Matteo Brioni

Lung Inhomogeneity in Patients with Acute Respiratory Distress Syndrome

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.

Mechanical Power and Development of Ventilator-induced Lung Injury.

Background:The ventilator works mechanically on the lung parenchyma. The authors set out to obtain the proof of concept that ventilator-induced lung injury (VILI) depends on the mechanical power applied to the lung. Methods:Mechanical power was defined as the function of transpulmonary pressure, tidal volume (TV), and respiratory rate. Three piglets were ventilated with a mechanical power known to be lethal (TV, 38 ml/kg; plateau pressure, 27 cm H2O; and respiratory rate, 15 breaths/min). Other groups (three piglets each) were ventilated with the same TV per kilogram and transpulmonary pressure but at the respiratory rates of 12, 9, 6, and 3 breaths/min. The authors identified a mechanical power threshold for VILI and did nine additional experiments at the respiratory rate of 35 breaths/min and mechanical power below (TV 11 ml/kg) and above (TV 22 ml/kg) the threshold. Results:In the 15 experiments to detect the threshold for VILI, up to a mechanical power of approximately 12 J/min (respiratory rate, 9 breaths/min), the computed tomography scans showed mostly isolated densities, whereas at the mechanical power above approximately 12 J/min, all piglets developed whole-lung edema. In the nine confirmatory experiments, the five piglets ventilated above the power threshold developed VILI, but the four piglets ventilated below did not. By grouping all 24 piglets, the authors found a significant relationship between the mechanical power applied to the lung and the increase in lung weight (r2 = 0.41, P = 0.001) and lung elastance (r2 = 0.33, P < 0.01) and decrease in PaO2/FIO2 (r2 = 0.40, P < 0.001) at the end of the study. Conclusion:In piglets, VILI develops if a mechanical power threshold is exceeded.

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.

Compressive Forces and Computed Tomography–derived Positive End-expiratory Pressure in 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).

The Prone Position in the Treatment of Patients with ARDS: Problems and Real Utility

Prone positioning is a life-saving treatment used in ARDS patients in order to improve oxygenation and reduce lung injury due to mechanical ventilation. The beneficial effects of this procedure are the result of complex mechanisms that cooperate in improving gas exchange and in reducing global “stress” and “strain” of the lung. Prone positioning seems to be more effective in extrapulmonary form of ARDS, where the main feature of the disease is represented by compression atelectasis in dependent lung regions caused by the gain in lung weight due to pulmonary edema. To date, it is recommended in ARDS patients that maintain a PaO2/FiO2 ratio lower than 150 mmHg even after optimization of mechanical ventilation. However, only the patients who react to prone positioning with a decrease in PaCO2 show a real benefit in terms of survival rate. The relationship between improvement in gas exchange and patient outcome still remains unclear. This is not a maneuver free of complications, and it is important to balance risks and benefits associated with the procedure. An expert team is required to safely prone the patient and to reduce the incidence of adverse effects.

Dissipated energy during protective mechanical ventilation

From literature we know that a cornerstone of the protective lung ventilation in Acute Respiratory Distress Syndrome (ARDS) patients[1] and during general anesthesia[2] is a low tidal volume. On the other hand, driving pressure seems to be the variable that best stratifies mortality risk[3]. Our hypothesis is that the combination of volume and pressure, that is the energy dissipated into respiratory system, is the main determinant of a ventilator-induced lung injury (VILI).

0994. Development of ventilatory-induced lung injury depends on energy dissipated into respiratory system

Mechanical ventilation with high volumes/pressures induces ventilatory induced lung injury (VILI). During each breath, part of the energy transmitted from ventilator to respiratory system is given back as elastic recoil and part is dissipated into the respiratory system; this amount of energy is measured by the hysteresis area of the pressure-volume (PV) curve of the respiratory system. Total dissipated energy into respiratory system, or dissipated inspiratory potency, equals to energy dissipated during every single breath multiplied by the respiratory rate (RR).

0894. Time course of VILI development: a CT scan study

Mechanical Ventilation at high tidal volumes and pressures induces in lung oedema which is undistinguishable from ARDS. It is possible that pleura, bronchi and vessels act as a natural stress raiser playing as local stress multipliers. [1]