Browsing by Author "Carlesso, Eleonora"

Objectives. The lung-protective strategy employs positive end expiratory pressure to keep open otherwise collapsed lung regions (anatomical recruitment). Improvement in venous admixture with positive end-expiratory pressure indicates functional recruitment to better gas exchange, which is not necessarily related to anatomical recruitment, because of possible global/regional perfusion modifications. Therefore, we aimed to assess the value of venous admixture (functional shunt) in estimating the fraction of nonaerated lung tissue (anatomical shunt compartment) and to describe their relationship. Design: Retrospective analysis of a previously published study. Setting: Intensive care units of four university hospitals. Patients. Fifty-nine patients with acute lung injury/acute respiratory distress syndrome. Interventions., Positive end-expiratory pressure trial at 5 and 15 cm H2O positive end-expiratory pressures. Measurements and Main Results: Anatomical shunt compartment (whole-lung computed tomography scan) and functional shunt (blood gas analysis) were assessed at 5 and 15 cm H2O positive end-expiratory pressures. Apparent perfusion ratio (perfusion per gram of nonaerated tissue/perfusion per gram of total lung tissue) was defined as the ratio of functional shunt to anatomical shunt compartment. Functional shunt was poorly correlated to the anatomical shunt compartment (r(2) =.174). The apparent perfusion ratio at 5 cm H2O positive end-expiratory pressure was widely distributed and averaged 1.25 +/- 0.80. The apparent perfusion ratios at 5 and 15 cm H2O positive end expiratory pressures were highly correlated, with a slope close to identity (y = 1.10 center dot x -0.03, r(2) =.759), suggesting unchanged blood flow distribution toward the nonaerated lung tissue, when increasing positive end-expiratory pressure. Conclusions. Functional shunt poorly estimates the anatomical shunt compartment, due to the large variability in apparent perfusion ratio. Changes in anatomical shunt compartment with increasing positive end-expiratory pressure, in each individual patient, may be estimated from changes in functional shunt, only if the anatomical functional shunt relationship at 5 cm H2O positive end-expiratory pressure is known.

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(2) = 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.

Background: It has been suggested that higher positive end-expiratory pressure (PEEP) should be used only in patients with higher lung recruitability. In this study, the authors investigated the relationship between the recruitability and the PEEP necessary to counteract the compressive forces leading to lung collapse. Methods: Fifty-one patients with acute respiratory distress syndrome (7 mild, 33 moderate, and 11 severe) were enrolled. Patients underwent whole-lung computed tomography (CT) scan at 5 and 45 cm H2O. Recruitability was measured as the amount of nonaerated tissue regaining inflation from 5 to 45 cm H2O. The compressive forces (superimposed pressure) were computed as the density times the sternum-vertebral height of the lung. CT-derived PEEP was computed as the sum of the transpulmonary pressure needed to overcome the maximal superimposed pressure and the pleural pressure needed to lift up the chest wall. Results: Maximal superimposed pressure ranged from 6 to 18 cm H2O, whereas CT-derived PEEP ranged from 7 to 28 cm H2O. Median recruitability was 15% of lung parenchyma (interquartile range, 7 to 21%). Maximal superimposed pressure was weakly related with lung recruitability (r(2) = 0.11, P = 0.02), whereas CT-derived PEEP was unrelated with lung recruitability (r(2) = 0.0003, P = 0.91). The maximal superimposed pressure was 12 +/- 3, 12 +/- 2, and 13 +/- 1 cm H2O in mild, moderate, and severe acute respiratory distress syndrome, respectively, (P = 0.0533) with a corresponding CT-derived PEEP of 16 +/- 5, 16 +/- 5, and 18 +/- 5 cm H2O (P = 0.48). Conclusions: Lung recruitability and CT scan-derived PEEP are unrelated. To overcome the compressive forces and to lift up the thoracic cage, a similar PEEP level is required in higher and lower recruiters (16.8 +/- 4 vs. 16.6 +/- 5.6, P = 1).

Background: Obesity is associated in healthy subjects with a great reduction in functional residual capacity and with a stiffening of lung and chest wall elastance, which promote alveolar collapse and hypoxaemia. Likewise, obese patients with acute respiratory distress syndrome (ARDS) could present greater derangements of respiratory mechanics than patients of normal weight. Methods: One hundred and one ARDS patients were enrolled. Partitioned respiratory mechanics and gas exchange were measured at 5 and 15 cm H2O of PEEP with a tidal volume of 6-8ml kg(-1) of predicted body weight. At 5 and 45 cm H2O of PEEP, two lung computed tomography scans were performed. Results: Patients were divided as follows according to BMI: normal weight (BMI <= 25 kgm(-2)), overweight (BMI between 25 and 30 kgm(-2)), and obese (BMI>30 kgm(-2)). Obese, overweight, and normal-weight groups presented a similar lung elastance (median [interquartile range], respectively: 17.7 [14.2-24.8], 20.9 [16.1-30.2], and 20.5 [15.2-23.6] cm H2O litre(-1) at 5 cm H2O of PEEP and 19.3 [15.5-26.3], 21.1 [17.4-29.2], and 17.1 [13.4-20.4] cm H2O litre(-1) at 15 cm H2O of PEEP) and chest elastance (respectively: 4.9 [3.18.8], 5.9 [3.8-8.7], and 7.8 [3.9-9.8] cm H2O litre(-1) at 5 cm H2O of PEEP and 6.5 [4.5-9.6], 6.6 [4.2-9.2], and 4.9 [2.4-7.6] cm H2O litre(-1) at 15 cm H2O of PEEP). Lung recruitability was not affected by the body weight (15.6 [6.3-23.4], 15.7 [9.8-22.2], and 11.3 [6.2-15.6]% for normal-weight, overweight, and obese groups, respectively). Lung gas volume was significantly lower whereas total superimposed pressure was significantly higher in the obese compared with the normal-weight group (1148 [680-1815] vs 827 [686-1213] ml and 17.4 [15.8-19.3] vs 19.3 [18.6-21.7] cm H2O, respectively). Conclusions: Obese ARDS patients do not present higher chest wall elastance and lung recruitability.

Patients with sepsis are poorly protected against acute respiratory acid-base derangements due to a lower noncarbonic buffer power, which is caused both by a reduction in the major noncarbonic buffers, i.e. hemoglobin and albumin, and by a reduced buffering capacity of albumin. Electrolyte shifts from and to the red blood cells determining acute variations in strong ion difference are the major buffering mechanism during acute respiratory acid-base disorders.

Rationale: Pressures and volumes needed to induce ventilator-induced lung injury in healthy lungs are far greater than those applied in diseased lungs. A possible explanation may be the presence of local inhomogeneities acting as pressure multipliers (stress raisers). Objectives: To quantify lung inhomogeneities in patients with acute respiratory distress syndrome (ARDS). Methods: Retrospective quantitative analysis of CT scan images of 148 patients with ARDS and 100 control subjects. An ideally homogeneous lung would have the same expansion in all regions; lung expansion was measured by CT scan as gas/tissue ratio and lung inhomogeneities were measured as lung regions with lower gas/tissue ratio than their neighboring lung regions. We defined as the extent of lung inhomogeneities the fraction of the lung showing an inflation ratio greater than 95th percentile of the control group (1.61). Measurements and Main Results: The extent of lung inhomogeneities increased with the severity of ARDS(14 +/- 5, 18 +/- 8, and 23 +/- 10% of lung volume in mild, moderate, and severe ARDS; P< 0.001) and correlated with the physiologic dead space (r(2) = 0.34; P< 0.0001). The application of positive end-expiratory pressure reduced the extent of lung inhomogeneities from 18 +/- 8 to 12 +/- 7% (P 0.0001) going from 5 to 45 cm H2O airway pressure. Lung inhomogeneities were greater in nonsurvivor patients than in survivor patients (20 +/- 9 vs. 17 +/- 7% of lung volume; P = 0.01) and were the only CT scan variable independently associated with mortality at backward logistic regression. Conclusions: Lung inhomogeneities are associated with overall disease severity and mortality. Increasing the airway pressures decreased but did not abolish the extent of lung inhomogeneities.

Rationale The effects of high positive end-expiratory pressure (PEEP) strictly depend on lung recruitability, which varies widely during acute respiratory distress syndrome (ARDS). Unfortunately, increasing PEEP may lead to opposing effects on two main factors potentially worsening the lung injury, that is, alveolar strain and intratidal opening and closing, being detrimental (increasing the former) or beneficial (decreasing the latter). Objectives: To investigate how lung recruitability influences alveolar strain and intratidal opening and closing after the application of high PEEP. Methods: We analyzed data from a database of 68 patients with acute lung injury or ARDS who underwent whole-lung computed tomography at 5, 15, and 45 cm H(2)O airway pressure. Measurements and Main Results: End-inspiratory nonaerated lung tissue was estimated from computed tomography pressure volume curves. Alveolar strain and opening and closing lung tissue were computed at 5 and 15 cm H(2)O PEEP. In patients with a higher percentage of potentially recruitable lung, the increase in PEEP markedly reduced opening and closing lung tissue (P < 0.001), whereas no differences were observed in patients with a lower percentage of potentially recruitable lung. In contrast, alveolar strain similarly increased in the two groups (P = 0.89). Opening and closing lung tissue was distributed mainly in the dependent and hilar lung regions, and it appeared to be an independent risk factor for death (odds ratio, 1.10 for each 10-g increase). Conclusions: In ARDS, especially in patients with higher lung recruitability, the beneficial impact of reducing intratidal alveolar opening and closing by increasing PEEP prevails over the effects of increasing alveolar strain.

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 (HO)-O-2 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.

Rationale: The assessment of lung recruitability in patients with acute respiratory distress syndrome (ARDS) may be important for planning recruitment maneuvers and setting positive end-expiratory pressure (PEEP). Objectives: To determine whether lung recruitment measured by respiratory mechanics is comparable with lung recruitment measured by computed tomography (CT). Methods: In 22 patients with ARDS, lung recruitment was assessed at 5 and 15 cm H2O PEEP by using respiratory mechanics-based methods: (1) increase in gas volume between two pressure-volume curves (P-Vrs curve); (2) increase in gas volume measured and predicted on the basis of expected end-expiratory lung volume and static compliance of the respiratory system (EELV-Cst,rs); as well as by CT scan: (3) decrease in noninflated lung tissue (CT [not inflated]); and (4) decrease in noninflated and poorly inflated tissue (CT [not + poorly inflated]). Measurements and Main Results: The P-Vrs curve recruitment was significantly higher than EELV-Cst,rs recruitment (423 +/- 223 ml vs. 315 +/- 201 ml; P < 0.001), but these measures were significantly related to each other (R-2 = 0.93; P < 0.001). CT (not inflated) recruitment was 77 +/- 86 g and CT (not + poorly inflated) was 80 +/- 67 g (P = 0.856), and these measures were also significantly related to each other (R-2 = 0.20; P = 0.04). Recruitment measured by respiratory mechanics was 54 +/- 28% (P-Vrs curve) and 39 +/- 25% (EELV-Cst,rs) of the gas volume at 5 cm H2O PEEP. Recruitment measured by CT scan was 5 +/- 5% (CT [not inflated]) and 6 +/- 6% (CT [not + poorly inflated]) of lung tissue. Conclusions: Respiratory mechanics and CT measure under the same term, "recruitment"-two different entities. The respiratory mechanics-based methods include gas entering in already open pulmonary units that improve their mechanical properties at higher PEEP. Consequently, they can be used to assess the overall improvement of inflation. The CT scan measures the amount of collapsed tissue that regains inflation.

Purpose: Open lung strategy during ARDS aims to decrease the ventilator-induced lung injury by minimizing the atelectrauma and stress/strain maldistribution. We aim to assess how much of the lung is opened and kept open within the limits of mechanical ventilation considered safe (i.e., plateau pressure 30 cmH(2)O, PEEP 15 cmH(2)O). Methods: Prospective study from two university hospitals. Thirty-three ARDS patients (5 mild, 10 moderate, 9 severe without extracorporeal support, ECMO, and 9 severe with it) underwent two low-dose end-expiratory CT scans at PEEP 5 and 15 cmH(2)O and four end-inspiratory CT scans (from 19 to 40 cmH(2)O). Recruitment was defined as the fraction of lung tissue which regained inflation. The atelectrauma was estimated as the difference between the intratidal tissue collapse at 5 and 15 cmH(2)O PEEP. Lung ventilation inhomogeneities were estimated as the ratio of inflation between neighboring lung units. Results: The lung tissue which is opened between 30 and 45 cmH(2)O (i. e., always closed at plateau 30 cmH(2)O) was 10 +/- 29, 54 +/- 86, 162 +/- 92, and 185 +/- 134 g in mild, moderate, and severe ARDS without and with ECMO, respectively (p < 0.05 mild versus severe without or with ECMO). The intratidal collapses were similar at PEEP 5 and 15 cmH(2)O (63 +/- 26 vs 39 +/- 32 g in mild ARDS, p = 0.23; 92 +/- 53 vs 78 +/- 142 g in moderate ARDS, p = 0.76; 110 +/- 91 vs 89 +/- 93, p = 0.57 in severe ARDS without ECMO; 135 +/- 100 vs 104 +/- 80, p = 0.32 in severe ARDS with ECMO). Increasing the applied airway pressure up to 45 cmH(2)O decreased the lung inhomogeneity slightly (but significantly) in mild and moderate ARDS, but not in severe ARDS. Conclusions: Data show that the prerequisites of the open lung strategy are not satisfied using PEEP up to 15 cmH2O and plateau pressure up to 30 cmH(2)O. For an effective open lung strategy, higher pressures are required. Therefore, risks of atelectrauma must be weighted versus risks of volutrauma.

To clarify whether the gas exchange response to prone position is associated with lung recruitability in mechanically ventilated patients with acute respiratory failure. In 32 patients, gas exchange response to prone position was investigated as a function of lung recruitability, measured by computed tomography in supine position. 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 +/- A 16 vs. 8 +/- A 6%; P = 0.02), higher baseline PaCO(2) (48 +/- A 8 vs. 41 +/- A 11 mmHg; P = 0.07), heavier lungs (1,968 +/- A 829 vs. 1,521 +/- A 342 g; P = 0.06) and more non-aerated tissue (1,009 +/- A 704 vs. 536 +/- A 188 g; P = 0.02) than those who did not. 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.

We hypothesized that the ventilator-related causes of lung injury may be unified in a single variable: the mechanical power. We assessed whether the mechanical power measured by the pressure-volume loops can be computed from its components: tidal volume (TV)/driving pressure (a dagger P (aw)), flow, positive end-expiratory pressure (PEEP), and respiratory rate (RR). If so, the relative contributions of each variable to the mechanical power can be estimated. We computed the mechanical power by multiplying each component of the equation of motion by the variation of volume and RR: where a dagger V is the tidal volume, ELrs is the elastance of the respiratory system, I:E is the inspiratory-to-expiratory time ratio, and R (aw) is the airway resistance. In 30 patients with normal lungs and in 50 ARDS patients, mechanical power was computed via the power equation and measured from the dynamic pressure-volume curve at 5 and 15 cmH(2)O PEEP and 6, 8, 10, and 12 ml/kg TV. We then computed the effects of the individual component variables on the mechanical power. Computed and measured mechanical powers were similar at 5 and 15 cmH(2)O PEEP both in normal subjects and in ARDS patients (slopes = 0.96, 1.06, 1.01, 1.12 respectively, R (2) > 0.96 and p < 0.0001 for all). The mechanical power increases exponentially with TV, a dagger P (aw), and flow (exponent = 2) as well as with RR (exponent = 1.4) and linearly with PEEP. The mechanical power equation may help estimate the contribution of the different ventilator-related causes of lung injury and of their variations. The equation can be easily implemented in every ventilator's software.