Lung inhomogeneities and time course of ventilator-induced mechanical injuries.

BACKGROUND: During mechanical ventilation, stress and strain may be locally multiplied in an inhomogeneous lung. The authors investigated whether, in healthy lungs, during high pressure/volume ventilation, injury begins at the interface of naturally inhomogeneous structures as visceral pleura, bronchi, vessels, and alveoli. The authors wished also to characterize the nature of the lesions (collapse vs. consolidation). METHODS: Twelve piglets were ventilated with strain greater than 2.5 (tidal volume/end-expiratory lung volume) until whole lung edema developed. At least every 3 h, the authors acquired end-expiratory/end-inspiratory computed tomography scans to identify the site and the number of new lesions. Lung inhomogeneities and recruitability were quantified. RESULTS: The first new densities developed after 8.4 ± 6.3 h (mean ± SD), and their number increased exponentially up to 15 ± 12 h. Afterward, they merged into full lung edema. A median of 61% (interquartile range, 57 to 76) of the lesions appeared in subpleural regions, 19% (interquartile range, 11 to 23) were peribronchial, and 19% (interquartile range, 6 to 25) were parenchymal (P < 0.0001). All the new densities were fully recruitable. Lung elastance and gas exchange deteriorated significantly after 18 ± 11 h, whereas lung edema developed after 20 ± 11 h. CONCLUSIONS: Most of the computed tomography scan new densities developed in nonhomogeneous lung regions. The damage in this model was primarily located in the interstitial space, causing alveolar collapse and consequent high recruitability.

Lung recruitability is better estimated according to the Berlin definition of acute respiratory distress syndrome at standard 5 cm H2O rather than higher positive end-expiratory pressure: a retrospective cohort study.

OBJECTIVES: The Berlin definition of acute respiratory distress syndrome has introduced three classes of severity according to PaO2/FIO2 thresholds. The level of positive end-expiratory pressure applied may greatly affect PaO2/FIO2, thereby masking acute respiratory distress syndrome severity, which should reflect the underlying lung injury (lung edema and recruitability). We hypothesized that the assessment of acute respiratory distress syndrome severity at standardized low positive end-expiratory pressure may improve the association between the underlying lung injury, as detected by CT, and PaO2/FIO2-derived severity. DESIGN: Retrospective analysis. SETTING: Four university hospitals (Italy, Germany, and Chile). PATIENTS: One hundred forty-eight patients with acute lung injury or acute respiratory distress syndrome according to the American-European Consensus Conference criteria. INTERVENTIONS: Patients underwent a three-step ventilator protocol (at clinical, 5 cm H2O, or 15 cm H2O positive end-expiratory pressure). Whole-lung CT scans were obtained at 5 and 45 cm H2O airway pressure. MEASUREMENTS AND MAIN RESULTS: Nine patients did not fulfill acute respiratory distress syndrome criteria of the novel Berlin definition. Patients were then classified according to PaO2/FIO2 assessed at clinical, 5 cm H2O, or 15 cm H2O positive end-expiratory pressure. At clinical positive end-expiratory pressure (11±3 cm H2O), patients with severe acute respiratory distress syndrome had a greater lung tissue weight and recruitability than patients with mild or moderate acute respiratory distress syndrome (p<0.001). At 5 cm H2O, 54% of patients with mild acute respiratory distress syndrome at clinical positive end-expiratory pressure were reclassified to either moderate or severe acute respiratory distress syndrome. In these patients, lung recruitability and clinical positive end-expiratory pressure were higher than in patients who remained in the mild subgroup (p<0.05). When patients were classified at 5 cm H2O, but not at clinical or 15 cm H2O, lung recruitability linearly increases with acute respiratory distress syndrome severity (5% [2-12%] vs 12% [7-18%] vs 23% [12-30%], respectively, p<0.001). The potentially recruitable lung was the only CT-derived variable independently associated with ICU mortality (p=0.007). CONCLUSIONS: The Berlin definition of acute respiratory distress syndrome assessed at 5 cm H2O allows a better evaluation of lung recruitability and edema than at higher positive end-expiratory pressure clinically set.

Low-dose chest computed tomography for quantitative and visual anatomical analysis in patients with acute respiratory distress syndrome.

PURPOSE: Chest computed tomography (CT) is a fundamental tool for the characterization of acute respiratory distress syndrome (ARDS). Its frequent use is, however, hindered by the associated radiation exposure. The aim of the present study was to evaluate, in patients with ARDS, the accuracy of quantitative and visual anatomical lung analysis performed on low-dose CT. We hypothesized that low-dose CT would provide accurate quantitative and visual anatomical results. METHODS: Chest CT was performed in 45 ARDS patients in static conditions at set airway pressures of 45 and 15 or 45 and 5 cmH2O. During each pause, two consecutive scans were obtained at two different tube current-time products (mAs). In 24 patients 110 mAs was coupled with 60 mAs; in 21 patients 110 was coupled with 30 mAs. All other CT parameters were kept unaltered. Quantitative and visual anatomical results obtained at different mAs were compared via Bland-Altman analysis. RESULTS: Good agreements were observed between 110 and 60 mAs and between 110 and 30 mAs both for quantitative and visual anatomical results (all biases below 1.5%). Estimated mean effective dose at 110, 60, and 30 mAs corresponded to 5.3 ± 1.6, 2.8 ± 0.8, and 1.4 ± 0.3 mSv, respectively. CONCLUSIONS: In patients with ARDS a reduction of mAs up to 30 (70 % effective dose reduction) can be achieved without significant effect on quantitative and visual anatomical results. Low-dose chest CT, with related quantitative and visual anatomical analysis, could be a valuable tool to characterize and potentially monitor lung disease in patients with ARDS.

Bedside selection of positive end-expiratory pressure in mild, moderate, and severe acute respiratory distress syndrome.

OBJECTIVE: Positive end-expiratory pressure exerts its effects keeping open at end-expiration previously collapsed areas of the lung; consequently, higher positive end-expiratory pressure should be limited to patients with high recruitability. We aimed to determine which bedside method would provide positive end-expiratory pressure better related to lung recruitability. DESIGN: Prospective study performed between 2008 and 2011. SETTING: Two university hospitals (Italy and Germany). PATIENTS: Fifty-one patients with acute respiratory distress syndrome. INTERVENTIONS: Whole lung CT scans were taken in static conditions at 5 and 45 cm H2O during an end-expiratory/end-inspiratory pause to measure lung recruitability. To select individual positive end-expiratory pressure, we applied bedside methods based on lung mechanics (ExPress, stress index), esophageal pressure, and oxygenation (higher positive end-expiratory pressure table of lung open ventilation study). MEASUREMENTS AND MAIN RESULTS: Patients were classified in mild, moderate and severe acute respiratory distress syndrome. Positive end-expiratory pressure levels selected by the ExPress, stress index, and absolute esophageal pressures methods were unrelated with lung recruitability, whereas positive end-expiratory pressure levels selected by the lung open ventilation method showed a weak relationship with lung recruitability (r = 0.29; p < 0.0001). When patients were classified according to the acute respiratory distress syndrome Berlin definition, the lung open ventilation method was the only one which gave lower positive end-expiratory pressure levels in mild and moderate acute respiratory distress syndrome compared with severe acute respiratory distress syndrome (8 ± 2 and 11 ± 3 cm H2O vs 15 ± 3 cm H2O; p < 0.05), whereas ExPress, stress index, and esophageal pressure methods gave similar positive end-expiratory pressure values in mild, moderate, and severe acute respiratory distress syndrome. The positive end-expiratory pressure selected by the different methods were unrelated to each other with the exception of the two methods based on lung mechanics (ExPress and stress index). CONCLUSIONS: Bedside positive end-expiratory pressure selection methods based on lung mechanics or absolute esophageal pressures provide positive end-expiratory pressure levels unrelated to lung recruitability and similar in mild, moderate, and severe acute respiratory distress syndrome, whereas the oxygenation-based method provided positive end-expiratory pressure levels related with lung recruitability progressively increasing from mild to moderate and severe acute respiratory distress syndrome.

Limits of normality of quantitative thoracic CT analysis.

INTRODUCTION: Although computed tomography (CT) is widely used to investigate different pathologies, quantitative data from normal populations are scarce. Reference values may be useful to estimate the anatomical or physiological changes induced by various diseases. METHODS: We analyzed 100 helical CT scans taken for clinical purposes and referred as nonpathological by the radiologist. Profiles were manually outlined on each CT scan slice and each voxel was classified according to its gas/tissue ratio. For regional analysis, the lungs were divided into 10 sterno-vertebral levels. RESULTS: We studied 53 males and 47 females (age 64 ± 13 years); males had a greater total lung volume, lung gas volume and lung tissue. Noninflated tissue averaged 7 ± 4% of the total lung weight, poorly inflated tissue averaged 18 ± 3%, normally inflated tissue averaged 65 ± 8% and overinflated tissue averaged 11 ± 7%. We found a significant correlation between lung weight and subject's height (P <0.0001, r2 = 0.49); the total lung capacity in a supine position was 4,066 ± 1,190 ml, ~1,800 ml less than the predicted total lung capacity in a sitting position. Superimposed pressure averaged 2.6 ± 0.5 cmH2O. CONCLUSION: Subjects without lung disease present significant amounts of poorly inflated and overinflated tissue. Normal lung weight can be predicted from patient's height with reasonable confidence.

Pleural effusion in patients with acute lung injury: a CT scan study.

OBJECTIVES: Pleural effusion is a frequent finding in patients with acute respiratory distress syndrome. To assess the effects of pleural effusion in patients with acute lung injury on lung volume, respiratory mechanics, gas exchange, lung recruitability, and response to positive end-expiratory pressure. DESIGN, SETTING, AND PATIENTS: A total of 129 acute lung injury or acute respiratory distress syndrome patients, 68 analyzed retrospectively and 61 prospectively, studied at two University Hospitals. INTERVENTIONS: Whole-lung CT was performed during two breath-holding pressures (5 and 45 cm H2O). Two levels of positive end-expiratory pressure (5 and 15 cm H2O) were randomly applied. MEASUREMENTS: Pleural effusion volume was determined on each CT scan section; respiratory system mechanics, gas exchange, and hemodynamics were measured at 5 and 15 cm H2O positive end-expiratory pressure. In 60 patients, elastances of lung and chest wall were computed, and lung and chest wall displacements were estimated. RESULTS: Patients were divided into higher and lower pleural effusion groups according to the median value (287 mL). Patients with higher pleural effusion were older (62±16 yr vs. 54±17 yr, p<0.01) with a lower minute ventilation (8.8±2.2 L/min vs. 10.1±2.9 L/min, p<0.01) and respiratory rate (16±5 bpm vs. 19±6 bpm, p<0.01) than those with lower pleural effusion. Both at 5 and 15 cm H2O of positive end-expiratory pressure PaO2/FIO2, respiratory system elastance, lung weight, normally aerated tissue, collapsed tissue, and lung and chest wall elastances were similar between the two groups. The thoracic cage expansion (405±172 mL vs. 80±87 mL, p<0.0001, for higher pleural effusion group vs. lower pleural effusion group) was greater than the estimated lung compression (178±124 mL vs. 23±29 mL, p<0.0001 for higher pleural effusion group vs. lower pleural effusion group, respectively). CONCLUSIONS: Pleural effusion in acute lung injury or acute respiratory distress syndrome patients is of modest entity and leads to a greater chest wall expansion than lung reduction, without affecting gas exchange or respiratory mechanics.

Visual anatomical lung CT scan assessment of lung recruitability.

PURPOSE: The computation of lung recruitability in acute respiratory distress syndrome (ARDS) is advocated to set positive end-expiratory pressure (PEEP) for preventing lung collapse. The quantitative lung CT scan, obtained by manual image processing, is the reference method but it is time consuming. The aim of this study was to evaluate the accuracy of a visual anatomical analysis compared with a quantitative lung CT scan analysis in assessing lung recruitability. METHODS: Fifty sets of two complete lung CT scans of ALI/ARDS patients computing lung recruitment were analyzed. Lung recruitability computed at an airway pressure of 5 and 45 cm H(2)O was defined as the percentage decrease in the collapsed/consolidated lung parenchyma assessed by two expert radiologists using a visual anatomical analysis and as the decrease in not aerated lung regions using a quantitative analysis computed by dedicated software. RESULTS: Lung recruitability was 11.3 % (interquartile range 7.39-16.41) and 15.5 % (interquartile range 8.18-21.43) with the visual anatomical and quantitative analysis, respectively. In the Bland-Altman analysis, the bias and agreement bands between the visual anatomical and quantitative analysis were -2.9 % (-11.8 to +5.9 %). The ROC curve showed that the optimal cutoff values for the visual anatomical analysis in predicting high versus low lung recruitability was 8.9 % (area under the ROC curve 0.9248, 95 % CI 0.8550-0.9946). Considering this cutoff, the sensitivity, specificity, and diagnostic accuracy were 0.96, 0.76, and 0.86, respectively. CONCLUSIONS: Visual anatomical analysis can classify patients into those with high and low lung recruitability allowing more intensivists to get access to lung recruitability assessment.

Lung stress and strain during mechanical ventilation: any safe threshold?

RATIONALE: Unphysiologic strain (the ratio between tidal volume and functional residual capacity) and stress (the transpulmonary pressure) can cause ventilator-induced lung damage. OBJECTIVES: To identify a strain-stress threshold (if any) above which ventilator-induced lung damage can occur. METHODS: Twenty-nine healthy pigs were mechanically ventilated for 54 hours with a tidal volume producing a strain between 0.45 and 3.30. Ventilator-induced lung damage was defined as net increase in lung weight. MEASUREMENTS AND MAIN RESULTS: Initial lung weight and functional residual capacity were measured with computed tomography. Final lung weight was measured using a balance. After setting tidal volume, data collection included respiratory system mechanics, gas exchange and hemodynamics (every 6 h); cytokine levels in serum (every 12 h) and bronchoalveolar lavage fluid (end of the experiment); and blood laboratory examination (start and end of the experiment). Two clusters of animals could be clearly identified: animals that increased their lung weight (n = 14) and those that did not (n = 15). Tidal volume was 38 ± 9 ml/kg in the former and 22 ± 8 ml/kg in the latter group, corresponding to a strain of 2.16 ± 0.58 and 1.29 ± 0.57 and a stress of 13 ± 5 and 8 ± 3 cm H(2)O, respectively. Lung weight gain was associated with deterioration in respiratory system mechanics, gas exchange, and hemodynamics, pulmonary and systemic inflammation and multiple organ dysfunction. CONCLUSIONS: In healthy pigs, ventilator-induced lung damage develops only when a strain greater than 1.5-2 is reached or overcome. Because of differences in intrinsic lung properties, caution is warranted in translating these findings to humans.

Relationship between gas exchange response to prone position and lung recruitability during acute respiratory failure.

PURPOSE: To clarify whether the gas exchange response to prone position is associated with lung recruitability in mechanically ventilated patients with acute respiratory failure. METHODS: In 32 patients, gas exchange response to prone position was investigated as a function of lung recruitability, measured by computed tomography in supine position. RESULTS: No relationship was found between increased oxygenation in prone position and lung recruitability. In contrast, the decrease of PaCO(2) was related with lung recruitability (R(2) 0.19; P = 0.01). Patients who decreased their PaCO(2) more than the median value (-0.9 mmHg) had a greater lung recruitability (19 +/- 16 vs. 8 +/- 6%; P = 0.02), higher baseline PaCO(2) (48 +/- 8 vs. 41 +/- 11 mmHg; P = 0.07), heavier lungs (1,968 +/- 829 vs. 1,521 +/- 342 g; P = 0.06) and more non-aerated tissue (1,009 +/- 704 vs. 536 +/- 188 g; P = 0.02) than those who did not. CONCLUSIONS: During prone position, changes in PaCO(2), but not in oxygenation, are associated with lung recruitability which, in turn, is associated with the severity of lung injury.

Prone position delays the progression of ventilator-induced lung injury in rats: does lung strain distribution play a role?

OBJECTIVE: To investigate if prone position delays the progression of experimental ventilator-induced lung injury, possibly due to a more homogeneous distribution of strain within lung parenchyma. DESIGN: Prospective, randomized, controlled trial. SETTING: Animal laboratory of a university hospital. SUBJECTS: Thirty-five Sprague Dawley male rats (weight 257 +/- 45 g). INTERVENTIONS: Mechanical ventilation in either supine or prone position and computed tomography scan analysis. MEASUREMENTS: : Animals were ventilated in supine (n = 15) or prone (n = 15) position until a similar ventilator-induced lung injury was reached. To do so, experiments were interrupted when respiratory system elastance was 150% of baseline. Ventilator-induced lung injury was assessed as lung wet-to-dry ratio and histology. Time to reach lung injury was considered as a main outcome measure. In five additional animals, computed tomography scans (GE Light Speed QX/I, thickness 1.25 mm, interval 0.6 mm, 100 MA, 100 Kv) were randomly taken at end-expiration and end-inspiration in both positions, and quantitative analysis was performed. Data are shown as mean +/- sd. MEASUREMENTS AND MAIN RESULTS: Similar ventilator-induced lung injury was reached (respiratory system elastance, wet-to-dry ratio, and histology). The time taken to achieve the target ventilator-induced lung injury was longer with prone position (73 +/- 37 mins vs. 112 +/- 42, supine vs. prone, p = .011). Computed tomography scan analysis performed before lung injury revealed that at end-expiration, the lung was wider in prone position (p = .004) and somewhat shorter (p = .09), despite similar lung volumes (p = .455). Lung density along the vertical axis increased significantly only in supine position (p = .002). Lung strain was greater in supine as opposed to prone position (width strain, 7.8 +/- 1.8% vs. 5.6 +/- 0.9, supine vs. prone, p = .029). CONCLUSIONS: Prone position delays the progression of ventilator-induced lung injury. Computed tomography scan analysis suggests that a more homogeneous distribution of strain may be implicated in the protective role of prone position against ventilator-induced lung injury.