1. Ventilator-Induced Lung Injury N Engl J Med 2013;369:2126-36. Arthur S. Slutsky, M.D., and V. Marco Ranieri, M.D 호흡기 내과 / R4 이민혜 Review Article

2. Introduction Purpose of mechanical ventilation: rest the respiratory muscles while providing adequate gas exchange Complication of mechanical ventilation –Barotrauma (i.e., gross air leaks) –Oxygen toxicity –Hemodynamic compromise Ventilator-induced lung injury: pathologically –Inflammatory-cell infiltrates –Hyaline membranes –Increased vascular permeability –Pulmonary edema

3. Pathophysiological Features Pressures in the Lung –When airflow is zero(e.g., at end inspiration): principal force maintaining inflation is the transpulmonary pressure –Transpulmonary pressure = alveolar pressure – pleural pressure –Lung volume and transpulmonary pressure are inextricably linked –Alveolar pressure: airway pressure during a period of zero flow –Pleural pressure: can be estimated in the broader clinical setting only by measurement of esophageal pressure Regional lung overdistention is a key factor in generating ventilator- induced lung injury

6. Biotrauma

7. Clinical Management Ventilation strategies –Low tidal volumes –High PEEP and recruitment maneuvers –High-frequency oscillatory ventilation Adjunctive strategies –Prone position –Partial or total extracorporeal support Pharmacologic interventions –Neuromuscular blocking agents –Antiinflammatory agents and stem cells

8. Ventilation Strategies: Low Tidal Volumes ARDS –Relatively non-aerated dependent lung regions vs. relatively normally aerated nondependent lung regions “Baby lung” –Decreased tidal volume (i.e., one that might be normal for a baby) –Prevent overinflation of the relatively small, normally aerated regions UpToDate ®

9. 6 ml/kg PBW12 ml/kg PBW N Engl J Med 2000;342:1301-8.

10. Ventilation Strategies: High PEEP Pulmonary edema and end-expiratory alveolar collapse characterize several forms of respiratory failure Low PEEP –Insufficient to stabilize alveoli keep them open –Increasing the likelihood of ventilator-induced lung injury from atelectrauma Higher PEEP –Impairment of venous return –Pulmonary overdistention N Engl J Med 2004;351:327-36.

11. PaO 2 :FIO 2 ≤200 JAMA 2010;303:865-873.

12. Ventilation Strategies: Recruitment Maneuvers Recruitment maneuvers –Brief application of a high level of continuous positive airway pressure, such as 35 to 40 cm H 2 O for 40 seconds –Open alveoli that have collapsed Theoretically reduce ventilator-induced lung injury The role of recruitment maneuvers in clinical practice remains uncertain –Questions about its effect on outcomes –Concerns regarding complications (e.g., hemodynamic compromise or pneumothorax)

13. Ventilation Strategies: Recruitment Maneuvers JAMA. 2010;304(23):2620-2627. TV: 10-12 ml/kg PBW PEEP: 3-5 cm H 2 O Apnea tests: disconnecting the ventilator Administrating high-flow oxygen Open circuit for airway suction TV: 10-12 ml/kg PBW PEEP: 3-5 cm H 2 O Apnea tests: disconnecting the ventilator Administrating high-flow oxygen Open circuit for airway suction TV: 6-8 ml/kg PBW PEEP: 8-10 cm H 2 O Apnea tests: using CPAP Recruitment maneuvers Closed circuit for airway suction TV: 6-8 ml/kg PBW PEEP: 8-10 cm H 2 O Apnea tests: using CPAP Recruitment maneuvers Closed circuit for airway suction

14. Ventilation Strategies: High-Frequency Oscillatory Ventilation High frequencies (up to 15 per second) Very small tidal volumes (sometimes less than the anatomic dead space)

15. BMJ 2010;340:c2327.

16. N Engl J Med 2013;368:795-805. N Engl J Med 2013;368:806-13. Patients with ARDS did not show improved outcomes with HFOV This type of ventilation cannot be recommended as first-line therapy

17. Adjunctive Strategies: Prone Position Increased end-expiratory lung volume Better ventilation–perfusion matching Less effect of the mass of the heart on the lower lobes Improved regional ventilation Studies in animals: minimize lung injury by increasing homogeneity of ventilation

18. Intensive Care Med 2010;36:585-599.

19. N Engl J Med 2013;368:2159-68.

20. Adjunctive Strategies: Partial or Total Extracorporeal Support Preventing ventilator-induced lung injury –Avoid mechanical ventilation –Instead use extracorporeal membrane oxygenation(ECMO) Combine mechanical ventilation with partial extracorporeal support –Intensity of ventilation that is needed to sustain life is decreased –Carbon dioxide is removed through an extracorporeal circuit –Decreased rate of complications as compared with full ECMO –Decreased rate of lung injury because tidal volumes can be reduced But further studies are required to show which mode of extracorporeal support to use

21. Pharmacologic Interventions: Neuromuscular Blocking Agents Patients with ARDS often “fight the ventilator”  aggravate ventilator-induced lung injury Administer a neuromuscular blocking agent –Patient–ventilator synchrony –Facilitate limitations on tidal volume and pressure The precise mechanism for the decreased mortality is unclear –Reduced serum cytokine levels –Decreased rate of multiorgan failure due to biotrauma

22. N Engl J Med 2010;363:1107-16.

23. Pharmacologic Interventions: Antiinflammatory Agents and Stem Cells Aim of pharmacologic interventions: minimizing biotrauma Not been reported in humans Studies in animals : antiinflammatory strategies and the use of mesenchymal stem cells have been investigated –Prevention of the consequences of ventilator-induced lung injury These treatments remain experimental and of unproven benefit

24. Areas of Uncertainty and Recommendations Although the trials described above help clinicians make difficult tradeoffs, they often do not address the complexity of many clinical situations Plateau pressure≤30 cm of water: may be too low in some patients –Markedly stiff chest wall: lungs may not be overdistended at 30 cm of water or even at higher plateau pressures –Higher plateau pressures: may be appropriate, even though the ARDS

25. Areas of Uncertainty and Recommendations Patients with relatively normal lungs: ventilation with low tidal volumes Smaller tidal volumes in patients without ARDS: may be associated with improved outcomes Ideal ventilation strategy remains to be determined More definitive studies are necessary before the use of such strategies becomes standard practice