Luton, United Kingdom). Change of position was manually performed by 3 nurses and 2 staff members. With the patient in the prone position, the arms were laid parallel to the body. Pillows were not used in order to increase abdomen kinetics. Care was taken to avoid eye damage or any nonphysiologic movements of the limbs during posture changes.
Instrumentation and Measurements
Blood Gas Analyses.
Arterial p  H, Pao2, and arterial carbon dioxide partial pressure were measured using a blood gas analyzer (278-blood gas system; Ciba Corning, Medfield, MA).
Respiratory Parameters.
The following respiratory parameters were recorded: exhaled tidal volume, peak inspiratory pressure, and respiratory rate were evaluated using a pneumotachograph (Spiro +; Saime, Savigny-le-Temple, France) and were recorded on a data acquisition and analysis system (Spiroscope 2.01; Saime).
Computed Tomographic Scanning.
Images were obtained by a Siemens Somaris tomograph (Siemens, Munich, Germany), with exposures taken at 120 kV and 250 mAs. An intravenous injection of 80 ml contrast medium was used to differentiate pleural effusions from nonaerated lung parenchyma. CT scans were obtained at a constant PEEP level during apnea. High-definition 1-mm-thick sections obtained at intervals of 10 mm and selected by means of a thoracic scout view were performed.
Computed Tomography Evaluation.
All indices were evaluated jointly by two radiologists (O. D. and S. G.) independent of the intensive care unit and while unaware of the clinical condition of the patients. As previously proposed, 25 the scans were evaluated at three representative levels: the apex (top of the upper aortic arch), the hilum (first section below the carina), and the base (2 cm above the highest diaphragm). Each transverse scan was divided into three sections: an anterior third (sternal), posterior third (vertebral), and middle third (central). The left and right lungs were analyzed individually. The final analysis consisted of 18 anatomic locations: three transverse levels (apex, hilum, and base), each of which was analyzed at three positions (sternal, central, and vertebral) in the left and right lungs. According to the Fleischner Society Nomenclature Committee, 26 CT attenuations were classified in CT consolidations (markedly increased attenuation, no visible vessels) and ground-glass opacifications (mild increased attenuation, visible vessels). At each of the 18 locations, the lung was scored as follows: normal lung (NL), ground-glass opacification (GG), and consolidation. For each location, a 0 was assigned when the morphologic features were essentially absent, a 1 was assigned when the morphologic features occupied one third or less of the subsection, a 2 was assigned when the morphologic features occupied one or two thirds of the subsection, and a 3 was assigned when the morphologic features occupied more than two thirds of the subsection. The sum of the subsection had to equal three. Because the cross-sectional areas of the hilar and basilar regions of the lung are greater than the area of the apical region, correction factors of 1.7 and 1.8, respectively, were used. 27 These corrections were applied to calculate the total disease score for each morphologic category as follows: total GG = GG apex + 1.7 GG hilum + 1.8 GG base (range, 0–81); total consolidation = consolidation apex + 1.7 consolidation hilum + 1.8 consolidation base (range, 0–81); total NL = NL apex + 1.7 NL hilum + 1.8 NL base (range, 0–81); and total lung disease = total GG + total consolidation (range, 0–81).
To evaluate the possible effect of the heart on lung function, four sections were studied as proposed by Albert and Hubmayr. 19 Briefly, these sections must be approximately evenly spaced from the carina to the most cephalad portion of the diaphragm. The cardiac and pleural margins were traced on 10 × 10-mm/cm graph paper. Perpendicular lines were drawn from the right and left lateral cardiac margins to the posterior chest wall. In each section, the relative volume of lung parenchyma beneath the heart was determined by counting the number of square millimeter boxes located medial to these lines in each hemithorax and expressing this as a percentage of the total number of square millimeter boxes present in each hemithorax. The percentage of consolidated lung located under the heart relative to total lung area or relative to the lung area located under the heart was evaluated using the same methodology. To evaluate the incidence of the shape of the lung on the improvement of oxygenation related to the prone position, the lung area (evaluated on the section above the diaphragm) was divided into two compartments (at 50% of the ventral-dorsal distance), the upper and the lower compartments.
Procedure.
Computed tomographic scan was performed in the 6-h period preceding the first trial of prone positioning. Baseline measurements (blood gas analysis and respiratory parameters) were evaluated with the patient in the supine position just before turning the patients prone. Blood gas analyses and respiratory parameters were then measured at the end of the 6-h period of prone positioning. Therefore, arterial blood gases were analyzed within the 12 h following CT examination.
Definitions.
A response to prone positioning was defined by at least a 33% increase in the Pao2/Fio2ratio when compared with supine position.
Statistical Methods
Data are expressed as mean ± SD. Statistical calculations were performed using the SPSS 8.0 package (SPSS Inc., Chicago, IL). Statistically significant differences were analyzed using the Student t  test for continuous variables and the chi-square test for categorical variables. The Mann-Whitney rank sum test or the Kruskal-Wallis test was used when variables were unequal among the groups. Two-way analyses of variance (with the factors being responders vs.  nonresponders and spatial location) were performed to evaluate the degree of lung injury. When appropriate, a post hoc  analysis was performed using a pairwise multicomparison procedure (Tukey test). P  < 0.05 indicated significance.
Results
Effect of Prone Positioning on Oxygenation
Transport and performance of CT scanning were not associated with relevant adverse effects necessitating a modification of ventilatory parameters or vasoactive agent requirements. Moreover, we did not observe adverse renal effects. When all 46 patients were considered, the Pao2/Fio2ratio increased from 117 ± 42 while in the supine position to 200 ± 76 mmHg while in the prone position (P  < 0.001 by Student paired t  test). There were 31 responders and 15 nonresponders. In the 31 responders, the Pao2/Fio2ratio increased from 116 ± 44 mmHg while in the supine position to 228 ± 67 mmHg when they were turned prone. In the 15 nonresponders, Pao2/Fio2ratio increased from 120 ± 39 while in the supine position to 141 ± 57 mmHg when turned prone (nonsignificant). Only 2 of the 15 nonresponders had a decrease in Pao2/Fio2ratio when turned prone. The characteristics of responders and nonresponders are summarized in table 1.
Table 1. Characteristics of Responders and Nonresponders
Image not available
Table 1. Characteristics of Responders and Nonresponders
×
Total Lung Disease
The mean total lung disease scores in responders and in nonresponders were similar (47.4 ± 17.4 for responders vs.  51.8 ± 20.5 for nonresponders), meaning that in both groups, approximately 60% of the lung was abnormal (58.5% in responders; 64.0% in nonresponders).
Types of Parenchymal Abnormalities
In responders, ground-glass opacification was as extensive as consolidation (mean total GG, 23.9 ± 15.4; mean total consolidation, 23.4 ± 10.8). In nonresponders, ground-glass opacification was also as extensive as consolidation (mean total GG, 26.2 ± 17.2; mean total consolidation, 25.6 ± 8.3). When the type of opacification (GG or consolidation) was compared, there was no difference between responders and nonresponders.
Regional Distribution
A two-way analysis of variance showed that there was no difference between responders and nonresponders concerning ground-glass opacifications. However, there was an effect of the spatial location (P  = 0.004;fig. 1). No interaction was found between the two factors (responders vs.  nonresponders and spatial location). In responders, ground-glass opacification was equally distributed among an anterior-posterior axis, whereas in nonresponders there was a predominance of ground-glass opacification in the central (hilar) one third of the lung as compared with the vertebral third (fig. 1). Concerning the consolidations, a two-way analysis of variance showed that there was no difference between responders and nonresponders. However, as for ground-glass opacifications, there was an effect of spatial location (P  < 0.001;fig. 2). No interaction was found between the two factors (responders vs.  nonresponders and spatial location). Consolidation predominated in the vertebral one third of the lung in both responders and nonresponders to the prone position (fig. 2).
Fig. 1. Distribution of ground-glass opacification according to the anteroposterior level (mean ± SD). *P  < 0.05 versus  central one third in nonresponders by Tukey test.
Fig. 1. Distribution of ground-glass opacification according to the anteroposterior level (mean ± SD). *P 
	< 0.05 versus 
	central one third in nonresponders by Tukey test.
Fig. 1. Distribution of ground-glass opacification according to the anteroposterior level (mean ± SD). *P  < 0.05 versus  central one third in nonresponders by Tukey test.
×
Fig. 2. Distribution of consolidation according to the anteroposterior level (mean ± SD). *P  < 0.001 versus  sternal one third and central one third.
Fig. 2. Distribution of consolidation according to the anteroposterior level (mean ± SD). *P 
	< 0.001 versus 
	sternal one third and central one third.
Fig. 2. Distribution of consolidation according to the anteroposterior level (mean ± SD). *P  < 0.001 versus  sternal one third and central one third.
×
When total lung disease was considered, there was no difference between responders and nonresponders. In contrast, the two-way analysis of variance showed that there was a significant effect of the level (sternal, central, vertebral;P  < 0.001) with a vertebral predominance of these abnormalities (fig. 3). No interaction was found between the two factors (responders vs.  nonresponders and spatial location).
Fig. 3. Distribution of total lung disease according to the anteroposterior level (mean ± SD). *P  < 0.05 versus  sternal one third in responders by Tukey test; **P  < 0.001 versus  sternal one third and central one third in nonresponders by Tukey test; #P  < 0.05 versus  central one third and P  < 0.001 versus  sternal one third in nonresponders by Tukey test.
Fig. 3. Distribution of total lung disease according to the anteroposterior level (mean ± SD). *P 
	< 0.05 versus 
	sternal one third in responders by Tukey test; **P 
	< 0.001 versus 
	sternal one third and central one third in nonresponders by Tukey test; #P 
	< 0.05 versus 
	central one third and P 
	< 0.001 versus 
	sternal one third in nonresponders by Tukey test.
Fig. 3. Distribution of total lung disease according to the anteroposterior level (mean ± SD). *P  < 0.05 versus  sternal one third in responders by Tukey test; **P  < 0.001 versus  sternal one third and central one third in nonresponders by Tukey test; #P  < 0.05 versus  central one third and P  < 0.001 versus  sternal one third in nonresponders by Tukey test.
×
When both sides (right lung, left lung) were considered separately, there was no predominance of ground-glass opacification or consolidation in responders when compared with nonresponders. The total lung disease was almost evenly distributed between the left and right lungs in both responders and nonresponders (fig. 4).
Fig. 4. Distribution of total lung disease according to the lung side (mean ± SD).
Fig. 4. Distribution of total lung disease according to the lung side (mean ± SD).
Fig. 4. Distribution of total lung disease according to the lung side (mean ± SD).
×
Ground-glass opacification and consolidation were also both evenly distributed according to the cranio-caudal direction in both responders and nonresponders. When total lung disease was analyzed according to the cranio-caudal direction, there was no difference between responders and nonresponders (fig. 5).
Fig. 5. Distribution of total lung disease according to the cranio-caudal direction (mean ± SD).
Fig. 5. Distribution of total lung disease according to the cranio-caudal direction (mean ± SD).
Fig. 5. Distribution of total lung disease according to the cranio-caudal direction (mean ± SD).
×
Compression of the Lungs by the Heart and Response to Prone Positioning
The cardiothoracic ratio measured on standard posterior-anterior chest roentgenograms was 0.51 ± 0.06 in responders and 0.49 ± 0.07 in nonresponders (nonsignificant). There was no correlation between cardiothoracic ratio and the improvement in oxygenation related to prone positioning.
The percentage of the lung located under the heart increased only for the left lung from section 1 (subcarinal level) to section 4 (susdiaphragmatic level) for both responders and nonresponders (P  < 0.001 by Kruskal-Wallis one-way analysis of variance on ranks;fig. 6). However, there was no difference between responders and nonresponders. When the percentage of consolidated lung located under the heart relative to total lung area was considered, there was more consolidated tissue in nonresponders than in responders (P  = 0.01 by analysis of variance;fig. 7). There was also a progressive increase in consolidated tissue from section 1 to section 4 for both responders and nonresponders (P  < 0.001 by analysis of variance;fig. 7). When the dependence of consolidated tissue located under the heart relative to lung area on cephalocaudal distance was compared for the two lungs, there was an increase from section 1 to section 4 only for the left lung for responders and nonresponders (P  < 0.001 by Kruskal-Wallis one-way analysis of variance on ranks;fig. 7).
Fig. 6. Percentage of lung located under the heart relative to total lung area. Median values (25th, 50th, and 75th percentiles) and largest and smallest values that are not outliers are reported. Outliers (cases with values between 1.5 and 3 box lengths from the upper or lower edge of the box) are presented as closed circles. *P  < 0.05 versus  section 1, †P  < 0.05 versus  sections 1 and 2, ‡P  < 0.05 versus  sections 1, 2, and 3, all by Student-Newman-Keuls method.
Fig. 6. Percentage of lung located under the heart relative to total lung area. Median values (25th, 50th, and 75th percentiles) and largest and smallest values that are not outliers are reported. Outliers (cases with values between 1.5 and 3 box lengths from the upper or lower edge of the box) are presented as closed circles. *P 
	< 0.05 versus 
	section 1, †P 
	< 0.05 versus 
	sections 1 and 2, ‡P 
	< 0.05 versus 
	sections 1, 2, and 3, all by Student-Newman-Keuls method.
Fig. 6. Percentage of lung located under the heart relative to total lung area. Median values (25th, 50th, and 75th percentiles) and largest and smallest values that are not outliers are reported. Outliers (cases with values between 1.5 and 3 box lengths from the upper or lower edge of the box) are presented as closed circles. *P  < 0.05 versus  section 1, †P  < 0.05 versus  sections 1 and 2, ‡P  < 0.05 versus  sections 1, 2, and 3, all by Student-Newman-Keuls method.
×
Fig. 7. Percentage of consolidated lung tissue located under the heart relative to total lung area. Median values (25th, 50th, and 75th percentiles) and largest and smallest values that are not outliers are reported. Outliers (cases with values between 1.5 and 3 box lengths from the upper or lower edge of the box) are presented as closed circles. *P  < 0.05 versus  section 1, †P  < 0.05 versus  sections 1 and 2, ‡P  < 0.05 versus  sections 1, 2, and 3, all by Student-Newman-Keuls method; ¶P  < 0.001 versus  section 1, #P  < 0.001 versus  sections 1 and 2, **P  < 0.02 versus  section 2, all by Tukey test.
Fig. 7. Percentage of consolidated lung tissue located under the heart relative to total lung area. Median values (25th, 50th, and 75th percentiles) and largest and smallest values that are not outliers are reported. Outliers (cases with values between 1.5 and 3 box lengths from the upper or lower edge of the box) are presented as closed circles. *P 
	< 0.05 versus 
	section 1, †P 
	< 0.05 versus 
	sections 1 and 2, ‡P 
	< 0.05 versus 
	sections 1, 2, and 3, all by Student-Newman-Keuls method; ¶P 
	< 0.001 versus 
	section 1, #P 
	< 0.001 versus 
	sections 1 and 2, **P 
	< 0.02 versus 
	section 2, all by Tukey test.
Fig. 7. Percentage of consolidated lung tissue located under the heart relative to total lung area. Median values (25th, 50th, and 75th percentiles) and largest and smallest values that are not outliers are reported. Outliers (cases with values between 1.5 and 3 box lengths from the upper or lower edge of the box) are presented as closed circles. *P  < 0.05 versus  section 1, †P  < 0.05 versus  sections 1 and 2, ‡P  < 0.05 versus  sections 1, 2, and 3, all by Student-Newman-Keuls method; ¶P  < 0.001 versus  section 1, #P  < 0.001 versus  sections 1 and 2, **P  < 0.02 versus  section 2, all by Tukey test.
×
When only the part of the lung located under the heart was analyzed, there was more consolidated tissue in nonresponders than in responders (P  = 0.001 by a two-way analysis of variance;fig. 8). However, the two-way analysis of variance showed that there was no effect of the section level and that there was no interaction between the presence or absence of a response and the section level.
Fig. 8. Percentage of consolidated tissue relative to lung area located under the heart (mean ± SD). *P  < 0.01 versus  nonresponders by Tukey test.
Fig. 8. Percentage of consolidated tissue relative to lung area located under the heart (mean ± SD). *P 
	< 0.01 versus 
	nonresponders by Tukey test.
Fig. 8. Percentage of consolidated tissue relative to lung area located under the heart (mean ± SD). *P  < 0.01 versus  nonresponders by Tukey test.
×
Effect of the Lung Shape
A two-way analysis of variance (with the factors being responders vs.  nonresponders and upper vs.  lower compartments) showed that there was no difference between responders and nonresponders concerning the upper and lower compartments relative areas (fig. 9). However, a difference was found between the two compartments (P  < 0.001).
Fig. 9. Relative lung area of upper and lower compartments (mean ± SD).
Fig. 9. Relative lung area of upper and lower compartments (mean ± SD).
Fig. 9. Relative lung area of upper and lower compartments (mean ± SD).
×
When the amount of consolidated lung tissue relative to total lung area was evaluated, no difference was found between responders and nonresponders, whereas the two-way analysis of variance identified a significant effect of the compartment (P  < 0.001). No interaction was found between the two factors (responders vs.  nonresponders and upper vs.  lower compartments) concerning the amount of consolidated lung tissue relative to total lung area.
Discussion
The primary finding of this study was that there was no predictive factor of response to prone positioning except a greater amount of consolidated tissue under the heart in nonresponders in the supine position than in responders in the prone position. Indeed, the predominance of posterior hyperattenuated lung areas on CT scan performed with patients in the supine position was not predictive of an improvement in oxygenation in response to the prone position. Therefore, we can speculate that the influence of the weight of the heart on the lung located beneath it when the patients are in the supine position is not a major contributing factor in the improvement in oxygenation observed in responders to prone positioning.
Based on roentgenographic studies, it has been thought that ARDS produces a diffuse and homogeneous increase in lung stiffness, resulting in decreased lung volume. However, research conducted by a number of groups has now shown that the effects of ARDS on the lungs are far from homogeneous, particularly in the early stages. 14,15,28,29 Indeed, from the available data, it appears that lung lesions are inhomogeneous, with morphologically intact areas coexisting with areas of abnormal lung density. 29,30 Using CT technology, it has been shown that radiographic densities predominate in the dependent (vertebral) lung regions while patients are in the supine position. In contrast, the nondependent (sternal) regions appear normal when patients are in the supine position. 29,31 The morphology of lung in patients with ARDS as determined by CT scanning in the current study appeared consistent with previous reports, 14,15,29,31–33 with dense regions located in the dependent regions of both lungs. The weight of the abdominal contents, acting against the diaphragmatic wall, generated an increase in the abdominal pressure, which is predominantly transmitted to the caudal and dependent lung regions and in turn leads to a cephalic displacement of posterior regions of the diaphragm. Froese and Bryan 34 found that, in supine, awake, spontaneously breathing humans, the dependent parts of the diaphragm moved more in a cephalocaudal direction than did the nondependent parts. They also observed that, during anesthesia with paralysis and mechanical ventilation, the pattern of diaphragm displacement was reversed, with more motion occurring in nondependent than in dependent regions, and that a cephalad shift of the end-expiratory position of the diaphragm occurred.
It has been reported that turning a patient from the supine to the prone position decreases dorsal consolidation and increases ventral consolidation within minutes. 35 Indeed, Gattinoni et al.  6 reported that there was a density redistribution by gravity when changing from the supine to the prone position: the nondependent regions tended to clear, whereas the dependent regions increased their density in either position. Gattinoni et al.  6 hypothesized that, in patients with ARDS, the decreased transpulmonary pressure along the vertical axis reduces alveolar size and induces collapse of potentially recruitable lung units. By performing two CT scans in the supine position separated by a 4-h period of prone positioning, Priolet et al.  36 showed that there was a 27.1% increase of normal lung segments on the second CT scan. However, Guérin et al.  , 37 comparing pressure-volume curves, reported that there was no correlation between the improvement in Pao2/Fio2related to the prone position and the alveolar recruitment. The weight of the heart on the dorsal lung is supposed to contribute to this problem, 38–40 as are the effects of the supine position on chest wall shape. 39,40 Indeed, alterations in lung shape going from the prone to supine position are likely to be associated with changes in the pattern of lung expansion. We tested the hypothesis suggesting that patients presenting a more triangular shape of the lung (i.e.  , upper lung area smaller than the lower lung area) respond better to the prone position than the patients with a more rectangular shape (i.e.  , upper area similar to the lower area). However, in the current study we did not find any difference between responders and nonresponders, even when the amount of consolidated lung tissue was taken into account. The CT scans in the majority of patients with ARDS caused by pulmonary disease have areas of consolidation that are presumably a result of the initial direct lung injury. In the current study, ARDS was related to a pneumonia or lung contusion in 59% of the 46 patients. Therefore, pneumonia and lung contusion could not be recruited as atelectasis, explaining in part the fact that there was no correlation between the amount of vertebral opacities and the response to the prone position. In the present study, we did not perform a second CT scan at end-inspiration, which could help to differentiate atelectasis from consolidation. However, we did not find any relation between the type of ARDS (pulmonary or extrapulmonary), the localization of the opacities, and the response to the prone position. However, one limit of the present conclusion is the relatively small number of patients 18 free of pneumonia or lung contusion. It is also possible that when lung tissue is fully diseased, no recruitment is possible when the patients are turned from the supine to the prone position. Moreover, it is also possible that three or four transverse images do not give a true sample of the lung. Another explanation is that PEEP acts differently when ARDS is related to a direct lung injury than when it is a result of an extrapulmonary cause. Indeed, as suggested by Rouby et al.  , 41 PEEP could induce overdistension of ventral lung regions in supine patients presenting lung injuries predominating in the posterior part of the lungs (and not in those presenting diffuse infiltrates). Therefore, when these patients are turned prone, it is conceivable that a more uniform pressure regimen across a vertical axis resulted in a better recruitment when increasing PEEP. It is also possible that improvement in Pao2on switching from the supine to the prone position occurs when a more homogenous distribution of alveolar inflation is present. Further studies are needed to test this hypothesis.
The compressive force exerted by the heart on the lungs was suggested by a study performed by Milic-Emili et al.  , 42 who found that esophageal pressure measured in the region of the heart in normal subjects averaged approximately 5 cm H2O more when patients were in the supine compared with the prone position. The compressive force of the heart would be greater in patients with cardiomegaly, as suggested by Wiener et al.  , 38 and would probably be reduced in those with the smaller hearts associated with lung distension. However, in the study by Wiener et al.  , 38 the mean cardiothoracic ratio was 0.66, whereas in the present study it was 0.51. This difference could partly explain the lack of correlation between responders and nonresponders for prone positioning concerning the percentage of the lung located under the heart reported in the current study. Using positron emission tomography, no difference in right-to-left lung density or lung expansion were seen in supine normal subjects at the midheart level. 43 A reasonable hypothesis would be that the effect of the heart on supine-prone differences in regional lung expansion would be present when the volume and weight of the heart is increased. In the study by Nakos et al.  , 44 the patients with congestive heart failure and cardiomegaly exhibited a significant, rapid, and persistent improvement in oxygenation. This improvement could be partly related to the decompression of the left lower lobe by the enlarged heart during prone positioning. However, the investigators observed a persisting improvement after turning the patients to the supine position. Moreover, they observed that oxygenation increased faster in responder-ARDS group than in patients presenting an hydrostatic pulmonary edema, suggesting that heart volume did not affect significantly response to prone positioning.
Even if Gattinoni et al.  45 recently reported that the prone position did not modify outcome, it is important to identify subsets of patients who should respond to the prone position, especially severely hypoxemic patients. Indeed, in the latter study, 45 mortality was reduced using the prone position in this subgroup of patients. The current study showed that there is no tomodensitometric predictive factor of response to the prone position. Further studies are required to find predictive factors of response to the prone position that are easy to routinely assess.
In conclusion, the preponderance of radiologic opacities in the dorsal territories of ARDS patients does not influence the improvement in oxygenation related to the prone position. There are no distinctive morphologic features in the pattern of lung disease measured by CT scanning performed with patients in the supine position that can predict response to the prone position.
References
Milberg J, Davis D, Steinberg K, Hudson L: Improved survival of patients with acute respiratory distress syndrome (ARDS): 1983–1993. JAMA 1995; 273: 306–9Milberg, J Davis, D Steinberg, K Hudson, L
Bryan A: Comments of a devil's advocate. Am Rev Respir Dis 1974; 110: 143–4Bryan, A
Chatte G, Sab J, Dubois J, Sirodot M, Gaussorgues P, Robert D: Prone position in mechanically ventilated patients with severe acute respiratory failure. Am J Respir Crit Care Med 1997; 155: 473–8Chatte, G Sab, J Dubois, J Sirodot, M Gaussorgues, P Robert, D
Douglas W, Rehder K, Beynen F, Sessler A, Marsh H: Improved oxygenation in patients with acute respiratory failure: The prone position. Am Rev Respir Dis 1977; 115: 559–66Douglas, W Rehder, K Beynen, F Sessler, A Marsh, H
Fridrich P, Krafft P, Hochleuthner H, Mauritz W: The effects of long-term prone positioning in patients with trauma-induced adult respiratory distress syndrome. Anesth Analg 1996; 83: 1206–11Fridrich, P Krafft, P Hochleuthner, H Mauritz, W
Gattinoni L, Pelosi P, Vitale G, Pesenti A, D'Andrea L, Mascheroni D: Body position changes redistribute lung computed-tomographic density in patients with acute respiratory failure. A nesthesiology 1991; 74: 15–23Gattinoni, L Pelosi, P Vitale, G Pesenti, A D'Andrea, L Mascheroni, D
Mure M, Glenny RW, Domino KB, Hlastala MP: Pulmonary gas exchange improves in the prone position with abdominal distension. Am J Respir Crit Care Med 1998; 157: 1785–90Mure, M Glenny, RW Domino, KB Hlastala, MP
Jolliet P, Bulpa P, Ritz M, Ricou B, Lopez J, Chevrolet J: Additive beneficial effects of the prone position, nitric oxide, and almitrine bismesylate on gas exchange and oxygen transport in acute respiratory distress syndrome. Crit Care Med 1997; 25: 786–94Jolliet, P Bulpa, P Ritz, M Ricou, B Lopez, J Chevrolet, J
Papazian L, Bregeon F, Gaillat F, Thirion X, Gainnier M, Gregoire R, Saux P, Gouin F, Jammes Y, Auffray JP: Respective and combined effects of prone position and inhaled nitric oxide in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 1998; 157: 580–5Papazian, L Bregeon, F Gaillat, F Thirion, X Gainnier, M Gregoire, R Saux, P Gouin, F Jammes, Y Auffray, JP
Bombino M, Gattinoni L, Pesenti A, Pistolesi M, Miniati M: The value of portable chest roentgenography in adult respiratory distress syndrome: Comparison with computed tomography. Chest 1991; 100: 762–9Bombino, M Gattinoni, L Pesenti, A Pistolesi, M Miniati, M
Goodman L: Congestive heart failure and adult respiratory distress syndrome: New insights using computed tomography. Radiol Clin North Am 1996; 34: 33–46Goodman, L
Greene R: Adult respiratory distress syndrome: Acute alveolar damage. Radiology 1987; 163: 57–66Greene, R
Malbouisson LM, Busch CJ, Puybasset L, Lu Q, Cluzel P, Rouby JJ: Role of the heart in the loss of aeration characterizing lower lobes in acute respiratory distress syndrome. CT Scan ARDS Study Group. Am J Respir Crit Care Med 2000; 161: 2005–12Malbouisson, LM Busch, CJ Puybasset, L Lu, Q Cluzel, P Rouby, JJ
Puybasset L, Cluzel P, Gusman P, Grenier P, Preteux F, Rouby J: Regional distribution of gas and tissue in acute respiratory distress syndrome: I. Consequences for lung morphology. Intensive Care Med 2000; 26: 857–69Puybasset, L Cluzel, P Gusman, P Grenier, P Preteux, F Rouby, J
Rouby J, Puybasset L, Cluzel P, Richecoeur J, Lu Q, Grenier P: Regional distribution of gas and tissue in acute respiratory distress syndrome: II. Physiological correlations and definition of an ARDS Severity Score. Intensive Care Med 2000; 26: 1046–56Rouby, J Puybasset, L Cluzel, P Richecoeur, J Lu, Q Grenier, P
Stark P, Greene R, Kott MM, Hall T, Vanderslice L: CT-findings in ARDS. Radiologe 1987; 27: 367–9Stark, P Greene, R Kott, MM Hall, T Vanderslice, L
Tagliabue M, Casella T, Zincone G, Fumagalli R, Salvini E: CT and chest radiography in the evaluation of adult respiratory distress syndrome. Acta Radiol 1994; 35: 230–4Tagliabue, M Casella, T Zincone, G Fumagalli, R Salvini, E
Lamm WJ, Graham MM, Albert RK: Mechanism by which the prone position improves oxygenation in acute lung injury. Am J Respir Crit Care Med 1994; 150: 184–93Lamm, WJ Graham, MM Albert, RK
Albert R, Hubmayr R: The prone position eliminates compression of the lungs by the heart. Am J Respir Crit Care Med 2000; 161: 1660–5Albert, R Hubmayr, R
Rutishauser WJ, Banchero N, Tsakiris AG, Edmundowicz AC, Wood EH: Pleural pressures at dorsal and ventral sites in supine and prone body positions. J Appl Physiol 1966; 21: 1500–10Rutishauser, WJ Banchero, N Tsakiris, AG Edmundowicz, AC Wood, EH
McMahon S, Proctor D, Permutt S: Pleural surface pressure in dogs. J Appl Physiol 1969; 27: 881–5McMahon, S Proctor, D Permutt, S
Banchero N, Schwartz PE, Tsakiris AG, Wood EH: Pleural and esophageal pressures in the upright body position. J Appl Physiol 1967; 23: 228–34Banchero, N Schwartz, PE Tsakiris, AG Wood, EH
Bernard G, Artigas A, Brigham K, Carlet J, Falke K, Hudson L, Lamy M, Legall J, Morris A, Spragg R: The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994; 149: 818–24Bernard, G Artigas, A Brigham, K Carlet, J Falke, K Hudson, L Lamy, M Legall, J Morris, A Spragg, R
Murray JF, Matthay MA, Luce JM, Flick MR: An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis 1988; 138: 720–3Murray, JF Matthay, MA Luce, JM Flick, MR
Goodman L, Fumagalli R, Tagliabue P, Tagliabue M, Ferrario M, Gattinoni L, Pesenti A: Adult respiratory distress syndrome due to pulmonary and extrapulmonary causes: CT, clinical, and functional correlations. Radiology 1999; 213: 545–52Goodman, L Fumagalli, R Tagliabue, P Tagliabue, M Ferrario, M Gattinoni, L Pesenti, A
Austin JH, Muller NL, Friedman PJ, Hansell DM, Naidich DP, Remy-Jardin M, Webb WR, Zerhouni EA: Glossary of terms for CT of the lungs: recommendations of the Nomenclature Committee of the Fleischner Society. Radiology 1996; 200: 327–31Austin, JH Muller, NL Friedman, PJ Hansell, DM Naidich, DP Remy-Jardin, M Webb, WR Zerhouni, EA
Owens CM, Evans TW, Keogh BF, Hansell DM: Computed tomography in established adult respiratory distress syndrome: Correlation with lung injury score. Chest 1994; 106: 1815–21Owens, CM Evans, TW Keogh, BF Hansell, DM
Marini JJ: Lung mechanics in the adult respiratory distress syndrome: Recent conceptual advances and implications for management. Clin Chest Med 1990; 11: 673–90Marini, JJ
Maunder R, Shuman W, McHugh J, Marglin S, Butler J: Preservation of normal lung regions in the adult respiratory distress syndrome: Analysis by computed tomography. JAMA 1986; 255: 2463–5Maunder, R Shuman, W McHugh, J Marglin, S Butler, J
Gattinoni L, Presenti A, Torresin A, Baglioni S, Rivolta M, Rossi F, Scarani F, Marcolin R, Cappelletti G: Adult respiratory distress syndrome profiles by computed tomography. J Thorac Imaging 1986; 1: 25–30Gattinoni, L Presenti, A Torresin, A Baglioni, S Rivolta, M Rossi, F Scarani, F Marcolin, R Cappelletti, G
Gattinoni L, Mascheroni D, Torresin A, Marcolin R, Fumagalli R, Vesconi S, Rossi GP, Rossi F, Baglioni S, Bassi F: Morphological response to positive end expiratory pressure in acute respiratory failure: Computerized tomography study. Intensive Care Med 1986; 12: 137–42Gattinoni, L Mascheroni, D Torresin, A Marcolin, R Fumagalli, R Vesconi, S Rossi, GP Rossi, F Baglioni, S Bassi, F
Gattinoni L, Pesenti A, Bombino M, Baglioni S, Rivolta M, Rossi G, Rossi R, Fumagalli R, Marcolin R, Mascheroni D, Torresin A: Relationships between lung computed tomographic density, gas exchange, and PEEP in acute respiratory failure. A nesthesiology 1988; 69: 824–32Gattinoni, L Pesenti, A Bombino, M Baglioni, S Rivolta, M Rossi, G Rossi, R Fumagalli, R Marcolin, R Mascheroni, D Torresin, A
Puybasset L, Cluzel P, Chao N, Slutsky AS, Coriat P, Rouby JJ: A computed tomography scan assessment of regional lung volume in acute lung injury. Am J Respir Crit Care Med 1998; 158: 1644–55Puybasset, L Cluzel, P Chao, N Slutsky, AS Coriat, P Rouby, JJ
Froese AB, Bryan AC: Effects of anesthesia and paralysis on diaphragmatic mechanics in man. A nesthesiology 1974; 41: 242–55Froese, AB Bryan, AC
Langer M, Mascheroni D, Marcolin R, Gattinoni L: The prone position in ARDS patients: A clinical study. Chest 1988; 94: 103–7Langer, M Mascheroni, D Marcolin, R Gattinoni, L
Priolet B, Tempelhoff G, Millet J, Cannamela A, Carton M, De La Condamine S, Ducreux J, Driencourt J: Ventilation assistée en décubitus ventral:Évaluation tomodensitométrique de son efficacité dans le traitement des condensations pulmonaires. Réanimation Urgences 1993; 2: 81–5Priolet, B Tempelhoff, G Millet, J Cannamela, A Carton, M De La Condamine, S Ducreux, J Driencourt, J
Guerin C, Badet M, Rosselli S, Heyer L, Sab J, Langevin B, Philit F, Fournier G, Robert D: Effects of prone position on alveolar recruitment and oxygenation in acute lung injury. Intensive Care Med 1999; 25: 1222–30Guerin, C Badet, M Rosselli, S Heyer, L Sab, J Langevin, B Philit, F Fournier, G Robert, D
Wiener CM, McKenna WJ, Myers MJ, Lavender JP, Hughes JM: Left lower lobe ventilation is reduced in patients with cardiomegaly in the supine but not the prone position. Am Rev Respir Dis 1990; 141: 150–5Wiener, CM McKenna, WJ Myers, MJ Lavender, JP Hughes, JM
Margulies SS, Rodarte JR: Shape of the chest wall in the prone and supine anesthetized dog. J Appl Physiol 1990; 68: 1970–8Margulies, SS Rodarte, JR
Liu S, Margulies SS, Wilson TA: Deformation of the dog lung in the chest wall. J Appl Physiol 1990; 68: 1979–87Liu, S Margulies, SS Wilson, TA
Rouby JJ: A lung computed tomographic assessment of positive end-expiratory pressure-induced lung overdistension. Am J Respir Crit Care Med 2000; 161: 1396–7Rouby, JJ
Milic-Emili J, Mead J, Turner J: Topograph of esophageal pressure as a function of posture in man. J Appl Physiol 1964; 19: 212–6Milic-Emili, J Mead, J Turner, J
Brudin LH, Rhodes CG, Valind SO, Wollmer P, Hughes JM: Regional lung density and blood volume in nonsmoking and smoking subjects measured by PET. J Appl Physiol 1987; 63: 1324–34Brudin, LH Rhodes, CG Valind, SO Wollmer, P Hughes, JM
Nakos G, Tsangaris I, Kostanti E, Nathanail C, Lachana A, Koulouras V, Kastani D: Effect of the prone position on patients with hydrostatic pulmonary edema compared with patients with acute respiratory distress syndrome and pulmonary fibrosis. Am J Respir Crit Care Med 2000; 161: 360–8Nakos, G Tsangaris, I Kostanti, E Nathanail, C Lachana, A Koulouras, V Kastani, D
Gattinoni L, Tognoni G, Pesenti A, Taccone P, Mascheroni D, Labarta V, Malacrida R, Di GP, Fumagalli R, Pelosi P, Brazzi L, Latini R: Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med 2001; 345: 568–73Gattinoni, L Tognoni, G Pesenti, A Taccone, P Mascheroni, D Labarta, V Malacrida, R Di, GP Fumagalli, R Pelosi, P Brazzi, L Latini, R
Fig. 1. Distribution of ground-glass opacification according to the anteroposterior level (mean ± SD). *P  < 0.05 versus  central one third in nonresponders by Tukey test.
Fig. 1. Distribution of ground-glass opacification according to the anteroposterior level (mean ± SD). *P 
	< 0.05 versus 
	central one third in nonresponders by Tukey test.
Fig. 1. Distribution of ground-glass opacification according to the anteroposterior level (mean ± SD). *P  < 0.05 versus  central one third in nonresponders by Tukey test.
×
Fig. 2. Distribution of consolidation according to the anteroposterior level (mean ± SD). *P  < 0.001 versus  sternal one third and central one third.
Fig. 2. Distribution of consolidation according to the anteroposterior level (mean ± SD). *P 
	< 0.001 versus 
	sternal one third and central one third.
Fig. 2. Distribution of consolidation according to the anteroposterior level (mean ± SD). *P  < 0.001 versus  sternal one third and central one third.
×
Fig. 3. Distribution of total lung disease according to the anteroposterior level (mean ± SD). *P  < 0.05 versus  sternal one third in responders by Tukey test; **P  < 0.001 versus  sternal one third and central one third in nonresponders by Tukey test; #P  < 0.05 versus  central one third and P  < 0.001 versus  sternal one third in nonresponders by Tukey test.
Fig. 3. Distribution of total lung disease according to the anteroposterior level (mean ± SD). *P 
	< 0.05 versus 
	sternal one third in responders by Tukey test; **P 
	< 0.001 versus 
	sternal one third and central one third in nonresponders by Tukey test; #P 
	< 0.05 versus 
	central one third and P 
	< 0.001 versus 
	sternal one third in nonresponders by Tukey test.
Fig. 3. Distribution of total lung disease according to the anteroposterior level (mean ± SD). *P  < 0.05 versus  sternal one third in responders by Tukey test; **P  < 0.001 versus  sternal one third and central one third in nonresponders by Tukey test; #P  < 0.05 versus  central one third and P  < 0.001 versus  sternal one third in nonresponders by Tukey test.
×
Fig. 4. Distribution of total lung disease according to the lung side (mean ± SD).
Fig. 4. Distribution of total lung disease according to the lung side (mean ± SD).
Fig. 4. Distribution of total lung disease according to the lung side (mean ± SD).
×
Fig. 5. Distribution of total lung disease according to the cranio-caudal direction (mean ± SD).
Fig. 5. Distribution of total lung disease according to the cranio-caudal direction (mean ± SD).
Fig. 5. Distribution of total lung disease according to the cranio-caudal direction (mean ± SD).
×
Fig. 6. Percentage of lung located under the heart relative to total lung area. Median values (25th, 50th, and 75th percentiles) and largest and smallest values that are not outliers are reported. Outliers (cases with values between 1.5 and 3 box lengths from the upper or lower edge of the box) are presented as closed circles. *P  < 0.05 versus  section 1, †P  < 0.05 versus  sections 1 and 2, ‡P  < 0.05 versus  sections 1, 2, and 3, all by Student-Newman-Keuls method.
Fig. 6. Percentage of lung located under the heart relative to total lung area. Median values (25th, 50th, and 75th percentiles) and largest and smallest values that are not outliers are reported. Outliers (cases with values between 1.5 and 3 box lengths from the upper or lower edge of the box) are presented as closed circles. *P 
	< 0.05 versus 
	section 1, †P 
	< 0.05 versus 
	sections 1 and 2, ‡P 
	< 0.05 versus 
	sections 1, 2, and 3, all by Student-Newman-Keuls method.
Fig. 6. Percentage of lung located under the heart relative to total lung area. Median values (25th, 50th, and 75th percentiles) and largest and smallest values that are not outliers are reported. Outliers (cases with values between 1.5 and 3 box lengths from the upper or lower edge of the box) are presented as closed circles. *P  < 0.05 versus  section 1, †P  < 0.05 versus  sections 1 and 2, ‡P  < 0.05 versus  sections 1, 2, and 3, all by Student-Newman-Keuls method.
×
Fig. 7. Percentage of consolidated lung tissue located under the heart relative to total lung area. Median values (25th, 50th, and 75th percentiles) and largest and smallest values that are not outliers are reported. Outliers (cases with values between 1.5 and 3 box lengths from the upper or lower edge of the box) are presented as closed circles. *P  < 0.05 versus  section 1, †P  < 0.05 versus  sections 1 and 2, ‡P  < 0.05 versus  sections 1, 2, and 3, all by Student-Newman-Keuls method; ¶P  < 0.001 versus  section 1, #P  < 0.001 versus  sections 1 and 2, **P  < 0.02 versus  section 2, all by Tukey test.
Fig. 7. Percentage of consolidated lung tissue located under the heart relative to total lung area. Median values (25th, 50th, and 75th percentiles) and largest and smallest values that are not outliers are reported. Outliers (cases with values between 1.5 and 3 box lengths from the upper or lower edge of the box) are presented as closed circles. *P 
	< 0.05 versus 
	section 1, †P 
	< 0.05 versus 
	sections 1 and 2, ‡P 
	< 0.05 versus 
	sections 1, 2, and 3, all by Student-Newman-Keuls method; ¶P 
	< 0.001 versus 
	section 1, #P 
	< 0.001 versus 
	sections 1 and 2, **P 
	< 0.02 versus 
	section 2, all by Tukey test.
Fig. 7. Percentage of consolidated lung tissue located under the heart relative to total lung area. Median values (25th, 50th, and 75th percentiles) and largest and smallest values that are not outliers are reported. Outliers (cases with values between 1.5 and 3 box lengths from the upper or lower edge of the box) are presented as closed circles. *P  < 0.05 versus  section 1, †P  < 0.05 versus  sections 1 and 2, ‡P  < 0.05 versus  sections 1, 2, and 3, all by Student-Newman-Keuls method; ¶P  < 0.001 versus  section 1, #P  < 0.001 versus  sections 1 and 2, **P  < 0.02 versus  section 2, all by Tukey test.
×
Fig. 8. Percentage of consolidated tissue relative to lung area located under the heart (mean ± SD). *P  < 0.01 versus  nonresponders by Tukey test.
Fig. 8. Percentage of consolidated tissue relative to lung area located under the heart (mean ± SD). *P 
	< 0.01 versus 
	nonresponders by Tukey test.
Fig. 8. Percentage of consolidated tissue relative to lung area located under the heart (mean ± SD). *P  < 0.01 versus  nonresponders by Tukey test.
×
Fig. 9. Relative lung area of upper and lower compartments (mean ± SD).
Fig. 9. Relative lung area of upper and lower compartments (mean ± SD).
Fig. 9. Relative lung area of upper and lower compartments (mean ± SD).
×
Table 1. Characteristics of Responders and Nonresponders
Image not available
Table 1. Characteristics of Responders and Nonresponders
×