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2. Pathophysiology • Gravitational dependent portions of the lungs may collapse • Anesthesia with sedation, neuromuscular, blockade, and mechanical ventilation, extremely obese people, chest wall impairment • Positive end-expiratory pressure(PEEP), high tidal volumes, or recruitment maneuvers • ARDS…extravascular lung water ↑ • High FiO2 and minute ventilation • Dead space fraction was higher among patients who died than among those who survived (0.63 0.10 vs. 0.54 0.09; p .001)……Nuckton et al.

3. Thoracic Radiograph andComputed Tomography

4. Mechanical Ventilation of ARDS Lungs • Evidence of Induced Lung Injury by Mechanical Ventilation and Repeated Derecruitment in Experimental Models of ARDS • Large tidal volume→ transpulmonary pressure↑ (35~40cm H20)→ microvascular permeability ↑ • Dreyfuss et al. High intermittent transpulmonary, positive pressure, ventilation-induced edemas (permeability edema type), severe ultrastructural alterations

5. Hernandez et al. • Rabbit-lung model injured after oleic acid • Greater capillary filtration coefficient after mechanical ventilation than either a normal lung or an injured lung without mechanical ventilation. • 1974, Webb and Tierney • Lung injury caused by high peak airway pressures and volumes • Reduced by the application of PEEP

6. Dogs…HCL injured lung • The level of PEEP and tidal volume • Ratio of wet lung weight and dry weight differs • High PEEP/low tidal volume (12.5 cm H2O, 15 mL/kg) reduced injury vs. Low PEEP/high tidal volume (3.2 cm H2O, 30 mL/kg) • Muscedere et al. Ex vivo rat lung model • PEEP > Pflex: no change in lung compliance • PEEP < Pflex: compliance↓, histologic injury↑ • PEEP=0: bronchioles injuries • PEEP = 4: alveolar duct injuries

7. Suh et al. repeated derecruitments can accentuate lung injury during M.V. • 24 New Zealand White rabbits: constant tidal volume ventilation (10mL/Kg) and lung injury by repeated saline lavage (PaO2<100) • Control group: PEEP at Pflex for 3 h • Non-derecruitment group: PEEP 2.7cm H2O for 1 h, then Pflex for 2 h • Derecruitment group: 10 mins at PEEP 2.7 cm H2O then 20 mins PEEP at Pflex

8. Control group • PaO2 > 500 mmHg for 3 h • Non-derecruitment group • 1h~ PaO2 40±16mmHg, 2h~ PaO2 >500mmHg • Derecruitment group • 220±130 mmHg at 3h, more hyaline membrane formation and higher mean bronchiolar injury score

9. Evidence of Lung Injury Protection byOpen Lung Concept Ventilatory Strategiesin the Experimental Setting • Open lung concept ventilatory strategy • Positive inspiration pressure 33 cm H2O, PEEP 15 cm H2O, I/E ratio 1:1, RR 100 • PaO2level, total lung volume, total lung capacity, and protein concentration of bronchoalveolar lavage = healthy controls • Positive inspiration pressure 26 cm H2O, PEEP 6 cm H2O, I/E ratio 1:2, RR 30 • PaO2level, total lung volume, total lung capacity ↓, protein concentration of bronchoalveolar lavage ↑ Rotta et al.

10. Decrement in Intensive Care Unit Mortality Rate and Decreased Inflammatory Mediator Activation With High PEEP/Low Tidal Volume Ventilation Plus Recruitment Maneuvers Vs. Low PEEP/High Tidal Volume • Lung-protective ventilation strategy • Recruitment maneuvers ( CPAP of 35–40 cm H2O for 40secs) with higher PEEP and tidal volumes < 6 mL/kg • 28-day intensive care unit survival rate of 62% • Conventional ventilation (lowest PEEP necessary for acceptable oxygenation with a tidal volume of 12 mL/kg) • Survival rate of 29% • Number needed to treat = 3; p < 0.001 Amato et al.

11. Post hoc analysis Amato et al.

12. Ranieri et al. • Higher PEEP/low tidal volume ventilation strategy > low PEEP/high tidal volume ventilation • ↓ ↓ Bronchoalveolar lavage and systemic blood levels of TNF-, IL-8, and IL-6 • Takeuchi et al. • HigherPEEP levels > adequate oxygenation • More effective in maintaining gas exchange and minimizing injury

13. The Concept of Pressure-Volume Envelopesof the Respiratory System

15. Lung Recruitment and a MoreHomogeneous Ventilation • According to thoracic tomography findings at the bedside, the ARDS lung is recruitable. • An ARDS lung that is more homogeneously ventilated may avoid injury from both overdistention and from repeated opening and closing of alveoli.

16. Possible Methods of RecruitingARDS Lungs • High CAPA Levels • Intermittent Sighs • Intermittent Stepwise High PEEP Levels With a Fixed Pressure Control Maneuver • The Prone position as a Recruitment Maneuver and as a Possible Rescue Therapy in Severe ARDS

17. High CPAP Levels • Recruitment maneuvers as CPAP 40 cm H2O for 40 seconds • 50% increase in PaO2/FiO2 • Non-responders (20±3%) • Responder group (175±23%) • Lower lung and chest elastance • Ventilated for a shorter period • Less hemodynamic impairment Grasso et al.

18. Intermittent Sighs • Lung-protective strategy x 2h → plus 3 consecutive sighs / minute at 45 cm H2Ox 1h → without sighs x 1h • ↑PaO2/FiO2and of the end-expiratory lung volume; ↓venous admixture and PaCO2during ventilation with sighs • Returned to baseline after 30 minutes of sighs interruptions Pelosi et al.

19. ARDS patients ventilated with PEEP 2cm H2O above Pflex and T.V. 6mL/Kg • (A) 3 cycles of PCV of 40 cm H2O for 6 secs every 3 hrs • (B) 3 cycles of PCV of 40, 50, and 60 cm H2O for 6 secs every 3 hrs • Further ↑ of the PaO2/FiO2 after 1hr & 6hrs without hemodynamic impairment Barbas et al.

20. Intermittent Stepwise High PEEP Levels With a Fixed Pressure Control Maneuver Mean PEEP: 22 ± 4 cm H2O After 6 hrs, PaO2+PaCO2 remained at 521.4±95.4 mm Hg with a PEEP titration strategy to keep the lung open. The PEEP titration strategy consisted of small, stepwise decrements of PEEP every 15–20 mins until a decrease in PaO2>5% of the previous PaO2 occurred. • 2-min steps of tidal ventilation (fixed 15-cm H2O pressure control) • Progressive PEEP levels (25, 30, 35, 40, and 45 cm H2O) until full recruitment.(defined as PaO2 +PaCO2 >400 mm Hg± 5% at FIO2 of 100%). • PaO2 +PaCO2 increased from 178.4 ± 76.5 mm Hg to487.8 ± 139.1 mm Hg. Okamoto et al.

21. The Prone Position as a RecruitmentManeuver and as a Possible Rescue Therapy in Severe ARDS. • High recruiting force in dorsal regions • Supine: higher local pleural pressure, heart & mediastinal contents • SaO2 ↑ 50% to 70% of ARDS patients • Gattinoni et al.most severe ARDS (PaO2/FiO2 < 88 and a TV>12mL/kg) • 10-day survival rate ↑ →early rescue maneuver • Severe ARDS (author’s experiences) • Not respond to recruit maneuvers → improvement after 6 hrs of prone positioning

22. Thoracic CT Scanning as a Tool to Optimize Recruitment and Ventilation of the ARDS Patient Expiratory phase; PEEP 25~45; PCV 15cmH2O 63.7% 256.7 394 28.6% 4.7% 92.3 CPAP: 40cmH2Ox40s; PEEP 2cm↑Pflex; TV:6mL/kg; Barbas et al.

23. Assessment of Regional Ventilation With Electrical Impedance Tomography • Kunst et al. • After lavage of 9 anesthetized pigs • ↑↑Impedance ratio of anterior/posterior thorax (from 1.75±0.63 to 4.51±2.22)→huge alveolar collapse of the posterior lungs • Open lung approach & open lung concept • Anterior/posterior impedance ratio↓↓ • Open lung approach: 1.1±0.3 • Open lung concept: 1.2±0.3

24. Scheme of EIT system Figure 1. Scheme of the Sheffield electrical impedance tomography system. Sixteen electrodes are attached around an object and connected to the electrical impedance tomography box. There, by means of back projection, the data obtained are reconstructed into images on which regional analysis can be performed and numeric values can be obtained.

25. Correlation of EIT and plethysmography Figure 2. Typical example of an electrical impedance tomography curve and a strain gauge plethysmography curve. A significant correlation between the increase in lung volume as measured by strain gauge plethysmography and impedance as measured by electrical impedance tomography was found when all of the curves obtained in the nine animals were taken into account (r2 =.76; p <.005). AU, arbitrary units. Solid line, electrical impedance tomography; broken line, strain gauge plethysmography

26. Plethysmography

27. Regional electrical impedance tomography Figure 5. Electrical impedance tomography image divided into four regions with their accessory pressure-impedance curves. The dark areas indicate areas in which no or little impedance changes occur. The light areas indicate areas of high impedance changes. AU, arbitrary units.

29. Future perspective • In the near future, thoracic computed tomography associated with high-performance monitoring of regional ventilation (electrical impedance tomography) may be used at the bedside to determine the optimal mechanical ventilation of patients with acute respiratory distress syndrome.

30. Conclusions • High airway pressures can open collapsed ARDS lungs and partially open edematous lungs • High PEEP levels/low tidal ventilation >low PEEP/high tidal volume ventilation ↓ bronchoalveolar and plasma inflammatory mediators & ↑survival.

31. Successful recruitment maneuver • PEEP • PCV applied and time (2 mins is thought to be an adequate time for a full recruitment) • Mechanism of injury (extrapulmonary ARDS can be recruited more easily than pulmonary ARDS) • Patient body position (the prone position seems to facilitate recruitment, especially of the left lower lobe of the injured lungs)

32. Thanks for your attention……